17 Nov 2014
Tony Andrews
Job Title
Many types of antibiotics are licensed for calf respiratory disease treatment. This shows the importance of the market and that no one type or group of therapeutic agent is able to deal with all cases.
Respiratory disease is likely to always be present in Britain, partly because the problem is multifactorial and often is an interaction between the calf, its environment and management, together with numerous different potential pathogens – including bacteria (now including mycoplasmas) and viruses, as well as other agents including parasites and fungi.
Respiratory disease is mainly a problem of housed animals, especially around the weaning period. While on occasions it occurs outside, it is much less frequent and shows the importance of housing and the environment in precipitating infections. Often, the management precipitants have resulted in varying degrees of stress, which lower resistance to infection and then allow pathogens, often already present in the animal or group, to multiply and cause illness. These major factors, plus the impact of the weather (as most problems occur during the autumn and winter months), result in bovine respiratory disease syndrome (BRDS) in the young weaned calf born in the dairy herd (variously called calf, enzootic, or acute pneumonia) and the weaned suckler calf (called transit or shipping fever or pasteurellosis).
Therefore, although most farmers and stock rearers wish to focus on treating the illness, it is more important to determine why the respiratory problems are arising. When problems occur year after year, it is up to all of us dealing with the animals to look at the causes and not just accede to the request to supply an antibiotic that is “stronger” or “different” to the one currently being used. Most primary pathogens are viruses and bacteria, and, although vaccination against them can provide useful protection, it is still not used widely enough.
An investigation at the time of disease problems can be cost-effective, as studies on the cost of pneumonia have shown the high costs of the problem and, in some circumstances, these costs continue after the outbreak ends. In an ideal world such investigations would occur with each dispensing of therapy. Often, identifying the main environmental and management factors and then altering them can incur minimal or small costs, but give very beneficial results.
While this article deals with treatment in young calves from the dairy herd, it is really a case of shutting the door after the horse has bolted. Even then it is not just a question of deciding on the appropriate antimicrobial preparation, but also placing it in context.
Many organisms can be involved in calf respiratory disease and viruses, including infectious bovine rhinotracheitis (IBR), bovine respiratory syncytial virus (BRSV), parainfluenza III (PI3) and bovine viral diarrhoea virus (BVDV), and mycoplasmas (Mycoplasma bovis, M dispar, Ureaplasma species) are often considered the primary pathogens.
However, other organisms, particularly bacteria (Mannheimia haemolytica, Pasteurella multocida, Histophilus somni) then result in disease signs and, although considered secondary, there are some situations with stressed animals where they are probably performing a primary function.
Whatever is the correct designation or classification, in most cases of calf pneumonia antibiotics work, indicating that a major component of the problem is caused by organisms susceptible to these therapeutic agents.
Looking at the disease, besides the damage directly caused by the organisms, inflammatory cells can cause problems as well as toxins and cytokines released by some pathogens, particularly M haemolytica. Thus, often antimicrobial therapy on its own will not produce the required response.
It is always a good policy in calf respiratory disease to treat as soon as signs begin. If this is done, the damage to the respiratory system is minimised. In addition, the affected animal should be isolated, as it is not always realised most infection is spread from animal to animal by contact. Thus, removal of any source of infection is likely to reduce the need for therapy or curative treatment of a group and, more importantly, often prevent the need for metaphylaxis or controlled treatment. This can be facilitated by having a separate hospital pen. If reinstating the animal to the group is considered a possible problem then one or two others can accompany it. The other reason for isolation is the calf can be more effectively monitored and whether it is eating and drinking satisfactorily can be assessed.
Although early treatment should be the mantra, it has been shown identification of illness by the stock person is later in the disease process than by a veterinary surgeon. This is another good reason to have veterinary involvement.
In the calf pneumonia cost study I undertook, one criticism was the number of calves that died was very low and so unrepresentative. However, this low mortality was probably because of the weekly veterinary visit to monitor the outbreak, which resulted in animals being detected that had not as yet been treated and others where treatment had ceased and it needed to be continued.
When a treatment course is initiated, there is always a temptation to stop as soon as signs subside. Often, it can be shown at this stage the illness has not finished and there will be continuing damage to the lungs and further therapy may later be required.
This is not usually a problem with some of the newer antimicrobials where duration of activity from one injection is often longer than the disease process and lung repair. It may also be helpful to have as long a duration as possible because by the time the antibiotic is no longer active there will be some degree of immunity to the specific pathogen causing the illness.
When results are not as expected with antimicrobials of long activity then it can be useful to use a course of treatment with antimicrobials of shorter duration. This allows a more flexible approach and the therapy can be more quickly altered. On some occasions where stockmanship is suspect, another advantage with a course of treatments may be the animal will be examined consciously or unconsciously with each injection given. However, in such cases compliance may be a problem.
Inevitably, the longer the duration of efficacy, the longer the withdrawal period will be. However, except in veal production, which is minimal in Britain, and in a few other circumstances, withdrawal periods in calf, or enzootic, pneumonia are of little consequence.
The early detection of individual animals with calf pneumonia and their immediate removal from a group can reduce the need for metaphylactic use. This obviously reduces costs, unnecessary treatments and the potential for antimicrobial resistance. Also, only using metaphylactic treatment when a percentage of the animals are showing signs within a short period can reduce the need for such therapy. By only using metaphylaxis in this way, most calves have been exposed to those precipitating factors and infections that have initiated the infection, thereby allowing immunity to form after they are removed from the animal.
Another potential way to deal with outbreaks is to check rectal temperatures daily and treat those with levels higher than an agreed threshold. Such treatment does require time, labour and suitable handling facilities, which are often lacking for these young animals.
Besides the different antibiotic groups having different characteristics, individual agents in a group can vary in their pharmacokinetics and pharmacodynamics and these can alter the outcome of therapy (Potter, 2011). While cost is a factor the financial consequences of calf pneumonia far outweigh those of any appropriate early treatment. The antimicrobial choice is also dependent on the reliability of the stock people involved, their ability to detect the early stages of illness and their adherence to the instructions given about treating the animals.
All farms where bovine respiratory disease occurs should have investigations undertaken to establish the profile of the microorganisms present and to determine treatments/preventions with a suitable spectrum of activity. This should include vaccines as well as treatments, curative or metaphylactic.
Antimicrobial sensitivity testing will also indicate those mole cules with a suitable range and level of activity. While this may seem theoretical, it can be used to justify the choice of treatment and is using antibiotics in a responsible way.
It is important such testing becomes routine as the onslaught about use of antimicrobials in farm animals is likely to worsen and intensify.
However efficacious an antibiotic is, it is of little use unless it can actually penetrate the diseased tissue and then kill or effectively stop the multiplication of the causal agent(s). Ideally, it should also concentrate at the site of infection. If done efficiently antimicrobial levels in the blood are minimal or almost nil a few hours after drug administration. Some antibiotics, such as the macrolides and fluoroquinolones, tend to concentrate at such pathological respiratory sites. This is because some antimicrobials are basic and the lungs are acidic, with the pathological parts being even more acidic.
All treatment regimes should be aimed at not causing or increasing antimicrobial resistance. There is still much debate about an agreed suitable formula for defining resistance and most countries do not have a systematic method for resistance surveillance. More data are available from North America than in most of Europe, but must always be reviewed in the context of what animals and where the disease outbreaks are being studied and whether any oral medication has been given to the animals at the time of the outbreak or previously.
Many of the newer antimicrobials used for calf pneumonia have little or no indication of resistance developing. However, this situation cannot be looked on with complacency as, inevitably, all antibiotics have the potential to induce resistance.
While the cost of a dose or course for an individual animal is important to the farmer, it should not be a limiting consideration. The choice of the right antibiotic for the particular situation is much more important as the early and compliant use of the correct treatment, whatever the cost, will be more cost-effective than the costs of the disease itself or any prolonged respiratory system damage due to an inappropriate choice being made.
In many instances, the inflammatory process initiated by the pathogens causes as much damage as the organisms themselves. Thus, reduction in the inflammatory changes allows improvement in clinical signs and, usually, will result in better outcomes. Therapies can allow improved respiratory function, as well as reducing the body temperature and any pain and enhancing the animal’s ability to eat. The drugs involved mainly stop the effects and synthesis of eicosanoids and include NSAIDs and glucocorticosteroids. These days NSAIDs tend to be used and have useful effects on pain, body temperature, and inflammation as well as not affecting the immune response. However, occasionally, where these appear not to be working, I have used corticosteroids with better results, particularly when oedema is present. Usually, provided they are used sparingly and where IBR or BVDV are not involved in the disease, corticosteroids may be successfully used as a second line of therapy.
In some cases of calf pneumonia, nutrition might not be adequate and this is always worth checking, especially where outcomes are not as expected. Various deficiencies can also occur. Sometimes, a dose of the fat-soluble vitamins A, D and E can improve response to the infection. Minerals such as copper and selenium may also be lacking.
As already stated, nursing is important, with separation of the calf, ensuring it is eating adequately, the feed is of high quality and it has a deep dry bed protected from draughts and damp. Ensuring a stress-free environment can aid and hasten recovery.
It is to be hoped records will have been kept of what happened in any pneumonia outbreak, if only to meet the legal requirement to record treatments. After any outbreak of calf pneumonia the event should be evaluated to determine whether the correct antimicrobial was used, how results might have been improved by better identification of ill animals or how their overall treatment and nursing could be better managed.
In addition, it should be possible to see whether future management can be altered to improve the environment, prevent the precipitating factors causing disease and introduce suitable preventive measures such as vaccination. Such analyses can help ensure the continued efficacy of those antimicrobials used to treat calf respiratory problems.
Table 1. Factors influencing choice and success of calf pneumonia treatment
