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Introduction to Pathogens
Eperythrozoon
Pathology
Eperythrozoon is a round structure enclosed by a single-layered, limiting membrane; it lacks a cell wall, stains Gram-negative, and contains no discernible organelles or nucleoid-like structures. Measuring 0.3 to 0.6 μm in diameter, it is a typical prokaryotic organism. Under the microscope, Eperythrozoon exhibits pleomorphism, appearing as rod-shaped, spherical, or ring-like forms. It can either attach to the surface of red blood cells or invade their interiors, causing the red cell membranes to become indented or deformed. Alternatively, it may exist freely in the plasma. Notably, while free in the plasma, the organism remains motile, whereas when parasitizing red blood cells, it loses its ability to move.
Figure 1: Scanning Electron Microscopy Observation (Reproduced from Reference 2)
Previously classified under the family Ehrlichiales, within the order Rickettsiales, recent 16S rRNA gene sequence analyses and electron microscopy observations have revealed that both Eperythrozoon and Haemobartonella lack cell walls, instead adhering to and growing on the surface of red blood cells. These organisms are closely related to the Mycoplasma pneumoniae group and should therefore be recognized as members of the Mycoplasmatales order. Based on their distinctive staining properties, obligate intracellular parasitism, sensitivity to tetracycline, and dependence on insect vectors, certain species—such as Eperythrozoon-like, oviform Eperythrozoon, oviform Eperythrozoon suis, Eperythrozoon wenyi, feline Haemobartonella, canine Haemobartonella, and murine Haemobartonella—have been reclassified into the Hemoplasma cluster. Notably, while the species Eperythrozoon-like remains in the genus Eperythrozoon and murine Haemobartonella retains its placement in the genus Haemobartonella, all other species have been reassigned to the genus Mycoplasma, prompting corresponding changes in their taxonomic names (as listed in Table 1, referenced from Source 1). Many of these organisms are associated with diseases such as eperythrozoonosis or haemobartonellosis.
Table 1: Major Members of Mycoplasma haemofelis and Their Characteristics
Epidemiology and Clinical Symptoms
Eperythrozoonosis is a zoonotic bloodborne infectious disease. It commonly affects vertebrates such as pigs, cattle, sheep, cats, and rodents; most infections are asymptomatic, yet the pathogen can persist in animals with latent infections for several years. Stress, immunosuppressive diseases, or splenectomy may trigger infected red blood cells to enter the bloodstream, leading to clinical signs such as anemia, general weakness, lethargy, fever, anorexia, diarrhea, vomiting, hypoglycemia, weight loss, reduced reproductive efficiency, hepatosplenomegaly, enlarged lymph nodes, and pale or jaundiced mucous membranes. Transmission vectors include fleas, lice, ticks, mosquitoes, and blood-sucking flies. The disease can also be transmitted vertically. As of now, there is no method available to fully culture Eperythrozoon in vitro, making it challenging to study its life cycle and the pathological mechanisms underlying infection. Today, Eperythrozoon has become a globally distributed disease that can infect multiple animal species—including humans—making it one of the most significant zoonotic pathogens worldwide.
Over the past three years, our laboratory has tested 463 monkey blood samples for Eperythrozoon, with 269 samples testing positive and 20 samples deemed suspect. The overall positivity rate was 58.10%.
Figure 2: Microscopic Observation of Wright's Stained Blood Smear (Referenced from Reference 2)
Hemotropic mycoplasmas possess adhesins that cause red blood cells to become indented due to the bacteria's adhesive action, ultimately disrupting the cells' cytoskeleton and increasing their fragility. The primary hallmark of infection is anemia, which in essence is an autoimmune disorder. This anemia arises because the red blood cells infected by the bacteria fail to enter the bloodstream—they are instead engulfed, processed, and presented by endothelial cells in the capillaries of the spleen and lymph nodes, as well as by macrophages—thus becoming self-antigens. These self-antigens trigger the production of IgM cold agglutinins, which not only bind to the infected red blood cells but also attach to uninfected ones, forming antigen-antibody complexes. These complexes then mediate the phagocytosis of red blood cells by host cells, leading to the development of anemia.
Figure 3: Acridine Orange Staining Microscopic Observation (Referenced from Reference 2)
Diagnosis
In clinical diagnostics, the diagnosis should be made based on a comprehensive evaluation of clinical symptoms, histological microscopic examination, serological tests, and molecular biology assays. Studies indicate that microscopic observation alone is a highly insensitive diagnostic method. Serological tests, such as the indirect hemagglutination inhibition assay or ELISA, can be used, but both have limitations and are better suited for monitoring infections within a population rather than for diagnosing individual cases. For individual case diagnosis, nucleic acid probes combined with PCR methods are more appropriate.
The Impact on Research
Hemotropic mycoplasma influences research due to its parasitic relationship with red blood cells. It shortens the half-life of red blood cells, can alter the function of the mononuclear phagocytic system, and may enhance rejection responses against transplantable tumors—while also potentially interfering with studies on other blood-borne parasitic diseases such as malaria and trypanosomiasis.
Prevention and Removal
Studies have shown that fluoroquinolone or tetracycline-class antibacterial drugs are effective against animals infected with Haemophilus mycoplasma, and combining these medications can enhance the clearance of the pathogen from host organisms. However, it’s important to note that these treatment regimens may not always completely eradicate Haemophilus mycoplasma in infected hosts. In fact, some animals continue to harbor subclinical infections throughout their lives even after antibiotic therapy, making it challenging to obtain quantitative data on production losses and, consequently, to accurately assess the economic impact caused by the disease.
The primary preventive measures include eliminating blood-sucking insects, strengthening livestock management to reduce adverse stress, and enhancing the animals' immune resistance. It is recommended to identify and remove any animals that test positive for infection. If this disease is confirmed within the experimental animal population, it may be necessary to resume breeding through embryo transplantation or cesarean section. Currently, no vaccine is available.
References
1. *Veterinary Microbiology (6th Edition)*, edited by Lu Chengping and Liu Yongjie
2. Yang Ruizhi, Li Lianrui, Song Huiqi, et al. Advances in Research on Mycoplasma haemofelis [J]. Modern Animal Husbandry Science & Technology, 2023(03):20-29.
3. Fan Jing, Guo Wenjie. Diagnosis and Control of Swine Haemophilus Meningitis [J]. China Animal Health Care, 2023, 25(03):25-26.
4. Weisbroth S H, Kohn D F, Boot R. Bacterial, Mycoplasmal and Mycotic Infections[M]. Elsevier Inc. 2006.
5. Biology and Diseases of Rats
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