- Email: [email protected]
Contagious agalactia: The shepherd’s nightmare
The Veterinary Journal 198 (2013) 5–6
Contents lists available at SciVerse ScienceDirect
The Veterinary Journal journal homepage: www.elsevier.com/locate/tvjl
Guest Editorial
Contagious agalactia: The shepherd’s nightmare
‘Fino a quando non saranno disponibili metodi diagnostici efficaci ed unvaccino protettivo, l’agalassia contagiosa continuera a rappresentare un incubo per I pastori Siciliani’ (‘Until there are effective diagnostics and a protective vaccine, contagious agalactia will remain a nightmare for Sicilian farmers’) (Mirri, 1956). Although there have been some improvements in diagnostics over the last 60 years since Professor Adelmo Mirri’s prediction, a good vaccine for contagious agalactia (CA) is still a long way off and the disease continues to haunt shepherds worldwide. The review by Dr Ángel Gómez-Martín and colleagues of the University of Murcia, Spain, in this issue of The Veterinary Journal describes some of these developments (Gómez-Martín et al., 2013). CA is probably one of the least well known of the diseases listed by the World Association for Animal Health (OIE) for their socio-economic impact, mainly because it is a disease felt by poor farmers often subsisting on marginal land who have a relatively small voice in the livestock industry. It is primarily a disease of sheep and goats that are kept for milk and dairy products using traditional husbandry rather than for production on an industrial scale. Consequently, its impact is localised, but can be very high, particularly where this type of farming represents the major source of income for the individual farmers. The low profit margins seen in this type of farming mean that there is rarely interest from commercial companies in making improvements to traditional, and sometimes ineffective, control measures and diagnostic tools. CA is an ancient disease, first described in Italy in the early 19th century, where it was known as ‘mal di sito’ because of its persistence on farms, enabling the contamination of successive flocks and herds. The disease is first noticed when milk production falls, usually a few days after the introduction of healthy carriers or from mixing with affected herds at pasture or water sources. Milk becomes abnormal and mastitic, then production ceases in one or both udders, often permanently. Keratoconjunctivitis and arthritis are chronic sequelae, particularly severe in young animals, preventing them from keeping up with the rest of the group during transhumance and other animal movements. CA is found wherever sheep and goats are kept, but concentrated in countries surrounding the Mediterranean and western Asia, especially in Iran and Mongolia, where large numbers of outbreaks are reported. Unusually for an OIE disease, four agents, all mycoplasmas, are listed as causing a clinically indistinguishable syndrome, although Mycoplasma agalactiae accounts for more than 80% of these infections; the other three pathogens are more often found in goats. There are indications that the disease is spreading, with increasing numbers of cases being seen in France and new outbreaks in Corsica.
The main impediments to successful control of CA are a lack of awareness and agreement internationally on the way forward. France favours culling of affected flocks, while Italy, Spain and Greece use a mixture of antimicrobial agents and vaccination in their endemically affected areas. Recent in vitro data has shown that most antibiotics are effective against M. agalactiae, which is in sharp contrast with the closely related pathogen of cattle, Mycoplasma bovis. This reflects the industrial scale of much cattle production where, because of widespread use, virtually all classes of antimicrobial agents are poorly effective. However the actual experience of antibiotic usage on small ruminant farms is less satisfactory and their use, while bringing about a quick clinical improvement, leaves long-term shedders contaminating the environment and posing risks to susceptible animals. Vaccination also leaves a lot to be desired. The majority are formalin-inactivated whole cell vaccines containing M. agalactiae and one or more of the other causative mycoplasmas, with limited or no published efficacy. One inactivated vaccine could not protect sheep from natural challenge, despite three annual vaccinations over the previous 3 years (Leon Vizcaino et al., 1995). More recently, in a small trial, no potency was evident in a similar commercial product following contact challenge (Agnone et al., 2013). Interestingly, a live attenuated vaccine, used successfully in Turkey for many decades, was safe and protective. While larger trials of commercial products are necessary, consideration should be given to using live vaccines (which are presently not allowed in Europe) in endemically affected areas. The development of DNA vaccines or recombinant vaccines has been reported, but these have not yet been used in the field. The inability to control CA in some parts of southern Europe is compounded by unnecessarily strict local veterinary legislation, which discourages farmers and veterinarians from reporting outbreaks. The prohibition on selling milk and delays in lifting restrictions can have a serious impact on the income of these small farmers. Consequently, the present number of reported outbreaks represents a large under-estimate. If the true socio-economic impact was known, then this may stimulate public veterinary services to instigate comprehensive control programmes. As with many mycoplasma diseases, early diagnosis is essential for successful treatment and control of outbreaks. Methods outlined in the review by Gómez-Martín et al. (2013), in particular the use of real time PCR, offer the possibility of rapid and sensitive detection of the causative mycoplasma directly in both the individual animal and in bulk tank milk. Another DNA amplification test, PCR-denaturing gradient gel electrophoresis (DGGE), has the added advantage of allowing the simultaneous detection
1090-0233/$ - see front matter Crown Copyright Ó 2013 Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tvjl.2013.06.017
6
Guest Editorial / The Veterinary Journal 198 (2013) 5–6
of all causative mycoplasmas in a single PCR reaction (McAuliffe et al., 2005). These tests should be rolled out to all laboratories involved in CA diagnosis for the monitoring of flock and herd health to enable a rapid response to disease outbreaks and to gauge the true extent of the disease. Finally, an area requiring more research is the association between M. agalactiae and the central nervous system. Gómez-Martín et al. (2013) review some of the reports of neurological disease associated with CA. At the Istituto Zooprofilattico Sperimentale (IZS) in Palermo, pioneering work on vaccines against CA was carried out by Professor Mirri and colleagues in the 1950s (Mirri and Gallo, 1954). Although discontinued now for obvious safety reasons, the first so-called farm vaccines were made from a combination of infected mammary glands and, surprisingly, brain tissue inactivated with formalin. A few years ago, we had the privilege of discovering Professor Mirri’s original research notes at the IZS library in Palermo and can confirm that the brain, obtained from naturally infected sheep, contained high concentrations of mycoplasma antigen, second only to the udder. How the mycoplasma colonises the brain, and what effect this has, is presently uncertain, but may account for a high percentage of undiagnosed inflammatory lesions presently classified as non-suppurative encephalitis. Guido Ruggero Loria Istituto Zooprofilattico Sperimentale della Sicilia Via G. Marinuzzi 3, 90129 Palermo, Italy E-mail address: [email protected]
Robin A.J. Nicholas Mycoplasma Group Animal Health and Veterinary Laboratories Agency (AHVLA) (Weybridge) Addlestone, Surrey KT15 3NB, UK E-mail address: [email protected]
References Agnone, A., La Manna, M., Sireci, G., Puleio, R., Usticano, A., Ozdemir, O., Nicholas, R.A.J., Chiaracane, V., Dieli, F., Di Marco, M., Loria, G.R., 2013. A comparison of the efficacy of commercial and experimental vaccines for contagious agalactia in sheep. Small Ruminant Research 112, 230–234. Gómez-Martín, A., Amores, J., Paterna, A., De la Fe, C., 2013. Contagious agalactia due to Mycoplasma species in small dairy ruminants: Epidemiology and prospects for diagnosis and control. The Veterinary Journal 198, 48–56. Leon Vizcaino, L., Garrido Abellan, F., Cubero Pablo, M.J., Perales, A., 1995. Immunoprophylaxis of caprine contagious agalactia due to Mycoplasma agalactiae with an inactivated vaccine. Veterinary Record 137, 266–269. McAuliffe, L., Ellis, R., Lawes, J., Ayling, R.D., Nicholas, R.A.J., 2005. 16S rDNA and DGGE: A single generic test for detecting and differentiating Mycoplasma species. Journal of Medical Microbiology 54, 1–9. Mirri, A., Gallo, C., 1954. Sull’eziologia dell’agalassia contagiosa degli ovini e dei caprini. Bollettino della Societa Italiana di Biologia Sperimentale 30, 56–58. Mirri, A., 1956. Agalassia contagiosa degli ovini e dei caprini. In: Stazzi, P., Mirri, A. (Eds.), Trattato di Malattie Infettive degli Animali Domestici, Ninth Ed. Cisalpino Editore, Palermo, Italy, pp. 881–891.
Contents lists available at SciVerse ScienceDirect
The Veterinary Journal journal homepage: www.elsevier.com/locate/tvjl
Guest Editorial
Contagious agalactia: The shepherd’s nightmare
‘Fino a quando non saranno disponibili metodi diagnostici efficaci ed unvaccino protettivo, l’agalassia contagiosa continuera a rappresentare un incubo per I pastori Siciliani’ (‘Until there are effective diagnostics and a protective vaccine, contagious agalactia will remain a nightmare for Sicilian farmers’) (Mirri, 1956). Although there have been some improvements in diagnostics over the last 60 years since Professor Adelmo Mirri’s prediction, a good vaccine for contagious agalactia (CA) is still a long way off and the disease continues to haunt shepherds worldwide. The review by Dr Ángel Gómez-Martín and colleagues of the University of Murcia, Spain, in this issue of The Veterinary Journal describes some of these developments (Gómez-Martín et al., 2013). CA is probably one of the least well known of the diseases listed by the World Association for Animal Health (OIE) for their socio-economic impact, mainly because it is a disease felt by poor farmers often subsisting on marginal land who have a relatively small voice in the livestock industry. It is primarily a disease of sheep and goats that are kept for milk and dairy products using traditional husbandry rather than for production on an industrial scale. Consequently, its impact is localised, but can be very high, particularly where this type of farming represents the major source of income for the individual farmers. The low profit margins seen in this type of farming mean that there is rarely interest from commercial companies in making improvements to traditional, and sometimes ineffective, control measures and diagnostic tools. CA is an ancient disease, first described in Italy in the early 19th century, where it was known as ‘mal di sito’ because of its persistence on farms, enabling the contamination of successive flocks and herds. The disease is first noticed when milk production falls, usually a few days after the introduction of healthy carriers or from mixing with affected herds at pasture or water sources. Milk becomes abnormal and mastitic, then production ceases in one or both udders, often permanently. Keratoconjunctivitis and arthritis are chronic sequelae, particularly severe in young animals, preventing them from keeping up with the rest of the group during transhumance and other animal movements. CA is found wherever sheep and goats are kept, but concentrated in countries surrounding the Mediterranean and western Asia, especially in Iran and Mongolia, where large numbers of outbreaks are reported. Unusually for an OIE disease, four agents, all mycoplasmas, are listed as causing a clinically indistinguishable syndrome, although Mycoplasma agalactiae accounts for more than 80% of these infections; the other three pathogens are more often found in goats. There are indications that the disease is spreading, with increasing numbers of cases being seen in France and new outbreaks in Corsica.
The main impediments to successful control of CA are a lack of awareness and agreement internationally on the way forward. France favours culling of affected flocks, while Italy, Spain and Greece use a mixture of antimicrobial agents and vaccination in their endemically affected areas. Recent in vitro data has shown that most antibiotics are effective against M. agalactiae, which is in sharp contrast with the closely related pathogen of cattle, Mycoplasma bovis. This reflects the industrial scale of much cattle production where, because of widespread use, virtually all classes of antimicrobial agents are poorly effective. However the actual experience of antibiotic usage on small ruminant farms is less satisfactory and their use, while bringing about a quick clinical improvement, leaves long-term shedders contaminating the environment and posing risks to susceptible animals. Vaccination also leaves a lot to be desired. The majority are formalin-inactivated whole cell vaccines containing M. agalactiae and one or more of the other causative mycoplasmas, with limited or no published efficacy. One inactivated vaccine could not protect sheep from natural challenge, despite three annual vaccinations over the previous 3 years (Leon Vizcaino et al., 1995). More recently, in a small trial, no potency was evident in a similar commercial product following contact challenge (Agnone et al., 2013). Interestingly, a live attenuated vaccine, used successfully in Turkey for many decades, was safe and protective. While larger trials of commercial products are necessary, consideration should be given to using live vaccines (which are presently not allowed in Europe) in endemically affected areas. The development of DNA vaccines or recombinant vaccines has been reported, but these have not yet been used in the field. The inability to control CA in some parts of southern Europe is compounded by unnecessarily strict local veterinary legislation, which discourages farmers and veterinarians from reporting outbreaks. The prohibition on selling milk and delays in lifting restrictions can have a serious impact on the income of these small farmers. Consequently, the present number of reported outbreaks represents a large under-estimate. If the true socio-economic impact was known, then this may stimulate public veterinary services to instigate comprehensive control programmes. As with many mycoplasma diseases, early diagnosis is essential for successful treatment and control of outbreaks. Methods outlined in the review by Gómez-Martín et al. (2013), in particular the use of real time PCR, offer the possibility of rapid and sensitive detection of the causative mycoplasma directly in both the individual animal and in bulk tank milk. Another DNA amplification test, PCR-denaturing gradient gel electrophoresis (DGGE), has the added advantage of allowing the simultaneous detection
1090-0233/$ - see front matter Crown Copyright Ó 2013 Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tvjl.2013.06.017
6
Guest Editorial / The Veterinary Journal 198 (2013) 5–6
of all causative mycoplasmas in a single PCR reaction (McAuliffe et al., 2005). These tests should be rolled out to all laboratories involved in CA diagnosis for the monitoring of flock and herd health to enable a rapid response to disease outbreaks and to gauge the true extent of the disease. Finally, an area requiring more research is the association between M. agalactiae and the central nervous system. Gómez-Martín et al. (2013) review some of the reports of neurological disease associated with CA. At the Istituto Zooprofilattico Sperimentale (IZS) in Palermo, pioneering work on vaccines against CA was carried out by Professor Mirri and colleagues in the 1950s (Mirri and Gallo, 1954). Although discontinued now for obvious safety reasons, the first so-called farm vaccines were made from a combination of infected mammary glands and, surprisingly, brain tissue inactivated with formalin. A few years ago, we had the privilege of discovering Professor Mirri’s original research notes at the IZS library in Palermo and can confirm that the brain, obtained from naturally infected sheep, contained high concentrations of mycoplasma antigen, second only to the udder. How the mycoplasma colonises the brain, and what effect this has, is presently uncertain, but may account for a high percentage of undiagnosed inflammatory lesions presently classified as non-suppurative encephalitis. Guido Ruggero Loria Istituto Zooprofilattico Sperimentale della Sicilia Via G. Marinuzzi 3, 90129 Palermo, Italy E-mail address: [email protected]
Robin A.J. Nicholas Mycoplasma Group Animal Health and Veterinary Laboratories Agency (AHVLA) (Weybridge) Addlestone, Surrey KT15 3NB, UK E-mail address: [email protected]
References Agnone, A., La Manna, M., Sireci, G., Puleio, R., Usticano, A., Ozdemir, O., Nicholas, R.A.J., Chiaracane, V., Dieli, F., Di Marco, M., Loria, G.R., 2013. A comparison of the efficacy of commercial and experimental vaccines for contagious agalactia in sheep. Small Ruminant Research 112, 230–234. Gómez-Martín, A., Amores, J., Paterna, A., De la Fe, C., 2013. Contagious agalactia due to Mycoplasma species in small dairy ruminants: Epidemiology and prospects for diagnosis and control. The Veterinary Journal 198, 48–56. Leon Vizcaino, L., Garrido Abellan, F., Cubero Pablo, M.J., Perales, A., 1995. Immunoprophylaxis of caprine contagious agalactia due to Mycoplasma agalactiae with an inactivated vaccine. Veterinary Record 137, 266–269. McAuliffe, L., Ellis, R., Lawes, J., Ayling, R.D., Nicholas, R.A.J., 2005. 16S rDNA and DGGE: A single generic test for detecting and differentiating Mycoplasma species. Journal of Medical Microbiology 54, 1–9. Mirri, A., Gallo, C., 1954. Sull’eziologia dell’agalassia contagiosa degli ovini e dei caprini. Bollettino della Societa Italiana di Biologia Sperimentale 30, 56–58. Mirri, A., 1956. Agalassia contagiosa degli ovini e dei caprini. In: Stazzi, P., Mirri, A. (Eds.), Trattato di Malattie Infettive degli Animali Domestici, Ninth Ed. Cisalpino Editore, Palermo, Italy, pp. 881–891.