Mycoplasma agalactiae and Contagious Agalactia in Sheep and Goats

Introduction

Contagious agalactia (CA) is a highly contagious, multisystemic disease of sheep and goats caused by Mycoplasma agalactiae. This pathogen is one of the most economically significant mycoplasmas affecting small ruminant production worldwide. The disease is characterized by mastitis, arthritis, keratoconjunctivitis, and, less frequently, pneumonia and abortion. Though often referred to simply as CA, the syndrome overlaps clinically with other mycoplasma infections in goats, such as contagious caprine pleuropneumonia (CCPP), which is caused by Mycoplasma capricolum subsp. capripneumoniae. However, CCPP primarily involves the respiratory tract, while CA is a systemic infection with a tropism for mammary gland, joints, and eyes.

This article provides an exhaustive, publication-grade review of M. agalactiae and contagious agalactia, incorporating recent advances in genomics, diagnostics, vaccine development, and antimicrobial therapy. The content is intended for veterinary microbiologists, diagnosticians, and livestock health professionals.

Etiology

Mycoplasma agalactiae is a member of the class Mollicutes, characterized by the lack of a cell wall, a small genome (approximately 0.8–1.0 Mb), and a reduced metabolic repertoire. The organism is pleomorphic, passing through 0.45 μm filters, and requires sterol-enriched media for growth. Its genome encodes a limited number of metabolic enzymes, rendering it dependent on the host for many nutrients.

Comparative genomic analysis of strain GM139 has highlighted a unique surface architecture and several putative virulence factors [1]. The surface lipoproteins, particularly members of the Vpma (variable proteins of Mycoplasma agalactiae) family, undergo high-frequency phase and size variation, facilitating immune evasion [1, 2]. Serum resistance has been linked to specific lipoprotein profiles; mutants lacking certain Vpma variants show increased susceptibility to complement-mediated killing [2]. These antigenic variation mechanisms present substantial hurdles for vaccine development [3].

M. agalactiae also possesses a conjugative system that allows horizontal gene transfer. Bacterial conjugation in this pathogen is influenced by eukaryotic host factors, suggesting that the host environment can modulate genetic exchange [4]. This may contribute to strain diversity and the spread of antimicrobial resistance determinants.

Epidemiology

Contagious agalactia is endemic in many Mediterranean countries, the Middle East, parts of Asia, and Africa [5, 6]. The disease is notifiable to the World Organisation for Animal Health (WOAH). Morbidity can reach 80% in naive flocks, while mortality is typically low but may increase in kids and lambs.

Transmission occurs primarily through direct contact with infected animals or indirectly via contaminated milk, fomites, and aerosols. The pathogen can persist in the udder of carrier ewes and does for months or years, serving as a reservoir. Recent evidence has identified Rhipicephalus bursa as a potential vector, with M. agalactiae anatomically localized in the salivary glands and midgut of naturally infected ticks [7]. This finding expands the known transmission routes and has implications for vector-borne spread.

Influences of natural and climatic conditions on disease distribution have been documented in sheep from Bessarabia, Ukraine, where temperature and humidity correlated with seasonal outbreaks [6]. Understanding these ecological drivers is critical for targeted biosecurity [5].

Clinical Signs and Pathology

The incubation period ranges from 2 to 24 days. The classic triad includes mastitis, arthritis, and keratoconjunctivitis, though not all animals present all three.

Mastitis is the most prominent feature in lactating females. The udder becomes swollen, firm, and painful. Milk secretion is reduced and becomes serous, clotted, or purulent. Chronically infected udders may develop fibrosis and abscessation. Histopathologically, there is an interstitial mastitis with lymphoplasmacytic infiltration, alveolitis, and loss of secretory epithelium.

Arthritis affects both lambs/kids and adults. Joints (carpal, tarsal, stifle) are swollen and painful, leading to lameness. Synovial fluid is turbid and may contain fibrin clots. Microscopic examination reveals synovitis with neutrophilic infiltrates, synovial cell hyperplasia, and pannus formation.

Keratoconjunctivitis presents as serous to mucopurulent ocular discharge, conjunctival hyperemia, corneal opacity, and occasionally ulceration. Lesions are usually bilateral.

Less common manifestations include pneumonia (especially in young animals), abortion, and orchitis. The respiratory form can mimic CCPP in goats, although pleural effusion is less pronounced.

Pathogenesis

Following inhalation or ingestion, M. agalactiae colonizes mucosal surfaces of the respiratory and digestive tracts. The organism then disseminates hematogenously to the mammary gland, joints, eyes, and other sites. Adhesion to host cells is mediated by surface lipoproteins and hemagglutinins [1].

The immune response elicited by recombinant membrane proteins has been characterized in goats [8]. Infected animals develop both humoral and cell-mediated responses, but the pathogen's antigenic variation allows it to persist [8, 2]. The Vpma system generates a diverse repertoire of surface antigens; the host immune system lags behind these changes, leading to chronic infection [3, 2].

Bacterial conjugation contributes to genomic plasticity, and host factors can upregulate the conjugative machinery [4]. This mechanism may facilitate the spread of genes encoding virulence factors or metabolic functions within the host.

Diagnostic Strategies

Accurate diagnosis is essential for control. The multi-platform diagnostic strategy recommended by De la Fe et al. combines clinical examination, culture, serology, and molecular methods [5].

Culture remains the gold standard but is slow and requires special media (e.g., modified Hayflick’s medium). Colonies exhibit a characteristic "fried-egg" appearance after 3–10 days of incubation in microaerophilic conditions.

Molecular detection using polymerase chain reaction (PCR) targeting the 16S rRNA gene or species-specific sequences (e.g., the uvrC or mgc2 genes) is rapid and sensitive. Real-time PCR assays allow quantification and are useful for subclinical shedders.

Serology is used for herd screening. Commercial enzyme-linked immunosorbent assays (ELISAs) detect antibodies against whole-cell antigens. A novel fusion protein candidate has shown promise for improved serodiagnosis, offering higher specificity by using recombinant antigens rather than whole-cell lysates [9].

Immunohistochemistry and fluorescence in situ hybridization can localize the pathogen in formalin-fixed tissues.

A diagnostic algorithm is presented in Figure 1.

flowchart TD
    A[Clinical suspicion of CA: mastitis, arthritis, keratoconjunctivitis], > B[Sample collection: milk, joint fluid, ocular swab, blood]
    B, > C{Diagnostic method}
    C, > D[PCR (molecular)]
    C, > E[Culture + identification]
    C, > F[Serology (ELISA)]
    D, > G[Positive: confirmatory]
    D, > H[Negative: consider other agents]
    E, > I[Positive: 'fried-egg' colonies]
    E, > J[Negative: retry with enriched media or PCR]
    F, > K[Positive: indicates exposure]
    F, > L[Negative: acute infection possible]
    G, > M[Report to WOAH / implement flock restrictions]
    I, > M
    K, > M

Table 1: Differential Diagnosis of Contagious Agalactia

Treatment and Antimicrobial Therapy

M. agalactiae lacks a cell wall, so β-lactams and other cell-wall-acting antibiotics are ineffective. Tetracyclines, macrolides, and fluoroquinolones are commonly used, but resistance is emerging.

Pharmacokinetic/pharmacodynamic (PK/PD) modeling for marbofloxacin in lactating sheep has been performed, providing optimized dosing regimens to achieve target attainment against M. agalactiae and Staphylococcus aureus [10]. In lactating goats, similar PK/PD evaluations have determined that marbofloxacin can be effective against coagulase-negative staphylococci and M. agalactiae [11]. Recommended dosages must consider milk withdrawal periods.

Antimicrobial susceptibility testing should be performed on isolates to guide therapy. Treatment may reduce clinical signs but often fails to eliminate the carrier state.

Vaccination and Immune Responses

Vaccination is a key control tool, but current vaccines offer incomplete protection. Both monovalent and bivalent autogenous vaccines have been evaluated in dairy sheep, eliciting humoral responses and reducing clinical severity but not preventing infection [12]. The major hurdle is antigenic diversity of M. agalactiae strains, driven by the Vpma system [3].

Recombinant membrane proteins have been explored as subunit vaccines. Studies in goats demonstrated that these proteins induce specific antibody responses and reduce bacterial shedding [8]. However, field efficacy remains to be proven.

A fusion protein combining multiple immunogenic domains has been designed for serodiagnosis and is also being investigated as a vaccine candidate [9]. Future vaccine strategies may incorporate conserved surface antigens or use live attenuated strains with targeted deletions of virulence genes [3].

Control and Biosecurity

Control programs rely on a combination of early detection, isolation of infected animals, antimicrobial treatment, vaccination, and biosecurity measures. A multi-platform diagnostic strategy integrated with biosecurity is fundamental in endemic areas [5]. Quarantine of introduced animals, segregation of age groups, and proper hygiene of milking equipment reduce transmission.

Because M. agalactiae can survive for days in milk and the environment, disinfection with quaternary ammonium compounds or chlorhexidine is recommended. In herds with confirmed infection, culling of chronic carrier animals may be economically justifiable. Vector control, given the discovery of R. bursa as a potential tick vector, merits further investigation [7].

Interaction between M. agalactiae and other endogenous bacterial strains, such as Enterococcus spp. and coagulase-negative Staphylococcus, may influence udder ecology and susceptibility to infection [13]. Furthermore, commercial and wild lactic acid bacteria strains have shown antibacterial potential against M. agalactiae in vitro, opening avenues for probiotic-based control strategies [14]. Addition of lactic acid bacteria to diluted ram semen has also been studied as a vehicle for vaginal inoculation, with observed antibacterial effects [15]. These microbiome modulation approaches could complement existing control measures.

Conclusions

Mycoplasma agalactiae remains a formidable pathogen of sheep and goats, causing substantial economic losses through chronic mastitis, lameness, and blindness. Recent advances in genomics [1], conjugation biology [4], and immune evasion mechanisms [2] have deepened understanding of pathogenesis. Diagnostic strategies have evolved to include multi-platform molecular and serological tools [5, 9]. Treatment is complicated by antimicrobial resistance, but PK/PD modeling offers rational dosing guidance [10, 11]. Vaccines need improvement [8, 3, 12], and integrated biosecurity remains the cornerstone of control [5]. The discovery of tick-borne transmission [7] and the role of host–microbiome interactions [15, 13, 14] open new avenues for research and intervention.

References

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[3] Barbosa MS, Sampaio BA, Spergser J et al. Mycoplasma agalactiae Vaccines: Current Status, Hurdles, and Opportunities Due to Advances in Pathogenicity Studies. Vaccines (Basel). 2024. URL: https://pubmed.ncbi.nlm.nih.gov/38400139/

[4] Derriche M, Nouvel LX, Gaudino M et al. Bacterial conjugation in the ruminant pathogen Mycoplasma agalactiae is influenced by eukaryotic host factors. Appl Environ Microbiol. 2025. URL: https://pubmed.ncbi.nlm.nih.gov/40422289/

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[6] Volodymyrovych Bohach M, Igorovych Bolotin V, Mykolaivych Bohach D et al. Influence of Natural and Climatic Conditions on the Distribution and Forms of Contagious Agalactia in Sheep in Bessarabia, Ukraine. J Vet Res. 2022. URL: https://pubmed.ncbi.nlm.nih.gov/36349124/

[7] Migliore S, Condorelli L, Galluzzo P et al. First Description of Mycoplasma agalactiae Anatomical Localization in Naturally Infected Hard Ticks (Rhipicephalus bursa). Microorganisms. 2024. URL: https://pubmed.ncbi.nlm.nih.gov/39065159/

[8] Sampaio BA, Barbosa MS, de Oliveira MG et al. Immune Responses Induced by Recombinant Membrane Proteins of Mycoplasma agalactiae in Goats. Vaccines (Basel). 2025. URL: https://pubmed.ncbi.nlm.nih.gov/40733723/

[9] Akbarzadeh-Niaki M, Derakhshandeh A, Kazemipour N et al. A novel fusion protein candidate for the serodiagnosis of Mycoplasma agalactiae infection. BMC Vet Res. 2022. URL: https://pubmed.ncbi.nlm.nih.gov/36581939/

[10] Serrano-Rodríguez JM, Fernández-Varón E, Muñoz-Rascón P et al. Pharmacokinetic/pharmacodynamic modeling in plasma and milk and Monte Carlo simulations of marbofloxacin against Staphylococcus aureus and Mycoplasma agalactiae in lactating sheep. J Dairy Sci. 2025. URL: https://pubmed.ncbi.nlm.nih.gov/40139363/

[11] Serrano-Rodríguez JM, Fernández-Varón E, Rodríguez CMC et al. Population pharmacokinetics and pharmacokinetic/pharmacodynamic evaluation of marbofloxacin against Coagulase-negative staphylococci, Staphylococcus aureus and Mycoplasma agalactiae pathogens in goats. Res Vet Sci. 2023. URL: https://pubmed.ncbi.nlm.nih.gov/37060837/

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