Respiratory diseases of small mammals (Proceedings)

Respiratory diseases in small mammals can be challenging. Although anatomy is similar, there are variations in anatomy that can predispose to certain diseases, or can interfere with interpretation of test results. The diseases these small patients acquire can vary greatly, and it can be extremely difficult to obtain samples for diagnostic evaluation, so it is important for the practitioner to be familiar with the common respiratory diseases in order to appropriately diagnose and treat these animals.

Ferret Respiratory Diseases

Among the small exotic species commonly kept as pets, ferrets are the most similar to dogs and cats. The thoracic cavity in ferrets is elongated, with the heart located between the 6th and 8th ribs, and the heart will be ausculted much more caudally than expected. Sinus arrhythmia is variation of normal in ferrets. The lungs are generous with respect to total body size. Radiographically, the ventral margin of the heart may be in contact with the sternum on a lateral view. Ferrets with respiratory disease or cardiac disease often exhibit general, non-specific signs such as lethargy, weakness, and hind limb paresis.

There are a wide variety of diseases that cause respiratory signs in ferrets. When in doubt with a ferret, remember the principles of traditional companion animal medicine. Ferrets can easily be intubated, usually with a 2.5 or 3.0 mm endotracheal tube. If there is pleural effusion, perform thoracocentesis. If there is cardiomegaly, pursue heart disease; if pulmonary consolidation is present, this supports pneumonia. Tracheal lavage, or even lung aspirates can be performed as in more traditional companion animal species. Diagnostics for the ferret are safe and readily available, and should not be overlooked.

Influenza

Ferrets are susceptible to Orthomyxoviridae, the human influenza viruses. This can be transmitted from ferret to human, ferret to ferret, or most commonly via human to ferret contact. Veterinarians and staff with cold or flu symptoms should wear a mask and wash hands prior to handling any ferret. Clinical signs, similar to humans, include lethargy, fever, sneezing, mucoid ocular and/or nasal discharge, and inappetence or anorexia. Fever, if present, typically lasts 48-72 hours. Although extremely uncommon, pneumonia is a sequela if secondary bacterial infection occurs. Diagnosis is based on clinical signs, history of exposure, and in many cases, duration of disease (see canine distemper virus, below). Virus isolation and ELISA for antibody are available but not commonly used. Leukopenia is an inconsistent finding. Treatment is limited to supportive care, usually fluid therapy and nutritional support (force feeding) if anorexia is severe. Human anti-influenza medications can be used. Antibiotics are only indicated if secondary bacterial infection is suspected or is imminent due to leukopenia. Pediatric cough suppressants or diphenhydramine can be used if necessary. Most ferrets with influenza do not require hospitalization. Clinical signs generally resolve within 5-7 days.

Canine Distemper Virus

Although rare, this is extremely important to recognize in ferrets, as the disease is nearly 100% fatal. Transmission is from infected dogs, other ferrets, or infected raccoons, but humans may serve as a mechanical vector. Clinical signs develop within 7-10 days of exposure, and may be similar initially to those of influenza virus. Ferrets may be presented with lethargy, fever, inappetence or anorexia, sneezing, mucopurulent ocular and nasal discharge, photophobia, porphyrin staining or dermatitis of the face and eyes, and hyperkeratosis of the footpads. The dermatitis and/or porphyrin staining of the face is pathognomonic for distemper in ferrets (looks like food allergy in a cat). Diagnosis is made by history (questionable vaccination history), potential exposure, clinical signs, and either fluorescent antibody staining or identification of the antigen in cells obtained for biopsy. There is no treatment; euthanasia is recommended. Keep separate from other ferrets and dogs.

Pneumonia

Pneumonia in ferrets is rare. Aspiration pneumonia may occur and will have a distribution similar to other companion animals. Diagnosis is based on radiography. Tracheal lavage is performed as in other species (3mm endotracheal tube will be appropriate for most ferrets). Treat with appropriate antimicrobials based on culture & sensitivity, supportive care, and perhaps nebulization and coupage. Evaluate radiographs carefully for megaesophagus if pneumonia is suspected.

Trauma

Ferrets are susceptible to falls, attacks by other animals, or being stepped on, making traumatic injuries perhaps the most commonly seen cause of respiratory distress, Pneumothorax is radiographically evident, and should be treated by thoracocentesis as in other species. Diaphragmatic hernia is also a possibility, although rare, and is also treated as in other species. Bite wounds and injuries should be lavaged and explored for penetration into either the thoracic or abdominal cavities.

Pleural Effusion

The two most common causes of pleural effusion are lymphoma and heartworm disease. This is the most common presentation of heartworm disease in ferrets. Diagnosis is most easily confirmed via ultrasound, but most heartworm antigen test kits can be used in ferrets (as long as they are not based on canine or feline red cells.) Limitations of commercial testing are as in cats; low worm burdens or single sex infections may lead to false negative results. Treat initially with thoracocentesis to relieve respiratory distress. Long-term treatment is beyond the scope of this article.

Ferrets with pleural effusion due to lymphoma generally have a mediastinal mass. Lymphoma in ferrets presents as it can in cats; it can be anywhere or everywhere. Mediastinal masses respond well to radiation in many cases. Thymomas also can occur, although rare, so ultrasound guided aspirate is recommended. Surgical excision is curative for thymoma.

Cardiac Disease

Similar to other species, clinical signs include cough, lethargy, rear leg weakness, inappetance. The most common form of cardiac disease is dilated cardiomyopathy. Diagnosis is made based on detection of a murmur or arrhythmia, radiographic evidence of cardiac enlargement, and ultrasound and EKG. Treatment is with diuretics, digoxin, nitroglycerin if needed, and ACE inhibitors. Pimobendan can be used, and indications are the same as in dogs. Ferrets also develop hypertrophic cardiomyopathy, and an unusual variation which seems to be a combination of hypertrophic and dilated.

Rabbit Respiratory Disease

Pasteurella multocida

Is endemic amongst most rabbits, and is the most common respiratory pathogen of rabbits. The organism is transmitted to the nasal passages via direct contact, fomites, and airborne spread. There are several serotypes; serotype A is most prevalent in chronic upper respiratory disease (URD) while serotype D most often causes septicemia. Virulence depends on several factors including adhesion properties, phagocyte resistance, endotoxins, and exotoxins. The incidence of infection increases with age.

Clinical signs of pasteurellosis include conjunctivitis, nasolacrimal duct obstruction, abscesses (anywhere), pneumonia, otitis, and septicemia. Pasteurellosis of the upper respiratory tract is commonly called "snuffles" because of the presence of nasal discharge, (often mucopurulent), which may even be evident on the medal aspect of the forearms as the rabbit grooms its face with the forepaws. Upper respiratory stertor may be ausculted over the nasal cavity and trachea. Hyperemia of the nasal mucosa may be evident in acute infection, and chronic infection may lead to severe atrophy of the turbinates. The organism can inhabit the nasolacrimal duct, causing conjunctivitis, and can travel via the eustachian tubes to the auditory canal, causing otitis media and vestibular disease.

Clinical signs of lower respiratory disease (pneumonia) caused by Pasteurella are non-specific, but may include anorexia, and lethargy, sometimes accompanied by weight loss and muscle wasting. Dyspnea and tachypnea are surprisingly rare. Rabbits showing dyspnea generally have a very poor prognosis.

Diagnosis of Pasteurella URD can be made by deep nasal culture. A mini-tip Culturette (No. 4 calcium alginate) is inserted deeply into the nostril ventromedially along the nasal septum. This will often cause sneezing and the expulsion of exudate for cytology. The author often adds the first 1-2 drops from a nasolacrimal flush to the sample to improve yield; the nasolacrimal flush may also aid in removing larger plugs from the nasal passages. Bacterial culture is also important in identifying secondary pathogens involved in a "flare-up". Thoracic radiographs are useful to determine the extent of lower respiratory disease. If pulmonary masses are present, ultrasound-guided fine needle aspirates may be obtained under sedation for cytology and culture of pulmonary masses. Tracheal lavage can also be performed for definitive diagnosis; exercise caution as these patients already have respiratory compromise and intubation is extremely challenging in rabbits. Hematology may be normal even in severely affected rabbits. Close attention should be given to the differential as a lymphopenia and heterophilia may be the only abnormality. Serologic testing (ELISA) does exist but has limitations. Acute infections may not show positive titers as it can take several weeks to develop significant antibody levels. Serology may be more reliable than cultures in detecting chronically affected animals.

A number of antimicrobials have been reported to be effective in treating pasteurellosis, including the fluoroquinolones, penicillin (SQ or IM, not orally), trimethoprim-sulfadiazine, and chloramphenicol. Whenever possible, treatment should be based on culture and sensitivity. The author prefers enrofloxacin or ciprofloxacin (15-20 mg/kg orally twice daily) or penicillin (60,000 units/kg subcutaneously every other day). Enrofloxacin should be limited to one subcutaneous injection followed by oral administration, as it may cause severe sterile abscess and tissue necrosis due to its extremely alkaline pH. It may also be given intravenously, but must be given diluted with saline and administered slowly. Ophthalmic solutions of ciprofloxacin, gentocin, or chloramphenicol can be used if conjunctivitis is present; drops will travel down the nasolacrimal duct better than ointment. Nebulization of antimicrobials can be used in conjunction with systemic antibiotics for upper or lower respiratory disease.

Treatment should continue for a minimum of 14 days in mild cases and up to several months in chronic infections. Total elimination of the organism is unlikely, as the bacteria may be retained deep within the nasal passages or elsewhere in the body. Long-term control of clinical signs and early detection of recurrence or recrudescence is probably a more realistic treatment goal.

Although Pasteurella-free rabbit colonies exist, pet rabbits are generally not from these colonies (most are research-bred SPF [specific pathogen free]). Although some sources recommend that newly acquired rabbits be examined and tested for pasteurellosis and treated with appropriate antibiotics if testing is positive, the author disagrees with treatment in an asymptomatic rabbit, because treatment may contribute to the development of resistant organisms. Other Pasteurella species may be commensal inhabitants and should be differentiated from P. multocida. A positive serology may also indicate that a rabbit has been exposed, mounted an effective immune response, and cleared the organism. At this time there is no vaccine for Pasteurella.

Staphylococcus aureus

The second most common organism identified from rabbits, and may be present in rabbits with and without respiratory disease. Some strains of S. aureus can produce toxins that can be lethal to rabbit neutrophils, and other substances that inhibit host immune response. Infection can cause rhinitis, fibrinous pneumonia, and pulmonary abscesses. Abscesses caused by S. aureus are similar to those caused by P. multocida and may be equally severe, if not worse. Staphylococcal species may be more resistant to antibiotics then P. multocida. Fluoroquinolones, chloramphenicol, or trimethoprim-sulfadiazine, are recommended if culture cannot be obtained. Fluoroquinolones in combination with injectable penicillin may improve efficacy.

Bordatella bronchiseptica

Gas been found in the nasal cavity of normal rabbits. Although this organism is considered normal flora, it may be a co pathogen or predisposing factor for Pasteurella infections. B. bronchiseptica is pathogenic to guinea pigs and dogs, so interactions or housing with these species should be avoided.

Mycoplasma spp. and Chlamydia spp.

Have also been implicated in mild to moderate respiratory disease in rabbits, but are difficult to culture or identify. Because these organisms are common pathogens of rats and mice, these species should not be housed with rabbits. Moraxella catarrhalis, Micrococcus catarrhalis, Neisseria spp., and S. epidermis are considered normal flora in rabbits. Viral diseases of the respiratory tract of rabbits are not well documented.

Non-infectious respiratory diseases of rabbits are less common. Allergic rhinitis and bronchitis may occur in rabbits. Remove any particulate bedding, including cedar, and improve ventilation. Rabbits should never be kept in plastic or glass enclosures. Antihistamines such as diphenhydramine (1-2 mg/kg PO BID) or hydroxazine (1-4 mg/kg PO BID) can be used, if needed. Respiratory toxins, such as ammonia from poor sanitary conditions, cigarette smoke, and pollutants may damage the nasal and respiratory mucosa and predispose rabbits to respiratory disease.

Perhaps the most common non-infectious cause of respiratory disease in rabbits is dental disease involving the upper molar or premolar teeth, incisors, or both. As a result of dental disease, root elongation may occur, impinging on the nasolacrimal duct or nasal passages, and causing potential nasolacrimal obstruction, boney remodeling, or other changes that may present clinically as respiratory disease. Molar radiographs under sedation, accompanied by oral exam, will aid in establishing the diagnosis.

Neoplastic disease can occur in rabbits and is most often associated with lung metastasis or uterine adenocarcinoma. Primary thymomas have been reported in rabbits of any age. (The thymus in rabbits persists throughout life) Lymphoma may also be present as a mediastinal mass. Exophthalmos is one clinical sign associated with thymoma or lymphoma as a result of obstruction to venous return from the head (do not confuse with glaucoma or third eyelid prolapse). Radiographs provide the diagnosis of either a thoracic mass or metastatic disease, but ultrasound-guided aspirate is recommended for diagnosis of thymoma or lymphoma. Both of these diseases respond well to radiation therapy. Unfortunately, adenocarcinoma and disseminated lymphoma are difficult to treat. Uterine adenocarcinoma metastases are often found on pre-surgical screening radiographs.

Respiratory Diseases of Rodents

Guinea Pigs

Bacterial pneumonia is the most common respiratory disease. The most frequently implicated pathogens are Bordatella bronchiseptica and Streptococcus pneumoniae. Clinical signs include dyspnea, inappetence or anorexia, ocular or nasal discharge. Radiographic changes include consolidation of lung lobes and air bronchograms. Tracheal lavage is possible for sample collection but very challenging. In some cases it is best to avoid stressing these dyspneic patients for diagnostic purposes. Treatment is with antimicrobials (based on culture and sensitivity if possible), coupage, nebulization, supportive care. (Chloramphenicol 30-50 mg/kg PO q12h; enrofloxacin 5-10 mg/kg PO q12h; trimethoprim sulfa 30 mg/kg PO q12h.)

Chinchilla

Primary respiratory disease is rare. Heart murmurs have been identified but have not been associated with significant cardiac disease in most cases.

Rats, Mice, Hamsters, Gerbils

Pneumonia is the most common respiratory disease of small rodents; especially rats and mice. The most common pathogens are Sendai virus and Mycoplasma pulmonis. In rats there is also a ciliated-associated respiratory (CAR) bacillus. In many cases, there is a synergism between these agents leading to immunocompromise and a severe chronic disease state. Clinical pneumonia often leads to development of severe nodular abscesses within the lungs which can radiographically resemble metastatic disease. Treatment is with antimicrobials, supportive care, nebulization and coupage as indicated. Treatment of these cases can be frustrating, as an incomplete response or recurrence is common because of the combination of pathogens. Cardiac disease can occur in hamsters; usually right-sided heart failure, but clinical signs are usually not apparent until ascites is severe.

Prairie dogs

Prairie dogs develop odontomas of the upper incisor tooth roots. Because these rodents are obligate nasal breathers, the boney changes surrounding the odontomas compress the floor of the nasal cavity, leading to open-mouth breathing, nasal flaring, and nasal discharge. In many patients, these signs are accompanied by a lack of growth of the upper incisor teeth. This is a waxing and waning disease, where bouts of upper respiratory stridor and difficulty are generally accompanied by lethargy and inappetence. It is usually not a life-threatening situation but may be perceived as acute onset by the owner. Treatment with oxygen and anti-inflammatories generally will at least partly resolve clinical signs, but long-term treatment is surgical.

References Available Upon Request