Abstract

Respiratory infection is relatively common in pet rabbits, guinea pigs, chinchillas, ferrets, and rats. Predisposing factors include age (i.e., most common in the young and geriatric), stress, improper environment and husbandry, and concurrent illness. Clinical signs include coughing, sneezing, nasal and ocular discharge, and dyspnea. Diagnosis may include radiography, computed tomography (CT), culture/sensitivity, cytology, bacterial polymerase chain reaction (PCR), and necropsy. Common etiologies include various gram-positive and gram-negative bacteria, Mycoplasma spp. Chlamydophila spp., and viruses; fungal infections are rare. Polymicrobial infections are not unusual. Treatment includes systemic antimicrobials, nebulization, oxygen, supplemental heat, and other supportive care measures. Prognosis varies by etiology and severity of the disease at presentation. Upper respiratory disease carries a better prognosis than pneumonia in most cases.

Introduction

Respiratory infection is a common presenting complaint in exotic companion mammals. It typically occurs in young, sick, debilitated, or immunodeficient animals when natural defense mechanisms have been eroded. Respiratory infection can be precipitated by stress such as shipment, unsanitary conditions, overcrowding, or social conflict among cage mates. Improper environment and husbandry have a significant impact on an individual’s resistance to infection. Extremes in temperature, humidity, exposure to waste, and poor nutrition all tend to increase one’s susceptibility to it. Likewise, the stress of concurrent infection, advanced age, dental disease, or other concurrent illness can lead to breakdown of the immune system and susceptibility to respiratory infection.

Clinical Signs

Clinical signs of respiratory infection include coughing, sneezing, wheezing, open-mouth breathing, and rapid respiration. Patients with respiratory infection may exhibit hunched posture, unkempt appearance, lethargy, unfocused eyes, disinterest in the surroundings, reduced appetite, weight loss, and/or diarrhea. Increased respiratory effort is usually manifested as pronounced abdominal movement when breathing, and open-mouth breathing occurs in the advanced stages. Discharge from the eyes or nose, and/or diarrhea may be present. A complete physical examination may reveal conjunctivitis, blepharospasm, and ocular or nasal discharge (found either on the face or matted, wet fur on the medial aspect of the forelegs due to facial grooming). Wheezing, crackles, increased bronchovesicular sounds, and/or rales may be ausculted. There may be tachypnea or overt dyspnea, and possibly a fever.

Diagnosis

Diagnosis of respiratory infection in small mammals begins with a thorough history and careful observation of the patient. The clinician should ask about diet, nutritional supplementation, the type of cage, bedding material, how often the cage is cleaned, the presence of other animals, and any new animals that may have been introduced. Also ask about the routine and whether any changes to the routine (e.g., pet sitter, new diet, death of bonded cage mate) have occurred recently.

The workup for upper respiratory infection generally begins with culture and sensitivity from a deep nasal swab but may also include cytology/culture of nasal/nasolacrimal flush, rhinoscopy, skull radiographs, and head CT. Workup for pneumonia generally involves thoracic radiographs. In a normal small mammal, the caudal lung lobes are large and well aerated. Evaluation of the cranial lung lobes may be difficult because in some species (e.g., guinea pigs) they are small. The classic radiographic appearance of bacterial pneumonia is an alveolar pattern, with air bronchograms in severe cases. Lesions can be diffuse, localized to a general area, or lobar in nature. If solitary masses are identified, differential diagnosis should include abscessation or consolidation of lung due to microbial infection.¹

The hemogram with a respiratory infection may or may not reflect an increase in total white blood cell count, even with pneumonia; a relative neutrophilia and/or lymphopenia are more common. Leucopenia can result from overwhelming bacterial infection, viral infection, or inflammation.

Culture and sensitivity testing should be done before antimicrobial therapy is started. A deep nasal swab is indicated for suspected upper respiratory infection; however, a tracheal wash is generally considered to be more accurate than a nasal swab for diagnosing pneumonia because it can provide material for cytologic exam and bacterial culture.² Identification of degenerative neutrophils containing bacterial debris in a tracheal wash specimen is highly supportive of the diagnosis of bacterial pneumonia. While not a widespread practice, transthoracic needle aspiration is another way to obtain lung samples for cytology and culture.³

Culture and sensitivity should test for both aerobic and anaerobic organisms, and empirical treatment with broad-spectrum antibiotics should start before results are available. In general, light growths of mixed bacterial populations are less important than the heavy growth of a single species in conjunction with a pathogenic response. Caution must be used when interpreting results; some labs will not report normal flora; however, in an immunocompromised individual, infection may result from normal flora that are opportunistic pathogens. In addition, the normal flora of many species still has not been established or is obscure. If culture cannot be done because antibiotics have already been started, then PCR should be considered. Bacterial PCR can also be helpful in identifying anaerobes (because these frequently do not survive the transport to the lab) and for getting results from an area where bacteria are likely to be dead (e.g., abscess, caseous pus). Where Chlamydophila is suspected (i.e., guinea pigs, C. caviae), a conjunctival scraping from affected individuals by will contain intracytoplasmic, coccoid, basophilic organisms (i.e., Chlamydia elementary and reticulate bodies), or a PCR test is available for this infection, as well.⁴

Necropsy findings from small mammals with respiratory infection will vary by duration and severity of the disease, and by the organism(s) involved. Upper respiratory infections will cause inflammation, pus, and mucous accumulation in the nasal passages, sometimes with focal areas of hemorrhage, abscessation, or necrosis. Mild and acute cases of pneumonia will result in lung congestion, and atelectasis. More severe and chronic pneumonia cases will exhibit suppurative lesions, fibrin adhesions and fibrosis. Severely affected individuals can develop pulmonary abscesses, granulomas, and consolidation. There may also be other organ involvement: lymphadenitis, myocarditis, peritonitis, meningitis, septicemia, tracheitis, bronchitis, otitis media, etc.^5,6

There are several non-infectious conditions that can cause respiratory distress in exotic companion mammals including nasal obstruction, heat stress, diaphragmatic hernia, pregnancy toxemia, and gastric torsion. Dyspnea and weakness may also be found with heart failure or pulmonary neoplasia.

Treatment

The ideal antibiotic treatment plan for bacterial respiratory infection in small mammals will provide “four-quadrant” coverage, will be bactericidal, easy to administer, safe, and not cause gastrointestinal disease. Antibiotics with a post-antibiotic effect (e.g., aminoglycosides, fluoroquinolones) are preferred, so “pulse therapy” can be employed. Post-antibiotic effect permits once a day dosing, which is less stressful to the patient and improves owner compliance. Aminoglycosides are potentially nephrotoxic; therefore, supplemental fluids are advisable.

As hindgut fermenters, small herbivores rely on active cecal flora for digestion. If antibiotics with a gram-positive spectrum are given, dysbiosis and the overgrowth of pathogenic bacteria will likely occur. Thus, the antibiotics amoxicillin, ampicillin, clindamycin, lincomycin erythromycin are avoided when treating small herbivores. The antibiotics least likely to affect cecal microorganisms include trimethoprim-sulfa, fluoroquinolones, chloramphenicol, aminoglycosides, and metronidazole. Antibiotics that pose an intermediate risk include oral cephalosporins, tetracycline, and doxycycline. In small mammals with a simple digestive tract (e.g., ferret, sugar glider, hedgehog), or minimal cecal fermentation (e.g., rat), the risk of antibiotic-associated gastrointestinal disease is minimal or greatly reduced.

Nebulization therapy is an important method of getting moisture and medication into the nasal passages, trachea, bronchi, and small airways.⁷ To adequately treat lower airways, nebulizers should secrete particles between 0.5 and 3.0 micrometers (a room humidifier will not suffice). Saline nebulization alone is helpful. When patients get dehydrated, the mucociliary escalator (ME) of the lower airways becomes impaired. The ME functions to trap particulates and bacteria and moves them craniad by the movement of cilia, to the oropharynx, where they can be coughed up and swallowed. The mucus layer is made up of two layers—the sol, which is watery, where the cilia move, and the gel lying on top, which traps particles. If the sol layer is depleted through dehydration, the cilia become trapped in the gel layer and movement is impeded, inhibiting the escalator. Systemic fluids and airway nebulization can contribute to the effective action of the mucociliary escalator by allowing the sol layer to perform as required. Nebulization can be used to deliver antibiotics directly to the airway surface, bypassing systemic circulation and minimizing side effects. Sometimes other agents are added: mucolytics (N-acetylcysteine), or bronchodilators (aminophylline, terbutaline). F10 Antiseptic Solution (www.F10products.co.uk) is a benzalkonium chloride/hexamethylene biguanide solution with topical antifungal and antibacterial activity. F10 may be added to saline at a rate of 1:250 and is recommended by many for nebulization 2–3 times a day.⁸ Use caution when nebulizing products that were not intended for that purpose (e.g., injectable Baytril), because some animals may respond to the ingredients with bronchoconstriction.⁹

There is a blood–bronchus barrier that limits penetration of drugs into the airway secretions much the same way the blood–brain barrier or the blood–prostate barrier prevents drug penetration into those tissues. Penetration into airway secretions is important since many bacterial airway infections remain largely on the luminal airway surface. Nebulization therapy bypasses the “blood–bronchus barrier” and provides topical treatment to the airway. It is important to remember than the major function of the respiratory defenses is the removal of particulates, so nebulized drugs are efficiently removed, and only a small portion of the administered medication reaches the lower airways. Therefore, it is also important to choose a systemic antibiotic that can penetrate the barrier. Lipid-soluble compounds are better able to penetrate the barrier and reach adequate concentrations at the airway surface: metronidazole, chloramphenicol, azithromycin, tetracycline, doxycycline, and fluoroquinolones penetrate the barrier better than penicillin-based antimicrobials; cephalosporins and aminoglycosides have intermediate penetration. Cough suppressants should be avoided when treating pneumonia, since the goal of treatment is to break up and eliminate airway debris and mucus. Gentle coupage (physiotherapy), frequent turning of patients, short walks, and mild to moderate exercise may help to encourage the clearance of sputum.

There are few specific therapies for viral pneumonia. Most viral diseases of rodents do not cause severe disease but can do so in very young animals or those carrying potential secondary bacterial pathogens. Polymicrobial infections are common and, as is the case with pneumonia in most other animals, in small mammals it can involve one or more bacteria or viruses. In many instances where bacteria and virus are both isolated, bacteria are secondary invaders. Provide antibiotics to prevent or treat the secondary bacterial infection, and provide supportive care measures.

Good supportive care is important to treatment success. Exotic companion mammals often present in an advanced state of disease and may not tolerate treatment unless initially stabilized with oxygen, fluids, warmth, and nutritional support. Oxygen supplementation should be provided when there is detectable tachypnea, dyspnea, cyanosis, open-mouth breathing, or when pulse oximeter readings fall below 94%. Oxygen can be provided in an oxygen cage for small animals. It should be humidified prior to use and is toxic over time. The maximum inspired oxygen concentration for long term use is 40%; higher levels may be used for two days or less.

Many exotic companion mammals are prey animals by nature and are nervous in captivity. Many small mammals, especially guinea pigs, are creatures of habit and do not handle changes in routine as well as dogs and cats. Small mammals should be hospitalized in a quiet area away from cats, barking dogs, and other loud noises. Provide a hide box, towel, or other shelter. Animals that are socialized and well adapted to their environment tend to have a much better response to hospital care. Bonded pairs may need to be kept in the hospital together in order to reduce stress. Probiotics have no proven benefits but may help to promote and reestablish healthy gut flora when treating with antibiotics.

Comments on Particular Species and Etiologies

Rabbits

Respiratory disease in rabbits is often caused by bacterial agents: Pasteurella multocida, Bordetella bronchiseptica, Staphylococcus aureus, and many others. Reports of viral pneumonia in pet rabbits are rare. Anorexia, weight loss, depression, and rapid fatigue are nonspecific signs, but in a rabbit should raise suspicion of lower respiratory tract disease. Rabbits often appear relatively normal, even with minimally functioning lungs.^6,10

Pasteurella infection can be chronic or acute. Chronic disease is likely to take the form of upper respiratory disease (“snuffles”). Runny eyes, runny nose, and sneezing can be recurrent, and antibiotics may only provide temporary relief. Pasteurella also causes pleuropneumonia or pericarditis, with abscesses developing in or around the lungs.

Bordetella is a common inhabitant of the respiratory tract of rabbits. Its prevalence increases with age. Bordetella bronchiseptica infection risk is greatest in young rabbits and in hosts with compromised immune function. Bordetella has local-acting cytotoxic effects that impair host defenses and may be an important predisposing factor in Pasteurella infections.

Staphylococcus aureus can be isolated from the respiratory tract of both healthy and diseased rabbits. While it is probably a secondary invader of compromised mucosa, S. aureus produces toxins that can block several host defenses. Like Pasteurella, disseminated infection can cause pneumonia and abscessation of the lungs and heart.

Guinea Pigs

Bacterial respiratory infection is considered to be one of the most significant diseases affecting guinea pigs. Pneumonia is the number one cause of death among guinea pigs in some surveys. Young guinea pigs are particularly at risk for infection. Many of the organisms that cause respiratory disease are acquired by guinea pigs as babies while they are still in the breeding colony, protected by maternal antibodies. Those with subclinical infection often continue to carry these pathogens, and only develop clinical disease later, when stress or concurrent illness occurs.

The course of infection can vary from mild upper respiratory infection with subtle clinical signs, to rapidly progressive and fatal pneumonia, associated with respiratory failure and/or sepsis. Guinea pigs are by nature very stoic and this combined with their natural tendency to hide disease means pneumonia is often advanced by the time clinical signs are noticed.

Rhinitis and pneumonia are usually associated with opportunistic microbes. The two most important pathogens are the bacteria Bordetella bronchiseptica and Streptococcus pneumoniae. Other common bacteria include Klebsiella pneumonia, Streptobacillus moniliformis, Staphylococcus aureus, E. coli, Pasteurella pneumotropica, Pasteurella multocida, Streptococcus zooepidemicus, Streptococcus pyogenes, Citrobacter freundii, Yersinia pseudotuberculosis, and Pseudomonas aeruginosa. Chlamydophila caviae usually causes mild, self-limiting conjunctivitis but can also contribute to stress and lower respiratory tract bacterial infections.^6,11

Guinea pigs may also develop viral pneumonia. Guinea pig adenovirus (GPAdV) can cause severe, necrotizing bronchopneumonia with high mortality. Parainfluenzavirus has also been shown to cause disease. Pneumonia in guinea pigs also can be caused by atypical organisms including Pneumocystis carinii and nematode parasites. Vitamin C should be supplemented, initially by injection 100 mg/kg subcutaneously, and then provided daily through hand feeding and fresh vitamin C-rich vegetables and fruit. Guinea pigs can be vaccinated against Bordetella with commercially available canine or porcine vaccines.^5,6

Chinchillas

Respiratory infections in chinchillas are relatively uncommon. Affected individuals usually are immunocompromised by age, nutritional status, or husbandry-related stress (overcrowding, high humidity, poor ventilation). Pneumonia in the chinchilla tends to be chronic, resulting in ocular or nasal discharge, lymphadenopathy, dyspnea, anorexia, depression, poor hair coat, and weight loss. Likely pathogens include Pasteurella, Bordetella, Streptococcus, Klebsiella, and Pseudomonas. Viral respiratory disease of chinchillas is not reported. Antibiotic combinations may be indicated. Prevention is by correcting husbandry and reducing stress.¹¹

Ferrets

Respiratory infections are uncommon. Viral causes include canine distemper and influenza virus. Bacteria reported to cause primary infection include Streptococcus zooepidemicus, S. pneumoniae, and groups C and G streptococci. Bacterial rhinitis and conjunctivitis, primarily seen in young, newly acquired animals usually responds to treatment with amoxicillin. Bacterial pneumonia in ferrets is typically suppurative, affecting the bronchial airways, the lung lobes, or both. Gram-negative bacterial pneumonia has been documented with Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Bordetella bronchiseptica and Listeria monocytogenes. Fungal infections (Pneumocystis carinii, blastomycosis and coccidiomycosis) are uncommon in pet ferrets. A novel Mycoplasma sp. causes a chronic bronchitis and persistent cough, with eventual death due to lung pathology.^12,13

Rats

Respiratory disease caused by infectious agents is the most common health problem in rats. Three major respiratory pathogens cause overt clinical disease: Mycoplasma pulmonis, Streptococcus pneumoniae, and Corynebacterium kutscheri. Two additional bacteria (cilia-associated respiratory [CAR] bacillus and Haemophilus spp.) and three viruses (Sendai virus [a parainfluenza virus], pneumonia virus of mice [a paramyxovirus], and rat respiratory virus [a hantavirus]) are minor respiratory pathogens that by themselves rarely cause overt disease.^6,14 A coronavirus of rats, sialodacryoadenitis (SDA) virus, is highly infectious and causes overt disease confined to the eyes, ears, nose and throat. These minor respiratory pathogens interact synergistically as co-pathogens with the major respiratory pathogens to produce two major clinical syndromes: chronic respiratory disease (CRD) and bacterial pneumonia.

CRD is also known as murine respiratory mycoplasmosis because M. pulmonis is the major component of the disease.¹⁵ Clinical signs are highly variable, and initial infection occurs without any clinical signs. Both upper and lower respiratory tracts are involved. Signs may include snuffling, nasal discharge, red tears, rapid respiration, weight loss, hunched posture, ruffled coat, and head tilt. CRD varies greatly in disease expression because of many environmental, host, and organismal factors that influence the host–pathogen relationship: cage ammonia levels, concurrent infection (Sendai virus, SDA virus, pneumonia virus of mice, rat respiratory virus, CAR bacillus), genetic susceptibility of host, virulence of Mycoplasma strain, and vitamin A or E deficiency. Antibiotic therapy (enrofloxacin/doxycycline combination, azithromycin) will not cure CRD but may alleviate clinical signs; affected animals typically have persistent M. pulmonis infection. Removing cage litter and replacing with clean paper daily may help reduce ammonia levels. Bronchodilators and short-acting corticosteroids are also sometimes helpful.

Bacterial pneumonia, the other major clinical syndrome, is nearly always caused by Streptococcus pneumoniae, usually with the help of M. pulmonis, Sendai virus, or CAR bacillus coinfection. Corynebacterium kutscheri causes pneumonia only in severely immunosuppressed individuals and is rare in pet rats. Pneumonia caused by S. pneumoniae can be of sudden onset. Young rats are more severely affected than older ones, and the only symptom may be sudden death. Signs in mature rats include dyspnea, snuffling, abdominal breathing, and purulent nasal exudate (nares and front paws). Tentative diagnosis can be made by a Gram stain of this exudate (will reveal numerous gram-positive diplococci). Because severe bacteremia and multiorgan abscesses/infarctions are common; antibiotic treatment must be aggressive. Beta-lactamase-resistant penicillins are recommended.

Prognosis

The prognosis for respiratory infection varies by etiology and severity of the disease at presentation. Most small herbivores are obligate nasal breathers; thus, blockage of the nasal passages can be deadly. Severely affected animals resort to open-mouth breathing, which reduces food and water intake and worsens overall condition. For this reason, even upper respiratory infections are a serious matter in most exotic companion mammals; however, upper respiratory infection can usually be managed with appropriate care. Pneumonia, on the other hand, is often difficult to reverse. Affected animals often have underlying immunodeficiency and tend to decline rather than recover. Prognosis becomes guarded once there is obvious respiratory distress.

Prevention

Many of the causes of respiratory infection in small exotic mammals are husbandry related, and corrections need to be made in order to prevent disease. Keeping a closed colony will ensure that new diseases are not introduced. New arrivals should go into quarantine, and they should not be mixed with the general population until there has been a reasonable quarantine period, usually 30–90 days.

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