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Brucella Melitensis Infection

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Selected content from the Animal Health and Production Compendium (© CAB International 2013). Distributed under license by African Union – Interafrican Bureau for Animal Resources.

Whilst this information is provided by experts, we advise that users seek veterinary advice where appropriate and check OIE manuals for recent changes to regulations, diagnostic tests, vaccines and treatments.

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Identity    Pathogen/s    Overview    Distribution    Distribution Map for Africa    Distribution Table for Africa    Hosts/Species Affected    Host Animals    Systems Affected    Epidemiology    Impact: Economic    Zoonoses and Food Safety    Diagnosis    Disease Course    Disease Treatment Table    Vaccines    Prevention and Control    References    Links to Websites    OIE Reference Experts and Laboratories

 

 Identity

Preferred Scientific Name
brucellosis (Brucella melitensis)
International Common Names
English
brucellosis in sheep, contagious abortion, Malta fever (in man), seminal vesiculitis, adenitis, in large animals

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 Pathogen/s

Brucella melitensis

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Overview

Before Brucella melitensis was recognized as the cause of Malta fever in man, a disease causing the same symptoms in countries bordering the Mediterranean was known as Fibris andulans. David Bruce, a British military medical officer stationed in Malta described the aetiology of the disease in man in 1884. The bacteriologist Zammit Themistocles, a member of the Mediterranean Fever Commission, isolated B. melitensis in 1897 from the milk of goats that had aborted. Zammit also discovered that drinking milk from these goats was the reason for outbreaks of Malta fever amongst British soldiers stationed in Malta. It soon became apparent that the disease is prevalent in Russia, the Balkans, Asia, Africa and other European countries, and that the organism also infects sheep.

Brucella melitensis primarily affects the reproductive tract of sheep and goats, and B. melitensis infection is characterized by abortion, retained placenta and, to a lesser extent, impaired fertility. Although B. melitensis infects mainly sheep and goats it is a zoonose that plays a significant role in the national economy and the public health of many developing countries.

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Distribution

Most Mediterranean countries have large numbers of flocks of sheep and goats infected with B. melitensis (Yantzis, 1984). Brucella melitensis is also prevalent in developing countries of South-West Asia, parts of Latin America and Africa where it constitutes a serious human health hazard.

In countries with organized brucellosis control some areas may be free from B. melitensis while other areas are still infected. This is because the geographic context and the methods of farming influence the spread of the infection. In mountainous areas grouping of flocks in valleys is common, as in the villages. This allows maintenance of brucellosis that may become enzootic. However, mountainous areas may also isolate infected from non-infected flocks and sporadic outbreaks of brucellosis may not spread to other areas. The data given in the geographic distribution table dates back 10-15 years and may reflect a situation resulting from geographical conditions. Most of the data is based on sero-epidemiological studies although it is generally accepted that only the isolation of Brucella confirms the presence of brucellosis. Therefore, the data must be looked upon as an indication for the presence of B. melitensis in an area or a country and not to what extend the area is infected.

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Distribution Map for Africa

Distribution Map for AfricaDistribution Map for Africa

present, no further details = Present, no further details    widespread = Widespread    localised = Localised
confined and subject to quarantine = Confined and subject to quarantine    occasional or few reports = Occasional or few reports
evidence of pathogen = Evidence of pathogen    last reported = Last reported...    presence unconfirmed = Presence unconfirmed

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 Distribution Table for Africa

The distribution in this summary table is based on all the information available. When several references are cited, they may give conflicting information on the status. Further information for individual references may be available in the Animal Health and Production Compendium. A table for worldwide distribution can also be found in the Animal Health and Production Compendium.

CountryDistributionLast ReportedOriginFirst ReportedInvasiveReferencesNotes
AFRICA
AlgeriaPresent    OIE, 2012/td> 
AngolaNo information available    OIE, 2012 
BeninDisease not reported    OIE, 2012 
BotswanaDisease not reported    OIE, 2012 
Burkina FasoNo information available    OIE, 2012 
BurundiReported present or known to be present    OIE, 2012 
CameroonNo information available    OIE, 2012 
Cape VerdeReported present or known to be present    OIE, 2012 
Central African RepublicDisease not reported    OIE, 2012 
ChadNo information available    OIE, 2012 
ComorosDisease not reported    OIE, 2012 
CongoNo information available    OIE, 2012 
Congo Democratic RepublicDisease not reported    OIE, 2012 
Côte d'IvoireNo information available    OIE, 2012 
DjiboutiDisease not reported    OIE, 2012 
EgyptPresent    El-Gohary & Hattab, 1992; OIE, 2012 
Equatorial GuineaNo information available    OIE, 2012 
EritreaPresent    OIE, 2012 
EthiopiaDisease not reported    OIE, 2012; Bekele & Kasali, 1990 
GabonNo information available    OIE, 2012 
GambiaNo information available    OIE, 2012 
GhanaDisease not reported    OIE, 2012 
GuineaNo information available    OIE, 2012 
Guinea-BissauNo information available    OIE, 2012 
KenyaNo information available    OIE, 2012; Kadohira et al., 1997 
LesothoDisease never reported    OIE, 2012 
LibyaReported present or known to be present    Boargob & Muhammed, 1989; OIE, 2012 
MadagascarDisease never reported    OIE, 2012 
MalawiNo information available    OIE, 2012 
MaliNo information available    OIE, 2012 
MauritiusDisease never reported    OIE, 2012 
MoroccoLast reported2011   OIE, 2012 
MozambiqueDisease not reported    OIE, 2012 
NamibiaPresent    OIE, 2012 
NigeriaNo information available    OIE, 2012; Amin & Silsmore, 1993 
RéunionDisease not reported    OIE, 2012 
RwandaNo information available    OIE, 2012 
Sao Tome and PrincipeNo information available    OIE, 2012 
SenegalNo information available    OIE, 2012 
SeychellesDisease not reported    OIE, 2012 
SomaliaPresent    Ostanello et al., 1999; OIE, 2012 
South AfricaLast reported2010   OIE, 2012; Ribeiro et al., 1990 
SudanDisease never reported    OIE, 2012 
SwazilandPresent    OIE, 2012 
TanzaniaDisease not reported    OIE, 2012 
TogoNo information available    OIE, 2012 
TunisiaPresent    OIE, 2012 
UgandaPresent    OIE, 2012; Oloffs et al., 1998 
ZambiaNo information available    OIE, 2012 
ZimbabweDisease not reported    OIE, 2012 

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 Hosts/Species Affected

Brucellae have definite host preferences. Secondary hosts play only a very small part if any in the maintenance or spread of a particular Brucella species. Brucella melitensis mainly infects sheep and goats, and in areas where B. melitensis is enzootic it is the major cause of abortion in those animals and very often also in cattle (Luchsinger and Anderson, 1967; Zowghi and Ebadi, 1985; Zowghi and Ebadi, 1988).

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Host Animals

Animal name Context 
Bos indicus (zebu) Domesticated host 
Bos taurus (cattle) Domesticated host 
Camelus dromedarius (dromedary camel) Domesticated host 
Canis Domesticated host, Wild host 
Capra hircus (goats) Domesticated host 
Homo sapiens Domesticated host 
Lama glama (llamas) Domesticated host 
Lama pacos (alpacas) Domesticated host 
Ovis aries (sheep) Domesticated host 
Sus scrofa (pigs)  

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Systems Affected

Mammary Glands - Large Ruminants
Mammary Glands - Small Ruminants
Reproductive - Large Ruminants
Reproductive - Small Ruminants

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Epidemiology

Brucellosis in sheep and goats is usually caused by B. melitensis. Infection with B. abortus is rare. The source of infection is an aborting animal. As in cattle, the surroundings where lambs are born to infected ewes or where abortion takes place become greatly contaminated. Animals may contract brucellosis by oral or cutaneous routes, or at birth. Infection by inhalation is also possible when healthy and aborting animals are kept in overcrowded pens with poor sanitary measures. Transmission of B. melitensis from flock to flock usually follows the movement of infected pregnant females. However it can also occur via an infected male. Wild animals and dogs may transmit parts of aborted foetuses to other areas (Alton, 1985; Mikolon et al., 1998a).

The incubation period after infection varies from 15 days to several months depending on the invasion site and the infecting dose. Therefore, it takes some time for signs of infection to occur. In naturally infected sheep the only symptom noted is abortion. In infected goats abortion and sometimes also mastitis can be observed. Infected goats that do not abort give less milk than uninfected goats. Abortion usually occurs at 3-4 months into pregnancy, and in a susceptible flock it may reach epidemic proportions. Goats that have aborted once are not likely to abort a second time. Sheep may abort a second time, as they can recover from the first infection. Both sheep and goats may shed Brucella with any subsequent parturition. Retention of the placenta may or may not occur. It is also possible that infected pregnant goats that have been born into an infected flock may give birth at the normal time (Stableforth and Galloway, 1959). Therefore, brucellosis in chronically infected flocks often becomes evident only through infected people who have been in contact with infected animals or consumed their milk or cheese.

Both sheep and goats may show signs of lameness, hygroma, and cough but the predilection sites of B. melitensis are the uterus, udder and the mammary lymph nodes in females and the testicles in males. Strangely enough, interference with fertility caused by orchitis seems to be limited. Infected sheep and goats may excrete Brucella in the milk for years but sheep may also cease excretion during one or more lactation periods (Alton, 1985; Stableforth and Galloway, 1959).

Resistance to infection

Resistance to infection resembles B. abortus infection in cattle. Age, sex and natural resistance to Brucella may influence the progression of infection. Sexually immature animals may show some resistance to infection whereas sexually mature animals are susceptible to infection, which in pregnant animals may result in abortion. Males are less susceptible to infection than females. There is very little difference between goat breeds in their susceptibility to the B.melitensis, whereas breeds of sheep differ in their susceptibility. Milking breeds of sheep seem to be more susceptible to B. melitensis infection than sheep kept for meat production (Alton, 1985).

Survival of Brucella in the environment

Temperature, humidity and pH of the environment influence the survival of B. melitensis as well as that of B. abortus. Brucellae are sensitive to direct sunlight, disinfectant and pasteurization. In dry conditions they survive only if embedded in protein. In optimal conditions Brucellae survive in tap water, damp soil, urine, aborted foetuses, uterine exudate and in frozen tissues (Davies and Casey, 1973: Wray 1975).

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Impact: Economic

There is no doubt that outbreaks of B. melitensis infection cause significant economic losses. Although the financial loss expressed in any currency may vary from one country to another, a few denominators are the same everywhere. The farmer suffers loss of income due to abortion, the consequent loss of milk production and a prolonged fattening time of lambs (meat production) due to birth of premature animals and low fertility rates. Human brucellosis causes physical and psychological suffering due to infection, hospitalization, the cost of drugs and the loss of work or income due to illness. The country incurs costs generated by prophylactic activities taken to control brucellosis, i.e. vaccination by the veterinarians and their assistants, vaccine costs and compensation paid to the farmers for sanitary slaughter of infected animals. Consequently, control and eradication of B. melitensis eventually pays off.

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Zoonoses and Food Safety

Brucella melitensis is a zoonotic disease causing a debilitating illness in human. Symptoms of acute brucellosis caused by Brucella melitensis are 'flu-like' and highly non-specific. Chronic brucellosis is an insidious disease with vague symptoms that might be confused with other diseases affecting various organ systems (Serter et al., 1991). Humans usually acquire brucellosis by consumption of raw milk or milk products (Thapar and Young, 1986). Brucellosis is also recognized as an occupational hazard for farmers, veterinarians, and workers in the meat industry in areas with enzootic B. melitensis. Humans working in the meat industry may contract brucellosis percutaneously, conjunctivally or by nasal mucous membrane infection. Veterinarians may become infected with brucellosis when handling aborted foetuses or apparently healthy calves born to infected cows, performing gynaecological and obstetric manipulations, or when handling Rev 1 vaccine (Glosser, 1972; Schnurrenberger et al., 1975; Dekeijzer, 1981; Peelman and Dekeyser, 1987).

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Diagnosis

Bacteriological examination of aborted material is time consuming, laborious, costly, and cannot routinely be used as a diagnostic procedure in developed or developing countries. Nevertheless, B. melitensis can be isolated from the lungs, liver, kidney, stomach contents abomasum and brain of aborted animals (Ribeiro et al., 1990). The counterimmuno-electrophoresis method, which detects Brucella antigens in suspect aborted material (Mahajan and Kulshreshtha, 1986) cannot be used everywhere, as it requires specialized laboratory equipment.

As abortion is the only symptom that indicates B. melitensis infection, serological tests are used to confirm brucellosis in suspect animals. Some countries have eradicated brucellosis from small ruminants with the aid of serological tests and the slaughter of positively reacting animals. However, many other countries are still trying to control brucellosis.

Control or eradication of brucellosis would not be a problem if an easy, rapid, sensitive and highly specific serological test existed. However, because each serological test has its advantages and disadvantages, no single test, or even a combination of tests, conclusively detects all infected animals in a flock. The commonly used tests are the Rose Bengal plate test (RBPT), serum agglutination test (SAT), complement fixation test (CFT), Coombs test, enzyme-linked immunosorbent assay (ELISA), Rivanol test, skin delayed-type hypersensitivity (SDTH) test and the Milk ring test (MRT).

The use of the RBPT which is easy to perform and is considered a valuable screening test (Farina, 1985) is less effective than the CFT at detecting brucellosis in individual sheep and goats (FAO/WHO, 1986). Furthermore, its efficacy is influenced by the cell concentration and the standardization procedure of the antigen (Hosie et al., 1985; Blasco et al., 1994a). The less frequently used Rivanol test has a specificity and sensitivity that equals that of the SAT and RBPT (Coker et al., 1990).

The SAT is relatively easy to perform and adequately detects acute infection. However, it may fail to agglutinate with Brucella antibodies present in sheep or goats sera and may give reactions with marked prozone-phenomenon (Renoux, et al., 1956; Goguer, 1965; Le Pennec, 1967). The Coombs test is highly sensitive and detects both IgG1 and IgG2 antibodies. Therefore, it is suggested to use the Coombs test when suspected animals test negative with the SAT or, when SAT and CFT give ambivalent serological test results (Farina, 1985; Acharya and Panda, 1985).

The CFT is considered to be the most effective test for diagnozing brucellosis in small ruminants (FAO/WHO, 1986) but has no particular advantage over the SAT performed in a hypertonic environment of 5-20% NaCl (Levchenco and Drozhzhin, 1958). Furthermore, sera from small ruminants may show anti-complementary activity in the CFT. Although the anti-complementary activity can be eliminated when the sera are inactivated for 55 minutes at 60° C (Bercovich, unpublished data) the test remains tedious to perform. Moreover, acutely or chronically infected animals as well as latent carriers may elude detection with the CFT (Karmann and Schloz, 1956; Farina, 1985; Blasco et al., 1994b). However, numerous studies demonstrate its specificity and its value for the detection of brucellosis, especially when used in combination with the SDTH test (Ebadi and Zowghi, 1983; Ebadi, 1984; Loquerie and Durand, 1984).

Since neither a single serological test nor a combined use of several serological tests detects all infected animals in a flock, detection of brucellosis remains a major problem in areas of low prevalence of brucellosis. Therefore, studies were conducted to choose a reliable diagnostic procedure by comparing serological tests with various ELISA procedures with or without the SDTH test. Most studies agree that the ELISA is as specific as the CFT but it is more sensitive. Yet, for a reliable diagnosis of infected animals studies suggest using the ELISA in combination with other tests (Bercovich et al., 1998; Jacques et al., 1998; Mikolon et al., 1998b). Other studies consider the ELISA suitable for screening flocks of sheep and goats for brucellosis (Biancifiori et al., 1996; Sting and Ortmann, 2000). Nevertheless, small ruminants should be tested with the ELISA, CFT and SDTH tests to prevent the spread of brucellosis after an outbreak of the disease in an area with low prevalence of brucellosis or in an area free from brucellosis (Bercovich et al., 1998).

The milk ring test that is widely used to detect brucellosis in dairy cattle is not sensitive enough to detect brucellosis in sheep (Shimi and Tabatabayi, 1981). However, because the test is simple and easy to perform it might be useful to detect Brucella antibodies in milk from dairy sheep and goats kept for cheese production. The MRT using 8-ml milk (Bercovich and Lagendijk, 1978) or the MRT performed on three parts sheep milk supplemented with one part pooled cow's milk, which tests negative for Brucella with the MRT, strongly increases the sensitivity of the test.

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Disease Course

The course of the disease is usually shorter in sheep than it is in cattle and goats. Sheep and goats are usually infected via the naso-pharynx route or subcutaneously. Invading Brucella usually localize the lymph nodes draining the invasion site, resulting in hyperplasia of the lymphoid and reticuloendothelial tissue and the infiltration of inflammatory cells. In susceptible animals Brucellae multiply in macrophages and eventually escape into the blood stream. Depending on the infection dose, abortion, mastitis, pyrexia, toxaemia or sudden death can occur in goats at the acute stage of the infection while sheep usually only abort (Enright 1990).

Pathologically B. melitensis infection in sheep and goats is very similar to B. abortus in cattle (FAO/WHO, 1986). Almost all organs can be infected including the brain, lungs, bones and muscles. In pregnant animals the bacteria will invade the uterus, multiplying in the placenta and the foetus. This usually leads to abortion or to the birth of infected lambs or kids and shedding of Brucellae into the environment. Excretion of Brucellae in uterine and vaginal discharges as well as in milk and urine is greatest in the first few days after abortion. Excretion in vaginal fluid and urine may last 4-6 months. Sheep may excrete Brucellae in milk for 1-3 weeks after abortion but in some cases it may also continue for up to 6 months. Goats may excrete Brucellae into the milk for a year or longer. In non-pregnant female animals chronic infection of the reticuloendothelial system results in latent carriers of B. melitensis, and causes orchitis in males (Stableforth and Galloway, 1959; Alton, 1985; Enright 1990).

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Disease Treatment Table

DrugDosage, administration and withdrawal timesLife stagesAdverse affectsDrug resistanceType
Brucella melitensis Rev 1 Follow manufacturer's instructions Gimmer Abortion, immune response, excretion. No Vaccine 

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Vaccines

VaccineDosage, Administration and Withdrawal TimesLife StagesAdverse Affects
Brucella melitensis Rev 1 Follow manufacturer's instructions -Sheep & Goats: Gimmer Abortion, immune response, excretion. 

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Prevention and Control

Effective control of brucellosis largely depends on the co-operation of the flock owner. Treatment of infected sheep and goats with antibiotics is not done because the antibiotics may appear in the human food chain and this would be disastrous for the cheese production industry. Instead, efforts are directed towards controlling and eradicating brucellosis from small ruminants. Serological testing and slaughter of the animals that react positively with Brucella antigens successfully eradicated brucellosis in several countries. This procedure, however, is not easy to apply in developing countries where usually animals are not tagged.

In areas with endemic brucellosis only vaccination against B. melitensis may reduce the number of infected flocks and eventually permit brucellosis control. Currently two vaccines are in use: the H38 and Rev 1. The H38 vaccine is composed of killed, smooth, virulent cells of B. melitensis in adjuvant. The vaccine gives good protection and can be administered to pregnant or lactating animals. However, because it stimulates a long lasting immune response (that interferes with the serological diagnosis of brucellosis) and it induces a marked skin reaction on the injection site of the vaccine it is not used very often (Alton, 1985; Plommet, 1991).

The Rev 1 vaccine is composed of living attenuated cells of B. melitensis and is used in most countries that vaccinate small ruminants against B. melitensis. Although vaccination with 1-2 x 109 CFU (classical dose) at 4-6 months old, or of non-pregnant adults protects the animals for several years the vaccine also has some disadvantages. Since the vaccine consists of living B. melitensis cells it may cause abortion in pregnant sheep and goats and it is excreted in the milk. While a year after vaccination most CFT results are negative, the antibody response to the vaccination may last longer than 24 months. To limit the risk of abortion and excretion of brucellae following the vaccination the conjunctival vaccination with 5 x 104 CFU was introduced. Conjunctival vaccination, with a reduced dose, is not only safer but it is also easier to apply (Alton, 1985; Plommet, 1991). Rev 1 vaccine it is an attenuated Brucella strain that is dangerous for man.

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References

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Links to Websites

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OIE Reference Experts and Laboratories

(OIE Reference Experts and Laboratories, accessed 30 May 2013)

Dra. Ana Maria Nicola
Dirección de Laboratorios y Control Técnico (DILAB)
Servicio Nacional de Sanidad y Calidad
Agroalimentaria (SENASA)
Av. Alexander Fleming, 1653
1640 Martínez
Pcia de Buenos Aires
ARGENTINA
Tel: +54-11 48 36 11 17 Fax: +54-11 48 36 11 17
Email: This email address is being protected from spambots. You need JavaScript enabled to view it.
Email: This email address is being protected from spambots. You need JavaScript enabled to view it.

Dr Bruno Garin-Bastuji
Agence Nationale de Sécurité de l'Alimentation, de l'Environnement et du Travail (Anses)
Laboratoire de Santé animale
Unité Zoonoses Bactériennes
23 avenue du Général de Gaulle
94706 Maisons-Alfort Cedex
FRANCE
Tel: +33 (0)1 49 77 13 00 Fax: +33 (0)1 49 77 13 44
Email: This email address is being protected from spambots. You need JavaScript enabled to view it.

Dr Heinrich Neubauer
Federal Research Centre for Virus Diseases of Animals (BFAV)
Friedrich-Loeffer Institute
Institute of Bacterial Infections and Zoonoses
Naumburger Str. 96a
07743 Jena
GERMANY
Tel: +49-3641 80 42 00 Fax: +49-3641 80 42 28
Email: This email address is being protected from spambots. You need JavaScript enabled to view it.

Dr Menachem Banai
Kimron Veterinary Institute
Department of Bacteriology
P.O. Box 12
Beit Dagan 50250
ISRAEL
Tel: +972-3 968 16 98 Fax: +972-3 968 17 53
Email: This email address is being protected from spambots. You need JavaScript enabled to view it.

Dr Massimo Scacchia
Istituto Zooprofilattico Sperimentale
dell'Abruzzo e del Molise 'G. Caporale'
CESME
National Centre for Exotic Diseases
Via Campo Boario
64100 Teramo
ITALY
Tel: +390-861 33 24 05 Fax: +390-861 33 22 51
Email: This email address is being protected from spambots. You need JavaScript enabled to view it.

Dr Judith Stack
Animal Health and Veterinary Laboratories Agency
New Haw, Addlestone
Surrey KT15 3NB
Weybridge
UNITED KINGDOM
Tel: +44-1932 35.76.10 Fax: +44-1932 35.72.16
Email: This email address is being protected from spambots. You need JavaScript enabled to view it.

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Date of report: 30/05/2013

© CAB International 2013. Distributed under license by African Union – Interafrican Bureau for Animal Resources.

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