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                    John Gay, DVM PhD DACVPM               AAHP                  FDIU             VCS


VM577 Vaccine Information Exercise

Version 1.1  1/10/08   Updated February 01, 2008

Introduction:

 The following is intended to provide guidance for going about determining the economics of using a pasteurellae (Mannheimia now) vaccine in calves, the question that came from the class discussion.

Please work in groups of several students each - multiple minds are better than one and it spreads the work around.

Task:

  1. Frame the question well that  you wish to answer.
    • For example: "Does the evidence show that using <vaccine X> at <timing> in <livestock class> under my client's circumstances is economically beneficial?"
    • In this case, we discussed the using the vaccine pre-weaning in calves that your client was going to ship to a feedlot and retain ownership. Hence, the client is interested in the economic benefit from reduced morbidity and mortality during weaning on the ranch and after being shipped to the feedyard.
  2. Pick the product; there are a number available that have a label claim against Mannheimia hemolytica (e.g., Boehringer Ingelheim Express 5-PHM, Pfizer "One Shot" (is it really only one shot? read the label closely), Fort Dodge Presponse, Intervet Vista Once SQ, and so on) but they differ. (Hint: vaccines under different brand names but having the same veterinary license number are effectively identical vaccines).
  3. What is the evidence? Search for the evidence - primary literature papers, meeting proceedings, manufactures technical literature, extension publications. The following is one approach:
    • First, refresh your memory on how BRD works with a good textbook (e.g., Smith or Blood, Radostits and Gay) or, for a quick synopsis, the on-line Merck Veterinary Manual (Pneumonic Pasteurellosis)
    • A quick place to start your search is Cornell Consultant - select bovine for the species and enter "pneumonia" for diagnosis keyword. Select "shipping fever". Consultant lists the recent clinically-relevant papers selected by Cornell clinicians.
    • Select a set of key search terms:
      • Using a good set of terms with the right truncation (e.g., "truncat*" and "AND", "OR" and "NOT" makes your searches more specific (less chaff) and sensitive (all the good papers)
      • For instructions on PubMed searching, see Searching PubMed
    • Search the on-line databases, such as PubMed. At WSU, go to the Database Index. (accessing PubMed or Web of Science through enables you to print out the article PDF if WSU has rights to it)
      • Try the following for a very powerful trace through the literature (not available outside WSU, unfortunately, while PubMed is):
        • On the WSU Database Index, select "Databases A to Z" and type in "Web of Science".
        • Click on "Web of Science". Click on "Web of Science" again. Click on "General Search".
        • Enter the search terms you have come up with ("mannheimia bovine bacterin efficacy" (no quotes) brings up 1 paper).
        • Click on the "Find @ WSU" button.
        • Click on the "Go" button and you reading the paper.
        • Go back to the Web of Science page and click on "Times Cited" - that brings up the citation of every newer paper that cited this paper.
          • Using this on older but key papers works well because authors writing newer papers in the area will often cite such papers
        • Go back to the Web of Science page and click on "Cited References" - now you have links to most of the cited papers and you can do the same process with them (note the Shewen and Wilkie paper - one of the early, key leucotoxin papers).
          • This is a great way to identify the important older papers; key older papers will often have a lot of citations
    • If you with all that haven't located good papers with the answer to your question, Google around for other stuff, such as extension publications.
      • Note the TexVAC program listed below, a google hit.
    • Other things you could try:
      • Go to your list of experts, search the AABP-L archives, post a question, call the company and so on
      • Watch the trade magazines; they often provide links to good information resources
      • Consider analogical evidence from similar systems with a similar problem. For example, pneumonic pasteurellosis is a major problem in dairy calves, which are often under more severe challenge than beef calves.
    • Note: The two papers I was thinking of are by BD Hunsaker (no "c") but the only way to access them online is through the AABP website (Bovine Practitioner, January '97, and the 2007 Proceedings). Neither appears in PubMed or Web of Science.
  4. What is the strength of this evidence? A critical step is evaluating the studies! Select the best evidence to apply to your client's herd.
  5. Make your recommendation based on the evaluation of the evidence.
    • Sufficient strong evidence? Answer "yes" or "no" and why so or why not. Commit yourself in writing, if you dare. Recall that "The faintest pencil is stronger than the strongest mind" and "Success has many fathers but failure is an orphan". If you want credit in the future, write it down.
    • Insufficient evidence? Suggest a randomized controlled clinical trial to find the answer, across multiple herds if necessary!
  6. For the purpose of the class discussion and results comparison (I'll make copies):
    • Summarize your group's findings, conclusion and recommendation in no more than one page of verbiage.
    • Provide the citations for all your sources, papers, names (for comparing sources)
    • Provide the search strings for the databases you used or otherwise describe how you found any papers you used (good sets of terms and using them well are key to successful searching)

Vaccination Programs: (modified from a presentation to livestock producers)

One size does not fit all!

Establishing a vaccination program for a herd requires consideration of complex issues. To quote Brand et al. (1996): "A vaccination program must be based on the disease status of the herd, reproductive status of youngstock and cows, potential interference by maternally derived antibodies, potential effects of vaccine-induced titers on suitability for export or introduction into bull studs, whether the herd is open or closed, prevailing farm and area conditions, national or regional vaccination strategies, the possible advantageous/disadvantageous post-vaccination sequalae, and the cost benefit ratio of a vaccination program (emphasis mine). Furthermore, the vaccination schedule should be known, as well as the antigenic form of vaccine to be used (inactivated, modified live, live, or deletion vaccine), route of administration (intramuscularly, subcutaneously, or intranasally), and whether a booster vaccination is needed and when." Because the immune system requires time to respond to vaccines, the final dose should be given sufficiently in advance that the animal can be fully protected when the exposure or stress occurs. Vaccines requiring priming doses must be given sufficiently ahead of the second dose for the second dose to stimulate adequate protection. Failure to follow the administration instructions in this regard is a common error that markedly reduces vaccine efficacy.

Many vaccines are likely only marginally beneficial, biological and economically.

Some vaccines, such as the oil adjuvant vibrio (Campylobacter fetus) and the muscle clostridial toxoids (e.g., Clostridium chauvoei (blackleg), Cl. Septicum (malignant edema)), are highly efficacious. At the other end of the spectrum are the older Pasteurella whole cell bacterins that don't contain leucotoxoids as some evidence suggests that they actually increase the severity of bovine respiratory disease under some circumstances. Others fall in between. For example, a controlled study of the trichomoniasis vaccine showed that 63% of vaccinated heifers delivered calves while only 32% of the controls did so and the vaccinates were culture positive for 3.8 weeks while controls were for 5.4 weeks (Kvasnicka Am J Vet Res 53:2023(1992)). Although the vaccine improved the situation, it certainly didn't prevent the problem. Other control measures such as rigorous testing of young bulls, culling of older bulls and late calvers may be more beneficial economically. Some vaccines such as leptospirosis are considerably more effective against non-host adapted strains than host-adapted strains. A general rule of thumb is that if a natural infection after birth results in a chronic carrier animal, which means that that animal's immune system was not able to eliminate the infection, then vaccination of that animal isn't going to stimulate the immune system sufficiently to prevent infection either. Thus, a general conclusion is that many vaccines will reduce the number of animals infected, will reduce the proportion of those that become clinical cases among those that are infected and will reduce the amount and duration of shedding in those that are infected.  But for many diseases vaccination will not completely prevent the problem and other control measures may be equally or more important. Unfortunately, it is human nature to look for the single magic bullet that can be given once and forgotten.

The evidence from sound studies of a positive economic benefit from the use of many vaccines across large numbers of herds is lacking. The lack of sound evidence doesn't necessarily mean that the cost-benefit isn't positive. Anecdotal evidence suggests that the severe clinical outbreaks of Type II BVD tended to occur in herds that were not properly vaccinated for BVD. For bovine respiratory disease, about half of the studies indicate equivocal benefit while half indicate marginal benefit of use in calves prior to weaning. As noted in the pneumonia example above, their use clearly doesn't completely prevent the problem. To get the needed evidence of benefit, producers need to make the evidence from sound randomized, multi-herd, concurrent controlled, blinded field trials a condition of purchase.

USDA vaccine licensing does not require evidence of efficacy in cattle under normal farm and ranch conditions and only requires evidence of efficacy against specific aspects of the disease.

The USDA provides minimal monitoring of vaccines for safety, purity, potency and efficacy, concentrating primarily on safety and purity (freedom from other infectious agents or toxic materials). This is done by monitoring the procedures and sanitation in the plants producing the product. To show efficacy of vaccines the manufacturer performs laboratory challenge of specially selected animals rather than using controlled field studies of vaccine efficacy under actual use conditions. In the Espeseth and Greenberg document on the "Published Articles" website referenced below, it states "It is generally more difficult to demonstrate significant efficacy under field conditions. Field efficacy studies are often inconclusive because of uncontrollable outside influences." Further, if other sound, independent evidence shows that a USDA-approved product is not efficacious under most circumstances, the law does not prevent its production or sale. Thus, a USDA-approved and licensed product may not be efficacious under the under field conditions. Further, the aspect of the disease against which efficacy must be demonstrated is quite specific. For example, for the BVD vaccines evidence of efficacy against the clinical gastointestinal disease syndrome is required but efficacy against fetal infection, which is essential for preventing the persistent carrier state and the most important component for control of BVD in breeding herds, is not unless it is a specific label claim.

For on-line information on USDA vaccine licensing policies, see USDA Center for Veterinary Biologics

Vaccine Program Recommendations

My recommendation is that in concert with their herd veterinarian, producers design a vaccination program for the specific circumstances of their herd. Without knowledge of the herd specifics and of the area I'm unwilling to make blanket recommendations. I also suggest that producers put their vaccine requirements out to bid. With the above caveats in mind, the following are on-line vaccine recommendations in title alphabetical order from a number of experts:

  • Designing Preventive Health Management Programs for Cattle Producers (Griffin, Perino, Rupp, Hamilton - Nebraska, doc
  • Great Plains Veterinary Education Center Files - index
  • Immunizations for Oklahoma Cow Herds (L Rice, University of Oklahoma, html)
  • Keep Herd Health Simple and Make it Fit the Beef Cattle Operation (EJ Richey, Florida, html pdf)
  • Preconditioning Programs: Vaccination, Nutrition, and Management (1999, NDSU AS-1160)
  • Preventive Herd Health Program (GL Stokka, Kansas, 1998, EP-50 pdf )
  • TAMU Ranch to Rail: Value Added Calf (TexVAC) Vaccination Management Program (33 pg. pdf, short pdf)

Some General Infectious Disease Concepts: (background information)

  • The Iceberg Principle: With most diseases in a herd, more subclinical (silent) cases occur than clinical cases.

Even in outbreak situations more animals in the affected group have infections and are subclinical or silent cases than there are clinical cases. For most diseases, both infectious and non-infectious, the ratio between clinical cases and subclinical cases is typically 1:5 to 1:20. Under some circumstances, a herd can be widely infected with an infectious agent but few if any clinical cases occur at all. For some infections such as Bovine Leukemia Virus (BLV) the ratio may be 1:100, meaning that clinical cases rarely occur. Many clinical cases are due to infectious agents that are in most herds most of the time but that usually don't cause clinical disease. Thus, the occurrence of clinical cases is an indicator that something is amiss in the management of those animals.

Good explanations of the balance between resistance and disease challenge and fitting these into the beef cow production cycle are those authored by Dr. Ed J. Richey, Univ of Florida Beef Extension veterinarian:

  • Keep herd health simple and make it fit the beef cattle operation (1991) (pdf)
  • Constructing Diagrams to Represent the Management System of a Beef Herd, Bulletin 278 (html, pdf)

Richey, E, R Hendry, S Cornwell (1992). Herd Health for the Beef Cattle Operation. The Bovine Proceedings 24:156-167.

For more information on the above epidemiologic concepts for disease in animal groups, see:

Epidemiology Concepts for Disease in Animal Groups

  • Infectious disease problems generally cannot be controlled by focusing solely on the clinically affected animals.

For on-line information on considerations in bovine salmonellosis control, see: Bovine Herd Salmonellosis, Including DT104: Eleven Characteristics to Keep in Mind.

  • Because subclinical (silent) cases of most diseases are more numerous than clinical cases in a herd, the economic cost of subclinical disease exceeds that of clinical disease.
  • New infectious agents often enter a herd and are unnoticed for some time before clinical disease occurs and a diagnosis is finally made.
  • Carriers of subclinical infection are the reason for the old but true saying that "Most disease is bought and paid for!" and are what keep it in a herd.
  • Quarantine isolation of purchased animals will not protect a herd against the chronic carriers of many infectious agents!
  • Even using the best laboratory tests, subclinical (silent) disease is considerably harder to detect and diagnose than is clinical disease and is more error-prone.
  • For many infectious diseases, the single most important piece of information that a purchaser can have is honest, sound knowledge about the status of the herd of origin with respect to the infections of concern.

Work with rather than against "Mother Nature":

  • Taking advantage of the opportunities that Mother Nature presents is far less costly and more effective than fighting Mother Nature, which is often a loosing battle.
  • Continued success is far more likely if a disease problem is attacked at multiple points rather than attacking it at a single control point.
For example of management practices to reduce calf scours, Prevention of neonatal calf diarrhea with the Sandhills Calving System (Dr. David Smith, U Nebraska, pdf)

Other On-line Information Sources:

The Internet contains a wealth of relevant materials, one reason being that a major mission of the agricultural extension service is to communicate information to producers. The Internet provides an excellent mechanism for doing so to the dispersed producer audience. As a result, many very useful extension publications are on the Web. The medical literature can also be searched for free on-line through the National Library of Medicine. Cornell Consultant also provides an on-line means of identifying the most recent relevant clinical literature as selected by Dr. Maurice White, a Cornell food animal clinician.

Cornell Consultant: A Diagnostic Support System for Veterinary Medicine (Dr. M E White)

This is a unique resource to establish differentials and to identify current papers on a disease.

National Library of Medicine PubMed

One of the great features of PubMed is the "related article" function that enables you to find the closely related papers that they have indexed close to a good hit that you have found.

References:

  • Brand, A, JPTM Noordhuizen, YH Schukken (1996). Herd Health and Production Management in Dairy Practice. Wageningen Pers, Wageningen.
  • Chenoweth, PJ, MW Sanderson (2005). Beef Practice: Cow-Calf Production Medicine, Blackwell Publishing.
  • NAHMS beef cow-calf studies (National Animal Health Monitoring System, 1997). Beef Cow-Calf Health & Management Practices (Beef '97) pdf.
  • Radostits, OM, ed. (2001). Herd Health: Food Animal Production Medicine, 3rd ed.WB Saunders, Philadelphia.

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