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Epidemiologic investigations into pinkeye disease of cattle in Australia1 thesis

Mac Kneipp
ses.library.usyd.edu.au

Posted Flock and Herd August 2025

Introduction

Pinkeye (Infectious bovine keratoconjunctivitis, (IBK)) is (said to be) the most important eye disease of cattle worldwide. This apparently well-recognised 'disease' affects animal health, production, welfare and antimicrobial use.

Disease prevalence and impact

An update on the incidence of pinkeye in Australia was supplied using a novel model of pinkeye medications as surrogate disease indicators. The Australian cattle industry loses considerably more from pinkeye than previously estimated. Annual sales of Orbenin® and Opticlox® Eye Ointment plus Terramycin® Pinkeye Aerosol retail at $9.67 million, indicating 2.8 million cattle (10.25% of national Australian herd) are affected with pinkeye per annum6 doi.org

By modelling the between-herd prevalence of IBK for beef cattle worldwide, Dr. Elliott Dennis of Nebraska University and I, found the average global prevalence was 2.78% (range 1.66% to 4.00%). Within-herd prevalence was highest in Europe/Central Asia at 4.88% and North America at 4.73%, while sub-Saharan Africa and Latin America/Caribbean regions have the lowest. There were insufficient published data at the time to estimate the global economic impact of IBK7, doi.org

On-farm experience with pinkeye in Australia

Epidemiologic modelling (descriptive, univariable, & multivariable logistic regression analyses) of data from responses (n = 1675) to an online Australia-wide survey about pinkeye on-farm revealed:

1. Pinkeye risk factors

The risk of pinkeye was higher on farms:

2. Attitudes to treatment of pinkeye

Australian farmers were more likely to treat for IBK more frequently if they:

The most used IBK treatments in Australia were cloxacillin pinkeye ointments, followed by eye patches, pinkeye spray, fly control and pinkeye powder.

Whilst farmers expressed frustration with IBK outcomes, calling the vet was ranked in the bottom half of treatment choices. Over half of those who had used subconjunctival injection, pinkeye ointments, eye patches, injectable antibiotics, or called a vet rated them as highly effective treatments. Kerosene is still used by some farmers. The most common reason for not treating pinkeye was that it was "too difficult to treat individuals"9. doi.org

3. Perceptions of the on-farm impacts of pinkeye

Australian farmers ranked pinkeye impact on farm productivity as high if they:

Pinkeye as an animal welfare issue was rated overall by the greatest number as high severity.

The median amount farmers reported spending on pinkeye in 2018 was $250 per farm. They reported spending more:

Pinkeye treatments

In a review of the evidence-base for treatment of IBK co-authored with Prof Annette O'Connor of Michigan State University, we concluded there was a lack of randomised controlled trials, so whilst several effective antibiotic treatments appear to be available, more evidence is needed15. doi.org

I conducted a comparison trial of popular interventions against naturally occurring pinkeye in Southwest Queensland. Out of nine herds, 416 beef calves (less than 1 year old) were enrolled and data from 301 calves (485 eyes) analysed. Eyes with pinkeye were scored as low, moderate or high severity at enrolment. They were allocated either cloxacillin ointment repeated at 48 hours (H) (clox), subconjunctival injection of a mix of penicillin and dexamethasone (SJ), intramuscular oxytetracycline (OTC), an eye patch (patch), or various combinations of these treatments (combo). Initially I had positive (pinkeye cases not treated) and negative (healthy eyes) controls, but positive controls were discontinued on humane grounds. Seven to 12 days later treated eyes were assessed as worse, stable, or better. Overall, for low severity pinkeye none of the treatments scored worse, and best results (stable or better) were recorded for those given combo or patch, followed by OTC, SJ, and clox, respectively. For moderate pinkeye, best results were combo, followed by patch. About a third of eyes treated with OTC, clox, or SJ were worse, and these treatments had similar results overall. For high severity pinkeye, only combo resulted in a score of better, the other interventions had similar poor results of around half the eyes scoring stable or worse. Clox resulted in the poorest scores in this group. These results are not published.

In a pilot study of one calf, we used high performance liquid chromatography (HPLC) to measure the concentration of antibiotics in tears following pinkeye treatment16. After subconjunctival penicillin/dexamethasone injection no penicillin was detectable. After topical ointment, cloxacillin waned more rapidly than previous studies indicated, with levels in tears 3.0 µg/mL for 4.42 H and was not detectable after 25.25 H. This indicates increased dosing frequency (8 to 10 hourly) of cloxacillin ointments is required16. hdl.handle.net

I reviewed the literature on the minimum inhibitory concentration (MIC) of penicillin and cloxacillin for Moraxella spp.17 hdl.handle.net

Pinkeye vaccines

In the first field trial of the effectiveness of the only commercial pinkeye vaccine in Australia, we analysed data from 649 beef calves in five extensively run herds over two pinkeye seasons in south-west Queensland. The incidence of pinkeye was not significantly different between vaccinated and control groups, both alone and after adjusting for sex and weight differences11.

In a two-year randomised blind control trial that I was part of, a conditional licensed Moraxella bovoculi vaccine was not protective against naturally occurring disease in Angus calves in Iowa14. doi.org

Some conclusions drawn

Our multi-author review, Future Directions for Research in IBK, identified knowledge gaps and suggested directions for future studies18. doi.org

Our MLA report (available online) Risk factors, treatment and prevention options for pinkeye disease in cattle. MLA Project B.AHE.0319. Dhand NK, et al., (2021)24, concluded; before rational treatment and prevention of pinkeye is possible a diagnosis and a knowledge of the risk factors involved, is required. Epidemiologic studies can clarify the importance of various component causes (risk factors) to enable better disease management8,23. Pinkeye control could be better targeted by focussing on young cattle and improving the grazing environment. Furthermore, evidence-based guidelines for treatment of pinkeye should be developed and use of outdated and unproven treatments discouraged. Like vaccine efforts, broad genetic studies of pinkeye are irrational, as they may only be studying heritability of 'eye disease' of cattle. It is vital that veterinarians and researchers keep up-to-date with, and disseminate, new evidence-based findings. Education of cattle veterinarians and producers may be the best way to improve pinkeye outcomes.

Thesis findings included that pinkeye is more prevalent in Australia and has a bigger impact than previously estimated. Farmers are aware of it as an animal welfare concern and looking for advice on how to mitigate and improve outcomes from the 'disease'.

With field pinkeye, a combination of treatments is better than any single intervention. Pinkeye may 'recover' without treatment. So may a broken leg, but recovery outcome may not be ideal. Doing nothing was abandoned early in the treatment trial because of poor outcomes. The earlier pinkeye is treated (when less severe) and the longer acting any treatment lasts, the better the outcome. With active pinkeye any reasonable eye treatment is better than none and more is better than less. Anecdotally, best outcomes for herds with pinkeye is achieved from veterinary assessment and advice on individualised treatment of affected animals, combined with pinkeye management protocols. During the trials, all herds with 'IBK outbreaks' improved or were 'cured'.

The commercial M bovis vaccine, Piligard®, did not prevent naturally occurring pinkeye in my trial in Queensland, nor did a M bovoculi vaccine in Iowa. My literature search found there is abundant evidence that pinkeye vaccines are not (and never have been) protective against naturally occurring disease. More vaccine trials are not required. Findings of existing studies are not being disseminated or heeded. Pinkeye vaccines fail because of lack of understanding of the disease, lack of understanding of mucosal immunology, and vested interests.

Disease case definition

To adequately diagnose, treat, and control disease you must first agree on what a disease case is. Instead of a literature review I offered a disease case definition and diagnostic approach to IBK. doi.org The clinical presentation of pinkeye in an individual animal is not pathognomonic. The eye changes are not specifically characteristic of any one particular disease. 'Pinkeye' is an old-fashioned catch-all umbrella term and should no longer be used. The case definition of IBK is a herd disease of cattle occurring in outbreaks affecting > 2% of calves and 0.6% of cows with rapid spread (mean time of 30 days) of clinical signs restricted to the eye, including conjunctivitis and keratitis with 10% or more developing corneal ulcers (keratitis)5.

What is really going on with pinkeye/IBK?

Most significantly, my thesis studies led me to the conclusion that pinkeye is not even a single disease entity and the infectious bacterial model of IBK is nonsensical. Pinkeye is a label farmers use to describe the bovine ocular response to a diverse range of eye injuries. IBK is a label vets and researchers use when this occurs in a herd. Despite evidence to the contrary, veterinarians are taught that pinkeye is an infectious eye disease caused by the bacterium Moraxella bovis, with moderate impact, well-understood risk factors, and effective treatments and vaccines available3,4. This explanation is inadequate. Many questions remain unanswered. Why do some herds have high levels of pinkeye, while others do not? Why do some individuals within a herd develop pinkeye and others do not? Why do some cattle get pinkeye in one eye and others get it in both eyes?

Faulty logic and misdirected effort

Inductive logic, drawing conclusions from (repeated) observations, is bottom-up reasoning, arriving at general conclusions from specific observations. The conclusion that a lowly virulent commensal gram-negative bacterium, M. bovis, is the primary cause of pinkeye/IBK appears to be a classic case of faulty inductive reasoning. What Bertrand Russell called "the fallacy of affirming the consequent". The fact the sun comes up every morning after the rooster crows does not mean the rooster crowing caused the sun to come up. Culturing a common inhabitant of the bovine ocular microbiome from eyes with pinkeye does not mean it caused the disease. Re-proving the results in similar experiments (swabbing eyes for Moraxella spp) is only confirmation bias because further repetitions of the events (cock crowing, sun rising) might be consistent with a hypothesis about causation but does not prove it true. Deductive logic is top-down reasoning, inferring that a general law of nature exists and applying that law to specific (observed) instances. The contagious bacterial model of pinkeye/IBK and its associated methods of diagnosis and interventions break many of the general laws of medicine, for example;

  1. A contagious bacterial disease of the eye should spread to both eyes of a susceptible individual.
  2. There are no bacterial primary pathogens of any animal's cornea. Other than herpesviruses, all infections of corneas are secondary to injury.
  3. Culture from ocular swabs is not routinely recommended for keratitis in other species, because of secondary invaders and contamination.
  4. Newer molecular biology techniques such as PCR and 16sRNA have failed to prove a causal relationship between Moraxella spp and IBK19-22.
  5. Moraxellae do not produce coagulase and cannot melt a cornea (yet this is one sign of pinkeye).
  6. Penicillin-derivatives, like cloxacillin, are not an empirical first-choice antibiotic for a gram-negative bacterial infection. In fact, after researchers in Missouri found M. bovis cultured from cattle with pinkeye was uniformly resistant to cloxacillin they incorporated it in a selective media to improve the isolation of that difficult-to-grow bacterium.
  7. It is not possible to induce protective immunity on mucosal surfaces by priming the systemic immune compartment. Seroconversion (IgG in the blood) does not provide ocular surface protection.
  8. There are many more exceptions made to accommodate the 130-year-old mislabelling of the stereotypical response of a bovine eye to (moderate to severe) injury as a disease entity (pinkeye) and the contemporaneous response in the eyes of cattle in a herd as a contagious outbreak (IBK).
  9. Pinkeye/IBK has appeared in veterinary literature for over 130 years2, yet remains an unsolved enigmatic 'disease', because the infectious disease narrative is wrong. IBK is not a disease at all!

References

  1. Kneipp M (2022) Epidemiologic investigations into pinkeye disease of cattle in Australia (Thesis) in Faculty of Science Sydney School of Veterinary Science, The University of Sydney: Sydney p 224
  2. Billings F (1889) Keratitis contagiosa in cattle Bulletin of Agriculture Experimental Station of Nebraska 3:247-252
  3. Sackett D et al. (2006) Assessing the economic cost of endemic disease on the production of Australian beef cattle and sheep production MLA Report AHW 87, Meat and Livestock Australia Meat and Livestock Australia Ltd, North Sydney NSW
  4. Lane J et al. (2015) Priority list of endemic diseases for the red meat industries Project B.AHE.0010 Final Report, in Project B.AHE.0010 Meat and Livestock Australia Meat and Livestock Australia North Sydney NSW
  5. Kneipp M (2021) Defining and Diagnosing Infectious Bovine Keratoconjunctivitis Veterinary Clinics of North America: Food Animal Practice 37(2):237-252
  6. Kneipp M et al. (2020) Current incidence treatment costs and seasonality of pinkeye in Australian cattle estimated from sales of three popular medications Preventive Veterinary Medicine 187:105232
  7. Dennis EJ and Kneipp M (2021) A Review of Global Prevalence and Economic Impacts of Infectious Bovine Keratoconjunctivitis Veterinary Clinics of North America: Food Animal Practice 37(2):355-369
  8. Kneipp M et al. (2021) Risk factors associated with pinkeye in Australian cattle Preventive Veterinary Medicine 194105432
  9. Kneipp M et al. (2021) Perceptions and practices of Australian cattle farmers for the treatment of pinkeye (infectious bovine keratoconjunctivitis) Preventive Veterinary Medicine 197:105504
  10. Kneipp M et al. (2022) Perceptions of Australian cattle farmers regarding the impact of pinkeye on farm productivity and animal welfare Preventive Veterinary Medicine 204:105665
  11. Kneipp M et al. (2022) A randomised control trial to evaluate the effectiveness of a commercial vaccine for pinkeye in Australian beef cattle Preventive Veterinary Medicine 210:105815
  12. Hille MM (2021) Moraxella Species Associated with Infectious Bovine Keratoconjunctivitis: Detection Characterization and Immunity (Thesis), in Integrative Biomedical Sciences University of Nebraska: Lincoln Nebraska
  13. Maier G, O'Connor AM and Sheedy D (2021) The Evidence Base for Prevention of Infectious Bovine Keratoconjunctivitis Through Vaccination Veterinary Clinics: Food Animal Practice 37(2):341-353
  14. O'Connor A et al. (2019) A 2-year randomized blinded controlled trial of a conditionally licensed Moraxella bovoculi vaccine to aid in prevention of infectious bovine keratoconjunctivitis in Angus beef calves Journal of Veterinary Internal Medicine 33(6):2786-2793
  15. O'Connor AM and M Kneipp (2021) Evidence Base for Treatment of Infectious Bovine Keratoconjunctivitis Veterinary Clinics of North America: Food Animal Practice 37(2):329-339
  16. Kneipp M et al. (2022) Chapter 8: High-performance liquid chromatography assays of cloxacillin and penicillin in the tears of a calf following treatment, in Sydney School of Veterinary Science The University of Sydney: Sydney p 198-204
  17. Kneipp M et al. (2022) Chapter 8 Supplementary material: The antimicrobial susceptibility of Moraxella spp to penicillin and cloxacillin, in Sydney School of Veterinary Science The University of Sydney: Sydney p 205-212
  18. O'Connor A.M et al. (2021) Future Directions for Research in Infectious Bovine Keratoconjunctivitis Veterinary Clinics of North America: Food Animal Practice 37(2):371-379
  19. O'Connor AM et al. (2012) Descriptive epidemiology of Moraxella bovis Moraxella bovoculi and Moraxella ovis in beef calves with naturally occurring infectious keratoconjunctivitis (Pinkeye) Veterinary Microbiology 155:374-380
  20. Schnee C et al. (2015) Point prevalence of infection with Mycoplasma bovoculi and Moraxella spp in cattle at different stages of infectious bovine keratoconjunctivitis The Veterinary Journal 203(1):92-96
  21. Cullen JN et al. (2017) Microbial community sequencing analysis of the calf eye microbiota and relationship to infectious bovine keratoconjunctivitis Veterinary Microbiology 207:267-279
  22. Zheng W et al. (2019) A multiplex real-time PCR assay for the detection and differentiation of five bovine pinkeye pathogens Journal of Microbiological Methods 160:87-92
  23. O'Connor AM (2007) Infectious Bovine Keratoconjunctivitis Management, in American Association of Bovine Practitioners Annual Conference Vancouver British Columbia: ProQuest AABP
  24. Dhand NK et al. (2021) Risk factors treatment and prevention options for pinkeye disease in cattle Project B.AHE.0319, in MLA Project B.AHE.0319 Meat & Livestock Australia Meat & Livestock Australia North Sydney NSW p 1-96

 

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