Infections

Epidemiologic studies of disease and death in foals up to six months of age indicate that the risk of disease is greatest in neonatal foals (first 7 days of life) [1]. The leading cause of death in this group is septicemia (blood borne bacterial infection). In most papers, failure of passive transfer is listed as the leading cause of these infections. The practice of assessing passive immunity was associated with decreased morbidity due to septicemia [1].
Editor's Comment - Many (>25%) of confirmed septicemia foals have greater than 800 mg/dl IgG. Additionally, many foals with low IgG are sick at birth and have poor vigor and vitality. It is my opinion that this high rate of infection in this age group is best explained by delayed gut closure and bacterial invasion across the "open" gut rather than low IgG. (See How to Prevent the Leading Cause of Death in Neonatal Foals: Opinion).

I. Septicemia [1-3]

The most common cause of death in foals admitted for intensive care.

1. Causative agents - US and British studies indicate majority have a gram-negative component. E. coli, Actinobacillus spp, Klebsiella spp, Enterobacter spp, Pseudomonasspp were most common. Streptococcal infection does occur but is usually in conjunction with a gram-negative.
2. Onset within 3-4 days of age.

1. Some infections develop in utero and will be present at birth.
2. Foals frequently show first physical signs after infection has already been established for a considerable period of time.

3. Predisposing conditions. Editor's Comment - What all these conditions have in common is exposure to pathogens prior to colostrum ingestion

1. Prematurity.
2. Delayed access to colostrum.
3. Failure to ingest adequate quantity of colostrum and specific antibody.
4. Maternal risk factors (See Management Approaches to the Newborn Foal Use of Risk Factors).
5. Maladjustment syndrome (See Neonatal Maladjustment Syndrome).
6. Twins.
7. Adverse environmental conditions.

4. Clinical signs - Often cannot differentiate from neonatal maladjustment syndrome.

1. Early signs may be depression, lethargy, decreased mammary sucking and a behavior change.

1. Fever (>102°F, 39°C) occurs in less than 50% of cases.
2. Hypothermia <100°F (37.8°C) not uncommon.

2. Advanced

1. Petechiation - Pinnae of ears, mucous membranes of oral cavity, vulva, (episcleral hemorrhages are common after normal foaling from birth canal pressure).
2. Anterior uveitis.
3. Diarrhea.
4. Coma, convulsions.
5. Respiratory distress.
6. Dehydration.
7. Poor pulse quality.
8. Swollen joints.

5. Clinical pathology of septic foals [2] - Obtain Stat.

1. <400 mg/dl serum IgG is common; some are within the 400-800 mg IgG range.
2. Complete blood count finding - Always do a WBC differential count.

1. Neutropenia <4000/ul. (Remember premature non-infected foals have neutropenia)
2. Neutrophilia >12,000/ul.
3. >50 band-neutrophils.
4. Toxic cells - Dohle bodies, toxic granulation or vacuolization in neutrophils.
5. Fibrinogen >400 mg/dl.
6. Hypoglycemia -50% of cases have glucose <80 mg/dl (4.4 mmol/l).
7. Arterial oxygen <70 mmHg in 40% of cases.
8. Acid-base status indicating a mild to severe acidosis is common.

6. Blood culture is indicated in any suspected case of sepsis (See Blood Culture).

1. Required of all foals entering intensive care unit.
2. Take before antibiotics or at trough periods before next administration.
3. Do not delay antimicrobial treatment of suspected septicemia to complete a "series" of cultures at 2 hour intervals. Take 1 set initially upon admission -provide workup and repeat in 1-2 hours and then begin antimicrobials intravenously if laboratory work does not rule out sepsis.
4. Negative in 50% of cases with septicemia.

7. Sepsis Score - A method of attempting to predict infection based on history, physical exam and clinical pathology designed by Brewer et al. [4], Table 1
8. Therapy

1. Antimicrobial.

1. Based on a review of UCD equine neonatal septicemia isolates from field and in-house cases, the probability for antimicrobial susceptibility:
   100%   Imipenem
   90-99%   Ciprofloxacin, Ceftazidime
   80-89%   Ceftriaxone, Amikacin, Netilmicin, Cefaperazone, Ceftizoxime
   70-79%   Aztreonam, Gentamicin
   60-69%   Ceftiofur, Chloramphenicol, Ticarcillin/Clavulanate, Trimethoprim/sulfamethoxazole, Ipericillin, Azlocillin
   50-59   Amoxicillin/clavulanate, Ampicillin/sublactam, Tetracycline, Cephalothin
   40-49%   Ticarcillin
   20-39%   Ampicillin, Penicillin G, Sulfamethazine
   <20%   Rifampin, Oxacillin, Erythromycin, Tylosin
2. See antimicrobial therapy - Guidelines for Drug Use in Equine Neonates and Drug Formulary-Equine Neonate.
3. Editor's Comment - The choice of starting antimicrobial therapy is a clinician’s choice. One popular combination is Cefitiofur 10 mg/kg IV slowly BID and Amikacin 21 mg/kg IV or IM once daily. This is based on our studies, with isolates we have found, and may vary geographically.

2. Plasma therapy to increase IgG (See Plasma Therapy).
3. Fluid therapy (See Fluid and Electrolyte Balance).

1. Correct any hypoglycemia.
2. Correct any acidosis and dehydration.
3. Maintain renal perfusion.
4. Shock and dehydration treatment (See Shock (SIRS) and Fluid and Electrolyte Balance).

4. Nutritional Support (See Parenteral Nutrition and Enteral Nutrition).
   Prognosis is guarded with blood culture positive foals; mortality may be 50% even with intensive care. When presented collapsed in semi coma prognosis very poor.

9. Complicating potential sequelae to septicemia. Osteomyelitis Corneal lesions Pneumonia Patent urachus Arthritis Joint infections Gastric ulcers

II. Pneumonia

1. Pneumonia is present in some cases of septicemia. Can be acquired in utero or develop following bacteremia and is also a complication of many compromised foals.

1. Auscultation not well correlated with pulmonic disease. A change in resting respiratory rate may be an indicator of developing pneumonia.
2. Pneumonia in neonatal foals is complicated by a lack of significant coughing as a symptom and defense mechanism.
3. Meconium aspiration is seen as a greenish staining of the medial canthus of the eye or nares.

2. Viral

1. Equine herpes 1-congenital.
2. Adenovirus produces anorexia, polypnea, nasal and ocular discharge. Foals recover unless immunosuppressed. Diagnosis is by inclusion body on post mortem of lung.

3. Differentiate pneumonia from:

1. Respiratory distress syndrome by radiographs, tracheal wash - Negative, blood culture negative. Often prematurity, dysmaturity associated.
2. Transient tachypnea has normal chest sounds, radiographs, and CBC, blood culture negative, acid base, and glucose normal but temperature may be increased Possible lack of central control mechanism for thermoregulation. Foals are bright, alert, nursing. May last >14 days.
3. Birth asphyxia or hypoxia.

1. History of foaling problems or maternal risk factors.

4. Assessment

1. Chest radiographs.
2. Blood gases - Arterial.
3. Physical exam

1. Increase in resting respiratory rate.
2. Auscultation variable.
3. Neonates frequently lack cough with severe pneumonia.

5. Therapy

1. Appropriate antimicrobial therapy for an adequate duration - Often 2-3 weeks.
2. Physical therapy consisting of nebulization, coupage, airway hygiene.

1. Sternal recumbency, oxygen, bronchial dilators.
2. Early ambulation.

III. Miscellaneous Infectious Conditions

1. Equine Herpes I

1. May be born fully mature and dead.
2. May have normal birth and become weak within hours, fail to rise, and may clinically resemble septicemia cases, often with neurologic signs.
3. Susceptible to secondary bacterial infection which can complicate diagnosis.
4. Immunosupression, neutropenia, lymphopenia, (WBC <2000/μL), hyperplasia or necrosis of thymus or spleen.
5. Interstitial pneumonia.
6. Diagnosis: PCR for EHV-1 on blood and nasal swab; postmortem lung tissue.
7. Inclusion bodies in lungs (histopathology) and postmortem PCR sensitivity found to be highest in the lungs [5].
8. Infected foals which have not nursed may have low serum neutralized antibody to EHV-1 from in utero infection and immunological response.
9. Acyclovir/Valacyclovir has been tried with unconfirmed success.
10. See Management Approaches to the Newborn Foal Use of Risk Factors for vaccination protocol.

2. Botulism [6,7] - Shaker foal syndrome - Causative organism is Clostridium botulinum, usually type B or C.

1. Clinical Signs

1. Onset may be gradual over 2-4 days or rapid over 12-36 hours.
2. Dysphagia.
3. Dribbling milk, inability to swallow.
4. Age: birth -8 months, most common under 8 weeks of age.
5. Dilated pupils -slowly responsive.
6. Muscle weakness
7. Eyelid and tail tone decreased.
8. Muscle fasciculations after standing or walking.
9. Ultimately collapse and respiratory failure and aspiration pneumonia.

2. Differential Diagnosis

1. Hypocalcemia, hypoglycemia
2. Septicemia
3. White muscle disease

3. Diagnosis

1. Toxin demonstration in serum not reliable in horses due to low amounts which cause disease.
2. Clostridium botulinum spores in intestine not diagnostic but present in 80% of foals with Botulism.
3. Toxin isolation from intestines.
4. CSF is normal.
5. Electromyography may aid diagnosis.

4. Treatment

1. Polyvalent equine antitoxin - Early in disease 200 ml dose - Expensive (See Plasma Therapy).
2. Penicillin - IV QID.
3. Nursing care.
4. TPN or tube feeding.
5. Aminoglycosides, 3, 4 diaminopyridine, aminopyridine, are all contraindicated.
6. Limit movement.
7. Provide ventilatory support if respiratory compromise develops.

5. Prevention

1. Botulism type B toxoid to pregnant mares three times before parturition with last dose 2-3 weeks before foaling.

3. Tetanus

1. Etiology

1. Clostridium tetani organism. It may develop within 7 days of birth, most common secondary to umbilical infections.

2. Clinical Signs

1. Dysphagia
2. Prolapse of 3rd eyelid
3. Stiff, reluctant to move
4. Tetanic muscle spasms - triggered by noise and touch
5. Nostrils flared, ears held back, tail partially elevated
6. Normal sensorium with convulsive type spasms
7. Opisthotonus

3. Differential Diagnosis

1. Hypocalcemia
2. Hypoglycemia
3. Meningitis has abnormal CSF, normal in tetanus
4. Strychnine poisoning
5. White muscle disease
6. Hyperkalemic periodic paralysis

4. Diagnosis

1. No laboratory tests to diagnose
2. Clinical signs, vaccination history and rule out other causes
3. Condition of umbilicus, or puncture wound to feet or body

5. Treatment

1. Penicillin IV QID
2. Tetanus antitoxin - 5000 units. (Binds toxin outside CNS only. Will not reverse toxin)
3. Sedation, muscle relaxants
4. Rest, quiet, nursing care, nutritional support
5. Ventilatory support - if indicated
6. Duration 20-30 days, prognosis poor

6. Prevention

1. Vaccination of mare with tetanus toxoid 3-4 weeks before foaling
2. Foals of unvaccinated dams should receive 1500 units tetanus antitoxin at birth
3. Provides 45 days of protection

4. Meningitis

1. Most commonly secondary to septicemia
2. Clinical signs initially are non-specific including depression, anorexia, weakness

1. May be followed by neurologic signs of twitching, hyperesthesia, ataxia, hypermetria, strabismus, nystagmus, anisocoria, head tilt, opisthotonus, blindness, ear and eyelid droop, intention tremor, recumbency [8].

3. Diagnosis - CSF tap (See Cerebrospinal Fluid Collection)

1. Protein increase - Greater than 150 mg/dl.
2. WBC - Mainly neutrophils >20 cells/ul.
3. Bacteria in Gram stain intracellularly.
4. Glucose <80% of blood glucose - May not be valid in foals.
5. Negative findings do not rule out meningitis.

4. Treatment

1. Systemic antimicrobials with good CNS penetration and gram-negative spectrum.
2. Trimethoprim sulfa - Limited spectrum.
3. Cefotaxime 25-40 mg/kg q 6-12 hr - Penetrates CNS, good for bacterial infections of CSF [9].
4. Other antibiotics may also penetrate an inflamed CNS.
5. Anticonvulsants
6. Supportive care
7. Ceftiofur does not penetrate the non inflammed CNS and probably is not a good choice in foals.
8. Human studies indicate dexamethasone (0.15 mg/kg) prior to antimicrobial therapy and for 4 days improves survival and decreases morbidity when used with 3rd generation cephalosporin that penetrates CNS.

5. Prognosis: Guarded to poor depending on duration and immune status of foal.

5. Tyzzer's Hepatitis (Clostridium piliformis infection)

1. Age 9-42 days, found dead or present with seizures, marked depression or coma, head-pressing, with noticeable icterus.
2. Usually a well fleshed foal; occur as individual cases.
3. Laboratory work reveals severe hypoglycemia, acidosis and elevated liver enzymes.
4. Palpate painful enlarged liver after i/v infusion of dextrose and bicarbonate - Biopsy liver to confirm.
5. Most foals die; however, recent works suggest some foals may survive with intensive care treatment consisting of antibiotics, fluids and total parenteral nutrition for 5-7 days [10,11].
6. In Arabian foals, check for SCID with this disease.

6. Candidiasis (systemic) - Seen in foals treated in intensive care with multiple antibiotics, venous catheters, urinary catheters, and endotracheal tubes [12].

1. Localized infection may occur on the tongue, nasal passages and intestinal tract.
2. Systemic infection produces fever, septicemia, joint infections, panophthalmitis, glossitis.
3. Treatment with amphotericin B; or fluconazole 4 or 5 mg/kg PO q 24 hrs for minimum of 4-6 weeks.

7. Listeria monocytogenes septicemia has been reported in a 21 day old foal [13].