Xishan Biology

Introduction to Pathogens

Rabbit Eimeria coccidia

Pathology

 

Coccidia of rabbits belong to the phylum Apicomplexa, class Sporozoa, order Eucoccidiorida, family Eimeriidae, and genus Eimeria. These single-celled protozoans parasitize the intestinal or hepatic bile duct epithelium of rabbits. Historically, the classification of coccidia in domestic rabbits has been plagued by taxonomic confusion, including synonyms and homonyms, leading to at least 25 species being described and named. However, with the advancement of techniques for isolating single oocysts, coupled with studies on SPF rabbits and morphological identification of coccidia (including characteristics such as the size and structural features of sporulated oocysts, sporulation time, incubation period, site of parasitism, and pathogenicity), 11 species have now been confirmed as valid through pure culture and detailed characterization (as shown in Table 1 and Figure 1, referenced from Source 4). These 11 species were further validated by 18S rRNA gene sequence analysis. They are: *Eimeria stiedai*, *Eimeria piriformis*, *Eimeria flavescens*, *Eimeria minuta*, *Eimeria intestinalis*, *Eimeria mesoglena*, *Eimeria wegeneri*, *Eimeria perforans*, *Eimeria magna*, *Eimeria ameba*, and *Eimeria caecati*. Notably, among these species, only *Eimeria stiedai* infects bile duct epithelial cells, while all others primarily reside within the intestinal mucosal epithelial cells.

Figure 1: Morphological Structure Diagrams of Sporulated Oocysts from 11 Rabbit Coccidia Species

Table 1: Morphological and Biological Characteristics of 11 Eimeria Species Parasitizing Rabbits

Epidemiology

 

The development of rabbit Eimeria coccidia does not require an intermediate host, classifying it as a direct-developing type. However, its developmental process is complex, involving alternating cycles of asexual and sexual reproduction, which include three distinct stages: schizogony, gametogony, and sporogony. The first two stages occur within bile duct epithelial cells (in the case of *Eimeria stiedai*) or intestinal epithelial cells (for various coccidia that parasitize the small and large intestines), while the final developmental stage takes place in the external environment (Figure 4, cited from Reference 1).

Figure 2: Infection with Eimeria stiedai

Day 7, first-generation mature schizonts

Figure 3: Infection by Eimeria stiedai

Day 11, Mature Microgametophyte

When rabbits eat or drink, they inadvertently swallow mature sporulated oocysts. Once inside the intestine, these oocysts are broken open under the action of bile and pancreatic enzymes, releasing the sporozoites, which actively invade the epithelial cells lining the intestinal (or bile duct) walls. Initially, these sporozoites transform into round-shaped trophozoites. As they grow, their nuclei undergo multiple divisions, giving rise to multinucleated forms, eventually developing into spherical schizonts that contain numerous banana-shaped merozoites. This entire process represents the first-generation schizogony. These merozoites then re-enter the epithelial cells of the intestine (or liver and bile ducts), initiating the second, third, and even fourth or fifth generations of schizogony. This cycle repeats repeatedly, causing extensive damage to the epithelial cells and ultimately leading to severe enteritis or hepatitis in rabbits. After completing schizogony, some merozoites differentiate into macrogametocytes, while others become microgametocytes. The macrogametocytes develop into macrogametes, whereas the microgametocytes give rise to numerous microgametes within their own structures. Finally, the macro- and microgametes fuse to form a zygote. Around the zygote, an oocyst wall gradually forms, encapsulating it as a fully developed oocyst. These oocysts then migrate into the intestinal lumen and are excreted along with the rabbit's feces. Under favorable environmental conditions—specifically at temperatures between 20°C and 28°C and humidity levels of 55% to 60%—the oocysts undergo sporogony. During this stage, four sporocysts are formed inside each oocyst, and within each sporocyst, two infectious sporozoites are produced. The fully matured oocysts, now containing these sporozoites, are referred to as sporulated oocysts.

Figure 4: Development of the intermediate Eimeria species within rabbit intestinal epithelial cells (A) and in the external environment (B)

The infection route of this disease is through ingestion of food and water. Young rabbits are primarily infected by consuming oocysts contaminated on the mother rabbit’s udders during nursing, while older rabbits mainly become infected by eating grass, consuming feed, or drinking contaminated water. Additionally, farm workers, equipment, wild rodents, and even flies can mechanically carry coccidia oocysts, thereby spreading the disease. Poor nutrition and inadequate hygiene conditions in rabbit housing—leading to contamination of feed and water with feces—greatly facilitate the occurrence and transmission of this illness. Adult rabbits often act as carriers, playing a critical role in the spread of coccidiosis among younger animals. The timing of outbreaks depends on temperature and humidity levels, typically peaking during warm, rainy seasons. However, if the temperature inside the rabbit house consistently stays above 10°C, coccidiosis can occur at any time.

Figure 5: Focal necrosis of hepatocytes in E. stiedai-infected chickens, observed 9 days post-infection

The destruction of epithelial cells by coccidia, the production of toxic substances, and the combined effects of intestinal bacteria are the primary factors contributing to pathogenesis. In affected rabbits, the central nervous system is continuously stimulated, disrupting the regulatory functions of various organ systems and leading to a wide range of clinical symptoms. When bile ducts and intestinal epithelium suffer severe damage, normal digestive processes become severely impaired, resulting in nutritional deficiencies, edema, as well as dilutional anemia and leukopenia. Moreover, the massive breakdown of intestinal epithelial cells creates an environment highly conducive to bacterial proliferation, triggering the excessive production of toxins in the intestinal contents. These toxins are subsequently absorbed into the bloodstream, causing systemic intoxication, clinically manifested as spasms, collapse, intestinal distension, and cerebral anemia.

Figure 6: Natural infection with E. stiedai in rabbits shows marked proliferation of hepatic fibrous tissue and layered arrangement of hepatocytes in the liver.

Clinical symptoms and pathological changes

 

Depending on the type of coccidia and the site of parasitism, rabbit coccidiosis is classified into three types: intestinal, hepatic, and mixed. Clinically, the mixed form is most commonly observed. Typical symptoms include reduced or complete loss of appetite, depression, sluggish movements, prolonged recumbency, increased discharge from the eyes and nose, excessive salivation, and damp fur around the mouth. Affected rabbits may also experience diarrhea—or alternately, episodes of diarrhea followed by constipation. Additionally, they often exhibit frequent urination or adopt a characteristic urination posture, with fecal matter frequently contaminating the hind limbs and the area around the anus. Due to intestinal distension, urinary retention in the bladder, and hepatomegaly, affected rabbits develop an enlarged abdominal circumference, and palpation of the liver region elicits pain. Sick rabbits become weak and emaciated, with pale conjunctiva and mild jaundice visible in the mucous membranes. In the later stages of the disease, young rabbits often display neurological symptoms, such as limb spasms and paralysis, ultimately succumbing to extreme debility. Mortality rates typically range from 40% to 70%, occasionally soaring as high as 80%. The disease usually lasts anywhere from ten days to several weeks. Even after recovery, affected rabbits often remain severely underweight and suffer from stunted growth and development.

Figure 7: Symptoms of Rabbit Coccidiosis (Image source: Internet)

When rabbits suffering from coccidiosis die, their bodies appear emaciated, with pale mucous membranes and fecal matter around the anus. In cases of hepatic coccidiosis, numerous white or yellowish-white nodules—ranging in size from millet to pea—are visible on both the surface and within the liver tissue, arranged along the small bile ducts (Figures 8 and 9, cited from Reference 5). When these nodules are examined under a microscope after being thinly spread, various developmental stages of the parasite can be observed, including schizonts, merozoites, gametocytes, and oocysts (Figures 2 and 3, cited from Reference 5). Over time, the contents of older lesions become thicker, eventually forming chalky, calcified deposits. In chronic hepatic coccidiosis, peribiliary fibrosis and interlobular connective tissue proliferation lead to atrophy of hepatocytes and a reduction in liver size, resulting in interstitial hepatitis (Figures 5 and 6, cited from Reference 5). Meanwhile, the gallbladder lining exhibits catarrhal inflammation, while the bile becomes thickened and contains numerous disintegrated epithelial cells. As for intestinal coccidiosis, the primary lesions occur in the intestines, characterized by congestion of intestinal blood vessels, dilation and thickening of the duodenum, and catarrhal inflammation of the mucosa. The small intestine is often filled with gas and copious amounts of mucus, accompanied by mucosal hyperemia and scattered pinpoint hemorrhages. In chronic cases, the intestinal mucosa turns pale grayish, covered with numerous tiny white nodules; microscopic examination reveals a high number of oocysts, and occasionally, small areas of purulent or necrotic lesions may also be present on the intestinal lining.

Figure 8: Liver infected with E. stiedai

Figure 9: Hepatic Nodular Lesions Formed by Infection with Eimeria stiedai

Impact

 

Coccidiosis in rabbits is one of the most common parasitic diseases affecting domestic rabbits, posing a significant threat to the rabbit farming industry. Currently, the main prevalent species in China include *Eimeria magna*, *Eimeria media*, and *Eimeria intestinalis*, though the dominant species vary somewhat depending on the region. Research indicates that *Eimeria flavescens*, *Eimeria stiedai*, and *Eimeria intestinalis* are highly pathogenic among rabbit coccidia, while *Eimeria magna*, *Eimeria piriformis*, *Eimeria media*, *Eimeria weishanensis*, and *Eimeria anatis* exhibit moderate pathogenicity. Meanwhile, *Eimeria minor* and *Eimeria perforans* cause only mild disease, and *Eimeria caecicola* is completely non-pathogenic.

Rabbits of all breeds are susceptible to Eimeria coccidia, particularly young rabbits from weaning up to 4 months of age, which exhibit high infection and mortality rates. In contrast, adult rabbits typically become long-term carriers, continuously shedding oocysts into the external environment. Even with prolonged medication, coccidiosis prevalence among rabbits remains stubbornly high, causing significant economic losses to the rabbit farming industry.

Over the past three years, our laboratory has tested a total of 105 rabbit coccidia samples, among which 45 were positive, resulting in a positivity rate of 42.86%.

Diagnosis

 

First, make a preliminary diagnosis based on epidemiological data, clinical symptoms, and pathological necropsy findings. Then, examine fecal samples using the saturated saltwater flotation method to detect oocysts, or prepare smears from scraped intestinal mucosa and liver lesion tissues for microscopic examination of coccidian oocysts, schizonts, or sporozoites. If numerous oocysts are found in the feces or if large numbers of coccidia at various developmental stages are identified within the lesions, the diagnosis of rabbit coccidiosis can be confirmed.

Prevention and Treatment

 

Currently, the treatment and prevention of coccidiosis in rabbits primarily rely on medications, and vaccine research targeting rabbit coccidia is also underway. The following drugs can be used for treatment or prevention:

(1) Sulfamethoxypyrimidine (SMM), mixed into the feed at a concentration of 0.1%, should be administered continuously for 3 to 5 days, followed by a one-week interval before starting another treatment course.

(2) Sulfadimidine (SM2) combined with trimethoprim (TMP), mixed at a ratio of 5:1, should be incorporated into the feed at a concentration of 0.02%. Administer this mixture continuously for 3 to 5 days, followed by a one-week break, then resume with another treatment course.

(3) A combination of 100 mg/kg clopidol and 8.35 mg/kg methylbenzoquate, marketed under the name Lerbek, when mixed into feed at these doses, can reduce oocyst shedding by 80% and increase weight gain by 41%.

(4) Robenidine, mixed at 30 mg/kg body weight into the feed, should be administered continuously for 5 days, followed by a repeat dose after an interval of 3 days.

(5) Diclazuril, when mixed into feed at a concentration of 1 mg/L and administered continuously for 1 to 2 months, can effectively prevent coccidiosis in rabbits.

(6) Monensin, added to feed at a concentration of 40 mg/L and administered continuously for 1 to 2 months, can effectively prevent coccidiosis in rabbits.

(7) Salinomycin, mixed into feed at a concentration of 50 mg/L and administered continuously for 1 to 2 months, can effectively prevent coccidiosis in rabbits.

Comprehensive preventive measures should also be implemented. Rabbit farms should be located in dry, sunny areas, ensuring that the premises remain well-drained. Rabbit hutches must be kept clean and properly ventilated. Young rabbits and adults should be housed separately, and any sick rabbits spotted should be immediately isolated and treated. Strengthen feeding management by paying close attention to the hygiene of both feed and drinking water, promptly removing feces to prevent contamination of hay and water sources. It is advisable to use wire rabbit cages equipped with mesh-bottomed floors, allowing droppings and urine to easily fall into a collection tray below. Cage equipment can be disinfected using boiling water, steam, or flame, or by exposing the cages directly to sunlight to kill oocysts. Additionally, carefully plan breeding schedules for does to avoid weaning young rabbits during the humid monsoon season. During peak seasons for coccidiosis, consider mixing preventive medications into the feed of weaned kits to effectively guard against this common rabbit disease.

References

 

1. *Veterinary Parasitology (2nd Revised Edition)*, edited by Kong Fanyao

2. "Veterinary Parasitology (3rd Edition)," edited by Ming Wang

3. Wang Xinqiu, Liu Lidan, Liao Guicheng, Liu Yuan, Huang Yijuan, Zeng Li, and Wong Yabiao. Advances in Epidemiological Investigation and Control Techniques for Rabbit Coccidiosis [J]. Chinese Journal of Rabbit Raising, 2018, (01):14-17+13.

4. Yan Wenchao, Suo Xun, Xue Bangqun. Current Status of Research on Coccidiosis in Domestic and Foreign Rabbits [J]. Chinese Journal of Rabbit Breeding, 2011, (05):21-26.

5. *Color Atlas of Animal Parasitic Diseases (2nd Edition)*, edited by Li Xiangrui

 

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