The Veterinary Journal 198 (2013) 5–6
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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 rap-
presentare un incubo per I pastori Siciliani’ (‘Until there are effec-
tive 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 produc-
tion 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. Keratoconjunc-
tivitis 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 infec-
tions; 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.
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
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 effec-
tive against M. agalactiae, which is in sharp contrast with the clo-
sely 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 sus-
ceptible animals.
Vaccination also leaves a lot to be desired. The majority are for-
malin-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 re-
cently, in a small trial, no potency was evident in a similar com-
mercial 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 out-
breaks. The prohibition on selling milk and delays in lifting restric-
tions 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 im-
pact 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 out-
lined 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 amplifica-
tion test, PCR-denaturing gradient gel electrophoresis (DGGE),
has the added advantage of allowing the simultaneous detection
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 be-
tween 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 car-
ried out by Professor Mirri and colleagues in the 1950s (Mirri and
Gallo, 1954). Although discontinued now for obvious safety rea-
sons, the first so-called farm vaccines were made from a combina-
tion 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: guidoruggero.loria@gmail.com
Robin A.J. Nicholas
Mycoplasma Group
Animal Health and Veterinary Laboratories Agency (AHVLA)
(Weybridge)
Addlestone, Surrey KT15 3NB, UK
E-mail address: robin.nicholas@ahvla.gsi.gov.uk
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.