Clinical manifestations, diagnosis, treatment, and prevention of Rhodococcus equi infections in foals

Giguère, Steeve; Prescott, John F.

doi:10.1016/s0378-1135(97)00099-0

Cited by 209 publications

(278 citation statements)

References 56 publications

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“…R. equi is a common soil organism, which frequently infects young horses (3), where similar pulmonary involvement, including abscess formation and cavitary pneumonia are most frequently observed (4). Virtually all isolates obtained from diseased animals, and a subset of R. equi isolated from infected people express virulence-associated protein A (VapA), 4 a surface-localized lipoprotein, the presence of which appears to be essential for intramacrophage replication (5). Infections in either humans or young horses can result in tissue damage and occasionally reduced lung function (6).…”

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Innate Immune Responses to Rhodococcus equi

Darrah

Monaco

Jain

et al. 2004

The Journal of Immunology

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We examined innate immune responses to the intracellular bacterium Rhodococcus equi and show that infection of macrophages with intact bacteria induced the rapid translocation of NF-κB and the production of a variety of proinflammatory mediators, including TNF, IL-12, and NO. Macrophages from mice deficient in MyD88 failed to translocate NF-KB and produced virtually no cytokines in response to R. equi infection, implicating a TLR pathway. TLR4 was not involved in this response, because C3H/HeJ macrophages were fully capable of responding to R. equi infection, and because RAW-264 cells transfected with a dominant negative form of TLR4 responded normally to infection by R. equi. A central role for TLR2 was identified. A TLR2 reporter cell was activated by R. equi, and RAW-264 cells transfected with a dominant negative TLR2 exhibited markedly reduced cytokine responses to R. equi. Moreover, macrophages from TLR2−/− mice exhibited diminished cytokine responses to R. equi. The role of the surface-localized R. equi lipoprotein VapA (virulence-associated protein A), in TLR2 activation was examined. Purified rVapA activated a TLR2-specific reporter cell, and it induced the maturation of dendritic cells and the production of cytokines from macrophages. Importantly, TLR2−/−-deficient but not TLR4−/−-deficient mice were found to be compromised in their ability to clear a challenge with virulent R. equi. We conclude that the efficient activation of innate immunity by R. equi may account for the relative lack of virulence of this organism in immunocompetent adults.

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Innate Immune Responses to Rhodococcus equi

Darrah

Monaco

Jain

et al. 2004

The Journal of Immunology

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“…Like in foals, human R. equi infection mainly affects the lungs, with clinical and pathological characteristics similar to pulmonary tuberculosis in immunocompromised patients. Although rare, granulomatous pneumonia, lymphadenitis, and abscesses caused by R. equi have been reported in a variety of mammals other than horses and humans (11,17,32,40).…”

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Identification and Mutagenesis by Allelic Exchange ofchoE, Encoding a Cholesterol Oxidase from the Intracellular PathogenRhodococcus equi

et al. 2001

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The virulence mechanisms of the facultative intracellular parasite Rhodococcus equi remain largely unknown. Among the candidate virulence factors of this pathogenic actinomycete is a secreted cholesterol oxidase, a putative membrane-damaging toxin. We identified and characterized the gene encoding this enzyme, the choE monocistron. Its protein product, ChoE, is homologous to other secreted cholesterol oxidases identified in Brevibacterium sterolicum and Streptomyces spp. ChoE also exhibits significant similarities to putative cholesterol oxidases encoded by Mycobacterium tuberculosis and Mycobacterium leprae. Genetic tools for use with R. equi are poorly developed. Here we describe the first targeted mutagenesis system available for this bacterium. It is based on a suicide plasmid, a selectable marker (the aacC4 apramycin resistance gene from Salmonella), and homologous recombination. The choE allele was disrupted by insertion of the aacC4 gene, cloned in pUC19 and introduced by electroporation in R. equi. choE recombinants were isolated at frequencies between 10 ؊2 and 10 ؊3 . Twelve percent of the recombinants were double-crossover choE mutants. The choE mutation was associated with loss of cooperative (CAMP-like) hemolysis with sphingomyelinase-producing bacteria (Listeria ivanovii). Functional complementation was achieved by expression of choE from pVK173-T, a pAL5000 derivative conferring hygromycin resistance. Our data demonstrate that ChoE is an important cytolytic factor for R. equi. The highly efficient targeted mutagenesis procedure that we used to generate choE isogenic mutants will be a valuable tool for the molecular analysis of R. equi virulence.

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“…Der Zeitpunkt zu dem HIP verabreicht werden soll, um den bestmöglichen Schutz zu gewähren, ist unbekannt. Empfohlen wird eine Transfusion vor der ersten R. equi-Exposition (Martens et al 1992) und eine zweite im Alter von etwa einem Monat (Giguère und Prescott 1997, Giguère et al 2002, Perkins et al 2002.…”

Section: Hyperimmunplasma Und Andere Ak-produkteunclassified

Prophylaxis of Rhodococcus equi pneumonia in foals – a review of literature

Schmitz¹,

Block²,

Lämmer³

et al. 2013

PHK

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ZusammenfassungRhodococcus equi (R. equi ) ist ein Bakterium, welches weltweit häufig chronisch verlaufende, abszedierende Bronchopneumonien bei Fohlen im Alter bis sechs Monaten verursacht. Im Gegensatz zu Fohlen entwickeln erwachsene Pferde nur äußerst selten eine Erkrankung durch eine Infektion durch R. equi. Dies liegt daran, dass die Th1-Immunantwort bei Adulten ausgeprägter ist als in der Neugeborenenphase und somit der intrazelluläre Keim auch in den Makrophagen abgetötet wird. Versuche, die Mutterstuten zu impfen haben zwar dazu geführt, dass hohe Konzentrationen an spezifischen Antikörper über das Kolostrum erfolgreich dem Fohlen übertragen wurden, aber die Erkrankungsrate wurde bei den Fohlen auf endemisch betroffenen Betrieben keinesfalls reduziert. Auch die Verabreichung von spezifischem Hyperimmunplasma bewirkt keinen Schutz der Fohlen vor der R. equi-Pneumonie. Diese enttäuschenden Ergebnisse lassen sich dadurch erklä-ren, dass bei einer Infektion der Fohlen mit R. equi die humorale Immunantwort mit spezifischen Antikörpern selbst in hohen Konzentrationen die Tiere nicht vor einer Erkrankung schützt. Es gibt Hinweise dafür, dass die Infektion durch R. equi vielmehr durch Mechanismen der zellulären Immunantwort abgewehrt wird. Weitere Ansätze zur Vorbeugung der R. equi-Pneumonie wie die prophylaktische Verabreichung von Antibiotika bei jungen Fohlen wurden in Erwägung gezogen und geprüft. Insgesamt erwies sich die Behandlung der Fohlen mit Antibiotika in den ersten Lebenswochen nicht als geeignet, um der R. equi-Erkrankung vorzubeugen. Bedauerlicherweise sind die bisherigen Anstrengungen, einen Impfstoff für Fohlen zu entwickeln, erfolglos geblieben. Erste Untersuchungen zeigen, dass Lebendimpfstoffe die Th1-Immunantwort bei Fohlen stimulieren und die Fohlen bei experimenteller Infektion mit R. equi-Bakterien vor der Erkrankung schützen. Allerdings liegen bisher keine Ergebnisse von Feldstudien über die Wirksamkeit von Lebendimpfstoffen zur Vorbeugung der R. equi-Pneumonie bei Fohlen vor. Schlüsselwörter: Rhodococcus equi / Fohlen / Vorbeugung / Literaturübersicht / Infektiologie / MikrobiologieProphylaxis of Rhodococcus equi pneumonia in foals -a review of literature Rhodococcus equi (R. equi) is a bacterium that causes sporadically and endemically chronic abscess-forming bronchopneumonia in foals under the age of six months. Adult horses in contrast to foals, usually successfully overcome the infection by R. equi. This is due to the effective Th1 immune response, which is more pronounced in adults than in the neonatal period and leads to the destruction of the intracellular pathogens. Attempts to vaccinate mares have actually led to high concentrations of specific antibodies transferred successfully via the colostrum to the foals, but the rate of R. equi pneumonia in foals on endemic farms was not reduced. The administration of specific hyperimmune plasma is not effective for the prevention of R. equi pneumonia either. These disappointing results can be explained by the fact that antibodies alone ...

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Clinical manifestations, diagnosis, treatment, and prevention of Rhodococcus equi infections in foals

Cited by 209 publications

References 56 publications

Innate Immune Responses to Rhodococcus equi

Innate Immune Responses to Rhodococcus equi

Identification and Mutagenesis by Allelic Exchange ofchoE, Encoding a Cholesterol Oxidase from the Intracellular PathogenRhodococcus equi

Prophylaxis of Rhodococcus equi pneumonia in foals – a review of literature

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