Field observations and experiences gained from the implementation of control measures against lumpy skin disease in South-East Europe between 2015 and 2017

Accepted Manuscript Title: Field observations and experiences gained from the implementation of control measures against lumpy skin disease in South-East Europe between 2015 and 2017 Authors: E.S.M. Tuppurainen, S-E. Antoniou, E. Tsiamadis, M. Topkaridou, T. Labus, Z. Debeljak, B. Plavˇsi´c, A. Miteva, T. Alexandrov, L. Pite, J. Boci, D. Marojevic, V. Kondratenko, Z. Atanasov, B. Murati, Z. Acinger-Rogic, L. Kohnle, P. Calistri, A. Broglia PII: DOI: Reference:

S0167-5877(18)30548-8 https://doi.org/10.1016/j.prevetmed.2018.12.006 PREVET 4600

To appear in:

PREVET

Received date: Revised date: Accepted date:

3 September 2018 12 December 2018 12 December 2018

Please cite this article as: Tuppurainen ESM, Antoniou S-E, Tsiamadis E, Topkaridou M, Labus T, Debeljak Z, Plavˇsi´c B, Miteva A, Alexandrov T, Pite L, Boci J, Marojevic D, Kondratenko V, Atanasov Z, Murati B, Acinger-Rogic Z, Kohnle L, Calistri P, Broglia A, Field observations and experiences gained from the implementation of control measures against lumpy skin disease in South-East Europe between 2015 and 2017, Preventive Veterinary Medicine (2018), https://doi.org/10.1016/j.prevetmed.2018.12.006 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Field observations and experiences gained from the implementation of control measures against lumpy skin disease in South-East Europe between 2015 and 2017

Tuppurainen E.S.M.1ǂ, Antoniou S-E.2, Tsiamadis E.3 Topkaridou M.4, Labus T.5, Debeljak Z.6, Plavšić B.7, Miteva A.8, Alexandrov T.9 Pite L.10, Boci J.11, Marojevic D.12, Kondratenko V.13,

SC R

IP T

Atanasov Z.13, Murati. B.14, Acinger-Rogic Z.15 Kohnle L.16, P. Calistri 17 and Broglia A18.

1

Independent Veterinary Consultant for Lumpy skin disease, Sheeppox and Goatpox

2

Department of Infectious and Parasitic Diseases, Animal Health Directorate, DG Veterinary

N

U

Services, Hellenic Ministry of Rural Development and Food, Athens, Greece 3

A

Veterinary Directorate, Regional Unit of Thessaloniki, Region of Central Macedonia,

Thessaloniki, Greece and Department of Animal Production, Faculty of Veterinary Medicine,

Department of Veterinary Medicine, Directorate of Rural Economy and Veterinary Medicine

ED

4

M

Aristotle University of Thessaloniki, Greece

of Evros, Alexandroupolis, Greece

Department for Animal Health, Welfare and Traceability, Veterinary Directorate, Ministry

PT

5,7

CC E

of Agriculture, Forestry and Water Management, Belgrade, Republic of Serbia 6

Veterinary Specialist Institute “Kraljevo”, Zicka 34, 36000, Kraljevo, Serbia

8,9

Bulgarian Food Safety Agency, Pencho Slaveikov 15A, 1606 Sofia, Bulgaria

A

10,11

Sector of Epidemiology and Identification and Registration, Ministry of Agriculture and

Rural Development, Sheshi Skënderbej 2, Tirana 1000, Albania 12

Administration for Food Safety, Veterinary and Phytosanitary affairs of Montenegro

13

Food and Veterinary Agency, Former Yugoslav Republic of Macedonia

* This designation is without prejudice to positions on status, and is in line with UNSCR 124

2 14

Food and Veterinary Agency, Kosovo*

15

Veterinary and Food Safety Directorate, Ministry of Agriculture, Croatia

16

Centre for Applied One Health Research and Policy Advice, College of Veterinary Medicine

and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong, SAR Istituto Zooprofilattico Sperimentale Abruzzo e Molise "Giuseppe Caporale", Teramo, Italy

18

European Food Safety Authority, Parma, Italy

SC R

Corresponding Author

Abstract

A

1.

N

U

ǂ

IP T

17

M

The first epidemics of lumpy skin disease (LSD) reported in Europe in 2015 severely affected

ED

the cattle farming sector in several Balkan countries. After the first incursion into Greece in 2015, the disease quickly spread across the Balkan region with over 7,000 outbreaks

PT

reported by the end of 2016. Thanks to a coordinated regional control and eradication policy, the spread of the disease was halted by the end of 2017. Regional large-scale

CC E

vaccination campaign with effective homologous vaccines and high vaccination coverage revealed to be essential for the successful control the disease, supported by other measures such as early detection of outbreaks, total or partial stamping out and restrictions on cattle

A

movements. The aim of this paper is to discuss the field observations, challenges and lessons learnt while dealing with the first LSD epidemics in Europe. The cross-border collaboration by the veterinary authorities of all affected countries, coordinated by the European Commission and the technical support provided by many other international organizations played a fundamental role in stopping the spread of a disease that otherwise

3 could have expanded further to the European territory causing a large damage to the whole European cattle farming industry. The experience obtained during the control of LSD epidemics indicates that in the future LSD spread can be effectively halted, provided that appropriate surveillance plans and vigilance remains in place in the areas at risk of re-

IP T

incursion, especially those bordering endemic countries.

2.

SC R

Keywords: Lumpy skin disease; cattle; Balkans; morbidity; control; stamping out; Vaccination

Introduction

U

Between 2012 and 2014, lumpy skin disease (LSD) affected most Middle Eastern

N

countries, Turkey and the part of Cyprus not controlled by the Republic of Cyprus (EFSA,

A

2015; Tuppurainen et al., 2014). In August 2015, LSD extended its boundaries to the

M

European Union (EU) territory, affecting first the Regional Unit of Evros in Greece, followed

ED

by seven Regional Units (RU) in the North East Greece, and then by the end of 2016 an additional 11 RUs (Tasioudi et al., 2016; Antoniou et al., 2017). In April 2016, the disease

PT

continued its spread to Bulgaria and Former Yugoslav Republic of Macedonia (FYROM), then in June to Serbia, Kosovo* and Albania, and finally in July to Montenegro (EFSA, 2017). In

CC E

order to halt the spread of the disease, vaccinations were initiated in affected and at-risk Greek RUs in 2015. When the scale of the problem became evident in early 2016, a regional large-scale vaccination campaign was launched in the Balkan region using homologous, live

A

attenuated vaccines and high vaccination coverage. In 2017, the positive results were already clearly visible; multiple outbreaks occurred only in Albania (379 outbreaks), whereas only some sporadic ones were reported in the FYROM (4) and in Greece (2). Figure 1 illustrates the annual evolution of LSD epidemics in Europe since 2014.

4 In addition to vaccination against the disease, the affected countries implemented a series of immediate measures, complying with the EU and national legislation. The aim of this paper is to describe the field observations made during the LSD outbreaks and experiences gained while implementing control and eradication measures in the Western Balkans. Strengths and limitations of these measures are

IP T

discussed in order to identify the critical points that can be addressed to enhance the

efficacy of the control of LSD in the future. The data presented here comprise mainly

SC R

field observations collected by the official veterinary authorities (VA) during the implementation of measures according to national legislative framework. Different

Context

A

3.

N

should be taken into consideration in any analysis.

U

practices implemented in affected countries influence the interpretation of data and

M

Some main characteristics of the geography of the region, farming structures and the EU legislative framework are reported in this section, with the aim of highlighting the

ED

constraints which the veterinary services of the affected countries were facing while

3.1.

PT

controlling the spread of the disease.

The Balkan region: geography and cattle farming structure

CC E

The geography, cattle farming structure and practices in the Balkans made the

management of LSD challenging for the field operations. Figure 2 illustrates the cattle density in the region. The Western Balkan region is a mixture of mountains and valleys, and

A

many smallholdings are located at high altitudes with rich, fertile soil and a suitable climate for adopting mixed crop/livestock farming. Access to the mountain villages and farms was not always easy for the veterinary services. Especially, in many cases small uphill holdings were accessible only via narrow rough roads, basically suitable only for four-wheel drive vehicles.

5 In many Balkan countries (with an exception of Greece), the majority of cattle owners were small-scale or backyard farmers, having less than 10 animals. In some countries like Albania and Montenegro, 75% of the farms had less than five animals (EFSA, 2017). As an example, in Montenegro the average farm size is 4.6 hectares, with an average of 3.3 breeding cattle. Figure 3 illustrates some examples on intensive, medium-sized and small-

IP T

scale cattle farming units in the region. In villages, small cattle holdings are located in very close proximity to each other with limited access to pastures of their own, making

SC R

communal grazing a common practice. Particularly, during spring and summer 2016, such a farming structure made the implementation of control measures more difficult and may

have contributed to the quick spread of LSD throughout the Balkan region by bringing into

U

contact infected and susceptible animals, originating from different holdings.

N

The socio-economic importance of cattle for smallholders is substantial as it

A

provides livelihoods for people in rural areas. Milk is usually consumed by the family and

M

surplus is used for small-scale production of cheese, yogurt and other milk products, to be

ED

sold locally for extra income. The calves are sold when cash is needed to cover some bigger expenses. In many of the farms visited by the Community Veterinary Emergency Team

PT

(CVET) in Montenegro and elsewhere, farms were composed by only one cow. Clear majority of the outbreaks were confirmed in small herds or backyard farms in

CC E

remote areas. In some areas of the Balkans, e.g. in parts of Montenegro, FYROM, Bosnia and Herzegovina and the western Serbia, in spring, summer and autumn, cattle are kept

A

outdoors or moved to large-size common pastures in the high-mountain areas. Long distance dissemination of lumpy skin disease virus (LSDV) into a new area

occurs mainly by live infected animals and may go unnoticed if transportation occurs when the animals are incubating the disease without yet showing any clinical signs. Blood-feeding vectors are usually responsible of local short-distance transmission of the virus (EFSA, 2017,

6 2018a). Seasonal transhumance farming is a commonly practiced farming tradition in the some parts of the Western Balkans. Cattle are moved to summer pastures usually in May, by walking or transported in open vehicles, mixing animals from different sources and allowing vectors to feed on animals. Timewise, the re-occurrence of LSD outbreaks in Greece in the middle of April 2016 and introduction of the disease into Bulgaria and FYROM was

IP T

overlapping with the start of the seasonal cattle movements. An epidemiological investigation carried out by the Bulgarian veterinary services indicated that LSDV was

SC R

transmitted by vectors, but it did not exclude the possible role of illegal movements of infected animals (Miteva et al, 2017). This observation is in agreement with the recent epidemiological studies by EFSA (2017). The average spread of LSDV in the Balkans was

U

estimated as 1 km per day and 7.3 kilometres per week (Mercier et al 2018). More in-depth

N

retrospective epidemiological studies are needed to investigate the possible spatial or

A

temporal association between the seasonal cattle movements and spread of the virus. These

M

studies might contribute to the formulation of appropriate control and eradication policies,

ED

not only for LSD but also other infectious cattle diseases. National contingency plan usually covers the seasonal cattle movements and

PT

communal grazing practices. Traditional farming practices may hamper the proper implementation of a strict ban of cattle movements. Particularly, if cattle are not vaccinated,

CC E

but also if they are vaccinated but the immunity is not yet fully established and if the start of an outbreak timewise overlaps with a need to transport cattle to summer pastures. On the other hand, it is highly probable that a sudden stop of both communal and seasonal grazing

A

practices would swiftly lead to nutritional and environmental animal welfare issues. As free-grazing beef cattle are usually semi-wild, they are difficult to restrain for clinical examination or vaccination. Under these circumstances, implementation of vaccination and other official controls were considerably time-consuming. This was one of the reasons for leaving these herds as last, or in some cases it was not done at all, as these

7 animals were aimed for slaughter within a very short time, thus leaving “pockets” of unvaccinated animals within the fully vaccinated regions. Moreover, as LSD vaccine is administered subcutaneously, injecting a correct dosage into an animal resisting handling may sometimes fail, particularly when large number of animals had to be vaccinated in a hurry during a hectic mass vaccination in a holding. European legislative framework

IP T

3.2.

Within the EU Member States (MS), Directive 82/894/EEC of 21 December 1982

SC R

covers notification of the disease via the Animal Disease Notification System (ADNS), Directive 90/425/EEC of 26 June 1990 intra-community trade in live animals and their

U

products and Directive 92/119/EEC of 17 December 1992 the control and eradication

N

measures.

A

In 2015 and 2016, the European Commission (EC) implemented country-specific

M

decisions, allowing the emergency vaccination against LSDV in confined regions of Greece and Bulgaria. However, in late 2016, these decisions were amended, classifying countries or

ED

zones as “infected” or “free-with-vaccination” (Commission Implementing Decision (EU) 2016/2008 and (EU) 2016/2009). Different trade conditions and bilateral trade agreements

PT

were allowed for live animals and their products. The new directives decreased the

CC E

hesitation of those countries that shared common borders with affected countries, to start pre-emptive vaccinations without a major impact on trade.

A

4.

LSD control measures in practice – strengths and limitations

The general control and eradication policy for LSD, like for most of the other high-

impact transboundary diseases of farmed animals, is based on early detection of outbreaks, total or partial stamping out, mass vaccination and restrictions or total ban of animal movements. Here below, each of these measures are discussed in the light of recent LSD outbreaks in the Balkan region.

8 4.1 Early detection of lumpy skin disease virus The early diagnosis is a prerequisite for successful control and prevention of LSD. However, the presence of a variable proportion of non-symptomatic affected animals, showing only generic, not pathognomonic clinical signs, may induce some delays in the early detection. Since LSD was an exotic disease for European countries, during the epidemic in

IP T

2016, LSD cases in naïve cattle population were presented with typical clinical signs, which

made early detection in the field and disease notification very reliable. Veterinary services in

SC R

the Balkans implemented awareness campaigns prior to outbreaks and succeed well in early warning and rapid response activities.

U

4.1.1 Recognizing clinical signs of lumpy skin disease in the field

N

Due to the LSD outbreaks in Turkey, the VAs in the Western Balkans started well in

A

time to prepare field veterinarians and farmers for the potential incursion of the disease by

M

distributing educational posters and leaflets on LSD, organizing meetings, workshops and training activities with various cattle farming stakeholders, preparing guidelines and

ED

checklists for official and field veterinarians. Daily communication with farmers and other

PT

stakeholders was established via web links and emergency phones. A thorough clinical examination, carried out by an experienced veterinarian, is

CC E

considered as an effective tool to carry out active clinical surveillance for LSD (EFSA, 2018b). Clinical cases with advanced skin lesions are hard to misinterpret with other cattle diseases,

A

particularly when several animals in a herd are showing similar symptoms at the same time. Several factors may affect the accuracy of the clinical examination, including field

veterinarians’ previous experience on LSD, immune status and severity of the disease in the host, and the time lack between infection and examination. Based on experiences obtained from historically endemic countries and cattle experiments carried out in a controlled environment, LSD can easily be suspected on the

9 basis of the clinical picture in animals, showing skin lesions week or two after infection. However, within the first week, even the most experienced veterinarian may not be able to determine whether the disease is LSD or not. In addition, the diagnostic tests start to give positive results only after approximately a week after infection (Babiuk et al 2008; EFSA, 2018b), leaving a window of four to six days during which animals may be incubating the

IP T

virus but there are not yet any clinical or diagnostic tools available to detect the infection. This should be considered when formulating cattle movement allowances and restriction

SC R

rules during an LSD outbreak. The differences in the length of persistence of the live virus or

viral antigen within the different sample materials are described in detail in EFSA Scientific Opinion on Lumpy skin disease (2015). A skin disorder caused by a warble fly (Hypoderma

U

spp.) was the most common differential diagnosis in Greece.

N

Passive clinical surveillance methods are based on the ability of various cattle-

A

farming stakeholders to promptly identify the clinical signs and lesions caused by LSD. In

M

some cases, farmers first observed lameness and oedema of the legs, accompanied by

ED

depression and a loss of appetite (Antoniou et al., 2017). As dairy herds were monitored twice a day, non-specific symptoms such as fever, sharp drop in milk production, lethargy,

PT

and weakness were often detected before the appearance of the typical skin lesions. The main clinical manifestations of the disease were numerous skin nodules scattered

CC E

throughout the body, especially in the flanks, back, and the lower parts of the abdomen. Nodules were prominent on the perineal region and the udder cleft. However, skin nodules were not always clearly detectable in animals with longer winter coat and, thus, detailed

A

palpation of the skin was necessary. In advanced cases, skin nodules became ulcerated and in some cases diarrhoea was apparent. Fever peak (>40.0oC) typically marks the onset of viraemia and can last for a week or more. Ulcerative pox lesions were common on the mucous membranes of the oral and nasal cavities and sometimes even in conjunctiva or cornea of the eyes. Due to these lesions nasal and ocular discharge and saliva became

10 contaminated with infectious virus. The mortality rate for LSD is usually low and in most cases due to secondary infections. In general, if animals with other underlying diseases or conditions are infected with LSDV, they usually show more severe generalized disease, which in many cases may lead to the death of the affected animal. In those countries where total stamping out was practiced throughout the epidemics

IP T

and herds were culled as soon as possible after the first positive case was detected, the

clinical manifestation of the disease varied depending on the length of time the virus was

SC R

allowed to circulate in the herd before the herd was culled. These differences on stamping

out practices among Balkan countries influenced accordingly the reported morbidity and

U

mortality rates.

N

Active surveillance included monitoring of the cattle holdings and clinical examination of

A

animals by official veterinarians.

M

4.1.2 Laboratory capacities

National and international reference laboratories played an essential role during the

ED

epizootic. Due to the previous sheeppox experience in Greece and as the threat of LSD

PT

incursion was imminent, most of the national reference laboratories (NRL) had already established the basic group-specific molecular methods for the detection of capripox virus,

CC E

and the staff were trained and fully competent to use those methods prior to the first occurrence of LSD. In many laboratories, the actual bottleneck, hampering testing of larger amount samples, was the insufficient number of thermocyclers because the machines were

A

used for testing samples of other diseases as well and many thermocycler models were able to process less than 40 samples per run. In addition, lack of robotic DNA extraction machines and a low number of laboratory technicians, particularly to cover the weekend or evening on-call duties were reported as major concerns.

11 The implementation of mass vaccination campaigns, using attenuated LSDV vaccines, raised the need for developing diagnostic tools to differentiate the LSDV field strain from the vaccine strain. Greek and Serbian NRLs developed real-time DIVA PCRs (Agianniotaki et al, 2017; Vidanović et al 2016) for LSDV. In addition, previously described molecular or sequencing methods were set up for the differentiation of vaccine from the

IP T

field strain. Several training activities for laboratory personnel were made available.

SC R

International Atomic Energy Agency provided NRLs with training and technology transfer in molecular diagnostic assays and assisted in sequencing, whereas the EU reference laboratory on capripoxvirus and other laboratories in the EU MSs contributed by training of

U

the laboratory personnel and by validating novel assays. A major step forward in serological

M

A

facilitating large-scale serological surveillance.

N

diagnostics occurred when a long-awaited ELISA became commercially available in 2016,

As an example of availability of diagnostic services, the Bulgarian NRL laboratory

ED

staff were working 24/7 at the time of epidemics, confirming that the outbreaks were detected during the official surveillance, mass vaccination or via passive surveillance by

PT

farmers’ notifications. Disease suspicions were not only associated with observed nodules, but also with raised body temperature, milk drop, lethargy and weakness. In Serbia, three

CC E

laboratories had diagnostic capacity for LSD with fully validated assays.

A

4.1.3 Morbidity and mortality Accurate evaluation of the morbidity and mortality rates in affected countries is

difficult because in majority of countries the vaccination campaigns were started when the virus was already widely circulating in the region, thus changing the epidemiological patterns of the infection through the reduction of animals susceptible to the disease.

12 The total morbidity and mortality data calculated as the number of reported cases out of susceptible animals in the Balkan countries is shown in Table 1. Excluding Albania, the mortality rates were in general low, ranging between a maximum of 2.6% in Greece in 2017 to less than 1% in Montenegro, FYROM and Kosovo* (Table 1). Most Balkan countries had a relatively low number of cattle, swift access to vaccines and carried out effective vaccination

IP T

campaigns within a short period of time. Not surprisingly, both morbidity and mortality rates were highest in Albania, where

SC R

virus circulation lasted for the longest period of time before the whole cattle population was

immunized. LSD was clinically diagnosed on 28th of June 2016. The first vaccinations against LSD were started on 26th of July 2016 but because only 59% of coverage, it failed to stop the

U

spread of the disease. During the first month when no vaccinations were practiced, the

N

morbidity was 35.5% (251/706), and the mortality rate 1.4% (107/706). However,

A

considering the whole year 2016, exceptionally high morbidity (42%) and mortality (12%)

ED

low vaccination coverage.

M

rates were reported by the Albanian VAs (Pite et al, 2017) which was probably due to such a

In 2016, the reported morbidity rates in Bulgaria, FYROM and Serbia were similar,

PT

and almost a double of that reported at the same time in Greece. Both Greece and Bulgaria implemented a total stamping out policy throughout the epidemics, whereas the other

CC E

Balkan countries only before commencement of vaccination campaign. In the Balkan countries morbidity rates were calculated based on the number of

A

animals identified with apparent clinical signs present at the day of the confirmation of the disease (Greece), or at the day of depopulation (Bulgaria, Serbia). These discrepancies could partially explain the observed difference in morbidity rates among countries. Further retrospective epidemiological studies are needed to explain such a difference in morbidity rates. In Bulgaria, the overall morbidity and mortality rates (13% and

13 1%, respectively) were observed immediately before the stamping out measure was implemented. The estimated population infection rate was 0.41% of the total cattle population (Table 1). In those holdings that were visited while vaccination was implemented, the clinical examination of cattle was systematically performed and samples taken in case of suspicions. Cases were reported based on clinical examination by veterinary officials and

IP T

farmers’ disease suspicions. Looking at the numbers of outbreaks and the morbidity rates observed in small

SC R

countries like Montenegro, Kosovo* and FYROM in 2016, it was clear that extremely swift

actions were required. Consequently, each country conducted a highly effective vaccination campaign within a very short time, reaching high vaccination coverage, thus halting the

N

U

spread of the disease in a shortest period of time.

A

4.2 Stamping out, disposal of carcasses and farmers’ compensation mechanisms

M

In order to comply with the Council Directive 92/119/EEC, a total stamping out must be implemented without delay, even after a single officially confirmed LSD case in the herd.

ED

The confirmation can be based on positive laboratory results or, in the event of an epidemic,

PT

clinical examination or an epidemiological link. During the 2015 epizootic in Greece, pre-emptive culling was implemented in 16% of

CC E

the LSD outbreaks. The median interval between the date of suspicion and the date of depopulation was 4 days in 2015 (3 and 7 days, 25th and 75th percentiles, respectively) and

A

13 days in 2016 (7 and 21 days, 25th and 75th percentiles, respectively) (Antoniou et al, 2017). In Bulgaria, significant difficulties were faced in attempt to conduct control and

eradication actions within such a short period of time. In 96% of Bulgarian LSD outbreaks, cattle were culled and contaminated materials were disposed by burying on-site within three to eight days following the laboratory confirmation. In some cases, eradication actions were started already on suspicion. Culling and disposal of carcasses, contaminated materials,

14 feed, as well as disinfection activities were a major financial burden, requiring infrastructure, trained personnel, equipment, and vehicles for culling, transport and disposal. In regions where a high number of outbreaks were detected within a short period of time, additional veterinary staff and support was obtained from other regions. In non-EU MSs, a total stamping out policy was practiced only until vaccinations

IP T

were started, after which a partial stamping out policy was implemented, i.e. culling only those animals showing clinical signs of LSD or tested positive with PCR. In Serbia, after the

SC R

onset of vaccinations, if an LSD positive case was detected within the vaccination zone,

selective stamping out was implemented. In order to avoid greater economic losses, the VAs emphasized the importance of the shortest possible time between confirmative diagnosis

U

and swift implementation of disease eradication measures and vaccinations. After culling

N

and disposal of cattle, disinfection of the holding and all equipment used, were performed.

A

All restrictions at infected farms were lifted after two incubation periods (56 days) had

M

elapsed since completion of disinfection measures.

ED

With regard to stamping out, Montenegro followed EFSA’s urgent advice on lumpy skin disease (EFSA, 2016). Partial stamping out was implemented by culling 557 cattle in 436

PT

holdings in which infection was confirmed by positive PCR test results of nasal swabs, skin

CC E

and/or blood samples.

As most of the holdings in the region had less than five animals, burying on-site was

a feasible option. In the region, rendering plants were not available, either they were

A

located too far away, or their capacity was totally insufficient to handle large numbers of animals. Carcasses were buried in three to four meters deep pit, covered with calcium carbonate powder and disinfectant and then layered by soil. Sometimes groundwater was unexpectedly detected during the preparation of the burial place and a different location had to be found, causing additional delay.

15 In remote regions, a major challenge with disposal of carcasses was the availability of excavators. Stamping out teams often had to wait until the digger tractor was transferred from the previous holding, making the working days for the stamping out team to last until the late night. Disposal of carcasses is likely to become a major concern if a large cattle farming

IP T

unit has to be depopulated. Therefore, many countries decided to prioritize vaccination of these farms.

SC R

Evaluation of the compensation value of the culled animals was carried out either by

the official veterinary inspectors, animal health officers, representatives from local

U

municipality and other livestock service departments. The owner usually received the

N

compensation within weeks from the government. However, when the outbreaks were

A

widely spread it was not easy to find vaccinated animals for replacement. No stamping out

M

policy was practiced in Albania which was the most affected country in the Western Balkan region. Albanian VAs, however, implemented an excellent way to compensate those animals

ED

that qualified for compensation: the government replaced animals with vaccinated improved-breed Jersey and Holstein heifers with better milk production, improving the

PT

general cattle genepool in the country. In Serbia, farmers were compensated with 100% of

CC E

the market price of culled animals by the Veterinary Directorate, few days after culling. Although killing of animals was conducted humanely and respecting animal welfare,

the procedure was highly stressful for farmers and veterinarians. In general, cattle owners

A

did not object culling of severely infected animals. However, euthanizing vaccinated animals, showing very mild if any clinical signs of the disease but tested positive for LSD in PCR, was more difficult to understand or accept. Many experienced veterinarians who had served their customers and friends for years, indicated this event as the most stressful professional experience during their careers. In Greece, the total stamping out policy resulted in a large

16 number of carcasses to be disposed, compromising milk and meat production, damaged the local rural economy and raised public, economic and environmental concerns (Antoniou et al., 2017). 4.3 Cattle movement restrictions In addition to vaccination, updated animal identification records and movement

IP T

controls are the key measures for LSD eradication. Authorized or illegal movement of infected animals with or without clinical signs is the most important way to spread LSD, both

SC R

over short and long distances. After the arrival of the index case into a new region, vectors

can then start disseminating the virus first within the herd and then to the neighbourhood

U

herds, although also other direct or indirect modes of transmission are known to occur.

N

In a real life, completely watertight control over cattle movements is highly

A

challenging to achieve, especially when the restrictions must be in force for several weeks or

M

even longer. Due to grazing, trade or other reasons and despite enhanced border and road

not officially allowed.

ED

controls, unauthorised cattle movements within and across the borders may occur, although

PT

As an initial response to the LSD outbreaks in Turkey in June 2015, Greece implemented a safeguard zone of 10 km along the Greek-Turkish border in the Evros RU

CC E

with enhanced surveillance of the cattle holdings and clinical examination of cattle before transport. Later, the same measures were implemented at the borders with FYROM and Albania. Inside the protection zones of 3 km, no bovine movements were allowed, not even

A

to slaughterhouses. Within the surveillance zones of 25 km, cattle were allowed to move to private pastures and directly to slaughterhouses located within these zones. At the beginning of the epizootic in November 2015, a total standstill of one month for all bovine animals was enforced, except for transport to the nearest slaughterhouses. Officially, no bovines were allowed to be transported to another Greek region outside the affected RU,

17 regardless of their health status, not even for immediate slaughter. Clinical examination and issuing a health certificate was mandatory before any transport and ante-mortem inspection was carried out at slaughterhouses by the state veterinarians (Antoniou et al., 2017). Interestingly, in Bulgaria, movement restrictions included in addition to all bovines, also small ruminants in case of mixed farms. Based on the epizootic situation and risk of

IP T

wide-scale spread of LSD, movement of ruminants from South to North and vice versa was forbidden. Any transport/movement of susceptible species was subject to official veterinary

SC R

control. Pastoralism, transhumance and related cattle movements were under a strict control. Enforced border and traffic controls were implemented.

U

An updated, user-friendly database for cattle identification, including movements

N

and health records, is an essential tool for disease control, vaccination campaigns and

A

epidemiological analysis. In addition, it will be of high importance in coming years when

M

official surveillance for the demonstration of a freedom-of-LSD status will be started. As an example, in Serbia, individual identification of bovines as well as registration and

ED

authorization of cattle movements are recorded in a central database, which was quickly upgraded to comprise the vaccination data. Animal and herd registration, traceability and

PT

movements of animals and products were assessed and controlled. Movement of infected animals to slaughter was not allowed. The ban on animal fairs, markets and other gatherings

CC E

of domestic ruminants and control of cattle transport, including small ruminants originating from mixed farms, together with animal identification, movement and health record

A

systems, significantly contributed to halting the spread of disease. Also in Albania, the control or total ban of animal movements from farms to abattoirs and to livestock markets was enforced. In Montenegro, one of the major issues during LSD crisis was to effectively control cattle movements. A ban of importation of live cattle from affected countries was in place

18 but uncontrolled movements or importations from Kosovo* and Albania were an issue. Summer pasture area shared between Montenegro, Albania and Kosovo* was considered to be one of the reasons for spreading the disease to Montenegro. 4.4 Vaccination All affected countries in the Balkans used LSDV-containing vaccines, so-called

IP T

homologous vaccines. The vaccine selection was based mainly on the experience and

evidence obtained from Israel during 2012-13 LSD outbreaks, where the use of homologous

SC R

vaccine halt the spread of the disease (Ben-Gera et al 2015). In Greece, the emergency

vaccination campaign was started two weeks after the beginning of the epizootic in Evros RU

U

in early September 2015 and by the end of December 2015, 146,000 cattle were vaccinated

N

in East Macedonia and Thrace and in Central Macedonia Regions.

A

In spring 2016, the EU established a vaccine bank for LSD and the first vaccines were

for all affected countries.

M

distributed to Greece, Bulgaria and FYROM. Later, the emergency vaccines were provided

ED

In early 2016, Bulgarian VAs were already expecting the incursion of LSD and two

PT

weeks after the reported index case in April, a vaccination campaign was started despite the limited extent of the infection in the country. Bulgarian VAs made a well-justified decision to

CC E

vaccinate the whole cattle population of 778,900 heads without delay, completing the whole operation within two and half months. The last suspected LSD case in Bulgaria was consequently reported on 28th of July 2016.

A

In Serbia, vaccination started three weeks after notification of first case, and 99%

vaccination coverage was achieved within three months. Based on risk analysis, the country was then divided in three zones (Figure 4): 

Zone А: emergency vaccination of cattle in the two infected districts of Pčinjski and Jablanički;

19 

Zone B: vaccination of cattle in infected and at-risk areas upon any occurrence of new outbreaks (specifically in the Braničevski District) and in certain holdings of larger capacity outside zones A and B, based on risk assessment;



Zone C: preventive vaccination in LSD-free areas. Prior to the second vaccination round of the whole bovine population in 2017,

IP T

vaccination of new-born, imported and other non-vaccinated cattle was implemented in order to immunize all susceptible animals.

SC R

Albania was the country most affected by LSD. The disease was first reported in early July 2016. Mass vaccination by private veterinary clinics was started within two weeks

U

of time and by October 2016, approximately 59% of cattle were vaccinated. However, two

N

months passed until more vaccines were obtained into the country. After the end of the first

A

vaccination campaign, the remaining unvaccinated cattle were scattered within the

M

municipalities around the country and new outbreaks were recorded on daily basis. The second vaccination phase lasted from December 2016 to January 2017, according to the

ED

availability of vaccines.

The general vaccination policy in Albania was to check the cattle for fever and other

PT

clinical signs of LSD. Only healthy animals were vaccinated and those showing clinical signs

CC E

were if required treated with supportive treatments (antibiotics and anti-inflammatories). However, the system was not perfect due to animals with silent infection or cases that were assumed to be LSD but were actually caused by something else, leaving a few unprotected

A

individuals to the otherwise vaccinated regions. The awareness campaign on farm biosecurity and good veterinary practice was addressed by all levels of the veterinary services. It was not possible to conduct stamping out. In May 2017, also private veterinarians were contracted to assist in the mass vaccination campaign. However, another 379 outbreaks were recorded in 2017 (Pite et al, 2017).

20 Figure 5 illustrates the vaccination coverage achieved within the region at different points of time of the epidemic and the reported outbreaks in the same period. 4.4.1. Effectiveness of vaccination In the Balkans, a regional vaccination coverage of more than 90% was achieved by January 2017, before the start of the following vector season of 2017 (Fig 5). After finalising

IP T

successful vaccination of the whole cattle population, outbreaks ceased within one month of

time in Bulgaria, Serbia, Montenegro and Kosovo*, providing strong evidence on the

SC R

effectiveness of mass vaccination in the field setting. The efficacy of the vaccine was experimentally confirmed by conducting challenge trials in a controlled environment by the

U

EU reference laboratory for LSD (Belgium) (Kris de Clercq, personal communication). The

N

effectiveness of the vaccination campaigns in the field was estimated by mathematical

A

modelling and survival analysis (Gubbins et al 2018; Klement et al 2018).

M

Due to the successful vaccination campaign and effective control of cattle movements, epizootics of LSD were controlled, and no new cases were recorded in 2017,

ED

except in those areas where vaccination of the whole cattle population was not fully completed: 385 outbreaks with 850 affected animals were notified in 2017, 379 in Albania,

PT

two outbreaks in Greece and four in FYROM. Elsewhere, LSD outbreaks were declared as

CC E

resolved in December 2016 (ADNS). Using a mathematical modelling tool, EFSA recently published a predictive simulation on the spread of the disease under different vaccination effectiveness and coverage scenarios. This

A

model indicates that with at least 90% vaccination coverage, two to three years vaccination campaigns (95% and 65% effectiveness, respectively) may be sufficient to eliminate LSD from the Balkan region, provided that no new introduction of the disease occurs from the neighbouring affected countries and negligible probability that the infectious virus can survive for years in the environment (EFSA, 2018b). The actual duration of protection

21 provided by the vaccination applied multiple times needs further evaluation, particularly in dairy and breeding cattle whose lifespan can be longer than 5 years. As in Albania the disease was already widely spread when vaccinations were initiated, animals showing clinical signs were often reported also in vaccinated herds up to three to four weeks post-vaccination. Eventually, the positive effects of vaccination were

IP T

also seen in Albania where, by the end of 2017, the vaccination coverage reached

approximately 70%, reducing the reported number of LSD outbreaks from a total of 3,567 in

SC R

2016 to 379 in 2017. 4.4.2. Supply of vaccines and procurement process

U

Within the EU, the initial approach before 2015 was that vaccination against LSD was

N

strictly prohibited. Nevertheless, it swiftly became evident that it was not possible to

A

effectively halt the spread of the disease without vaccination, and finally also preventive

M

vaccinations were approved in 2016 in Croatia.

The financial and administrative procedures associated with vaccine tendering and

ED

procurement were time-consuming, causing delays in starting the vaccination campaigns,

PT

and affected equally all countries involved. In addition, sudden increase in vaccine demand caused temporary delays in manufacturers’ production capacity, but, as expected for live

CC E

vaccines, they were swiftly sorted out. The possibility to obtain initial emergency vaccines from the EU vaccine bank for

LSD, allowed implementation of mass vaccinations swiftly when most urgently needed,

A

without having to wait for the time-consuming tendering process to be finalized. In Serbia, the costs of the control and eradication measures were covered by the budget of the Republic of Serbia. This included the purchase of vaccines, the costs of the vaccination measure, active surveillance, diagnostic tests, compensation of dead and culled animals, as well as other appropriate measures on infected farms with the aim of preventing

22 the spread of epidemics. Payments were quick and redistribution of the sufficient numbers of vaccines to affected districts were carried out in timely manner in accordance with the spread of the disease. Distribution of vaccines and vaccination of animals was recorded in well developed software application which was a part of animal identification and veterinary information system.

IP T

4.4.3 Vaccine adverse reactions

In Europe homologous live attenuated LSD vaccines were widely used and no

SC R

outbreaks caused by the vaccine strain have so far been reported. Recently, Croatian

scientists isolated and sequenced a LSD vaccine strain from an animal, showing adverse skin

U

reaction after vaccination. Sequencing data confirmed that after a passage in cattle the

N

genome of the vaccine virus remained stable with 100% similarity to the original vaccine

A

virus (Lojkić et al 2018). This finding provides further confirmation that the use of the live

passage in a vaccinated animal.

M

vaccine is safe, and it is unlikely that the vaccine strain will regain the virulence after a

ED

According to the vaccine producers, the development of protective immunity takes approximately two to three weeks and vaccine may cause a local reaction at the vaccination

PT

site, sometimes generalized skin lesions and a temporary decrease in milk production. A

CC E

warning is included in the vaccine package insert, and the farmers and veterinarians were informed about possible vaccine side effects. Indeed, in most countries, farmers complained about clinical signs after vaccination,

A

mainly temporary fever, lump at the vaccination site and reduction of milk production. Except in Croatia and Bosnia and Herzegovina, LSDV was already circulating in the Balkans when vaccinations were started, making it difficult to evaluate if the clinical signs detected in vaccinated animals were caused by the vaccine strain, the field strain or both. Nevertheless, in order to assess the impact of side effects of vaccination, a properly

23 conducted analytical study is required, therefore the information presented in this section should be considered as observational evidence that cannot prove yet the association between vaccination and adverse effects. According to Israeli experience, LSD vaccine caused only mild adverse effects at a very low incidence (0.38%) (Ben Gera et al, 2015). However, the Israeli cattle were already

IP T

vaccinated once with SPP RM65 strain vaccine which, according to the authors, was likely to reduce the observed adverse effects (Ben Gera et al, 2015).

SC R

Detection of clinical signs in vaccinated herds led to complicated situations in the field. With regard to stamping out measures, Directive 92/119 EEC does not differentiate if

U

the clinical signs after vaccination are caused by the vaccine or field strain

N

Common side effects observed in Greece were transient decline in milk production,

A

loss of appetite and swelling and/or skin nodules around the injection site. Generalized

M

symptoms after vaccination were officially reported in two herds and the vaccine strain was identified by the laboratory analysis. These herds were considered as suspicious, and kept

ED

under official supervision by the VAs until the laboratory results were obtained.

PT

In Greece, 31% of the total confirmed outbreaks concerned vaccinated farms and all the relevant measures were implemented. At a later stage, when DIVA-PCR was available,

CC E

analysis to differentiate field from vaccine strain was performed on the stored samples collected from all affected farms. The vaccine strain alone was identified in the stored samples only of three outbreaks of vaccinated herds (1.3 % of the total number of

A

outbreaks) whereas in the rest, the field strain was identified. According to Greek VAs, the policy of culling fully vaccinated herds created doubts

amongst farmers on the necessity and effectiveness of vaccination itself. Consequently, Greece VAs proposed the establishment of epidemiological and legislative procedures to

24 avoid the implementation of total stamping out if only a sporadic LSDV-positive animal was detected in a fully-vaccinated herds with established immunity (Antoniou et al, 2017). In Bulgaria, 21% of the outbreaks were confirmed between 3 and 21 days after vaccination, whereas the rest of the outbreaks were reported in non-vaccinated herds. Although laboratory analysis of collected samples confirmed the presence of LSD virus, it

”skin lumps” post-vaccination were treated as LSD field virus-infected animals.

IP T

was not tested if the causative agent was LSD vaccine or field strain. All animals that showed

SC R

In Serbia, clinical symptoms of LSD were observed three to seven days after vaccination. Decline in milk production was observed and in some individual cases there was

U

abortion. Laboratory testing was performed using DIVA PCR (Vidanović et al. 2016). Abortion

N

cases were investigated and some differential diagnostic tests were negative. However, no

A

definite conclusions should be made whether abortions were linked to the use of live LSD

M

vaccine as also numerous other pathogens and factors can cause abortions in cattle. In Albania, 159 suspected vaccine adverse reactions were reported in 2016.

ED

Unfortunately, at that time, no PCR method were available in the Albanian reference laboratory to investigate if the clinical signs observed in vaccinated cattle were caused by

PT

the virulent field strain or the vaccine virus itself. After vaccinations in 2017, the number

CC E

clinical signs observed in vaccinated animals decreased to 30. In Montenegro, adverse reactions were observed in cattle after administration of

the LSDV vaccine only after the first vaccination campaign. A large number of animals

A

showed mild skin reaction four to five days post-vaccination which then disappear in a couple of days. In addition, a fall in milk production, fever, abortion and in some cases, deaths were observed. In the beginning, it was impossible to differentiate between the vaccine and the field strain, but later a DIVA test method was set up at Diagnostic Veterinary Laboratory and is currently used.

25 Although vaccinated, the immune response of some individuals may not be sufficient to develop full protection against highly virulent field strain. These individuals are a clear risk during the high vector activity seasons, particularly in herds located close to borders with disease-free country. Consequently, even in vaccinated herds those animals showing skin lesions caused by the field virus should be removed from the herd as a highest

IP T

priority. Rapid DIVA PCR methods assist in avoiding unnecessary losses. Long field experience obtained from endemic countries supports the observation

SC R

that when the animals are vaccinated for the second time they usually do not show anymore

adverse reactions. This was indeed observed in Montenegro, Albania and elsewhere:

U

adverse effects were rarely reported after the second vaccination campaign.

N

To date, only a few scientific reports have been published on adverse reactions after

A

vaccination against LSD (Abutarbush et al 2016; Katsoulos et al, 2016).

M

Large-scale preventive vaccinations were carried out in Croatia and Bosnia and Herzegovina in 2016 and 2017. From these countries it was possible to obtain further

ED

information on the side effects of the vaccine without interference by the field strain (Bedeković et al 2017). Initial data reported by Croatian VAs through pharmacovigilance

PT

system showed adverse reactions post-vaccination in 0.19% of the vaccinated farms, in

CC E

0.09% of the vaccinated animals with 0.02% deaths (EFSA, 2017). The majority of symptoms were reported within two weeks after vaccination and included fever, decrease in milk production and oedema at the injection site. More detailed analysis of the data on LSD

A

vaccine adverse effects in a naïve cattle population in Croatia and Bosnia and Herzegovina will hopefully be carried out and published in the near future. 5.

Conclusions In 2015-2018, the control of LSD in Europe was successful, enabled by high

awareness on LSD throughout the cattle farming industry and cooperative farmers,

26 availability of effective vaccines and, above all, the cross-border collaboration of the VAs in the affected and at-risk countries, allowing swift response to LSD outbreaks throughout the Balkans. Official and private veterinarians demonstrated their capacity to effectively conduct mass vaccinations and other disease control measures within a short period of time. GFTADs provided an international platform to agree on harmonised regional vaccination plans

IP T

and countries received a substantial amount of support by other international organizations. The availability of effective vaccines and support by the EU vaccine bank speeded up the

SC R

immunization of the whole cattle population in the region.

Despite LSD outbreaks seem to be currently under control, the VAs in the Balkans need to remain vigilant in regard possible recurrence of LSD into the EU territory. Re-

U

incursion may originate either within the affected EU MSs, from Turkish Thrace or from the

A

N

East.

M

LSDV is a very stable virus and typically in endemic regions LSD outbreaks occur in cycles with several years between (Tuppurainen and Oura, 2012). The actual mechanism

ED

how long and where the virus can remain infectious outside the host, needs to be investigated. LSDV is known to survive in shaded premises for at least six months (OIE,

PT

2017), possibly within dried skin scabs shed into the environment by recovering animals. Properly conducted cleansing and disinfection of animal sheds and facilities can inactivate

CC E

the virus. However, not much is known on whether infectious LSDV survives in the farm environment and pastures and if so, will it disappear by time, in case cattle population

A

remains immune. It is also not known if a natural reservoir for the virus exists. An alternative arrival route for LSD to enter the EU territory is via affected

neighbouring regions. The disease is considered as endemic in Turkey and outbreaks are annually reported. The total number of cattle population in Turkey is around 17 million, making it considerably more challenging and expensive to maintain annual vaccination

27 regimes covered solely by governmental funding. Seasonal cattle movements are common and in the European point of view, movement of cattle, sheep or goats from the Eastern to Western parts of Turkey are of concern. On both Turkish and Greek sides of the river Evros, semi-wild beef cattle are kept free-ranging. With an exception of breeding animals, the life span of beef cattle is approximately 12 to 24 months. After vaccination against LSD are

IP T

ceased, the number of fully susceptible cattle population will rapidly increase at the most vulnerable location.

SC R

Whatever stamping out policy is in place, it is highly recommended that at least

those animals that show generalised skin lesions are removed from the herd without delay. More importantly, the time between suspicion or confirmation of an LSDV infection and

U

completion of the stamping out measure must be kept less than a week. This is particularly

N

important when outbreaks occur in those regions, bordering countries where animals are

A

not vaccinated yet, even though the distance to the borders would seem to be long. Due to

M

vector transmission and potential unauthorized movement of animals, even a short

ED

presence of infected animals is a substantial risk in a region where the vaccination coverage is low, or vaccination coverage is high but full immunity is not yet developed in surrounding

PT

herds.

In case an outbreak occurs within a fully vaccinated region where immunity against

CC E

LSD has already been established, only sporadic cases will occur in those individuals that for some or another reason were not able to develop immunity. The choice of culling the whole

A

herd is questionable in this particular case and often poorly accepted by cattle owners. Cattle movement allowances need a thorough consideration as well as the

possibility to set up penalties for farmers who are caught on unauthorized cattle trade or transport during an outbreak. Cattle transport personnel hold the key role in stopping sick animals to leave the farm. However, it should be bear in mind that a conflict of interest may

28 exist amongst cattle owners, traders and authorities, and proper road access control may need to be in place. In case of suspicion, readily available clear instructions what to do and who to contact, would be of help to support animal traders or cattle truck drivers when handling with unexpectedly found susceptible cases and decisions need to be made fast. Experience obtained during the LSD epidemics clearly demonstrates that LSD

IP T

outbreaks can effectively be halted. From whatever direction the next threat of incursion will come, the goal of the future policies and contingency plans should be to create a system

SC R

that does not allow such extensive spread of the disease as occurred in 2015-2016. Tools, methods and knowledge are already available, but most importantly, a proactive spirit of

Acknowledgements

N

6.

U

collaboration amongst all parties is needed and has been the key of success.

A

Veterinary Authorities of the affected countries who despite their other duties and extensive

M

workload, were willing to share their experiences and data on LSD outbreaks in the framework of good cooperation and better control and eradication of the disease.

ED

The members of the CVET Kris De Clercq, Pip Beard and Joseph Domenech and the

PT

representatives from European Commission (DG SANTE) Dimitrios Dilaveris, Francisco Reviriego Gordejo, Bernard Van Goethem, Francesco Berlingieri and Nicolas Krieger.

CC E

DISCLAIMER

The present article is published under the sole responsibility of the authors and may not be

A

considered as an EFSA scientific output. The positions and opinions presented in this article are those of the authors alone and do not necessarily represent the views or any official position or scientific works of EFSA. To know about the views or scientific outputs of EFSA, please consult http://www.efsa.europa.eu. 7.

REFERENCES

29 Abutarbush, S. M., Hananeh, W. M., Ramadan, W., Al Sheyab, O. M., Alnajjar, A. R., Al Zoubi, I. G., Knowles, N. J., Bachanek-Bankowska, K. & Tuppurainen, E. S. 2016. Adverse reactions to field vaccination against lumpy skin disease in Jordan. Transbound. Emerg. Dis. 63(2), 213-219. Agianniotaki, E. I., Tasioudi, K. E., Chaintoutis, S. C., Iliadou, P., Mangana-Vougiouka, O.,

IP T

Kirtzalidou, A., AlexandropoulosT., Sachpatzidis A., Plevraki E., Dovas C.I., Chondrokouki, E. 2017. Lumpy skin disease outbreaks in Greece during 2015-16, implementation of

SC R

emergency immunization and genetic differentiation between field isolates and vaccine virus strains. Vet. Microbiol., 201, 78–84, doi: 10.1016/j.vetmic.2016.12.037.

U

Antoniou S-E., Tsiamadis E., Tasioudi K.E., Moraitis S., Plevraki E., Sachpatzidis Α.

N

Perdikaris S., Vitalis T., Arakas N., Lianou D., Chondrokouki E., Malemis I.,

A

Alexandropoulos T., Dile C., 2017, Lumpy Skin Disease in Greece: An European approach

M

of the management of the disease, in FAO EMPRES-Animal Health 360: Special edition on Lumpy Skin Disease No. 47, 19-22.

ED

Babiuk, S., Bowden, T.R., Parkyn, G., Dalman, B., Manning, L., Neufeld, J., Embury-Hyatt, C., Copps, J., Boyle, D.B., 2008. Quantification of lumpy skin disease virus following

PT

experimental infection in cattle. Transbound. Emerg. Dis. 55, 299–307; doi:

CC E

10.1111/j.1865-1682.2008.01024. Bedeković T., Šimić I., Kresić N., Lojkić I. 2017. Detection of lumpy skin disease virus in

A

skin lesions, blood, nasal swabs and milk following preventive vaccination. Transbound. Emerg. Dis. (July), 6–11; doi: 10.1111/tbed.12730. Ben-Gera J, Klement E, Khinich E, et al (2015) Comparison of the efficacy of Neethling lumpy skin disease virus and x10RM65 sheep-pox live attenuated vaccines for the prevention of lumpy skin disease - The results of a randomized controlled field study. Vaccine 33:4837–42.

30 EFSA (European Food Safety Authority), 2017. Lumpy skin disease: I. Data collection and analysis. EFSA Journal, 15, 1831-4732, doi: 10.1111/tbed.12497. EFSA (European Food Safety Authority), 2018a. Lumpy skin disease II. Data collection and analysis. EFSA Journal 2018;16(2):5176, 33 pp; DOI: 10.2903/j.efsa.2018.5176. EFSA (European Food Safety Authority), Calistri P, DeClercq K, De Vleeschauwer A,

IP T

Gubbins S, Klement E, Stegeman A, Cortinas Abrahantes J, Antoniou S-E, Broglia A and Gogin A, 2018b. Scientific report on lumpy skin disease: scientific and technical

SC R

assistance on control and surveillance activities. EFSA Journal 2018;16(10):5452, 46 pp. https://doi.org/10.2903/j.efsa.2018.5452

lumpy

skin

disease.

EFSA

Journal

2015;13(1):3986,

73

pp.

N

on

U

EFSA AHAW Panel (EFSA Panel on Animal Health and Welfare), 2015. Scientific Opinion

A

doi:10.2903/j.efsa.2015.3986

advice

on

lumpy

skin

M

EFSA AHAW Panel (EFSA Panel on Animal Health and Welfare), 2016. Statement: Urgent disease.

EFSA

Journal

2016;14(8):4573,

27

pp.

ED

doi:10.2903/j.efsa.2016.4573.

PT

Gubbins S, Stegeman A, Klement E, Pite L, Broglia A and Cortiñas Abrahantes J, 2018. Inferences about the transmission of lumpy skin disease virus between farms from

CC E

outbreaks in Albania during 2016. Preventive Veterinary Medicine, submitted. Klement E, Broglia A, Antoniou SE, Tsiamadis E, Plevraki E, Petrović T, Polaček V,

A

Debeljak Z, Miteva A, Alexandrov T, Marojevic D, Pite L, Kondratenko V, Atanasov Z, Gubbins, Stegeman and Cortiñas Abrahantes J, 2018. Neethling vaccine proved highly effective in controlling Lumpy skin disease epidemics in the Balkans. Preventive Veterinary Medicine, in press.

31 Katsoulos P.D., Chaintoutis S.C., Dovas C.I., Polizopoulou Z.S., Brellou G.D., Agianniotaki E.I., Tasioudi K.E., Chondrokouki E., Papadopoulos O., Karatzias H., Boscos C., 2017. Investigation on the incidence of adverse reactions, viraemia and haematological changes following field immunization of cattle using a live attenuated vaccine against lumpy skin disease. Transbound. Emerg. Dis. doi:10.1111/tbed.12646.

IP T

Lojkić, I., Šimić, I., Krešić, N., Bedeković, T., 2018. Complete Genome Sequence of a

Lumpy Skin Disease Virus Strain Isolated from the Skin of a Vaccinated Animal. Genome

SC R

Announc. 6:e00482-1, 1–2.

Mercier A, Arsevska E, Bournez L, Bronner A., Calavas D., Cauchard J., Falala S., Caufour

U

P., Tisseuil C., Lefrançois T., Lancelot R. (2018). Spread rate of lumpy skin disease in the

N

Balkans, 2015-2016. Transbound Emerg Dis 65 (1), 240–243.

A

Miteva A., Alexandrov T., Zdravkova A., Petkova Ivanova P., Chobanov G., Ivanova E.

M

(2017). Emergence of lumpy skin disease in Bulgaria: epidemiological situation, control and eradication. In FAO EMPRES-Animal Health 360: Special edition on Lumpy Skin

ED

Disease No. 47, 23-25.

PT

World Organisation for Animal Health (2017) - Manual of Diagnostic Tests and Vaccines for Terrestrial Animals. OIE, Paris. http://www.oie.int/en/international-standard-

CC E

setting/terrestrialmanual/access-online/ Pite L., Fero E., Ago A., Xhepa M., Boci J., Vodica A., Rizvanolli E., Lilo A. (2017). Lumpy

A

skin disease epidemics in Albania. In FAO EMPRES-Animal Health 360: Special edition on Lumpy Skin Disease No. 47, 32-33. Tasioudi K.E., Antoniou S-E, Iliadou P., Sachpatzidis A., Plevraki E., Agianniotaki E.I., Fouki C., Mangana-Vougiouka E., Chondrokouki E., Dile C. (2016). Emergence of Lumpy Skin Disease in Greece 2015, Transbound Emerg Dis. 63(3), 260–265.

32 Tuppurainen E.S.M. and Oura C.A.L. (2012) Review: Lumpy skin disease: an emerging threat to Europe, the Middle East and Asia. Transbound Emerg Dis 59:40–48. Tuppurainen E and Oura C, 2014. EDITORIAL Lumpy skin disease: an African cattle disease getting closer to the EU. Veterinary Record, 175, 300-301; doi: 10.1136/vr.g5808.

IP T

Vidanović D., Šekler M., Petrović T., Debeljak Z., Vasković N., Matović K., Hoffmann B. (2016). Real-time PCR assays for the specific detection of field Balkan strains of lumpy

SC R

skin disease virus. Acta Veterinaria-Beograd 66 (4), 444-454; DOI: 10.1515/acve-2016-

A

CC E

PT

ED

M

A

N

U

0038.

N

U

SC R

IP T

33

A

CC E

PT

ED

M

A

Figure 1 Lumpy skin disease outbreaks notified in Europe in 2014–2017 (Data source: ADNS and national veterinary authorities)

N

U

SC R

IP T

34

A

CC E

PT

ED

M

A

Figure 2 Map of cattle density in the Balkan region and related orography

N

U

SC R

IP T

35

A

CC E

PT

ED

M

A

Figure 3 Intensive, medium-sized and small-scale cattle farming units in the Balkan region

N

U

SC R

IP T

36

A

CC E

PT

ED

M

A

Figure 4 Vaccination zones in Serbia and Kosovo* in 2016 (zones A: emergency vaccination of animals in the two infected districts; zone B: vaccination of cattle in infected and at-risk areas upon any occurrence of new outbreaks and of cattle in large holdings outside zones A and B, based on risk assessment; zone C: preventive vaccination in LSD-free areas)

N

U

SC R

IP T

37

A

CC E

PT

ED

M

A

Figure 5 Percentage of vaccinated animals in the region in 2016 and 2017 in different periods of the epidemics and reported outbreaks (in red the active ones related to that month, in grey the past ones)

38 Table 1. Number of reported outbreaks, overall morbidity and mortality rates (number of reported sick or dead animals out of all susceptible animals present in the outbreaks) in the Balkan countries

Number of outbreaks

N/A

3567

42%

12%

379

Bulgaria

0

N/A

N/A

217

13.0%

1.0%

0

FYROM

0

N/A

N/A

1454

14.5%

0.0%

Greece

117

9.9%

0.7%

104

7.0%

Kosovo*

0

N/A

N/A

1304

14.4%

Montenegro

0

N/A

N/A

436

Serbia

0

N/A

N/A

N/A

N/A

4

2.6%

0.6%

1.5%

2

11.5%

2.6%

0.0%

0

N/A

N/A

20%

0.5%

0

N/A

N/A

225

13.3%

2.1%

0

N/A

N/A

N

IP T 4.8%

U

26.8%

M

ED PT CC E A

Mortality

Mortality

N/A

Morbidity

Morbidity

0

SC R

Number of outbreaks

Albania

A

Mortality

2017

Morbidity

2016

Number of outbreaks

2015