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Basics

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BASICS

Definition!!navigator!!

PHF is an acute and potentially fatal enterotyphlocolitis of horses caused by infection with the monocytotropic rickettsia Neorickettsia risticii (formerly known as Ehrlichia risticii).

Pathophysiology!!navigator!!

  • The pathophysiology of PHF is poorly understood
  • N. risticii is a Gram-negative, obligate intracellular bacterium with a predilection for blood monocytes and tissue macrophages. Within days of infection, N. risticii can be found in blood monocytes. N. risticii survives within phagosomes in macrophages by inhibiting phagosome–lysosome fusion. The neoricketsemia persists throughout the disease
  • The pathogen has a predilection for the large colon and cecum, but is occasionally found in the jejunum and small colon. Mild cases of PHF without diarrhea have evidence of colitis. It is possible that many pathophysiologic changes observed in horses with PHF are secondary to effects of altered colonic flora

Systems Affected!!navigator!!

  • Gastrointestinal—cecum and large colon
  • Cardiovascular—dehydration and shock may develop in severe cases
  • Reproductive—occasional abortion

Genetics!!navigator!!

N/A

Incidence/Prevalence!!navigator!!

In Ohio, 13–20% of horses on racetracks had serologic evidence of exposure to N. risticii, although only 10–20% of them had clinical signs of the disease.

Geographic Distribution!!navigator!!

PHF has been reported in the USA, Canada, South America, Europe, and India.

Signalment!!navigator!!

All breeds and all ages may be affected. Horses <1 year of age less commonly develop PHF than adult horses. Clinical cases of PHF occur sporadically, with rarely more than 5% of horses on any one affected farm. Only in a significant epizootic infection does the attack rate on individual farms become high (20–50%).

Signs!!navigator!!

  • The majority of clinical disease appears to be mild or subclinical. In overt clinical illness, the manifestation of colitis is common in all cases. Not all cases show colic or diarrhea
  • Depression (90%)
  • Anorexia (80%)
  • Fever (70%)
  • Ileus (70%)—signs of ileus are one of the most consistent clinical findings
  • Diarrhea ( 60%)—mild to severe, watery, pipe-stream diarrhea present in 45–60% of cases. Course of diarrhea ranges from 1 to 10 days
  • Mild colic (30%) may accompany diarrhea
  • Congested mucous membranes (70%)
  • Dehydration
  • Laminitis (usually involving all 4 feet) develops in about 20–25%
  • Mortality rate from PHF—5–30%
  • Clinical course is usually 5–10 days without treatment
  • Infrequent abortion may occur

Causes!!navigator!!

  • Infection with N. risticii, an obligate intracellular Gram-negative bacteria
  • Different strains of N. risticii identified; not all pathogenic
  • N. risticii DNA has been found in trematodes (virgulate cercariae) that parasitize freshwater snails in endemic areas
  • During periods of warm water temperatures, cercariae infected with N. risticii are released from the snails, infecting and developing into metacercariae in the second intermediate host, aquatic insects, such as caddis flies, mayflies, damselflies, dragonflies, and stoneflies
  • Horses grazing near rivers or creeks could conceivably be exposed to N. risticii through skin penetration by infected cercariae in water, or ingest metacercariae in a second intermediate host such as an aquatic insect along with grass, consume adult insects trapped on the water surface, or consume adult insects that are attracted by stable lights or accumulate in feed and water
  • No evidence for the spread of PHF by arthropod vectors
  • Seasonal pattern in temperate climates with most clinical cases of PHF occurring mid to late summer

Risk Factors!!navigator!!

Endemic areas have been identified. N. risticii infection has been strongly associated with rivers, lakes, or other aquatic habitats. Increased risk of PHF is associated with horses grazing pastures bordering waterways; horses coming from an area with a high PHF prevalence or a farm with history of PHF; or travel to an area with a high incidence of PHF.

Diagnosis

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DIAGNOSIS

Differential Diagnosis!!navigator!!

All other causes of enterocolitis—acute salmonellosis, clostridial colitis, cyathostomes, antibiotic-induced colitis, intestinal ileus secondary to displacement or obstruction, NSAID toxicity, cantharidin toxicity; peritonitis; dietary changes.

CBC/Biochemistry/Urinalysis!!navigator!!

  • Hematology highly variable
  • Elevated packed cell volume and total plasma protein are common abnormalities. Hypoproteinemia may also be present
  • Leukopenia with a neutropenia and lymphopenia may initially be present, and within a few days a marked leukocytosis may occur
  • Hyponatremia
  • Hypochloremia
  • Hypokalemia
  • Metabolic acidosis
  • ±Prerenal azotemia

Other Laboratory Tests!!navigator!!

N/A

Imaging!!navigator!!

N/A

Other Diagnostic Procedures!!navigator!!

  • Definitive diagnosis should be based on isolation of N. risticii from blood culture or detection of the DNA of N. risticii from the blood or feces of an infected horse. Isolation of the organism requires collecting heparinized blood and harvesting buffy coat for cell culture
  • N. risticii-specific PCR assays that detect the partial 16S rRNA gene of N. risticii have facilitated PHF diagnosis. In naturally infected horses, PCR on peripheral blood and feces is more sensitive than blood culture. PCR may also be used in the detection of N. risticii DNA in fresh or formalin-fixed and paraffin-embedded colon tissue
  • Serologic tests—IFA or ELISA tests of limited diagnostic value in a clinical case. IFA test has been the most widely used diagnostic test for PHF; however, interpretation of results difficult. PHF diagnosed by demonstrating a4-fold increase or decrease in titers between acute and convalescent serum samples
  • Failure to seroconvert does not rule out PHF. Expected antibody titer of naturally affected horses is >1:80. Persistence of high antibody titers (1:2560) for more than 1 year has been noted in clinical and subclinical cases after natural infection

Pathologic Findings!!navigator!!

  • Gross distention of large colon and cecum with fluid contents
  • Histologically—lesions mild: superficial epithelial necrosis, erosion, and fibrin effusion
  • Silver stains—N. risticii seen as small, brown to black, intracellular dots (0.4–0.9 µm) in the apical cytoplasm of crypt enterocytes and also in the cytoplasm of macrophages in the lamina propria

Treatment

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TREATMENT

Appropriate Health Care!!navigator!!

Mild cases can be managed on the farm. Severely affected animals may require intensive care. As other causes of some of the clinical signs are potentially highly infectious (e.g. salmonellosis), animals should be managed in isolation. Early, appropriate treatment gives the best chance for a successful outcome.

Activity!!navigator!!

Stall rest during therapy is recommended.

Diet!!navigator!!

Grass hay diet is recommended until fecal consistency is normal.

Client Education!!navigator!!

N/A

Surgical Considerations!!navigator!!

N/A

Medications

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MEDICATIONS

Drug(s) of Choice!!navigator!!

  • Oxytetracycline 6.6 mg/kg IV every 24 h for 5 days treatment of choice. A rapid recovery and dramatic decrease in fatality rate is observed when oxytetracycline therapy is commenced within 24 h after the development of fever
  • NSAIDs, such as flunixin meglumine (1.1 mg/kg IV every 12 h), may be useful to treat endotoxemia

Fluids!!navigator!!

IV isotonic crystalloid fluid replacement therapy is extremely important in the treatment of hypovolemia and shock.

Contraindications!!navigator!!

N/A

Precautions!!navigator!!

  • Diarrhea may occur in horses receiving parenteral antibiotics
  • Nephrotoxicity possible with oxytetracycline, especially in a dehydrated horse, or with the concurrent administration of NSAIDs

Alternative Drugs!!navigator!!

N/A

Follow-up

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FOLLOW-UP

Patient Monitoring!!navigator!!

Relapses rare following cessation of IV oxytetracycline therapy. If relapse occurs, administer a second course of IV oxytetracycline.

Prevention/Avoidance!!navigator!!

  • Contact with recovered or currently ill animals not associated with the development of PHF
  • Natural infection with PHF induces a protective immunity for as long as 20 months
  • Horses do not remain chronic carriers
  • Access to freshwater streams and ponds should be limited in endemic areas
  • Horses in endemic areas may be vaccinated with an inactivated cell vaccine between early spring and early summer. Require 2-dose primary series 3–4 weeks apart. Revaccination at 6–12 month intervals dependent on whether in highly endemic area. High rate of vaccination failure (up to 89%) reported in endemic areas attributed to extensive variability in the major surface antigens and lack of cross-protection between strains. Anecdotal reports of reduced severity of clinical signs in vaccinated horses

Possible Complications!!navigator!!

  • Acute or chronic laminitis in 20–25% of PHF cases
  • Thrombophlebitis
  • Disseminated intravascular coagulopathy

Expected Course and Prognosis!!navigator!!

Horses with mild signs treated early in the course of the disease show a dramatic response to therapy and can be clinically normal in 3–5 days. Horses with more severe and longstanding problems require a longer period of therapy; if secondary problems are present, the clinical course may be much longer and the outcome less favorable.

Miscellaneous

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MISCELLANEOUS

Synonyms!!navigator!!

  • Equine monocytic ehrlichiosis
  • Equine ehrlichial colitis
  • Equine neorickettsiosis

Abbreviations!!navigator!!

  • ELISA = enzyme-limited immunosorbent assay
  • IFA = indirect fluorescent antibody
  • NSAID = nonsteroidal anti-inflammatory drug
  • PCR = polymerase chain reaction
  • PHF = Potomac horse fever

Suggested Reading

Bertin FR, Reising A, Slovis NM, et al. Clinical and clinicopathological factors associated with survival in 44 horses with equine neorickettsiosis (Potomac horse fever). J Vet Intern Med 2013;27:15281534.

Madigan JE, Pusterla N. Life cycle of Potomac horse fever—implications for diagnosis, treatment, and control: a review. Proc Am Assoc Equine Pract 2005;51:158162.

Pusterla N, Leutenegger CM, Sigrist B, et al. Detection and quantitation of Ehrlichia risticii genomic DNA by real-time PCR in infected horses and snails. Vet Parasitol 2000;90:129135.

Rikihisa Y. New findings on members of the family Anaplasmataceae of veterinary importance. Ann N Y Acad Sci 2006;1078:438445.

Author(s)

Author: John D. Baird

Consulting Editors: Henry Stämpfli and Olimpo Oliver-Espinosa