Bovine respiratory disease (BRD) is an endemic disease and one of the most common and costly diseases affecting cattle today. In the US the annual economic cost of BRD has been estimated as approaching $1 billion (Coetzee, 2019). Looking at costs for individual cases, Andrews (2000) estimated a single case of pneumonia carries a mean cost of £43.26 per sick dairy calf and a mean cost of £82.10 per sick suckler calf. These figures reflect both the immediate cost of treating the disease as well as the lifetime decrease in production and increased risk of the animal being lost from the herd. Over the last 40 years a vast amount of research has focused on BRD. A review by Fulton in 2009 identified over 2900 research papers on the different aspects of this disease complex, and since then the knowledge base has continued to grow. However, despite this wealth of knowledge BRD remains a significant clinical concern and one of the key reasons for the use of antimicrobials on farm. So, where the do the opportunities lie? And how in the face of increasing scrutiny on the use of antimicrobials do we manage this multifactorial disease effectively without compromising animal welfare or productivity?
Antimicrobials remain the mainstay of most treatment regimens for BRD and in around 82% of cases there is positive response to treatment (see Figure 1). However, 14.9% of calves treated for BRD also receive a second treatment, and then 12% of those cattle go on to receive a third treatment. Of the cattle that receive a third treatment for BRD, 37.9% respond favourably to the treatment, 22.1% are diagnosed chronically ill, and 30.5% die despite the treatment. When comparing the percentage of inventory that responds to the treatment and the percentage of inventory that dies for each treatment round, by the time we reach the third treatment the percentage that respond is getting very close to the percentage that die from BRD, highlighting the need to achieve early treatment success. These figures also provide guidance on the prognosis of animals requiring repeated treatment.
Improving the accuracy of diagnosis
Accurate and early diagnosis of BRD is a critical facet of any therapeutic programme. All too frequently there are delays in identifying animals requiring treatment or an acceptance of a low level of chronic disease within a group. Cattle are prey animals and consequently will often mask signs of sickness, especially in presence of humans (Weary et al, 2009). Therefore, a proportion of cattle with BRD are never detected by farm staff (i.e. false negatives). Studies in abattoirs have shown high incidence of lung lesions in animals with no history of being identified as having had, or being treated for, respiratory disease. Wittum et al (1996) identified lung lesions at slaughter in 37% of animals with no recorded history of respiratory disease. Recent studies in the UK demonstrated similar results with a survey of lung lesions at slaughter for veal calves identifying moderate to severe lung lesions (Figure 2) in 35% of animals surveyed and 64% of those having no recorded treatments for BRD (Williams et al, 2016). Conversely, clinical signs typically used to diagnose BRD (e.g. depression, anorexia, fever) are not always specific to this disease condition. Cattle diagnosed with BRD may thus not be truly affected by this disease (false positives) and it is therefore important that when engaging with producers about this topic we ensure that the message about the need for early intervention does not result in over treatment.
Different strategies have been implemented to assess and identify active pneumonia in cattle. For producers, diagnosis of active pneumonia is typically based on visual signs of respiratory disease (e.g. anorexia, depression, nasal and ocular discharge, cough, and ear position), associated or not with an increased rectal temperature. In recent years, systematic scoring systems (Figure 3) such as the Wisconsin Calf health Score (McGuirk, 2008) and the California Health Score (Love et al, 2014) have been increasingly used by farmers and veterinary surgeons to screen calves for active pneumonia and monitor respiratory health at a group level. For veterinary surgeons, diagnosis of active pneumonia is typically based on the presence of visual signs of respiratory disease and abnormal lung sounds, such as increased bronchial sounds, crackles, wheezes, or the absence of respiratory sounds, on thoracic auscultation, but the accuracy of auscultation, is questionable, with a moderate sensitivity (72.9%) and quite poor specificity (53.3%) (Buczinski et al, 2016). The use of technology is, however, improving the accuracy of auscultation: a computer-aided auscultation device (Whisper Stethoscope, Merck) has a reported sensitivity and specificity of 93 and 90% respectively (Mang et al, 2015).
In the last few years there has been increasing interest in the use of thoracic ultrasound as a tool for diagnosis of BRD. A key driver for this has been the demand for better sensitivity and specificity for BRD diagnosis. In two studies looking at the use of thoracic ultrasound (Rabeling et al, 1998; Ollivett and Buczinski, 2014), sensitivity for detection of lung consolidation was been found to be 85 and 94%, while specificity was 99 and 100%. Glover (2017) highlighted several potential applications for thoracic ultrasound in clinical practice:
- Increasing the reliability of BRD diagnosis, especially in cases where there are few other clinical signs
- Assessing recovery post treatment
- Assessing the diagnostic ability of farm staff
- Detecting calves in the early stages of disease
- Ruling out chronic BRD in cases of poor growth rates and ill thrift.
Ultrasound has also been used as a screening tool for future performance; Teixeira et al (2017) used ultrasound to screen heifers at 60 days of age for lung lesions and then followed them through into their first lactation. Heifers detected with lung consolidation at day 60 of life had a higher age at first calving, a higher hazard of death, and a lower hazard of pregnancy than heifers without lung consolidation. Additionally, a tendency for lower pregnancy to first service was reported for heifers with lung consolidation when compared with heifers without lung lesions.
While many of the systems and technologies discussed so far can help increase the accuracy of BRD diagnosis they do little to facilitate more rapid identification. One of the key determinants of treatment success is how rapidly therapy is initiated. A review of the NOAH compendium will identify over 50 antimicrobial products licensed for the treatment of BRD in the UK. While each of these products will have different pharmacokinetic properties (T-max, C-max etc), clinically the rate determining steps in achieving effective concentrations at the site of infection is most likely going to be how rapidly the diseased animal is identified (Figure 4) and how quickly steps are taken to administer treatment.
Technology is beginning to be implemented as a means of speeding up the detection of BRD on farm. Thermometry has been one area that there has been focus on; either using direct monitoring devices such as reticulo-ruminal boluses and eartags or through remote technology such as infrared thermography. The driver for automated temperature monitoring has been the observation that the febrile response preceded other clinical signs by 12–136 hours in one study (Timsit et al, 2011a), and by an average of 50 h in another (Timsit et al, 2011b). The use of thermometry to identify animals in the early stages of respiratory disease has also been explored as a means of reducing the need for antimicrobial treatment. Mahendran et al (2017) looked at how the proportion of animals identified as having BRD based on fever detected by the use Fevertags responded to treatment with a non-steroidal anti-inflammatory drug (NSAID) alone without the need for an antimicrobial.
Other non-invasive technologies showing real potential for aiding the early detection of BRD include accelerometers. Accelerometers have been adopted widely in the dairy sector for identification of oestrus behaviour and monitoring mobility, and now as the technology improves and units become smaller and cheaper there is increasing potential for their use to monitor activity in calves as an aid to disease identification.
Use of antimicrobials
Prudent use of antimicrobials is the judicious practice of medical principles and the cost-effective use of antimicrobials which maximises clinical therapeutic effect while minimising drug-related toxicity and the development of antimicrobial resistance (WHO 2001). BRD represents a major indication for cattle antimicrobials worldwide and was highlighted as a key reason for use in beef cattle in the UK by the RUMA Target Task Force report (2017). The potential to avoid the need for antimicrobial treatment altogether was highlighted earlier, although there is still much work to be done in this area to understand the longer-term implications of simply treating early cases with NSAIDs.
Johnson and Pendell (2017) showed that animals receiving multiple antimicrobial treatments exhibited higher mortality rates. Alongside the issue of reducing response it is important to consider the potential risk for promoting the development of antimicrobial resistance; Coetzee et al (2019) showed that the potential for selection of antibiotic-resistant bacteria increased when more treatments were administered. In their exploratory study they also presented data that suggest that first-line treatment, with a bacteriostatic antimicrobial followed by retreatment with a bactericidal antimicrobial may be associated with an increased risk of selection for antimicrobial resistance. They proposed that this was likely due to the bacteriostatic activity antagonising the effect of the bactericidal products; specifically, because the bactericidal drugs act on bacteria in their growth phase the inhibition of bacterial replication by bacteriostatic drugs may result in diminished activity of the subsequent treatment. While further investigation is required it does highlight the potential for resistance posed by multiple different drug treatments and the importance of careful consideration when drawing up treatment protocols or looking at follow-up antimicrobial treatments.
Group antimicrobial treatments as part of the control of BRD outbreaks remain relatively common place, despite a limited evidence-base on their effectiveness and their long-term impact. A systematic review and meta-analysis of antimicrobials used for mass-medication found that antimicrobial mass medications lead to a mean overall relative reduction in disease burden (Baptiste and Kyvsgaard, 2017), but did not economically lower the absolute risk for either displaying visual BRD symptoms or being selected for further antimicrobial treatments. It highlighted that while there was some short-term gain, the long-term impact was more variable, pointing to the need for management and environmental changes in order to truly control BRD.
Disease prevention
While maximising treatment efficacy it is important the goal should always be disease prevention. Bovine respiratory disease is a multifactorial disease complex and it is important to consider all the potential risk factors when looking at control programmes. Table 1 highlights several the key areas to consider
Table 1. Key areas to consider when approaching bovine respiratory disease holistically
| Factor | Examples |
|---|---|
| Herd immunity | Use of vaccinesNaturally acquired immunity (e.g. from colostrum) |
| Animal stress factors | Factors promoting immunosuppression:WeaningCastrationDehorning |
| Animal husbandry practices | Factors that promote contagious disease:Over stockingTransportMixing animals from different sourcesMixing animals of different agesPoor biosecurity |
One area of focus is the use of vaccination. We are privileged to have several different vaccines available to us, however market penetration is not as high as it could be; it is beyond the scope of this article to give a full appraisal of all the products available and there are other reviews available on this topic (Sherwin, 2017). When considering vaccination programmes, it is important to look at the specific set of disease challenges and risk factors present on each farm; there is not a ‘one size fits all’ programme for BRD. Vaccines must be used before the risk period for disease rather than being administered to high-risk, stressed calves under high infection pressure. Vaccines are only a single component of the balancing act between infection pressure and immunity and outcomes and their success will be compromised if they are not employed alongside other steps to reduce the infection pressure.
A major obstacle to control of BRD is the segmented infrastructure of the cattle industry (Ives and Richeson, 2015). Calves and cattle move through the industry potentially changing ownership at a number of different points. These changes result in transport, co-mingling from various sources, minimal biosecurity and other stressors providing opportunity for immunosuppression and pathogen colonisation of the lower respiratory tract. While this infrastructure persists, BRD will remain a major risk because of the factors present immediately before and after arrival of cattle on farm. Integrated supply chains provide some opportunity to mitigate some of the risk factors as all stakeholders will benefit from the improved performance. Sourcing from known sources enables better control of infectious disease and closer working relationships can enable consistency of nutrition and allow vaccines to be employed at the optimum time before potential high-risk periods.
Conclusions
BRD remains a significant clinical challenge on many farms. Advances in technology are providing new opportunities for veterinary surgeons to engage with their clients about this disease through increasing the ability to identify the disease early, providing more accurate diagnosis and enabling better monitoring at a group or herd level. Focus on disease prevention and the use of tools such as vaccination and improved management needs to continue to help reduce the use of antimicrobials. There remains a need for the use of antimicrobials in the treatment of BRD, but it is important that steps are taken to ensure that they are being used in line with the principles of prudent use.
KEY POINTS
- Bovine respiratory disease (BRD) remains a key issue affecting animal health and welfare across the globe.
- Achieving an accurate and early diagnosis is a key step to ensuring a successful therapeutic outcome and can be facilitated by the increased uptake of technology on farm.
- While antimicrobials remain an a essential part of the therapeutic repertoire for BRD it is important that they are used in accordance with the principles of prudent use.
- When making decisions about therapeutics it is important to take into account previous treatment history as previous treatments with different classes of antimicrobials can impact on the likelihood of successful treatment.
- Effective BRD control can only be achieved by looking at the issue holistically and managing if all the risk factors present.