EISEVIER Veterinary Microbiology 56 (1997) 163- 165

veterinary microbiology

Preface

An overview of the Havemeyer Foundation Workshop on ‘Rhodococcus equi and neonatal immunology of the foal’

Against the backdrop of superb summer days in Ontario, the Workshop brought together scientists with an interesting mixture of backgrounds for two days of intense and rewarding discussions, and agreements between individuals for future collabora- tions.

The discovery of the virulence plasmid in foal and pig isolates of R. equi, the increasing frequency of R. equi infection in human patients with AIDS, the increasing understanding and importance of intracellular infections which also relates to the emergence of AIDS, and the ThlTh2 paradigm in immunity in the mouse and human, have all contributed to making R. equi of increased interest in infectious disease and immunology. In addition, the effective control of enzootic R. equi pneumonia of horse breeding farms by the administration to foals of hyperimmune plasma, as well as the expense of antibiotic treatment and the increasing antibiotic resistance being recognized, has focused interest in defining the active principle in the plasma.

No attempt was made to reach consensus on issues relating to rhodococcal infections in foals but a number of themes where further work or clarification is needed merged from the discussion; some are discussed in the overviews published in this issue.

Firstly, R. equi pneumonia in foals on enzootically affected farms is being controlled effectively by administration of hyperimmune plasma from donor horses immunized with R. equi antigens. This is often administered at both 2-3 and 21-25 days of age, or only once at 21-25 days of age in foals of mares immunized with these antigens. It seems generally accepted that the active principle is immunoglobulin against one or more antigens of R. equi, perhaps including VapA (and work by Becu and Femandez described in this issue supports this). However, the Workshop was adamant that this ‘dogma’ has in fact not been, but needs to be, unequivocally demonstrated with appropriate evidence. For example the description by Bror Morein at the Workshop that R. equi pneumonia has been successfully controlled in farms in Hungary by immuniza- tion against equine herpesvirus 2 (Vet. Microbial. 1996; 51:55-68) argues that the efficacy of hyperimmune plasma might be the result of antibody to EHV2. This central point of the effective factor in hyperimmune plasma needs to be clarified.

A second theme that emerged from the Workshop was that, although considerable

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advances had been made in understanding the cellular basis of immunity to R. equi in mice, and mice genetically defective in various components of the innate immune system were being used to identify different elements responsible for immunity to R. equi, mice are not foals. The Thl and Th2 paradigm of immunity in mice needs to be validated in the foal. Indeed, R. equi may be an ideal model with which to validate the paradigm. Surprisingly, no clear model of the basis of the peculiar susceptibility of foals to R. equi infection emerged from the Workshop. It may be, as Hondalus and Mosser’s work suggests, as simple as homing by virulent R. equi into macrophages through the Mac1 complement receptor rather than through the Fc receptor, in the absence of antibody, or may be considerably more complex. Work in immunologically defective mice may help establish a working model explaining the susceptibility of foals, but also may be totally irrelevant to the foal.

Understanding of the basis of virulence of R. equi is still poor. The fact that isolates in AIDS patients are often not of the foal or pig virulent type shows that virulence is considerably more complex than just VapA and related proteins. Iain Sutcliffe’s article on the likely structure and components of the outer envelope of the organism may be highly relevant in this regard. As Mary Hondalus pointed out, there is also a need to define the role of some of the several additional putative virulence factors, such as the cholesterol oxidase, by fulfilling Falkow’s molecular Koch’s postulates. The virulence plasmid of foal isolates needs to be entirely sequenced to better understand its function and that of those isolated from intermediately virulent strains. There is fertile ground for interaction between medical workers interested in understanding the pathogenesis of the infection in AIDS patients and veterinary workers interested in understanding virulence of the organism in foals, although the foal does not seem to be a model for AIDS related R. equi pneumonia.

Resistance to erythromycin and rifampin is increasing, so that there is urgency not only in improving immunization and in understanding its basis, but also in finding alternative antibiotic (or possibly cytokine) treatments. There is still disagreement about optimal dosing and dosage forms of erythromycin; this should be clarified. Vancomycin and imipenem have become the mainstays of antimicrobial treatment in human patients with R. equi pneumonia. Clinicians might explore the application and pharmacokinetic behaviour of these drugs, perhaps as initial short term therapies, in foals with R. equi pneumonia, as well as the value, use and safety of enrofloxacin for the same purpose. A problem of colitis in the mares of foals administered erythromycin was highlighted as another reason to move from antimicrobial drug treatment to effective immunization techniques.

The problem of R. equi pneumonia in foals relates to build up of virulent bacteria on farms used for rearing foals. We have little information of what, if anything, might be practically done to decontaminate heavily infected paddocks. There is potentially fruitful work to be done in this area.

The organizers are grateful to the Havemeyer Foundation for its support of the Workshop, in particular Gene Pranzo its President, and Doug Antczak, its Scientific Director. We are grateful to the Chairs of the different sessions (Steeve Giguere, Stephen Hines, Mark Holmes, Mary Hondalus, Patrice Nordmann, Shinji Takai), the equine immunologists Paul Lunn and David Horohov, and the many participants for

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making it an enjoyable and productive Workshop. We thank the Conferences Office of the University of Guelph, who smoothed many of the organizational aspects, and Robert Rinfret for help before and during the Workshop.

John Prescott Mark Holmes

Julie Yager Shinji Takal