Neospora caninum is a microscopic protozoal parasite with worldwide distribution. Many domestic animals (eg, dogs, cattle, sheep, goats, water buffalo, horses, chickens) and wild and captive animals (eg, deer, rhinoceros, rodents, rabbits, coyotes, wolves, foxes) can be infected. Neosporosis is one of the most common causes of bovine abortion, especially in intensively farmed cows.
A second Neospora species, Neospora hughesi, is a cause of myelitis in horses and shares clinical features with equine protozoal myelitis.
Etiology of Neosporosis in Cattle
The etiological agent of neosporosis is N caninum, an intracellular cyst-forming protist belonging to the subphylum Apicomplexa, closely related to parasites such as Toxoplasma gondii and Sarcocystis spp. Three infective stages have been described: sporozoites, tachyzoites, and bradyzoites:
Sporozoites are located inside oocysts, which are the resistant forms excreted in feces of the definitive host (a canid). Oocysts are released without sporulation; then, with appropriate environmental temperature and humidity, two sporocysts containing four sporozoites each develop inside each oocyst.
Two infective stages are found in cattle (intermediate host): 1) the tachyzoite, which is the stage responsible for the acute phase of infection, tissue damage, and systemic dissemination; and 2) the bradyzoite, which is a slowly replicating stage that resides within cysts in nervous and muscle tissues, where the parasite evades the host's immune response.
Cysts containing bradyzoites are present during the chronic phase of N caninum infection and are responsible for persistent infection.
Epidemiology of Neosporosis in Cattle
Life Cycle and Transmission
Dogs and wild canids, such as gray wolves, coyotes, and dingoes, are definitive hosts of N caninum (see Neosporosis in Dogs). Cattle and other mammals, such as axis deer, European bison, sheep, water buffalo, and white-tailed deer, as well as domestic dogs and wild canids, are intermediate hosts. Both the parasite and the disease have been detected in alpacas, antelope, black-tailed deer, Eld's deer, equids, goats, llamas, parma wallabies, pine martens, red foxes, and rhinoceros.
The life cycle of N caninum is indirect, with dogs and cattle, respectively, acting as the definitive and intermediate hosts of greatest importance (see N caninum life cycle diagram). Dogs have been shown to become infected by eating infected cattle (including the placentas from aborted fetuses) and deer, and they are presumed to become infected by consuming raw meat derived from other wild animals as well.
Courtesy of Dr. Luis-Miguel Ortega-Mora.
The sexual cycle of N caninum takes place in the dog's intestine, and oocysts are eliminated in their feces. The asexual cycle occurs in the intermediate host. After the dog ingests sporulated oocysts, sporozoites are released and transform into tachyzoites, which multiply into several cell types during the acute phase of the disease. In the chronic phase, the host's immune response favors the differentiation of tachyzoites into bradyzoites, giving rise to tissue cysts.
Bradyzoites can be transformed back into tachyzoites during life stages of immunomodulation (eg, pregnancy). The parasite can then cross the placenta and infect the fetus. If gestation progresses, congenitally infected calves will be born persistently infected with cysts in brain and muscles. The host remains infected for life and can transmit infection via successive or intermittent pregnancies.
N caninum has multiple modes of transmission in cattle (see transmission route diagram):
Courtesy of Dr. Luis-Miguel Ortega-Mora.
Horizontal (postnatal) transmission is due to ingestion of water or food contaminated with sporulated oocysts.
Vertical (transplacental or congenital) transmission occurs when the parasite is transmitted from dam to fetus during pregnancy. Depending on the origin of infection in the dam, two modes of vertical transmission are differentiated:
Exogenous transmission occurs in cows that become infected by consuming sporulated oocysts during pregnancy.
Endogenous transmission occurs in females that are chronically infected carriers of cysts containing bradyzoites that reactivate to infective tachyzoites during pregnancy.
Vertical transmission of N caninum maintains infection endemically in affected herds, because chronically infected females very efficiently transmit the parasite to offspring in successive pregnancies. However, vertical transmission rates appear to decrease as females age, probably because they develop partial protective immunity.
Risk Factors
The main risk factors for infection by N caninum in cattle include breed (breeds differ in seroprevalence, possibly because of differences in management), the presence of dogs or other canids and other possible hosts, and poor hygiene and biosecurity.
The most notable risk factors for abortion caused by N caninum are the following:
Seropositivity: Seropositive cows have a greater risk of abortion, which increases with increases in antibody titer.
History of reproductive failure: Congenitally infected animals that have previously aborted have an increased risk of subsequent abortion.
Diet: Poor-quality forage and moldy silage have been linked to abortion epidemics.
Parasite isolate: Different isolates vary greatly in virulence and ability to induce abortion.
Clinical Findings of Neosporosis in Cattle
Nonpregnant cattle infected by N caninum generally are not clinically affected. In pregnant cattle (both dairy and beef), the most relevant clinical sign is abortion. Abortions are more common when infection occurs during the first or second third of gestation; infection in the last third of gestation results in the birth of congenitally infected calves, which either are healthy or, less commonly, have clinical signs.
Macroscopically, aborted fetuses can appear autolytic or mummified, and the placenta can show nonspecific lesions such as edema and necrotic foci in the cotyledons. Microscopic lesions are inflammatory, nonsuppurative, and necrotic. In fetuses, lesions are concentrated in the CNS; however, lesions can also occur in the heart and liver and, to a lesser extent, in the kidneys, skeletal muscles, and lungs.
The severity of neosporosis lesions is greater when infection occurs earlier in gestation. Occasionally, weak calves are born with neuromuscular signs that vary from slight incoordination, through ataxia, hyperextension of the limbs, and exophthalmos, to complete paralysis.
Neosporosis in cattle herds has both endemic and epidemic abortion patterns; however, a herd can have a high infection prevalence without a noticeable abortion problem.
Endemic abortion is associated mainly with the reactivation of persistent infections (bradyzoites) during pregnancy, followed by transplacental transmission to the fetus (endogenous transplacental transmission, EnTT). Occasional transmission from dogs or other canids can compound the problem.
Epidemic abortion is a possible consequence of sudden, large-scale transmission to pregnant cattle (exogenous transplacental transmission, ExTT), presumably by ingestion of a mixed ration or of water contaminated with canine feces that contain oocysts.
Diagnosis of Neosporosis in Cattle
Histological evaluation
Serological testing
PCR assay
Because neosporosis is only one of many causes of abortion in cattle, diagnostic efforts should focus on an array of possible causes.
Aborted fetuses, together with the placenta and a serum sample from the aborting dam, should be submitted to a veterinary diagnostic laboratory for histological analysis. Examination of multiple fetuses increases the odds of accurate diagnosis.
If it is impractical to submit an entire fetus, as many as possible of the following tissues should be submitted for testing to exclude other causes of abortion: aseptically collected and chilled brain, heart, liver, spleen, abomasal fluid, lung, thymus, kidney, adrenal gland, skeletal muscle (eg, tongue and diaphragm), placental cotyledon, and thoracoabdominal fluid from the fetus, as well as serum from the aborting dam.
Diagnosis of neosporosis in aborted bovine fetuses focuses on two pillars: 1) detection of the parasite in target tissues (preferably brain, heart, and liver) by PCR assay or immunohistochemical evaluation, and 2) detection of the parasite in the same tissues via histological examination. In addition, antibodies against the parasite can be detected in thoracic and/or abdominal fluid in fetuses > 5 months old via serological techniques.
The lesion that is nearly pathognomonic for neosporosis-induced abortion in cattle fetuses is multifocal nonsuppurative encephalomyelitis with perivascular cuffs, necrosis, and microgliosis. In addition, multifocal nonsuppurative myocarditis and myositis, as well as nonsuppurative periportal hepatitis with variable hepatic necrosis, can be observed (see histological images).
Courtesy of Dr. Luis-Miguel Ortega-Mora.
Confidence in a neosporosis diagnosis increases with an increasing titer of N caninum antibodies in the aborting dam: high seropositive reactions at the time of abortion have greater predictive value than low seropositive reactions.
Toxoplasmosis, a common cause of abortion in sheep and goats, is characterized by lesions similar to those of neosporosis; however, toxoplasmosis-induced abortion in cattle is rare.
Serological tests (eg, ELISA) are effective for postnatal diagnosis of N caninum infection in cattle. Specific antibody detection in tank milk (milk stored in bulk on a farm and tested to assess herd health) is useful to detect intraherd prevalences > 10%–15%. In addition, serological testing can identify infected replacement animals before their introduction into the herd.
During investigation of an abortion outbreak, serological testing of a small number of aborted and nonaborted cattle (generally ≥ 10 per group) enables the association of N caninum infection with abortion to be verified by calculation of the “odds ratio.” A substantial association between seropositivity and abortion confirms the involvement of neosporosis.
When neosporosis involvement has been confirmed, more exhaustive analysis should be carried out to determine the following parameters:
prevalence within the herd
prevalence by age groups
serological concordance between dams and daughters
avidity of the antibodies against the parasite in aborted and seropositive animals (the presence of high-avidity antibodies is characteristic of chronic infections associated with EnTT)
This diagnostic approach can reveal the magnitude of the problem and the predominant mode of transmission, providing critical information for addressing how to control neosporosis. However, seropositivity does not necessarily mean an animal will abort in the future.
Treatment of Neosporosis in Cattle
There is no approved treatment for neosporosis in cattle.
Control of Neosporosis in Cattle
Strategic testing
Biosecurity
Prevention of horizontal transmission
Both dairy and beef cattle herds commonly have at least a small percentage of N caninum–infected animals. Although lowering the risk of transmission is a useful goal, complete eradication of N caninum infection from a herd is usually impractical. The choice of control measures depends on how prevalent the disease is and on what the desired objectives are for a given herd. The prevalence of infection on farms with declared outbreaks must be decreased, and the spread of infection must be avoided through prevention of both horizontal and vertical transmission.
The following measures can be taken to control EnTT of neosporosis:
Test-and-cull can be performed on seropositive animals using a cost-benefit ratio. In general, animals with a history of abortion, animals with seropositive offspring, and animals that are old or have low production value should be culled.
Embryos from seropositive cows of high genetic merit can be transferred to noninfected recipients.
In dairy herds, insemination of seropositive Friesian cows with semen from beef breeds decreases the risk of abortion during infection.
Seropositive animals must be replaced with seronegative animals. Serological testing of calves 5–6 months old can help identify seropositive individuals.
Measures to control horizontal transmission and prevent ExTT of neosporosis include the following:
Contact between cattle and dogs or other canids should be prevented or at least minimized.
Feedstuffs used in mixed rations should be protected from contamination by canine feces. Large dairies can erect dog-proof fences around areas where feedstuffs are stored outdoors, and automatic gates can be installed to facilitate the daily traffic of heavy machinery while keeping out dogs. Smaller dairy farms might be able to protect feedstuffs by storing them in barns, grain bins, and silos.
Dead cattle, offal from home slaughter, aborted fetuses, and placentas should be discarded in a manner that prevents dogs from ingesting them, becoming infected, and shedding N caninum oocysts on the farm.
In farms free of clinically evident infection, calves and heifers should be tested to ensure they are seronegative, and biosecurity measures should be enforced.
Zoonotic Risk of Neosporosis in Cattle
Despite its similarity to T gondii, a known pathogen of humans, N caninum has not been clearly associated with any human disease. Nonetheless, laboratory workers should guard against inoculation, because fetal lesions have occurred in parenterally inoculated primates.
Key Points
Neosporosis is one of the major infectious causes of bovine abortion.
Fetal diagnosis is based on histological investigation of lesions and detection of the parasite in fetal target organs and the placenta. Serological testing is essential for postnatal diagnosis and control.
Because no treatment or vaccine for neosporosis is available, control measures are based on diagnosis, biosecurity, and prevention of transmission.
For More Information
Dubey JP, Hemphill A, Calero-Bernal R, Schares G. Neosporosis in Animals. CRC Press; 2017.
Dubey JP, Schares G, Ortega-Mora LM. Epidemiology and control of neosporosis and Neospora caninum.Clin Microbiol Rev. 2007;20(2):323-367.
Hecker YP, González-Ortega S, Cano S, Ortega-Mora LM, Horcajo P. Bovine infectious abortion: a systematic review and meta-analysis. Front Vet Sci. 2023;10:1249410.
Horcajo P, Regidor-Cerrillo J, Aguado-Martínez A, Hemphill A, Ortega-Mora LM. Vaccines for bovine neosporosis: current status and key aspects for development. Parasite Immunol. 2016;38(12):709-723.
Reichel MP, McAllister MM, Pomroy WE, Campero C, Ortega-Mora LM, Ellis JT. Control options for Neospora caninum—is there anything new or are we going backwards?Parasitology. 2014;141(11):1455-1470.
