Eric L. Schroeder
Investigating Respiratory Disease Outbreaks
Outbreaks of respiratory disease are common in horses and result in significant economic loss. Viral infections, including equine influenza virus, equine herpesviruses (EHV-1, EHV-4), equine arteritis virus (EVA), equine rhinitis virus A and B (ERAV and ERBV), and equine adenovirus (EAdV-1), are the most frequent cause of upper respiratory tract disease (URTD) in all types of horses. The clinical manifestation of these viral diseases can vary among horses and is not always virus specific. The severity of clinical signs can be diminished by previous infection, with naive horses usually having more severe morbidity and higher mortality rates. The most common bacteria that cause respiratory disease outbreaks are Streptococcus equi subsp zooepidemicus and Streptococcus equi subsp equi, with the latter causing the clinical condition known as strangles. Early diagnosis of respiratory tract disease is important in determining outcome because implementation of disease management and treatment can enable containment of infection and can help prevent a catastrophic event.
Investigation of a respiratory disease outbreak requires knowledge of the most common respiratory viral and bacterial diseases, the relative risk for exposure and infection, the mode of dissemination, the screening and diagnostic methods, and the current treatments. It is also important to know how to institute isolation and biosecurity plans and to know whether the disease outbreak is reportable. This chapter includes a brief synopsis of the most common viral and bacterial infections that cause respiratory disease outbreaks that can potentially result in morbidity, mortality, and economic loss. For each disease, information is provided on the etiology and pathogenesis, clinical signs, diagnostic methods, and treatment. Information on biosecurity plans and how to manage an outbreak of respiratory disease can be found in Chapters 30 and 31, respectively.
Approach to Investigating an Outbreak of Respiratory Tract Disease
When a veterinarian is first contacted about a potential respiratory disease outbreak, it is crucial to obtain as much information as possible before visiting the affected premises. This information should include the history of the outbreak, particularly opportunities for transmission of infectious disease, such as the introduction of any new animals to the stables, travel of resident animals to shows or other events where high concentrations of horses are brought together, and the history and evidence of recent respiratory illness at the stables. The vaccination status of the herd and any other relevant medical history must be ascertained from medical records or by questioning the owner or trainer. Assimilation of these data will allow for the likely etiologic agents to be recognized and ranked in order of importance. Next, the veterinarian should ascertain the clinical signs of the affected animals and the duration and progression of such signs so that an initial etiologic rule-out list can be formulated. For example, how many horses are affected and are these animals febrile or inappetent? How many are coughing, if any? What is the nature of any nasal discharge? Do any of the animals have swollen or ruptured lymph nodes? This information should be used to assemble a sufficient plan for the farm visit investigation, identify diagnostic supplies needed for the investigation, allow for institution of an initial biosecurity containment plan to prevent potential spread, provide case point source identification, ascertain how the disease has spread and over what length of time, and, lastly, allow for needed communication with local stable staff, trainers, owners, and state veterinary officials.
Before going to the farm, the veterinarian should ascertain what measures the stable has already implemented. It should be determined whether the manager has instituted his or her own biosecurity measures, whether the infected animals have been isolated on or off the premises, and how infected horses are being monitored. The answers to these questions are necessary to generate an appropriate investigative plan that will ensure efficient examination of the premises and infected animals without cross-contamination and further spread of the disease by personnel or fomites. No infected case should be missed, and all diagnostic testing must be performed to ensure the maximum amount of information is gained from each test.
The Visit to the Farm or Stable
Upon arrival at the farm, it is vitally important that the plan for examination of the animals be reviewed, modified if necessary, and followed to prevent cross-contamination and failure to examine a group of animals. Before examinations and sample collections begin, protective clothing must be donned not only to prevent transmission among groups of animals but also to prevent contamination of the veterinary vehicle and equipment. The protective clothing should consist of disposable gowns or other type of barrier wear, boot covers, gloves, and hats in sufficient quantities to allow for changes between each group of animals.
Investigation, examination, and sample collection should begin with the noninfected group of animals, progress to the exposed but still healthy group, and end with the sick animals. At no time should the attending veterinarian or other medical staff go back to a previous group without proper attention to the instituted biosecurity plan. This examination sequence has several advantages. It identifies any apparently healthy animals with subclinical signs of infection that need to be moved to the infected group and allows for discussion with the owners, trainers, and barn staff on use of the biosecurity plan to prevent infection of the healthy isolated animals.
Specifics of biosecurity planning are described in Chapter 30, but the simplest plan is to dedicate a separate group of staff for each group of animals. These individuals should not handle, treat, feed, or groom any animal outside their group. Each staff group needs separate supplies and allotments of animal feed and water and a means to dispose of manure so that it is not a fomite for disease transmission. Ideally, there should be foot baths (1 part bleach added to 4 parts water) outside all major foot traffic areas as well as multiple places for people to wash their hands. Foot baths should be changed at least once daily because of accumulation of organic debris.
The following samples should be placed into individual biosecurity bags, labeled with the animal’s signalment, and shipped to the appropriate laboratory for diagnostic evaluation: blood (citrated, ethylenediaminetetraacetic acid [EDTA], and serum), deep nasopharyngeal swabs, and samples from draining lymph nodes. Samples should be taken from all infected animals and from several that are apparently healthy, especially if breaches in the biosecurity plan are suspected. Depending on the suspected or diagnosed disease, further sampling to evaluate for a rising antibody titer may be warranted for disease confirmation.
Ideally, each animal on the premises, or at least the infected and exposed animals, should undergo complete physical examination by the attending veterinarian, with results recorded in the case record or log. The barn staff can be instructed to record rectal temperature, respiratory rate and effort, evidence of draining lymph nodes, and frequency of coughing twice daily. These also should be written in each animal’s daily log to evaluate disease progression. These seemingly insignificant findings are essential for assessing disease progression and determining whether any imposed quarantine can be removed by the attending veterinarian.
If there are several sick infected animals, daily treatment and patient assessment should be provided by the attending veterinarian. This will prevent problems that can arise from multiple people treating the sick animals and helps prevent unknown accidental disease transmission to equipment and thence to other healthy animals.
Synopses of the Most Common Equine Infectious Respiratory Diseases
Equine Influenza Virus
Etiology and Pathogenesis
Equine influenza viruses are enveloped single-stranded RNA viruses in the family of Orthomyxoviridae. They affect all equids and are the most common cause of upper respiratory tract disease. Because they are extremely infectious and cause high morbidity, influenza infections have worldwide implications. Only influenza type A virus is infective to equids. This type is further subdivided into subtypes based on the surface glycoprotein expression of hemagglutinin (HA) and neuraminidase (NA). The HA determines host specificity and serves as the virus receptor–binding protein, and the NA is embedded in the M2 ion channel protein in the host-derived lipid envelope. Most recent outbreaks of influenza A have been caused by virus subtypes H7N7 and H3N8, with recent divergence of the H3N8 subtype into two distinct evolutionary lineages: the European and the American lineages, the latter of which has given rise to three American-like lineages (see Chapter 39 for more information).
In an exposed horse, the virus undergoes rapid replication within the respiratory epithelial cells and is released into the local environment, leading to pathologic changes throughout the entire respiratory tract with the most prominent lesions being in the lower airways. At the cellular level, the virus causes apoptosis and death of the ciliated respiratory epithelial cells of the trachea and bronchioles, leading to massive disruption of the mucociliary apparatus and accumulation of bacteria, mucus, and environmental debris.
Clinical Presentation
Clinical signs are manifested rapidly, usually within 3 to 5 days of viral exposure. The immune status of the exposed or infected horse dictates disease severity: naive horses develop substantial morbidity with the potential for death loss, whereas immunocompetence gained through natural infection or by vaccination decreases morbidity. Mortality rate is usually low unless the virus is of high virulence and the horses are unvaccinated. The clinically affected horse is pyrexic (temperature up to 105° F) and has a serous nasal discharge, deep dry cough, depression, and anorexia. In a few cases, lower limb edema, peripheral lymphadenopathy, myositis, and myalgia are present. Fever is usually the first clinical sign. The cough may last for days to weeks after all other clinical signs have resolved. Upper airway endoscopy will reveal moderate to severe pharyngitis and tracheitis, with mucus seen in the trachea. Uncomplicated cases of equine influenza A typically resolve 7 to 14 days after infection; however, severe secondary complications such as weight loss, bacterial pneumonia, myositis, limb edema, myalgia, and myocarditis can last for weeks.
Diagnosis and Sample Collection
In most horses, complete blood count and serum chemistry values are within normal limits. The severely affected horse may, however, have a normocytic normochromic anemia and leukopenia (neutropenia and lymphopenia). Polymerase chain reaction (PCR) testing of deep nasopharyngeal swabs allows for rapid detection of virus antigen and diagnosis and is usually the diagnostic test of choice. Further serologic testing (complement fixation, hemagglutination inhibition, virus neutralization, and enzyme-linked immunosorbent assay [ELISA]) can be performed to confirm the diagnosis, with the most common test used being virus neutralization for determination of titer. Virus culture and virus isolation from deep nasopharyngeal swabs provide little diagnostic information unless the specimens were collected within the first 24 hours of exposure.
Treatment
The major goals of treatment include supportive care, management of fever and inappetence through judicious use of nonsteroidal antiinflammatory drugs (NSAIDs), and institution of a biosecurity plan because of the highly contagious and infectious nature of this virus. The use of antiviral drugs has shown little efficacy in diminishing clinical signs or providing a disease cure. Furthermore, the disease must be reported, so communication with state veterinary officials is required.
Equine Herpesvirus
Etiology and Pathogenesis
Equine herpesviruses (EHV-1 and EHV-4) are double-stranded DNA viruses of the family Herpesviridae and subfamily alphaherpesvirinae (see Chapter 37). Herpesviruses have a worldwide distribution, and most horses, donkeys, and mules are infected by 2 years of age. Equine herpesviruses follow a cyclic pattern of host infection, development of host latency, reactivation, environmental shedding, and transmission to susceptible horses. This cycle makes herpesvirus and the neurologic mutant strain significant factors in respiratory disease outbreaks, and results in yearly publicity for disease outbreaks. Transmission of the virus is through aerosolization, fomites, and vertical transmission. Host infection occurs in the respiratory tract, with viral shedding continuing for 7 days, followed by virus migration to local lymph nodes, leukocyte-associated viremia, and dissemination to other organ systems. Latency is established in both the lymphoreticular system and the trigeminal nerve ganglion; reactivation results in reinfection of the upper respiratory tract and environmental shedding of the latent virus. This enables persistent, long-term environmental shedding and lifelong infection in the host.
Clinical Presentation
Both EHV-1 and EHV-4 cause URTD, with the clinical signs of EHV-1 infection being more severe than those seen with EHV-4 infection. The initial incubation period is 1 to 3 days, depending on the susceptibility of the infected horse. Usually, the virus causes clinical disease in horses less than 3 years of age. The disease can affect a single horse but more commonly causes an outbreak, affecting several horses of various ages with varying degrees of illness and severity of clinical signs. Signs include a transient biphasic fever, with the first peak associated with the upper respiratory tract infection and occurring 24 to 48 hours after infection. The second peak is seen at 4 to 8 days and is associated with viremia. Depression and anorexia are often evident, along with progressive serous nasal discharge that develops into mucopurulent discharge by day 5 to 7 after infection. Other clinical abnormalities include lymphadenopathy, lethargy, lower limb edema, and mild ocular discharge. Previous exposure to the virus is associated with less severe clinical signs or subclinical infection, which makes diagnosis more difficult.