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Maedi–Visna virus infection in sheep. History and present knowledge
Comparative Immunology, Microbiology & Infectious Diseases 27 (2004) 1–5 www.elsevier.com/locate/cimid
Maedi –Visna virus infection in sheep. History and present knowledge Otto Christian Straub* Federal Research Centre for Virus Diseases of Animals, P.O. Box 1149, Tu¨bingen D-72001, Germany Accepted 18 November 2002
Abstract Briefly the history of maedi– visna and the major clinical symptoms are described. Examples are presented to demonstrate that the genetic composition of a breed determines whether or not sheep become sick after an infection with maedi – visna virus (mvv) or develop solely specific antibodies. The major pathway of transmission is not colostrum and milk, but a cell containing increased nasal discharge in cases of respiratory distress. The role of the environment and prophylactic measures against parasites is stressed, because even sheep of highly susceptible breeds can survive an infection under optimal conditions. The virus and subsequently the disease simply die out. The cooperation between clinicians and laboratories is necessary. q 2004 Elsevier Ltd. All rights reserved. Keywords: Sheep; Maedi –visna virus; Infection; Breed; Immunity; Clinical symptoms; Tests
Re´sume´ L’historique de la maladie maedi–visna et les symptoˆmes cliniques essentiels sont brie`vement de´crits. Des exemples sont pre´sente´s qui de´montrent que c’est la composition ge´ne´tique d’un troupeau qui de´termine si les moutons deviennent malades apre`s une infection du virus maedi – visna ou s’ils deve´loppent simplement des anticorps spe´cifiques. La voie prinicipale de transmission n’est ni le colostrum, ni le lait mais une cellule du mucus nasal. Le roˆle de l’environnement et des mesures profilactites contre les parasites sont sousligne´s, car des races hautement sensibles pourraient survivre a` l’infection lorsqu’elles sont place´es sous des conditions optimales d’environnement. La coope´ration entre cliniciens et laboratoire est essentielle. q 2004 Elsevier Ltd. All rights reserved. Mots-cle´: Mouton; Virus maedi– visna; Infection; Race; Immunite´; Symptoˆmes cliniques; Tests
* Fax: þ49-7071-63671. E-mail address: [email protected] (O.C. Straub). 0147-9571/$ - see front matter q 2004 Elsevier Ltd. All rights reserved. doi:10.1016/S0147-9571(02)00078-4
2
O.C. Straub / Comp. Immun. Microbiol. Infect. Dis. 27 (2004) 1–5
1. Introduction Maedi –visna or ovine progressive pneumonia was the first member of the lentivirus infections and recognised as an independent disease of sheep. It was also the first member of a new category of diseases, the slow infections, discovered and described by the Icelandic scientist Sigurdsson in 1954 [1]. It seems appropriate to deal with this infection from a historical point of view, because the outstanding work of Sigurdsson [1] does not receive the attention it deserves. He was the first scientist who recognised that besides acute and chronic infections another category of infections existed, the ‘slow infections’. He described in sheep as characteristic a ‘long latent period’, not synonymous with incubation period, because the virus is propagated and spread in the body without any clinical sign for months and years followed by a continuous progress of clinical signs after their first appearance leading eventually to severe sickness and death of the sheep. The infectious nature of the disease named in Icelandic ‘purra maedi’ ¼ dry maedi (maedi—Icelandic for dyspnoea) had been recognised much earlier. It became evident that the disease had been introduced by an import of Karakul sheep from Germany in 1933. The importation had the goal to improve the Icelandic native breed. As it turned out the same Karakul sheep introduced also pulmonary adenomatosis and paratuberculosis [2], and of course visna (in Icelandic ‘shrinking’—meaning of the spinal cord). It was years later when the viruses of maedi and visna had been isolated and characterised that they are strains of the same, now identified as maedi – visna virus (MVV), a lentivirus. The clinical signs of the two diseases are listed in Table 1. Adenomatosis was named ‘wota maedi’ (in Icelandic watery dyspnoea). The shepherds differentiated between wota and purra maedi by lifting sick sheep with their hind legs. In cases of adenomatosis lots of watery nasal discharge flown out of the nostrils, in the cases of dry maedi no nasal discharge was notified. The designation MVV was chosen in order to honour the outstanding work of the Icelandic scientists [3]. Most countries use by now this terminology except in the USA, where the disease is still called ‘ovine progressive pneumonia (OPP)’.
Table 1 The clinical symptoms of maedi and visna Major clinical signs of maedi
Of visna
Dry cough Expiratory dyspnoea Body temperature only in terminal stage due to secondary infection elevated Emaciation in spite of good appetite and feed intake Strain dependent mastitis and/or arthritis
Weakness in the hind legs, progressing, Finally complete paralysis Digestive tract not involved No rise in body temperature Sometimes central nervous disorders
O.C. Straub / Comp. Immun. Microbiol. Infect. Dis. 27 (2004) 1–5
3
2. The role of the breeds in developing clinical signs The imported Karakul sheep never developed obvious clinical signs of Maedi – visna which raised the question of a breed predisposition. The Icelandic scientists suggested that the native sheeps were extremely susceptible. Inquiries revealed that this isolated flock of Karakul sheep still existed in 1970 in the German Democratic Republic (East Germany). The original flock had been imported in 1901 from Astrachan (Russia). From the exterior they seemed to be the right source to improve the Icelandic native breed. During these years from 1901 to 1970 maedi was never detected in the isolated German flock. The same result was reported from six foreign countries which had received sheep from this flock after 1945. In discussions with W. Hadlow (1970, personal communication) in Montana, where maedi is known as Montana Sheep Disease the genetic composition of two new breeds— Columbia and Targhee—was studied and found out that they had one breed in common: Corriedale. In the same year maedi (OPP) was detected in a purebred Corriedale flock in the USA. In East Germany the occurrence of maedi in a flock of Merinomeat Sheep was reported in 1967 [4] and in 1972 in a West German flock [5] of the same breed. That breed has in its genetic composition also Corriedale blood. The research on maedi –visna in Germany was started in 1969 after a first flock of some 300 Texel sheep imported from The Netherlands developed the characteristic symptoms of maedi, which had never been observed before [3]. The disease was well known in Holland and called ‘Zwoegerziekte’—in France ‘La Bouhite’—and when the Dutch authorities were asked why they had never reported the occurrence of this disease in their country and prohibited the export, the answer was, ‘why should we report this, since you exported the disease to Iceland’ (G.F. De Boer, personal communication, 1970). Great Britain had been free of maedi – visna until the virus introduced by Texel sheep from France in the seventies. Shepherds in Scotland had been warned against the importation of Texel sheep from Holland, but that signal did not stop them from importing Texel sheep. They later used as an excuse that the sheep did not come from Holland but from France. In the meantime an eradication programme has been inaugurated in the United Kingdom after many flocks had been infected.
3. Research in Germany Immediately after the occurrence of maedi in Germany a research programme was started after the first virus isolation in 1969, described in 1970 [3] and continued until the year 2000 at the Federal Research Centre in Tu¨bingen using four different breeds from native flocks: Texel, Finnsheep, Ile de France and Merinocountry sheep (‘Merinolandschafe’). This breed has no Corriedale portion in its genetic code. After many generations of sheep the following result was obtained. All breeds except Merinocountry sheep developed clinical signs of the disease, the majority maedi, the minority visna. At the beginning of the study sheep of all four breeds had developed humoral antibodies against the MVV but the number of sero-positive declined constantly (Table 2).
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O.C. Straub / Comp. Immun. Microbiol. Infect. Dis. 27 (2004) 1–5
Table 2 Example of the development of the number of sheep negative for MVV. Originally—1970—the whole flock was sero-positive Year
Number of sheep
Sero-positive
Sero-negative
1984 1986 1988 1992
18 29 22 22
13 16 11 3
5 13 11 19
The study ended in 2000 when the last sero-positive but clinically normal ram was sacrificed due to old age.
Why did maedi –visna die out? - All sheep—rams and ewes together—were constantly housed and received regular prophylactic treatment against parasites. Their body temperature was measured daily for years and shearing performed once yearly. Help in parturition was rarely necessary, and if then in Texel sheep because of their broad heads. An artificial transmission experiment was started when the number of sero-positive animals had decreased to only a few. Eight sheep received 4 –40 ml of blood from seropositive clinically unaffected sheep. None of the recipients developed humoral antibodies. It could thus be demonstrated that the original through contact infected animals had eliminated the virus completely. A final ring test was carried out with 31 laboratories in Austria, Germany and Switzerland. They received 23 serum samples from sheep and goats to be tested for humoral antibodies against maedi – visna and caprine arthritis—encephalitis virus—the lentivirus of goats. All but one laboratory, which used Western blot, employed either an immunodiffusion test (IDT) and/or an ELISA. Seven duplicates of goat sera and six of sheep sera were included in the two series of 23 samples in order to determine the within laboratory error. Both tests were reliable for the diagnosis of Maedi –visna but Westernblotting proved less suitable [6].
4. The eradication programme In various German states a programme was started to eradicate maedi –visna. After a serological survey positive and negative sheep are separated. Offspring from sero-positive ewes may remain with the does for 1 month because the passively acquired antibodies prevent transmission in most animals. Controls start at an age of 6 months and are to be continued in 6 months intervals. Sero-positive animals are instantly eliminated. Pursuing this programme lead in a relative short time to sero-negative flocks.
5. Discussion Which conclusions can be drawn from the results obtained in Germany and also elsewhere.
O.C. Straub / Comp. Immun. Microbiol. Infect. Dis. 27 (2004) 1–5
5
1. Only certain breeds develop clinical signs after an infection with MVV. It appears that coarse wool type sheep are more susceptible than fine wool type sheep. 2. The environment plays a most important role. The best example is Iceland, where sheep are crowded in small huts during the cold season leading to rapid transmission by nasal discharge containing lots of infectious cells in contrast to the low prevalence in Montana where the sheep are kept extensively on pasture (one sheep per 5 acres). 3. Regular prophylactic treatment with anthelmintic drugs reduces the risk of transmission, because infestation with lung worms favours the spread of maedi – visna. 4. With the modern genetic techniques it should be possible to identify the loci responsible for resistance or predisposition in the various breeds. 5. Sheep in flocks known to be maedi – visna positive exhibiting signs of respiratory disease, especially nasal discharge should be separated and treated until no discharge is visible. 6. In cases where adenomatosis occurs in the same flock, the better choice may be to slaughter the whole flock—there is no danger in consuming the meat, if the sheep does not show acute signs of disease - than living with a constant threat of losing too many sheep. 7. Many authors claim that milk plays a major role in transmission. From the German experience was concluded that the cell containing nasal discharge is the main source. 8. A cooperation between clinicians and laboratories seems to be essential for the exertion of future investigations. Eradication programmes have been started in many countries world wide, all of them based solely on serological examinations. This is all right in rich countries like Switzerland [7]. But especially in third world countries like Ethiopia [8] special attention should be drawn to the occurrence of clinical signs. It could well be that one of the two breeds—Menz and Horro—which have been examined does not develop clinical signs, but is resistant.
References [1] Sigurdsson B. 1954 s. Straub, OC1970a. [2] Straub OC. Die Visna/Maedi-Krankheiten des Schafes. Tiera¨rztl Umschau 1970;25:373– 5. ¨ ber die Isolierung von Maedi/Visna-Virus (MVV) aus einem deutschen [3] Straub OC. U Schafbestand. Berl Mu¨nch Tiera¨rztl Wschr 1970;83:357 – 60. [4] Seffner W, Lippmann R. Mh Vet-Med 1967;22:901 – 6. s. Schaltenbrand und Straub, 1972. [5] Schaltenbrand G, Straub OC. Visna/Maedi in einer unterfra¨nkischen Merinofleischschafherde. Dtsch Tiera¨rztl Wschr 1972;79:10– 12. [6] Straub OC, Pfaff E. Ergebnisse eines Ringversuches zum Nachweis von humoralen Antiko¨rpern gegen die Lentiviren von Schaf und Ziege. Tiera¨rztl Umschau 1999;54:571 – 8. [7] Scheer-Czechowski P, Vogt H-R, Tontis A, Peterhans E, Zanoni R. Pilotprojekt zur Sanierung der Maedi – Visna bei Walliser Schwarznasenschafen. Schweiz Arch Tierheilk 2000;142: 155–64. [8] Ayelet G, Roger F, Tibbo F, Tembely YS. Survey of maedi– visna (MV) in Ethiopian highland sheep. Vet J 2001;161:208– 10.
Maedi –Visna virus infection in sheep. History and present knowledge Otto Christian Straub* Federal Research Centre for Virus Diseases of Animals, P.O. Box 1149, Tu¨bingen D-72001, Germany Accepted 18 November 2002
Abstract Briefly the history of maedi– visna and the major clinical symptoms are described. Examples are presented to demonstrate that the genetic composition of a breed determines whether or not sheep become sick after an infection with maedi – visna virus (mvv) or develop solely specific antibodies. The major pathway of transmission is not colostrum and milk, but a cell containing increased nasal discharge in cases of respiratory distress. The role of the environment and prophylactic measures against parasites is stressed, because even sheep of highly susceptible breeds can survive an infection under optimal conditions. The virus and subsequently the disease simply die out. The cooperation between clinicians and laboratories is necessary. q 2004 Elsevier Ltd. All rights reserved. Keywords: Sheep; Maedi –visna virus; Infection; Breed; Immunity; Clinical symptoms; Tests
Re´sume´ L’historique de la maladie maedi–visna et les symptoˆmes cliniques essentiels sont brie`vement de´crits. Des exemples sont pre´sente´s qui de´montrent que c’est la composition ge´ne´tique d’un troupeau qui de´termine si les moutons deviennent malades apre`s une infection du virus maedi – visna ou s’ils deve´loppent simplement des anticorps spe´cifiques. La voie prinicipale de transmission n’est ni le colostrum, ni le lait mais une cellule du mucus nasal. Le roˆle de l’environnement et des mesures profilactites contre les parasites sont sousligne´s, car des races hautement sensibles pourraient survivre a` l’infection lorsqu’elles sont place´es sous des conditions optimales d’environnement. La coope´ration entre cliniciens et laboratoire est essentielle. q 2004 Elsevier Ltd. All rights reserved. Mots-cle´: Mouton; Virus maedi– visna; Infection; Race; Immunite´; Symptoˆmes cliniques; Tests
* Fax: þ49-7071-63671. E-mail address: [email protected] (O.C. Straub). 0147-9571/$ - see front matter q 2004 Elsevier Ltd. All rights reserved. doi:10.1016/S0147-9571(02)00078-4
2
O.C. Straub / Comp. Immun. Microbiol. Infect. Dis. 27 (2004) 1–5
1. Introduction Maedi –visna or ovine progressive pneumonia was the first member of the lentivirus infections and recognised as an independent disease of sheep. It was also the first member of a new category of diseases, the slow infections, discovered and described by the Icelandic scientist Sigurdsson in 1954 [1]. It seems appropriate to deal with this infection from a historical point of view, because the outstanding work of Sigurdsson [1] does not receive the attention it deserves. He was the first scientist who recognised that besides acute and chronic infections another category of infections existed, the ‘slow infections’. He described in sheep as characteristic a ‘long latent period’, not synonymous with incubation period, because the virus is propagated and spread in the body without any clinical sign for months and years followed by a continuous progress of clinical signs after their first appearance leading eventually to severe sickness and death of the sheep. The infectious nature of the disease named in Icelandic ‘purra maedi’ ¼ dry maedi (maedi—Icelandic for dyspnoea) had been recognised much earlier. It became evident that the disease had been introduced by an import of Karakul sheep from Germany in 1933. The importation had the goal to improve the Icelandic native breed. As it turned out the same Karakul sheep introduced also pulmonary adenomatosis and paratuberculosis [2], and of course visna (in Icelandic ‘shrinking’—meaning of the spinal cord). It was years later when the viruses of maedi and visna had been isolated and characterised that they are strains of the same, now identified as maedi – visna virus (MVV), a lentivirus. The clinical signs of the two diseases are listed in Table 1. Adenomatosis was named ‘wota maedi’ (in Icelandic watery dyspnoea). The shepherds differentiated between wota and purra maedi by lifting sick sheep with their hind legs. In cases of adenomatosis lots of watery nasal discharge flown out of the nostrils, in the cases of dry maedi no nasal discharge was notified. The designation MVV was chosen in order to honour the outstanding work of the Icelandic scientists [3]. Most countries use by now this terminology except in the USA, where the disease is still called ‘ovine progressive pneumonia (OPP)’.
Table 1 The clinical symptoms of maedi and visna Major clinical signs of maedi
Of visna
Dry cough Expiratory dyspnoea Body temperature only in terminal stage due to secondary infection elevated Emaciation in spite of good appetite and feed intake Strain dependent mastitis and/or arthritis
Weakness in the hind legs, progressing, Finally complete paralysis Digestive tract not involved No rise in body temperature Sometimes central nervous disorders
O.C. Straub / Comp. Immun. Microbiol. Infect. Dis. 27 (2004) 1–5
3
2. The role of the breeds in developing clinical signs The imported Karakul sheep never developed obvious clinical signs of Maedi – visna which raised the question of a breed predisposition. The Icelandic scientists suggested that the native sheeps were extremely susceptible. Inquiries revealed that this isolated flock of Karakul sheep still existed in 1970 in the German Democratic Republic (East Germany). The original flock had been imported in 1901 from Astrachan (Russia). From the exterior they seemed to be the right source to improve the Icelandic native breed. During these years from 1901 to 1970 maedi was never detected in the isolated German flock. The same result was reported from six foreign countries which had received sheep from this flock after 1945. In discussions with W. Hadlow (1970, personal communication) in Montana, where maedi is known as Montana Sheep Disease the genetic composition of two new breeds— Columbia and Targhee—was studied and found out that they had one breed in common: Corriedale. In the same year maedi (OPP) was detected in a purebred Corriedale flock in the USA. In East Germany the occurrence of maedi in a flock of Merinomeat Sheep was reported in 1967 [4] and in 1972 in a West German flock [5] of the same breed. That breed has in its genetic composition also Corriedale blood. The research on maedi –visna in Germany was started in 1969 after a first flock of some 300 Texel sheep imported from The Netherlands developed the characteristic symptoms of maedi, which had never been observed before [3]. The disease was well known in Holland and called ‘Zwoegerziekte’—in France ‘La Bouhite’—and when the Dutch authorities were asked why they had never reported the occurrence of this disease in their country and prohibited the export, the answer was, ‘why should we report this, since you exported the disease to Iceland’ (G.F. De Boer, personal communication, 1970). Great Britain had been free of maedi – visna until the virus introduced by Texel sheep from France in the seventies. Shepherds in Scotland had been warned against the importation of Texel sheep from Holland, but that signal did not stop them from importing Texel sheep. They later used as an excuse that the sheep did not come from Holland but from France. In the meantime an eradication programme has been inaugurated in the United Kingdom after many flocks had been infected.
3. Research in Germany Immediately after the occurrence of maedi in Germany a research programme was started after the first virus isolation in 1969, described in 1970 [3] and continued until the year 2000 at the Federal Research Centre in Tu¨bingen using four different breeds from native flocks: Texel, Finnsheep, Ile de France and Merinocountry sheep (‘Merinolandschafe’). This breed has no Corriedale portion in its genetic code. After many generations of sheep the following result was obtained. All breeds except Merinocountry sheep developed clinical signs of the disease, the majority maedi, the minority visna. At the beginning of the study sheep of all four breeds had developed humoral antibodies against the MVV but the number of sero-positive declined constantly (Table 2).
4
O.C. Straub / Comp. Immun. Microbiol. Infect. Dis. 27 (2004) 1–5
Table 2 Example of the development of the number of sheep negative for MVV. Originally—1970—the whole flock was sero-positive Year
Number of sheep
Sero-positive
Sero-negative
1984 1986 1988 1992
18 29 22 22
13 16 11 3
5 13 11 19
The study ended in 2000 when the last sero-positive but clinically normal ram was sacrificed due to old age.
Why did maedi –visna die out? - All sheep—rams and ewes together—were constantly housed and received regular prophylactic treatment against parasites. Their body temperature was measured daily for years and shearing performed once yearly. Help in parturition was rarely necessary, and if then in Texel sheep because of their broad heads. An artificial transmission experiment was started when the number of sero-positive animals had decreased to only a few. Eight sheep received 4 –40 ml of blood from seropositive clinically unaffected sheep. None of the recipients developed humoral antibodies. It could thus be demonstrated that the original through contact infected animals had eliminated the virus completely. A final ring test was carried out with 31 laboratories in Austria, Germany and Switzerland. They received 23 serum samples from sheep and goats to be tested for humoral antibodies against maedi – visna and caprine arthritis—encephalitis virus—the lentivirus of goats. All but one laboratory, which used Western blot, employed either an immunodiffusion test (IDT) and/or an ELISA. Seven duplicates of goat sera and six of sheep sera were included in the two series of 23 samples in order to determine the within laboratory error. Both tests were reliable for the diagnosis of Maedi –visna but Westernblotting proved less suitable [6].
4. The eradication programme In various German states a programme was started to eradicate maedi –visna. After a serological survey positive and negative sheep are separated. Offspring from sero-positive ewes may remain with the does for 1 month because the passively acquired antibodies prevent transmission in most animals. Controls start at an age of 6 months and are to be continued in 6 months intervals. Sero-positive animals are instantly eliminated. Pursuing this programme lead in a relative short time to sero-negative flocks.
5. Discussion Which conclusions can be drawn from the results obtained in Germany and also elsewhere.
O.C. Straub / Comp. Immun. Microbiol. Infect. Dis. 27 (2004) 1–5
5
1. Only certain breeds develop clinical signs after an infection with MVV. It appears that coarse wool type sheep are more susceptible than fine wool type sheep. 2. The environment plays a most important role. The best example is Iceland, where sheep are crowded in small huts during the cold season leading to rapid transmission by nasal discharge containing lots of infectious cells in contrast to the low prevalence in Montana where the sheep are kept extensively on pasture (one sheep per 5 acres). 3. Regular prophylactic treatment with anthelmintic drugs reduces the risk of transmission, because infestation with lung worms favours the spread of maedi – visna. 4. With the modern genetic techniques it should be possible to identify the loci responsible for resistance or predisposition in the various breeds. 5. Sheep in flocks known to be maedi – visna positive exhibiting signs of respiratory disease, especially nasal discharge should be separated and treated until no discharge is visible. 6. In cases where adenomatosis occurs in the same flock, the better choice may be to slaughter the whole flock—there is no danger in consuming the meat, if the sheep does not show acute signs of disease - than living with a constant threat of losing too many sheep. 7. Many authors claim that milk plays a major role in transmission. From the German experience was concluded that the cell containing nasal discharge is the main source. 8. A cooperation between clinicians and laboratories seems to be essential for the exertion of future investigations. Eradication programmes have been started in many countries world wide, all of them based solely on serological examinations. This is all right in rich countries like Switzerland [7]. But especially in third world countries like Ethiopia [8] special attention should be drawn to the occurrence of clinical signs. It could well be that one of the two breeds—Menz and Horro—which have been examined does not develop clinical signs, but is resistant.
References [1] Sigurdsson B. 1954 s. Straub, OC1970a. [2] Straub OC. Die Visna/Maedi-Krankheiten des Schafes. Tiera¨rztl Umschau 1970;25:373– 5. ¨ ber die Isolierung von Maedi/Visna-Virus (MVV) aus einem deutschen [3] Straub OC. U Schafbestand. Berl Mu¨nch Tiera¨rztl Wschr 1970;83:357 – 60. [4] Seffner W, Lippmann R. Mh Vet-Med 1967;22:901 – 6. s. Schaltenbrand und Straub, 1972. [5] Schaltenbrand G, Straub OC. Visna/Maedi in einer unterfra¨nkischen Merinofleischschafherde. Dtsch Tiera¨rztl Wschr 1972;79:10– 12. [6] Straub OC, Pfaff E. Ergebnisse eines Ringversuches zum Nachweis von humoralen Antiko¨rpern gegen die Lentiviren von Schaf und Ziege. Tiera¨rztl Umschau 1999;54:571 – 8. [7] Scheer-Czechowski P, Vogt H-R, Tontis A, Peterhans E, Zanoni R. Pilotprojekt zur Sanierung der Maedi – Visna bei Walliser Schwarznasenschafen. Schweiz Arch Tierheilk 2000;142: 155–64. [8] Ayelet G, Roger F, Tibbo F, Tembely YS. Survey of maedi– visna (MV) in Ethiopian highland sheep. Vet J 2001;161:208– 10.