FRANK J. MILNE STATE-OF-THE-ART LECTURE 7. Rhodococcus Equi Infection


Gumshoe Sleuthing A local Thoroughbred breeding farm, which had a resident veterinarian, Dr. Noel Muller, was having significant R. equi problems. One year they had 8 deaths and 26 confirmed cases, and Dr. Muller was asking us for some help. Sharon Heitala had just completed her PhD on R. equi and found there was some evidence for humoral immunity. Dr. Muller said they were willing to try anything, so we made a bacterin (a killed or weakened bacteria for use as a vaccine) out of an isolate from the farm, vaccinated donors and harvested the plasma, froze the plasma, and administered it within 24 hours of birth one time. The results were stunning. The first year we used the plasma there were 68 foals and no deaths or foals requiring treatment for R. equi. The next year we gave plasma (1 liter post birth) to 101 foals, and 14 foals did not receive plasma. Only 3% of plasma-treated foals developed R. equi pneumonia, with no deaths, compared to 6 of the 14 (43%) foals that did not receive plasma, 2 of which died. Why this worked so well compared to today’s plasma treatments to prevent R. equi is part of an ongoing study to be discussed in the Milne lecture.


Etiology


Rhodococcus equi, a gram positive coccobacillus, causes chronic purulent bronchopneumonia in foals less than 6 months of age and is a significant cause of wastage to the equine breeding industry, espe- cially on farms where the disease is endemic. An 80 to 90 kb plasmid encoding nine virulence-associ- ated proteins (Vaps), termed VapA, VapC-VapI, and pseudo-VapE, is important for pathogenicity. VapA appears to be the most significant of these proteins. The organism is ubiquitous in the soil, particularly dry and dusty soil, and bedding on equine farms such that foals are exposed to R. equi within the first few days of life. The majority of exposed foals develop protective immune responses; however, some foals appear susceptible to infection due to an immaturity of their immune system.125 Epidemiological study of R. equi pneumonia has de- termined a seasonal incidence that peaks late spring and summer when the high number of foals coin- cides with an increased risk of aerosol challenge from the environment and/or herd mates.126 An excellent review of the immunological response to R. equi is provided by Dawson et al.127


Overview of the Use of Hyperimmune Plasma


The observation that R. equi pneumonia typically coincides with the decline in maternal antibodies suggests that antibodies play a protective role and is the basis for administering hyperimmune plasma.128,129 The goal of specific hyperimmune plasma is to provide the foal with a broad spectrum of specific anti-R. equi antibodies, and perhaps other immunomodulators, to enhance the humoral re-


sponse to infection. Use of hyperimmune plasma for prevention of R. equi pneumonia has shown in- consistent results. A reduction in foal morbidity and mortality has been reported by some au- thors128,130–134; however, other studies have de- scribed hyperimmune plasma as unsuccessful in preventing R. equi disease.135–137 The mechanism by which hyperimmune plasma


may have a protective effect is unknown. Purified immunoglobulin specific for VapA and VapC gave similar protection against R. equi disease as com- mercially available hyperimmune plasma suggest- ing a primary protective role for antibodies against R. equi VapA and VapC.133 However, there ap- pears to be no correlation between total serum IgG concentrations and the concentration of specific anti-R. equi antibody, and colostrum-derived R. equi antibody is not as protective as R. equi antibodies provided by hyperimmune plasma.128,138 Hyper- immune plasma may provide other, unknown, non- specific immune factors that are absent from colostrum, such as fibronectin, complement, and cytokines.128 The effectiveness of hyperimmune plasma is likely


to be affected by the dose, timing of administration, innate immune system competence, management conditions, and number of virulent bacteria in the environment.127 Plasma containing low quantity and/or quality of specific anti-R. equi antibodies, such as against VapA and VapC, is unlikely to be efficacious. Use of a vaccine strain genetically dif- ferent to field strains or inappropriate donor vaccine dose and adjuvant are just two possible causes of such plasma. Environmental management of contamination is


also important in prevention of disease and should be used in conjunction with immunoprophylaxis. Infected foals are a major source of contamination, shedding up to 106 CFU of virulent R. equi/gram of feces.139 Additionally healthy foals and mares may excrete up to 105 R. equi/gram of feces.140,141 The removal of infected manure alone, without other preventative measures, has failed to reduce R. equi disease on an Australian farm.142 Aerosol trans- mission between foals from the respiratory tract has also recently been suggested as another means of disease transmission in the field.143 It is unknown if administration of hyperimmune plasma reduces bacterial shedding from infected foals via the respi- ratory or gastrointestinal tract.


8. Studies in Transitions of Neonatal Consciousness: Why Foals Do Not Gallop In Utero


Gumshoe Sleuthing


Since starting our neonatal critical care unit at UC Davis in the late 1980s, we have treated many of what is termed the “dummy foal.” Many different names for this condition have been proposed, all revolving around the assumption that the cause is low oxygen or poor perfusion; Hypoxic Ischemic En-


AAEP PROCEEDINGS  Vol. 60  2014 121


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