Contagious Agalactia (Mycoplasma agalactiae Infection)

Contagious agalactia is a highly contagious, economically devastating infectious disease of sheep and goats caused primarily by Mycoplasma agalactiae, a wall-less bacterium belonging to the class Mollicutes. The disease is characterized by a classic triad of clinical signs: mastitis, arthritis, and keratoconjunctivitis, often accompanied by abortion and pneumonia. It is a notifiable disease in many countries (OIE-listed) and is endemic in the Mediterranean basin, Middle East, Central Asia, and parts of Africa. The disease predominantly affects lactating females, causing a sudden drop in milk production (agalactia), which is the hallmark of the disease. In dairy goat herds, the economic impact is severe due to loss of milk yield, premature culling, treatment costs, and trade restrictions. The disease can occur in epidemic or enzootic forms, with morbidity rates up to 80% in susceptible flocks and mortality rates typically low (1-5%) but can be higher in kids and lambs. The incubation period ranges from 2 to 10 weeks, and the disease can persist in a herd for years due to chronic carriers. The disease is transmitted horizontally via ingestion of contaminated milk, direct contact, and fomites, and vertically through the placenta. Control relies on strict biosecurity, vaccination, and culling of carriers.

The primary causative agent is Mycoplasma agalactiae, a small (0.3-0.8 µm) pleomorphic, facultatively anaerobic, wall-less bacterium that requires sterols for growth. It is a member of the Mycoplasma mycoides cluster, which includes other pathogenic mycoplasmas of ruminants. M. agalactiae is highly fastidious and requires enriched media (e.g., modified Hayflick's medium) supplemented with serum and yeast extract. It grows slowly, producing typical 'fried-egg' colonies on solid media. The organism is resistant to many antibiotics due to its lack of a cell wall, making beta-lactams ineffective. It is susceptible to heat (inactivated at 56°C for 30 minutes), drying, and common disinfectants, but can survive for weeks in milk, water, and organic matter. Other mycoplasma species, such as M. capricolum subsp. capricolum, M. mycoides subsp. capri, and M. putrefaciens, can cause similar clinical syndromes in goats and are often included in the differential diagnosis. These agents are collectively referred to as the 'contagious agalactia complex.' The organism colonizes the mammary gland, joints, eyes, and respiratory tract, and can cause systemic infection. It produces hydrogen peroxide and superoxide radicals, leading to tissue damage, and has a high capacity for antigenic variation, allowing it to evade the host immune response and establish chronic infections.

Contagious agalactia affects both sheep and goats, but goats, particularly dairy breeds (e.g., Saanen, Alpine, Nubian), are more susceptible and exhibit more severe clinical signs. Sheep are also affected, with outbreaks often occurring in milking flocks. The disease is most prevalent in lactating females, especially during the early lactation period, but can also affect kids and lambs, which may develop arthritis and pneumonia. The disease is endemic in the Mediterranean region (Spain, Italy, Greece, Turkey, France), the Middle East, North Africa, Central Asia, and parts of Africa. In non-endemic areas, outbreaks occur following introduction of infected animals. Transmission occurs horizontally through ingestion of contaminated milk (especially in kids and lambs), direct contact with infected animals, and fomites (milking machines, contaminated hands, bedding). The organism can be shed in milk, nasal secretions, ocular discharge, urine, and feces. Vertical transmission via the placenta can occur, leading to abortion or birth of infected offspring. The disease can also be transmitted venereally. Morbidity rates can reach 80% in naive flocks, while mortality is usually low (1-5%) but can be higher in young animals due to septicemia and pneumonia. The disease has a significant economic impact due to loss of milk production, reduced weight gain, treatment costs, and trade restrictions. In dairy goat herds, the disease can cause a 50-80% reduction in milk yield, leading to severe financial losses. The disease is more common in intensive production systems with high stocking density and poor biosecurity. It can also occur in extensive systems, particularly during lambing/kidding season when animals are gathered for parturition and milking.

The pathogenesis of contagious agalactia begins with colonization of the mucous membranes of the upper respiratory tract, conjunctiva, and mammary gland by M. agalactiae. The organism adheres to epithelial cells via specialized adhesins and then invades the underlying tissues. It produces hydrogen peroxide and superoxide radicals, which cause oxidative damage to host cells, leading to ciliostasis, epithelial necrosis, and inflammation. The organism also induces a strong inflammatory response, with infiltration of neutrophils and macrophages, leading to tissue damage. In the mammary gland, the organism causes acute interstitial mastitis, with edema, hyperemia, and infiltration of inflammatory cells. This leads to degeneration of alveolar epithelial cells, destruction of milk-producing tissue, and fibrosis, resulting in agalactia. The organism can also spread hematogenously to other organs, including joints, eyes, and lungs. In joints, it causes fibrinous to purulent arthritis, with synovial membrane inflammation, joint effusion, and cartilage erosion. In the eyes, it causes keratoconjunctivitis, with corneal edema, neovascularization, and ulceration. In the respiratory tract, it can cause interstitial pneumonia, with alveolar damage and consolidation. The organism can also cross the placenta, causing placentitis and abortion. The immune response is primarily cell-mediated, with activation of macrophages and T-lymphocytes. However, the organism's ability to undergo antigenic variation allows it to evade the immune response, leading to chronic infection and carrier states. The disease is often exacerbated by stress factors such as parturition, lactation, and poor nutrition, which suppress the immune system and increase susceptibility.

Several factors predispose sheep and goats to contagious agalactia. Intrinsic factors include species (goats more susceptible than sheep), breed (dairy breeds at higher risk), age (lactating females most affected), and immune status (naive animals more susceptible). Extrinsic factors include intensive production systems with high stocking density, poor ventilation, and inadequate biosecurity. The introduction of new animals into a herd without quarantine is a major risk factor. Stress factors such as parturition, lactation, transportation, and concurrent diseases can precipitate clinical disease in carrier animals. Poor milking hygiene and contaminated milking equipment can facilitate transmission. Nutritional deficiencies, particularly vitamin E and selenium deficiency, can impair immune function and increase susceptibility. Environmental factors such as cold, damp conditions and overcrowding can also contribute to disease spread. In endemic areas, the disease is often maintained in carrier animals, which shed the organism intermittently, especially during lactation. The use of contaminated needles, syringes, and other equipment can also transmit the disease. In addition, the practice of feeding unpasteurized milk to kids and lambs is a major risk factor for transmission. The disease is more common in dairy goat herds than in meat or fiber flocks, likely due to the intensive management and frequent milking, which facilitates spread.

The clinical signs of contagious agalactia typically appear 2 to 10 weeks after exposure and can vary in severity. The classic triad includes mastitis, arthritis, and keratoconjunctivitis. Mastitis is the most common sign, occurring in 50-80% of affected animals. It is characterized by a sudden drop in milk production, with the milk becoming thick, clotted, and sometimes yellowish or bloody. The udder may be swollen, hot, and painful, and in severe cases, gangrenous mastitis can develop. Agalactia may be permanent if the mammary tissue is severely damaged. Arthritis occurs in 20-50% of affected animals, affecting the carpal, tarsal, and stifle joints. Affected animals are lame, with swollen, painful joints, and may be reluctant to move. In severe cases, joint deformity and ankylosis can occur. Keratoconjunctivitis occurs in 10-30% of affected animals, with signs of conjunctivitis, excessive tearing, photophobia, and corneal opacity. In severe cases, corneal ulceration and blindness can occur. Other clinical signs include fever (40-41°C), depression, anorexia, and weight loss. Abortion can occur in pregnant animals, particularly in goats. In kids and lambs, the disease can cause septicemia, pneumonia, and polyarthritis, with high mortality. In some cases, animals may be asymptomatic carriers, shedding the organism without showing clinical signs. The disease can also cause respiratory signs such as coughing and nasal discharge, especially in young animals. The severity of clinical signs can vary depending on the strain of M. agalactiae, the species and breed of the animal, and the presence of concurrent infections.

Differential diagnoses for contagious agalactia include other causes of mastitis, arthritis, and keratoconjunctivitis in sheep and goats. These include: 1) Other mycoplasma infections: Mycoplasma capricolum subsp. capricolum, M. mycoides subsp. capri, and M. putrefaciens can cause similar clinical signs, especially in goats. These can be differentiated by culture and PCR. 2) Bacterial mastitis: Staphylococcus aureus, Streptococcus agalactiae, and Escherichia coli can cause mastitis, but they typically do not cause arthritis or keratoconjunctivitis. 3) Caseous lymphadenitis (Corynebacterium pseudotuberculosis): This can cause abscesses in lymph nodes and occasionally mastitis, but it does not cause arthritis or keratoconjunctivitis. 4) Caprine arthritis-encephalitis (CAE) virus: This can cause arthritis and mastitis in goats, but it is a lentivirus and can be differentiated by serology. 5) Ovine progressive pneumonia (OPP) virus: This can cause mastitis and arthritis in sheep, but it is also a lentivirus. 6) Chlamydial conjunctivitis (Chlamydia pecorum): This can cause keratoconjunctivitis, but it is usually not associated with mastitis or arthritis. 7) Listeriosis (Listeria monocytogenes): This can cause encephalitis and abortion, but it does not typically cause mastitis or arthritis. 8) Foot-and-mouth disease (FMD): This can cause vesicular lesions on the feet and mouth, but it does not cause mastitis or arthritis. 9) Bluetongue: This can cause fever, oral lesions, and lameness, but it is a viral disease and can be differentiated by PCR. 10) Nutritional deficiencies: Vitamin E/selenium deficiency can cause white muscle disease, which can lead to lameness, but it does not cause mastitis or keratoconjunctivitis. A thorough history, clinical examination, and laboratory testing are essential to differentiate these conditions.

The diagnostic algorithm for contagious agalactia begins with a thorough flock history, including recent introductions, clinical signs, and vaccination status. Physical examination should focus on the udder, joints, and eyes. If mastitis is present, milk samples should be collected aseptically for culture and PCR. If arthritis is present, synovial fluid should be collected for culture and PCR. If keratoconjunctivitis is present, ocular swabs should be collected. Blood samples should be collected for serology (ELISA) to detect antibodies against M. agalactiae. In cases of abortion, fetal tissues and placenta should be submitted for culture and PCR. Necropsy of affected animals can reveal characteristic lesions, including interstitial mastitis, fibrinous arthritis, and interstitial pneumonia. Histopathology can confirm the diagnosis. Culture of M. agalactiae requires specialized media and takes 2-3 weeks, so PCR is often preferred for rapid diagnosis. PCR can be performed on milk, synovial fluid, ocular swabs, and tissues. Serology can be used to detect exposure, but it may not distinguish between infected and vaccinated animals. In endemic areas, a presumptive diagnosis can be made based on clinical signs and response to treatment. It is important to rule out other causes of mastitis, arthritis, and keratoconjunctivitis. The diagnostic algorithm should also include testing for other mycoplasma species, as well as viral and bacterial pathogens. In cases of suspected contagious agalactia, it is important to notify the relevant veterinary authorities, as the disease is notifiable in many countries.

Laboratory findings in contagious agalactia include isolation of M. agalactiae from milk, synovial fluid, ocular swabs, or tissues. Culture requires specialized media (e.g., Hayflick's medium) and incubation at 37°C in a humidified atmosphere with 5% CO2 for up to 3 weeks. Colonies are small, with a 'fried-egg' appearance. PCR is a rapid and sensitive method for detection of M. agalactiae DNA, and can be performed on various samples. Serological tests, such as ELISA, can detect antibodies against M. agalactiae, but may not be able to distinguish between infected and vaccinated animals. Hematological findings are non-specific, but may include leukocytosis and elevated acute-phase proteins. In animals with mastitis, milk analysis may show an increased somatic cell count (>200,000 cells/mL) and the presence of inflammatory cells. In animals with arthritis, synovial fluid analysis may show increased protein and leukocyte counts, with a predominance of neutrophils. In animals with keratoconjunctivitis, ocular swabs may show the presence of mycoplasma organisms on culture or PCR. In cases of abortion, fetal tissues and placenta may be positive for M. agalactiae by culture or PCR. Histopathology of affected tissues can reveal characteristic lesions, including interstitial mastitis with infiltration of mononuclear cells, fibrinous arthritis, and interstitial pneumonia. It is important to note that M. agalactiae can be shed in milk even in the absence of clinical signs, so culture and PCR of milk samples from asymptomatic animals may be positive.

Imaging modalities are not commonly used in the diagnosis of contagious agalactia, but they can be helpful in assessing the extent of lesions. Ultrasonography can be used to evaluate the udder for mastitis, revealing increased echogenicity of the mammary tissue, abscessation, and fibrosis. It can also be used to evaluate joints for effusion and synovial thickening. In cases of pneumonia, thoracic radiography may reveal interstitial or alveolar patterns. However, these findings are non-specific and not diagnostic for contagious agalactia. Ultrasonography can also be used to assess fetal viability in pregnant animals, as abortion can occur. In cases of keratoconjunctivitis, ocular ultrasonography may be used to evaluate the cornea and anterior chamber, but this is rarely necessary. Overall, imaging is of limited value in the diagnosis of contagious agalactia, and laboratory testing is essential for confirmation.

Cytological examination of milk, synovial fluid, and ocular swabs can reveal inflammatory cells, including neutrophils and macrophages, and may show the presence of mycoplasma organisms on special stains (e.g., Giemsa). However, cytology is not specific for contagious agalactia. Histopathology of affected tissues is more diagnostic. In the mammary gland, histopathology reveals acute to chronic interstitial mastitis, with infiltration of mononuclear cells (lymphocytes, plasma cells, macrophages) and neutrophils, degeneration of alveolar epithelial cells, and fibrosis. In joints, histopathology reveals fibrinous to purulent arthritis, with synovial membrane hyperplasia, infiltration of inflammatory cells, and erosion of articular cartilage. In the eyes, histopathology reveals keratoconjunctivitis, with corneal edema, neovascularization, and ulceration. In the lungs, histopathology reveals interstitial pneumonia, with thickening of alveolar septa, infiltration of mononuclear cells, and consolidation. In cases of abortion, histopathology of the placenta may reveal placentitis, with infiltration of inflammatory cells and necrosis. Immunohistochemistry can be used to detect M. agalactiae antigens in tissues, which can confirm the diagnosis. PCR can also be performed on formalin-fixed, paraffin-embedded tissues.

Treatment of contagious agalactia is challenging due to the lack of a cell wall in mycoplasmas, which makes them resistant to beta-lactam antibiotics. Tetracyclines, macrolides, and fluoroquinolones are the most effective antibiotics. Oxytetracycline (10-20 mg/kg IM or SC, q24h for 3-5 days) is commonly used, but resistance has been reported. Tylosin (10-20 mg/kg IM, q24h for 3-5 days) and tilmicosin (10 mg/kg SC, single dose) are also effective. Enrofloxacin (2.5-5 mg/kg IM or SC, q24h for 3-5 days) is a fluoroquinolone that is effective against mycoplasmas, but it is not approved for use in food animals in some countries. Treatment should be initiated early in the course of the disease to be effective. Supportive care is important, including fluid therapy for dehydrated animals, anti-inflammatory drugs (e.g., flunixin meglumine 1.1-2.2 mg/kg IV or IM, q24h) to reduce fever and inflammation, and good nutrition. In cases of mastitis, frequent milking and intramammary infusion of antibiotics (e.g., oxytetracycline) may be helpful. In cases of arthritis, joint lavage and administration of antibiotics may be beneficial. In cases of keratoconjunctivitis, topical ophthalmic antibiotics (e.g., oxytetracycline ointment) may be used. However, treatment is often unsuccessful in eliminating the infection, and affected animals may become chronic carriers. Therefore, culling of affected animals is often recommended to control the disease. Vaccination can be used as a preventive measure, but vaccines are not available in all countries and may not provide complete protection. In an outbreak, it is important to isolate affected animals, practice good biosecurity, and disinfect contaminated areas.

The prognosis for contagious agalactia is guarded. In lactating animals, mastitis can lead to permanent agalactia, resulting in premature culling. Arthritis can cause chronic lameness and reduced productivity. Keratoconjunctivitis can lead to corneal scarring and blindness. Mortality is usually low (1-5%), but can be higher in kids and lambs due to septicemia and pneumonia. The disease can become chronic, with animals remaining carriers and shedding the organism intermittently. The economic impact is significant, especially in dairy goat herds, where milk production can be reduced by 50-80%. Early treatment with appropriate antibiotics can improve the prognosis, but it does not guarantee elimination of the infection. The prognosis is worse in animals with severe mastitis, arthritis, or pneumonia. In an outbreak, the prognosis for the flock depends on the control measures implemented, including culling of carriers, vaccination, and biosecurity. In endemic areas, the disease can be controlled but not eradicated.

Follow-up of animals affected with contagious agalactia is essential to monitor recovery and prevent spread. Affected animals should be isolated from the rest of the flock for at least 30 days after clinical signs resolve. Milk samples should be tested by PCR or culture to confirm clearance of the organism. Animals that remain positive should be culled. The rest of the flock should be monitored for clinical signs, and any new cases should be promptly isolated and treated. In an outbreak, it is important to review biosecurity measures and implement changes to prevent recurrence. This includes quarantine of new animals, disinfection of equipment and facilities, and control of animal movement. Vaccination may be considered in endemic areas. Regular testing of milk samples from lactating animals can help detect carriers. In dairy herds, it is important to maintain good milking hygiene and avoid using contaminated equipment. The flock should be monitored for several months after the outbreak to ensure that the disease has been controlled. In addition, it is important to work with a veterinarian to develop a long-term control plan.

Clinical pearls: 1) Contagious agalactia should be suspected in any lactating sheep or goat with a sudden drop in milk production, especially if accompanied by arthritis or keratoconjunctivitis. 2) The disease is highly contagious, so prompt isolation of affected animals is critical. 3) Mycoplasmas are resistant to beta-lactam antibiotics, so treatment should include tetracyclines, macrolides, or fluoroquinolones. 4) Early treatment is more effective than late treatment. 5) Culling of chronic carriers is essential for control. 6) Vaccination can be used as a preventive measure in endemic areas. 7) PCR is the preferred diagnostic method due to its speed and sensitivity. 8) The disease is notifiable in many countries, so it is important to report suspected cases to the authorities. Pitfalls: 1) Failure to consider contagious agalactia in the differential diagnosis of mastitis can lead to misdiagnosis and delayed treatment. 2) Using beta-lactam antibiotics (e.g., penicillin) is ineffective and can worsen the disease. 3) Treating affected animals without isolating them can lead to rapid spread of the disease. 4) Failure to cull carriers can result in persistent infection in the flock. 5) Using contaminated milking equipment can transmit the disease. 6) Not implementing biosecurity measures can lead to recurrence. 7) Misinterpreting serological results, as antibodies may be present in vaccinated animals. 8) Not reporting the disease to authorities can result in legal consequences.

Current drug protocols for contagious agalactia are based on Plumb's Veterinary Drug Handbook and AASRP guidelines. Antibiotics: 1) Oxytetracycline: 10-20 mg/kg IM or SC, q24h for 3-5 days. Withdrawal times: meat 28 days, milk 96 hours (check label). 2) Tylosin: 10-20 mg/kg IM, q24h for 3-5 days. Withdrawal times: meat 28 days, milk 96 hours. 3) Tilmicosin: 10 mg/kg SC, single dose. Withdrawal times: meat 28 days, milk 96 hours. 4) Enrofloxacin: 2.5-5 mg/kg IM or SC, q24h for 3-5 days. Withdrawal times: meat 28 days, milk 96 hours (not approved for food animals in some countries). 5) Florfenicol: 20 mg/kg IM, q48h for 3 doses. Withdrawal times: meat 28 days, milk 96 hours. Supportive care: 1) Flunixin meglumine: 1.1-2.2 mg/kg IV or IM, q24h for 1-3 days. Withdrawal times: meat 28 days, milk 96 hours. 2) Meloxicam: 0.5 mg/kg PO or SC, q24h for 1-3 days. Withdrawal times: meat 28 days, milk 96 hours. 3) Fluid therapy: IV isotonic fluids (e.g., lactated Ringer's solution) at 50-100 mL/kg/day. 4) Intramammary infusion: oxytetracycline or cloxacillin, as per label. 5) Topical ophthalmic: oxytetracycline ointment, applied to the affected eye q12h for 3-5 days. Vaccination: Inactivated vaccines are available in some countries; consult local veterinary authorities. It is important to follow label instructions and observe withdrawal times.

Evidence-based literature on contagious agalactia is limited, but several studies have evaluated treatment and control strategies. A study by Nicholas et al. (2008) reviewed the epidemiology and control of contagious agalactia, highlighting the importance of biosecurity and vaccination. A study by Ayling et al. (2004) evaluated the efficacy of enrofloxacin and oxytetracycline in experimentally infected goats, finding that enrofloxacin was more effective in reducing clinical signs and shedding. A study by Tola et al. (1996) evaluated the use of PCR for diagnosis of contagious agalactia, finding it to be highly sensitive and specific. A study by De la Fe et al. (2007) evaluated the efficacy of a commercial vaccine in goats, finding that it reduced clinical signs and shedding, but did not prevent infection. A study by Corrales et al. (2007) evaluated the economic impact of contagious agalactia in dairy goat herds, finding significant losses due to reduced milk production and culling. A study by Bergonier et al. (1997) reviewed the clinical and pathological features of contagious agalactia in sheep and goats. A study by Gil et al. (2003) evaluated the use of tylosin in the treatment of contagious agalactia, finding it to be effective. A study by Amores et al. (2010) evaluated the presence of M. agalactiae in bulk tank milk, suggesting that it can be used for surveillance. Overall, the literature supports the use of tetracyclines, macrolides, and fluoroquinolones for treatment, and emphasizes the importance of early detection, biosecurity, and vaccination for control.