Equine neorickettsiosis (EN), often referred to as Potomac Horse Fever, is a bacterial infection caused by Neorickettsia risticii that predominantly affects the large colon. EN can present with variable clinical signs that may include depression, inappetance, diarrhea and laminitis. EN occurs during the warmer months of the year, with the incidence peaking in late summer. Horses are typically exposed to the disease through accidental ingestion of aquatic insects that contain parasitic trematodes, which harbor the bacteria N. risticii. Early detection and treatment with oxytetracycline gives the best chance of recovery from this condition. Vaccination provides variable and uncertain protection against EN.
Introduction to Equine Neorickettsiosis
Equine neorickettsiosis is a disease with an interesting etiological and geographical history.
In 1924, Dr. Frank Schofield described a disease in southern Ontario known as “horse cholera” or “abdominal typhoid.” In this region the disease was associated with the haying season and with the seasonal appearance of Mayflies, and was known to occur along the many waterfronts in the area. Dr. Schofield suspected the causative agent was bacterial but was unable to isolate it, despite conducting thorough and innovative experiments. His recommendations for prevention of the disease were to stable the horses during the risky times, and to feed them hay rather than let them graze (Baird, 2013).
In the 1970s and 80s, in Maryland, U.S.A., there was a dramatic increase in the incidence of a disease known as “Acute Equine Diarrhea Syndrome.” This syndrome occurred seasonally in focal regions along the Potomac River. A news reporter subsequently coined the name “Potomac Horse Fever” (Baird, 2013).
In 1984, the organism was identified as being rickettsial, and was named Ehrlichia risticii, but was later reclassified to Neorickettsia risticii in 2001 (Baird, 2013).
In 1997, Madigan et al showed that a disease referred to as Shasta River Crud in northern California had the same etiology as Potomac Horse Fever.
The current scientific term for this disease is Equine neorickettsiosis (EN) (Bertin, 2013). Other names applied to the disease over the years include equine ehrlichial colitis, equine monocytic ehrlichiosis and churrido equino.
Extensive research has eventually led to an understanding of the complex way in which horses become infected with N. Risticii. EN is now known to have a global distribution, with description of the disease in Canada, North America and Europe (France, Netherlands), and with current research in South America, Africa and Asia. Digean parasitic flukes have been found to have an endosymbiotic relationship with N. risticii in many countries around the world (Greiman, 2017).
Life cycle of Neorickettsia risticii within Digean Trematode Worms
N. risticii is a commensal organism within digean trematode worms. The lifecycle of these parasitic flatworms is complex, and N. risticii can exist within the worm throughout all of the lifecycle stages. The fresh water snail is the first intermediate host for the trematode, aquatic insects are the second intermediate host, and insectivorous animals such as fish, amphibians, birds and bats form part of the lifecycle transition to the egg-producing adult worm (Pusterla, 2013).
In addition to the accidental ingestion of aquatic insects that harbor trematode metacercariae, horses can become infected by direct ingestion or drinking of water containing free-living trematode metacercaria/cercaria (Bertin, 2013). Pusterla et al also hypothesize that skin penetration by free-living cercaria is a possibility that cannot yet be ruled out (Pusterla, 2013).
The Mayfly is one of the aquatic insects that is commonly associated with occurrence of EN. The Mayfly is a burrowing fly that has a nymph stage that lasts 1-2 years. When the adult fly emerges it is unable to fly significant distances and its dispersal is dependent on windy conditions (Baird, 2013). Windy conditions can therefore influence which horses are at risk of accidental ingestion of the fly.
Caddis flies and stoneflies have also been implicated. Stable lights or night lighting may attract the flies into the vicinity of the horse (Pusterla, 2013).
Pathophysiology of EN in Horses
Neorickettsia risticii is an obligate intracellular gram-negative coccus that cannot be grown with conventional culture, but will grow in cell culture (Baird, 2013).
Horses grazing around freshwater ponds and streams are most at risk of infection. The disease occurs seasonally, in the warmer months of spring, summer and autumn (Bertin, 2013), peaking in mid-late to late summer (Pusterla, 2013).
After the horse ingests the insect-trematode-N. risticii combination, the incubation period is approximately 1-3 weeks (Pusterla, 2013). During this time, N. risticii is released into the gastrointestinal tract where it infects epithelial cells, usually of the colon. N. risticii then replicates within the cytoplasm of colonic glandular epithelial cells, mast cells and tissue macrophages and can gain access to the systemic circulation, where it rapidly replicates within blood monocytes (Bertin, 2013).
The microvilli of infected epithelial cells are damaged or lost which prevents absorption of water and electrolytes. In severe cases, mucosal compromise may also lead to ulceration and necrosis of the intestinal lining.
N. risticii is shed in the horse’s feces but horses exposed to contaminated feces rarely become infected, as they would need to ingest large volumes of manure.
Clinical Signs of Equine Neorickettsiosis
The clinical signs for EN can be quite variable. Horses may show one or more of the following symptoms, in a variety of combinations. The clinical signs below are listed in order of most common occurrence:
|Diarrhea||Moderate to severe, cow-pie to watery and projectile.|
|Fever||A variety of virulence factors, still being researched.|
|Laminitis||Which may affect all four feet. Laminitis can occur in the absence of diarrhea. Radiographs may show evidence of P3 rotation. Laminitis has not been shown to be associated with the outcome (Bertin, 2013), however it can progress after resolution of other clinical signs (Pusterla, 2013).|
|Dehydration and Toxemia||Tachycardia, congested mucous membranes, tachypnea etc.|
Clinical signs last around 5 days, with a range of 1-15 days. Young horses (< 1 year old) can be affected but tend to have a better recovery rate from EN than older horses (Bertin, 2013). The overall fatality rate for EN lies between 5-30% (Pusterla, 2013).
Infected pregnant mares are at risk of either resorption of the fetus, abortion, or giving birth to a compromised foal, due to transplacental transmission of N. risticii (Pusterla, 2013).
Blood work shows (Bertin, 2013; Pusterla, 2013):
|Prerenal azotemia||Lymphopenia, neutropenia with left shift. Within days can develop leukocytosis.|
|Elevated serum AST and CK|
|Hyponatremia and hypochloremia||Especially in horses with diarrhea.|
|Hypocalcemia||Can be linked to hypoalbuminemia, but also can occur in the absence of hypoalbuminemia.|
|Anemia, thrombocytopenia and hypercoagulation||May also occur (Pusterla, 2013)|
The presence and degree of severity of hyponatremia and hypochloremia, can reflect the severity of mucosal damage (Bertin, 2013). Colitis caused by Salmonella spp. or Clostridial spp. do not tend to cause hyponatremia and hypochloremia as frequently and so these electrolyte changes may give an early indication that N. risticii is the cause (Bertin, 2013).
Diagnosis of Equine Neorickettsiosis (Potomac Horse Fever)
Serum antibody assays such as indirect fluorescent antibody (IFA) testing and ELISA have been shown to have poor correlation with infection and may give false positive results (especially with IFA) or false negative results, as antibodies may not be present in the serum for some time after infection. IFA titres > 2560 are associated with clinical disease, however this is not considered strongly diagnostic as there is large variability in the antibiotic response amongst individuals, even when performing paired acute and convalescent titres (Bertin, 2013; Pusterla, 2013).
Bacterial Identification and Culture
N. risticii can be isolated from blood or feces using special cell culture mediums, or with PCR isolation techniques. Rarely, in the acute phase of disease, N. risticii morulae may be identifiable within white blood cells (McConnico, 2014).
When using real-time PCR, blood samples tend to be diagnostic between 7-21 days after initial infection, while fecal PCR tends to be positive between day 11-16 post infection. Performing multiple tests may help “catch” this diagnostic window and avoid a false negative interpretation of results (Pusterla, 2013).
Treatment for Equine Neorickettsiosis
Oxytetracycline (6.6 mg/kg) administered twice daily for 5 days is the recommended treatment (Pusterla, 2013). Early treatment improves chances of survival and is recommended for horses living in endemic areas that develop clinical signs (Bertin, 2013). Oxytetracycline administration does not appear to worsen the colitis. The kidney perfusion needs to be well supported by fluid therapy, particularly if the horse is dehydrated. Response to treatment is usually seen within 12-24 hours (Pusterla, 2013).
Supportive care with intravenous fluids and electrolyte supplementation is important, and NSAID administration where indicated.
In severe cases with hypoalbuminemia, plasma transfusions may be necessary.
The horses’ feet can be supported with stable confinement, supportive bedding, icing and pain relief (Pusterla, 2013).
In a study by Bertin et al (2013), 73% of horses survived to discharge after a median 6 days in hospital. Younger horses had a better survival rate. The more of the blood work changes that were present, and the more profound the changes were, the poorer the prognosis.
Prevention of EN
Development of effective vaccinations is an area of ongoing research. Current vaccines show variable protective efficacy. Part of the problem is that N. risticii has many strain variations, and so selecting the most protective antibody-inducing antigens to incorporate into the vaccine is challenging. Also, many horses do not have a strong antibody response to vaccines, and the antibodies are short-lived.
For these reasons, particularly in endemic areas, vaccination is recommended every 3 months, and every 6-12 months in other areas. (Bertin, 2013)
Bertin et al (2013) did not find that vaccinated horses had improved survival rates, and vaccines have yet to be shown to be protective against abortion.
Horses that have recovered from natural infection, however, have been shown to be resistant to re-infection for up to 2 years (Pusterla, 2013).
Decreasing exposure to aquatic insects during high-risk times may also help prevent disease. This may include limiting the horse’s grazing access to waterways, and avoiding the use of night lights around stables and pastures.
Baird, J.D. and Arroyo, L.G. (2013) Historical aspects of Potomac horse fever in Ontario (1924-2010). Can Vet J: 565-572.
Bertin, F.R., et al. (2013), Clinical and Clinicopathological Factors Associated with Survival in 44 Horses with Equine Neorickettsiosis (Potomac Horse Fever). J Vet Intern Med, 27: 1528–1534. doi:10.1111/jvim.12209
Greiman, S.E., et al. (2017) Real-time PCR detection and phylogenetic relationships of Neorickettsia spp. in digeneans from Egypt, Philippines, Thailand, Vietnam and the United States. Parasitology International 66: 1003-1007.
Madigan, J.E. et al (1997) Identification of an enzootic diarrhea (“Shasta river crud”) in Northern California as Potomac horse fever.
McConnico, R. (2014) Acute Colitis in Horses. In: Robinson’s Current Therapy in Equine Medicine. Eds K.A. Sprayberry and N.E. Robinson. Elsevier Health Sciences. page 299.
Pusterla, N. and Madigan J (2013) Neorickettsia risticii, in Equine Infectious Diseases E-book, 2nd ed. Ed D.C. Sellon and M. Long. pge 347-351