Rhodococcus equi is a bacterial pathogen that primarily affects foals, leading to pneumonia and other systemic infections. It is a significant concern in equine health due to its impact on the respiratory system of young horses. The bacterium is found in soil and can be inhaled by foals, leading to infection. Clinical signs of Rhodococcus equi infection in foals include coughing, fever, and respiratory distress. Diagnosis is typically confirmed through bacterial culture or polymerase chain reaction (PCR) testing. Management of the disease involves antimicrobial therapy and supportive care. This page compiles peer-reviewed research studies and scholarly articles that explore the pathogenesis, diagnosis, treatment, and prevention of Rhodococcus equi infections in horses.
Petry S, Sévin C, Kozak S, Foucher N, Laugier C, Linster M, Breuil MF, Dupuis MC, Hans A, Duquesne F, Tapprest J.Study of the rifampicin resistance of Rhodococcus equi strains isolated from French horses over a 20-year period. Rifampicin susceptibility was tested by disk diffusion (DD) and broth macrodilution methods, and rpoB gene sequencing and MLST were performed on 40 R. equi strains, 50.0% of which were non-susceptible to rifampicin. Consistency of results was observed between rifampicin susceptibility testing and rpoB sequencing. Strains non-susceptible to rifampicin by DD had a substitution at one of the sites (Asp516, His526 and Ser531) frequently encountered and conferring rifampicin resistance....
Bianchi MV, Mello LS, Ribeiro PR, Wentz MF, Stolf AS, Lopes BC, de Andrade CP, Snel GGM, Sonne L, Driemeier D, Pavarini SP.We document the causes and pathological findings in 50 cases of equine pneumonia and pleuritis in Southern Brazil. Suppurative (17/50), pyogranulomatous (14/50), aspiration (5/50), mycotic (4/50), bronchointerstitial (3/50), embolic (3/50) and eosinophilic granulomatous pneumonia (1/50) and pleuritis (3/50) were the main conditions identified. Streptococcus spp. were identified in 11 cases of suppurative pneumonia. Suppurative pneumonia was further divided into acute (8/17), subacute (6/17) and chronic (3/17) based on the morphological pattern of lesions. Rhodococcus equi was identified in all...
Kalinowski M, Jarosz Ł, Grądzki Z.Rhodococcus equi is an opportunistic, intracellular saprophyte that causes severe pyogranulomatous pneumonia in foals. The bacterium displays in vitro susceptibility to many antibiotics. The highest efficacy against R. equi in vitro and in vivo is achieved by using a combination of rifampicin and macrolide antibiotics. Recent years have seen an upward trend in the minimum inhibitory concentration (MIC) of rifampicin and erythromycin, suggesting increasing resistance of R. equi to these antibiotics. The aim of the study was to determine the antimicrobial activity of 24 selected antibiotics...
Huber L, Giguère S, Slovis NM, Álvarez-Narváez S, Hart KA, Greiter M, Morris ERA, Cohen ND.The use of mass antimicrobial treatment has been linked to the emergence of antimicrobial resistance in human and animal pathogens. Using whole-genome single-molecule real-time (SMRT) sequencing, we characterized genomic variability of multidrug-resistant Rhodococcus equi isolated from soil samples from 100 farms endemic for R. equi infections in Kentucky. We discovered the novel erm(51)-encoding resistance to MLS in R. equi isolates from soil of horse-breeding farms. Erm(51) is inserted in a transposon (TnErm51) that is associated with a putative conjugative plasmid (pRErm51), a mobilizable p...
Álvarez-Narváez S, Giguère S, Berghaus LJ, Dailey C, Vázquez-Boland JA.Conjugation is one of the main mechanisms involved in the spread and maintenance of antibiotic resistance in bacterial populations. We recently showed that the emerging macrolide resistance in the soilborne equine and zoonotic pathogen is conferred by the (46) gene carried on the 87-kb conjugative plasmid pRErm46. Here, we investigated the conjugal transferability of pRErm46 to 14 representative bacteria likely encountered by in the environmental habitat. mating experiments demonstrated conjugation to different members of the genus as well as to and spp. at frequencies ranging from ∼10...
Arnold-Lehna D, Venner M, Berghaus LJ, Berghaus R, Giguère S.There is a lack of data on the efficacy of treatment of Rhodococcus equi pneumonia in association with an optimised selection of foals. Objective: To evaluate whether targeted treatment protocols resulting in decreased antimicrobial use impact foal mortality rates. Methods: Retrospective study. Methods: Three hundred and thirty foals with pneumonia per year were randomly selected from 2008 to 2016. All foals were examined once weekly from birth until weaning. A physical examination of the respiratory tract, body temperature, haematology and an ultrasonographic examination of the lungs was incl...
Wetzig M, Venner M, Giguère S.Given the importance of rifampin in treatment protocols for tuberculosis in people, its use in veterinary medicine is under increasing scrutiny in some countries and alternatives might be needed in the near future. Objective: This study was set up to evaluate whether azithromycin combined with doxycycline is effective for the treatment of bronchopneumonia in foals and noninferior to the combination of azithromycin and rifampin. Methods: This is a controlled, randomised and double-blinded clinical trial. Two hundred and forty foals on a farm endemic for infections caused by Rhodococcus equi wer...
Álvarez-Narváez S, Berghaus LJ, Morris ERA, Willingham-Lane JM, Slovis NM, Giguere S, Cohen ND.The practice of prophylactic administration of a macrolide antimicrobial with rifampin (MaR) to apparently healthy foals with pulmonary lesions identified by thoracic ultrasonography (i.e., subclinically pneumonic foals) is common in the United States. The practice has been associated epidemiologically with emergence of R. equi resistant to MaR. Here, we report direct evidence of multi-drug resistance among foals treated with MaR. In silico and in vitro analysis of the fecal microbiome and resistome of 38 subclinically pneumonic foals treated with either MaR (n = 19) or gallium maltolate (...
Ruocco NA, Luedke LK, Fortier LA, Ducharme NG, Reesink HL.The most common pathologic manifestation of , a gram-positive, facultative intracellular bacterium, is pyogranulomatous pneumonia in foals and weanlings. Hematogenous spread of bacteria may subsequently occur, resulting in joint sepsis, osteomyelitis, or subcutaneous abscessation. Medical records from horses presenting to the Cornell University Equine Hospital from 1998 to 2018 were reviewed for cases diagnosed with joint and/or bone infection, and information about case progression and outcome were analyzed. We hypothesized that, despite advances in diagnostic imaging, antimicrobials and ant...
Erol E, Locke S, Saied A, Cruz Penn MJ, Smith J, Fortner J, Carter C.Mainstay therapy for rhodococcosis in foals is the combination of rifampicin and a macrolide. While emergence of resistance to rifampicin and macrolides has been reported, studies demonstrating the development of resistance to such drugs is limited in necropsied foals with rhodococcosis. In this study, the foal necropsy records between 01/01/2011 and 08/30/2019 were reviewed for culture-positive R. equi with MICs and, whether or not the affected foals received any mainstay dual therapy before their deaths. Resistance to antimicrobials in the R. equi isolates from necropsied foals were then com...
Álvarez-Narváez S, Logue CM, Barbieri NL, Berghaus LJ, Giguère S.Rhodococcus equi (R. equi) infections are endemic in many horse facilities in the United States resulting significant economic loses annually. Currently, there is no commercial vaccine available and the emergence of isolates that are resistant to the current treatment and prophylaxis using antibiotics prompts closer surveillance of this pathogen. Objective: This study compares three different genotyping techniques, Pulsed Field Gel Electrophoresis (PFGE), Multilocus Sequence Typing (MLST) and whole genome SNP-based phylogeny to determine the most accurate method to monitor the spread of macrol...
da Silveira BP, Gressler LT, Cargnelutti JF, Bordin AI, de Vargas AC.The ability of Rhodococcus equi to survive in macrophages and cause pneumonia in foals depends on vapA and rhbC genes, which produce the virulence-associated protein A (VapA) and the rhequichelin siderophore, respectively. Virulent R. equi acquires Fe from transferrin by unknown mechanisms. Our objectives were to determine the role of GAPDH in Fe homeostasis, to further characterize GAPDH, rhbC, and vapA expression under iron homeostasis, and to document the occurrence of rhbC gene in R. equi isolates. Therefore, vapA + R. equi was cultured under excessive, physiologic, and restricted iron c...
Álvarez-Narváez S, Giguère S, Anastasi E, Hearn J, Scortti M, Vázquez-Boland JA.Antibiotic use has been linked to changes in the population structure of human pathogens and the clonal expansion of multidrug-resistant (MDR) strains among healthcare- and community-acquired infections. Here we present a compelling example in a veterinary pathogen, , the causative agent of a severe pulmonary infection affecting foals worldwide. We show that the (46) gene responsible for emerging macrolide resistance among equine isolates in the United States is part of a 6.9-kb transposable element, Tn, actively mobilized by an IS family transposase. Tn is carried on an 87-kb conjugative pla...
Willingham-Lane JM, Berghaus LJ, Berghaus RD, Hart KA, Giguère S.The soil-dwelling, saprophytic actinomycete is a facultative intracellular pathogen of macrophages and causes severe bronchopneumonia when inhaled by susceptible foals. Standard treatment for disease is dual-antimicrobial therapy with a macrolide and rifampin. Thoracic ultrasonography and early treatment with antimicrobials prior to the development of clinical signs are used as means of controlling endemic infection on many farms. Concurrently with the increased use of macrolides and rifampin for chemoprophylaxis and the treatment of subclinically affected foals, a significant increase in t...
Saied AA, Bryan LK, Bolin DC. infection in horses is common and is characterized by pyogranulomatous pneumonia and ulcerative enterocolitis. clinical disease in cattle, however, is rare and typically manifests as granulomatous lymphadenitis discovered in the abattoir. A 19-mo-old female Santa Gertrudis had a history of intermittent inappetence and weight loss for a 3-mo period before euthanasia. Gross and histologic examination revealed severe, chronic, ulcerative, and granulomatous inflammation in the tongue, pharynx, and small intestine. Also, the heifer had severe, granulomatous pharyngeal and mesenteric lymphadenitis...
Huber L, Giguère S, Cohen ND, Slovis NM, Hanafi A, Schuckert A, Berghaus L, Greiter M, Hart KA.The combination of a macrolide and rifampicin has been the mainstay of therapy in foals with Rhodococcus equi pneumonia for decades. Recent studies suggest that mass antimicrobial treatment of subclinically affected foals over time has selected for antimicrobial resistance. Our objective was to estimate the prevalence of R. equi strains resistant to macrolides and rifampicin at horse breeding farms in Kentucky. A hundred breeding farms in Kentucky were surveyed and R. equi were cultured from soil samples. Data were analyzed with logistic regression and generalized linear modeling (P < 0...
Vázquez-Boland JA, Meijer WG.Rhodococcus equi is the only recognized animal pathogenic species within an extended genus of metabolically versatile Actinobacteria of considerable biotechnological interest. Best known as a horse pathogen, R. equi is commonly isolated from other animal species, particularly pigs and ruminants, and causes severe opportunistic infections in people. As typical in the rhodococci, R. equi niche specialization is extrachromosomally determined, via a conjugative virulence plasmid that promotes intramacrophage survival. Progress in the molecular understanding of R. equi and its recent rise as a nove...
Kahn SK, Blodgett GP, Canaday NM, Bevevino KE, Rocha JN, Bordin AI, Cohen ND.Transfusing foals with Rhodococcus equi hyperimmune plasma (REHIP) is a standard practice at many horse-breeding farms to help prevent R. equi pneumonia. At many large breeding farms, pneumonia is most commonly recognized as subclinical based on thoracic ultrasonography findings. The efficacy of REHIP transfusion and the impact of the volume of plasma transfused for reducing the cumulative incidence of subclinical R. equi pneumonia are unknown. A retrospective cohort study was conducted among foals born and residing through weaning at a large breeding farm. Foals were transfused with either ...
Vitale V, Sgorbini M, Cuteri V, Preziuso S, Attili AR, Bonelli F.The distinction between lower respiratory tract infections caused by Rhodococcus equi and those caused by other pathogens is difficult. The aim of this retrospective study was to describe cytological findings in bronchoalveolar lavage fluid (BALF) of foals with pneumonia caused by R. equi or other bacteria. Nineteen foals aged from 3 weeks to 6 months with evidence of respiratory disease between 2015 and 2016 were selected from the database of the Veterinary Teaching Hospital "Mario Modenato" of the University of Pisa. Eight foals of 19 (42.1%) had R. equi pneumonia, whereas 11 of 19 (57.9...
Folmar CN, Cywes-Bentley C, Bordin AI, Rocha JN, Bray JM, Kahn SK, Schuckert AE, Pier GB, Cohen ND.The bacterium Rhodococcus equi can cause severe pneumonia in foals. The absence of a licensed vaccine and limited effectiveness of commercial R. equi hyperimmune plasma (RE-HIP) create a great need for improved prevention of this disease. Objective: Plasma hyperimmune to the capsular polysaccharide poly-N-acetyl glucosamine (PNAG) would be significantly more effective than RE-HIP at mediating complement deposition and opsonophagocytic killing (OPK) of R. equi. Methods: Venipuncture was performed on 9 Quarter Horses. Methods: The ability of the following plasma sources to mediate complement com...
Sanz MG, Bradway DS, Horohov DW, Baszler TV. is the most common cause of pneumonia in young foals. Pneumonic foals are an important source of environmental contamination as they shed higher amounts of in their faeces than unaffected foals. As -specific hyperimmune plasma (HIP) lessens clinical pneumonia, we hypothesise that its use would result in decreased faecal shedding of by foals. Neonatal foals were either given HIP (n=12) or nothing (n=9, control) shortly after birth and were then experimentally infected with Faeces were collected before and on weeks 2, 3, 5 and 7 after infection. Presence of virulent was tested using qPCR. T...
Huber L, Giguère S, Cohen ND, Slovis NM, Berghaus L, Greiter M, Hart KA.Rhodococcus equi causes severe pneumonia in foals and is most often recognized in people as an opportunistic pathogen. Longitudinal studies examining antimicrobial-resistant R. equi from environmental samples are lacking. We hypothesized that antimicrobial-resistant R. equi would be detectable in the ground (pasture soil or stall bedding) and air at breeding farms with previous documentation of foals infected with resistant isolates, and that concentrations of resistant isolates would increase over time during the foaling season. In this prospective cohort study, ground and air samples were co...
Willingham-Lane JM, Berghaus LJ, Berghaus RD, Hart KA, Giguère S. is a leading cause of severe pneumonia in foals. Standard treatment is dual antimicrobial therapy with a macrolide and rifampin, but the emergence of macrolide- and rifampin-resistant isolates is an increasing problem. The objective of this study was to determine the effect of macrolide and/or rifampin resistance on fitness of Three unique isogenic sets were created, each consisting of four strains, as follows: a susceptible parent isolate, strains resistant to macrolides or rifampin, and a dual macrolide- and rifampin-resistant strain. Each isogenic set's bacterial growth curve was genera...
Duchesne R, Castagnet S, Maillard K, Petry S, Cattoir V, Giard JC, Leon A.This study aimed to analyse antimicrobial susceptibility evolution of equine pathogens isolated from clinical samples from 2006-2016. A collection of 25 813 bacterial isolates was studied, clustered according to their origins (respiratory tract, cutaneous, genital and other), and analysed for their antimicrobial susceptibility using the disk diffusion method. The most frequently isolated pathogens were group C Streptococci (27.6%), Escherichia coli (20.0%), Staphylococcus aureus (7.8%), Pseudomonas aeruginosa (4.0%), Enterobacter spp. (3.4%), Klebsiella pneumoniae (2.4%), and Rhodococcus equi ...
Tarancón I, Leiva M, Jose-Cunilleras E, Ríos J, Peña T.To describe ocular findings associated with Rhodococcus equi bronchopneumonia in foals, and to determine whether severity of the ocular lesions is related with outcome. Methods: Foals diagnosed with R equi infection at the VTH-UAB from January 2002 to December 2017. Methods: Rhodococcus equi infection was diagnosed by means of clinical signs, radiographic/ultrasonographic findings, and/or positive culture. In all the foals, a complete ophthalmic examination by a boarded ophthalmologist was performed and ocular signs were recorded and graded (0-4). Results: Thirty-nine foals were included in t...
Huber L, Giguère S, Slovis NM, Carter CN, Barr BS, Cohen ND, Elam J, Erol E, Locke SJ, Phillips ED, Smith JL.The objective of this study was to determine the prevalence of strains resistant to macrolides and rifampin over time in clinical samples from foals submitted to diagnostic laboratories in central Kentucky. We performed a retrospective observational study of all clinical samples from foals that were submitted to veterinary diagnostic laboratories in Kentucky between January 1995 and December 2017. Samples were included if the bacterium was cultured and tested for susceptibility to erythromycin or rifampin. susceptibility testing to erythromycin was available for 2,169 isolates of , while s...
Coleman MC, Blodgett GP, Bevevino KE, Ivanek R, Cummings KJ, Carter GK, Cohen ND.The occurrence of Rhodococcus equi at farms varies, with disease occurring endemically at some farms, but only sporadically, or not at all at other farms. Only some foals residing on endemic farms develop clinical signs of disease. Limited evidence is available regarding foal-level risk factors for the development of R. equi pneumonia. The purpose of this study was to identify foal-level risk factors associated with the development of R. equi pneumonia among foals at a large breeding farm in Texas with a recurrent problem of R. equi pneumonia. A retrospective cohort study was conducted usin...
Willingham-Lane JM, Coulson GB, Hondalus MK.Rhodococcus equi is a facultative intracellular bacterium of macrophages and is an important pathogen of animals and immunocompromised people wherein disease results in abcessation of the lungs and other sites. Prior work has shown that the presence of the major virulence determinant, VapA, encoded on the pVAPA-type plasmid, disrupts normal phagosome development and is essential for bacterial replication within macrophages. pVAPA- type plasmids are typical of R. equi strains derived from foals while strains from pigs carry plasmids of the pVAPB-type, lacking vapA, and those from humans harbor ...
Kalinowski M, Grądzki Z, Jarosz Ł, Adaszek Ł.Rhodococcus equi (R. hoagii) is an opportunistic pathogen commonly found in foals up to 6 months old and animal environment. The R. equi genome contains genetically stable chromosomal DNA and an 80-90 kb plasmid containing vapA gene, responsible for virulence. Most reports from around the world focus on the determination of R. equi plasmid profiles. Few studies have attempted to determine differences in nucleotide sequences between virulent strains of R. equi isolated from foals and breeding environment. The aim of the study was to perform a molecular analysis of a fragment of the chromosomal ...
Cohen ND, Carter CN, Scott HM, Chaffin MK, Smith JL, Grimm MB, Kuskie KR, Takai S, Martens RJ.To determine whether soil concentrations of total or virulent Rhodococcus equi differed among breeding farms with and without foals with pneumonia caused by R equi. Methods: 37 farms in central Kentucky. Procedures-During January, March, and July 2006, the total concentration of R equi and concentration of virulent R equi were determined by use of quantitative bacteriologic culture and a colony immunoblot technique, respectively, in soil specimens obtained from farms. Differences in concentrations and proportion of virulent isolates within and among time points were compared among farms. Resul...
Cauchard S, Bermúdez-Humarán LG, Blugeon S, Laugier C, Langella P, Cauchard J.Rhodococcus equi causes severe pneumonia in foals and has recently gained attention as a significant opportunistic pathogen in immunocompromised humans. However, no effective vaccine to prevent rhodococcosis is currently available. In this study, we have engineered the food-grade bacterium Lactococcus lactis to secrete the virulence-associated protein A from R. equi (LL-VapA). The immunogenic potential of LL-VapA strain was then evaluated after either intragastric or intranasal immunization in mice either alone or in combination with LL-Lep, a recombinant strain of L. lactis secreting biologic...
Hooper-McGrevy KE, Wilkie BN, Prescott JF.The purpose of this study was to determine whether foals immunized orally from 2 days of age with virulent Rhodococcus equi developed a protective pulmonary immune response and to characterise the antibody response of the immunized foals to the virulence-associated proteins (Vaps) of the bacterium. Two groups of foals were used. One (n=4) was given live R. equi ATCC 33701 orally at 2, 7, and 14 days of age. The second group comprised three non-immunized foals age-matched to the vaccinates. At 3 weeks of age, 1 week after the final immunization, both groups were challenged intrabronchially with...
Anastasi E, Giguère S, Berghaus LJ, Hondalus MK, Willingham-Lane JM, MacArthur I, Cohen ND, Roberts MC, Vazquez-Boland JA.The objective of this study was to identify the molecular mechanism of macrolide resistance in the actinomycete Rhodococcus equi, a major equine pathogen and zoonotic agent causing opportunistic infections in people. Methods: Macrolide-resistant (n = 62) and macrolide-susceptible (n = 62) clinical isolates of R. equi from foals in the USA were studied. WGS of 18 macrolide-resistant and 6 macrolide-susceptible R. equi was performed. Representative sequences of all known macrolide resistance genes identified to date were used to search the genome assemblies for putative homologues. PCR w...
Adler DMT, Damborg P, Verwilghen DR.Lameness is the most commonly reported health problem in horses, and lameness investigations which include local anaesthetic injections are routinely performed by equine practitioners. Through this process, bacteria can enter the tissues perforated by the needle and may cause local infections at the injection site. The objective of this in vitro study was to investigate if local anaesthetics at concentrations available in commercially available solutions could inhibit growth and/or kill bacteria that could be inoculated into the synovial space or soft tissues during injection. This study evalu...
Madigan JE, Hietala S, Muller N.A 2-year field study was performed to determine the capability of increasing Rhodococcus equi specific antibody in foals via plasma transfusion or mare vaccination, to determine the kinetics of R. equi (ELISA) antibody decay and to assess the protective effects of these procedures in foals on a farm endemic for R. equi. Plasma donors were vaccinated with a killed R. equi bacterin and produced high levels of anti-R. equi antibodies, which were harvested by plasmapheresis. In Experiment 1, 68 foals were given 1 litre of hyperimmune plasma intravenously (i.v.) between 1-60 days of age. Foal plasm...
Huber L, Giguère S, Cohen ND, Slovis NM, Hanafi A, Schuckert A, Berghaus L, Greiter M, Hart KA.The combination of a macrolide and rifampicin has been the mainstay of therapy in foals with Rhodococcus equi pneumonia for decades. Recent studies suggest that mass antimicrobial treatment of subclinically affected foals over time has selected for antimicrobial resistance. Our objective was to estimate the prevalence of R. equi strains resistant to macrolides and rifampicin at horse breeding farms in Kentucky. A hundred breeding farms in Kentucky were surveyed and R. equi were cultured from soil samples. Data were analyzed with logistic regression and generalized linear modeling (P < 0...
Ferraz LC, Bernardes ES, Oliveira AF, Ruas LP, Fermino ML, Soares SG, Loyola AM, Oliver C, Jamur MC, Hsu DK, Liu FT, Chammas R, Roque-Barreira MC.Galectin-3 is a beta-galactoside-binding lectin implicated in the fine-tuning of innate immunity. Rhodococcus equi, a facultative intracellular bacterium of macrophages, causes severe granulomatous bronchopneumonia in young horses and immunocompromised humans. The aim of this study is to investigate the role of galectin-3 in the innate resistance mechanism against R. equi infection. The bacterial challenge of galectin-3-deficient mice (gal3-/-) and their wild-type counterpart (gal3+/+) revealed that the LD50 for the gal3(-/-) mice was about seven times higher than that for the gal3+/+ mice. Wh...
Hines MT, Paasch KM, Alperin DC, Palmer GH, Westhoff NC, Hines SA.Rhodococcal pneumonia is an important disease of young horses that is not seen in immunocompetent adults. Since all foals are normally exposed to Rhodococcus equi in their environment, we hypothesized that most develop protective immune responses. Furthermore, these antigen-specific responses were hypothesized to operate throughout adult life to prevent rhodococcal pneumonia. A better understanding of the mechanisms of immune clearance in adult horses would help define the requirements for an effective vaccine in foals. Adult horses were challenged with virulent R. equi by intrabronchial inocu...
Makrai L, Takai S, Tamura M, Tsukamoto A, Sekimoto R, Sasaki Y, Kakuda T, Tsubaki S, Varga J, Fodor L, Solymosi N, Major A.Rhodococcus equi isolates (204) obtained from foals (lung abscesses, lymph nodes, nasal discharge, rectal swabs) bred in 15 studs located throughout Hungary, isolates from soil samples, lymph nodes of pigs and from lesions of human patients were examined to determine genotypic diversity of virulence-associated plasmids. Isolates were tested for the presence of 15-17 kDa virulence-associated protein antigen (VapA) and 20k Da (VapB) genes by polymerase chain reaction (PCR). Plasmid DNAs were isolated and analysed by digestion with restriction endonucleases for estimation of size and comparison o...
Dawson TRMY, Horohov DW, Meijer WG, Muscatello G.Rhodococcus equi is recognised to cause chronic purulent bronchopneumonia in foals of less than 6 months of age. Virulent strains of the bacteria possess a large 80-90 kb plasmid encoding several virulence-associated proteins, including virulence-associated protein A (VapA), which is associated with disease. R. equi pneumonia can represent significant costs and wastage to the equine breeding industry, especially on stud farms where the disease is endemic. This article reviews knowledge of the equine immune response, both in the immune adult and susceptible neonate, with respect to this pathoge...
Berghaus LJ, Giguère S, Guldbech K.The objectives of this study were to determine the mutant prevention concentration (MPC), time above the MPC and mutant selection window for 10 antimicrobial agents against Rhodococcus equi and to determine if the combination of a macrolide with rifampin would decrease emergence of resistant mutants. Antimicrobial agents investigated (erythromycin, clarithromycin, azithromycin, rifampin, amikacin, gentamicin, enrofloxacin, vancomycin, imipenem, and doxycycline) were selected based on in vitro activity and frequency of use in foals or people infected with R. equi. Each antimicrobial agent or co...
Hoffman AM, Viel L, Prescott JF, Rosendal S, Thorsen J.Undifferentiated distal respiratory tract disease (nasal discharge, cough, pneumonia) in foals (1 to 8 months old) is a burdensome economic problem on breeding farms; yet, the infective agents associated with these episodes have not been well described. Possible causes of these episodes of illness were investigated by culturing specimens of proximal and distal airways of clinically diseased foals (n = 101), prior to any treatment, for aerobic and anaerobic bacteria and viruses (rhinoviruses, equine arteritis virus, equine herpesvirus subtype 1 [EHV-1], influenza virus, and adenovirus). Pairs o...
Rodríguez-Lázaro D, Lewis DA, Ocampo-Sosa AA, Fogarty U, Makrai L, Navas J, Scortti M, Hernández M, Vázquez-Boland JA.We developed a novel quantitative real-time PCR (Q-PCR) method for the soil actinomycete Rhodococcus equi, an important horse pathogen and emerging human pathogen. Species-specific quantification was achieved by targeting the chromosomal monocopy gene choE, universally conserved in R. equi. The choE Q-PCR included an internal amplification control (IAC) for identification of false negatives. A second Q-PCR targeted the virulence plasmid gene vapA, carried by most horse isolates but infrequently found in isolates from other sources. The choE-IAC and vapA assays were 100% sensitive and specific ...
Sanz M, Loynachan A, Sun L, Oliveira A, Breheny P, Horohov DW.While Rhodococcus equi remains the most common cause of subacute or chronic granulomatous bronchopneumonia in foals, development of a relevant model to study R. equi infection has proven difficult. The objective of this study was to identify a challenge dose of R. equi that resulted in slow progressive disease, spontaneous regression of lung lesions and age-dependent susceptibility. Foals less than one-week of age were challenged intratracheally using either 10(6), 10(5), 10(4), 10(3) or 10(2) cfu of R. equi. Two doses (10(3) cfu and 10(5) cfu) were used to challenge 2 and 3-week-old, and 3 an...
Johnson JA, Prescott JF, Markham RJ.Six foals were inoculated intrabronchially with a suspension of Corynebacterium equi. Six weeks before this challenge, three foals were vaccinated with a C. equi bacterin. Three foals were unvaccinated controls. All foals developed a severe bronchopneumonia in the inoculated lung, indicating that vaccination was not protective. Three foals (two vaccinated, one control) were killed eight to nine days after infection. One control died on day 9 with lesions of disseminated intravascular coagulation. The remaining two foals (one vaccinated, one control) were killed on day 17. C. equi was cultured ...
Båverud V.In human medicine, Clostridium (C.) difficile is since many years a well-known cause of nosocomial diarrhea induced by antibiotic treatment. In horses, C. difficile was recently suggested as a possible enteric pathogen. The bacterium is associated with acute colitis in mature horses following treatment with antibiotics. C. difficile, and/or its cytotoxin, is also associated with acute colitis in mares when their foals are being treated with erythromycin and rifampicin for Rhodococcus equi pneumonia. The colitis can have resulted from an accidental ingestion of erythromycin by the mares. In an ...
Chirino-Trejo JM, Prescott JF, Yager JA.Two groups of three one to three week old foals were immunized orally on four occasions over five weeks with two strains of Rhodococcus equi, a clinical isolate from a pneumonic foal and a laboratory passaged Congo red negative variant of this strain. Three nonimmunized foals of similar age acted as controls. Three weeks after the last immunization, all foals were challenged on five occasions over seven days by aerosol infection with about 10(10) of the pneumonic foal isolate on each occasion. Control foals became seriously ill and were euthanized. Immunization with either strain protected foa...
Prescott JF, Nicholson VM, Patterson MC, Zandona Meleiro MC, Caterino de Araujo A, Yager JA, Holmes MA.To evaluate use of the virulence-associated protein of Rhodococcus equi in immunizing foals against R equi pneumonia. Methods: Eight (experimental group) and 6 (controls) mares with their foals. Methods: Virulence-associated protein extracted from R equi was used to prepare an acetone-precipitated. Triton X-extracted (APTX) antigen. After determination of the efficacy of passive immunization, in untreated foals or in foals given plasma from a horse vaccinated with APTX antigen or from a nonvaccinated horse, a field trial was done to evaluate the efficacy of vaccination of 8 mares, twice with A...
Martens RJ, Fiske RA, Renshaw HW.Subacute pyogranulomatous pneumonia was experimentally induced in 3 neonatal foals following multiple challenge with aerosols containing Corynebacterium equi. On each of 7 consecutive days the foals were exposed to approximately 3.5 X 10(7) viable C equi in droplets small enough to reach the terminal airways. Clinical, pathological and bacteriological features of the induced syndrome were indistinguishable from those exhibited by cases with spontaneous subacute C equi foal pneumonia. Radiographic evidence of advanced pulmonary damage preceded the appearance of clinical signs and ante mortem cu...
Muscatello G.Various challenges face clinicians and farm managers in diagnosing, treating and preventing Rhodococcus equi pneumonia. The use of ultrasound imaging has aided in the early diagnosis of the disease, reducing treatment duration and improving therapeutic outcomes. Antimicrobial resistance in R. equi is an emerging issue that necessitates prudent antimicrobial therapy of diseased foals. Alternative methods of disease transmission, such as contagious foal-to-foal aerosol transmission, may need to be addressed to complement dust reduction environmental strategies and to minimise the overall risk of...
Ainsworth DM, Eicker SW, Yeagar AE, Sweeney CR, Viel L, Tesarowski D, Lavoie JP, Hoffman A, Paradis MR, Reed SM, Erb HN, Davidow E, Nalevanko M.To determine whether physical examination, laboratory, or radiographic abnormalities in foals with Rhodococcus equi infection were associated with survival, ability to race at least once after recovery, or, for foals that survived and went on to race, subsequent racing performance. Methods: Retrospective study. Methods: 49 Thoroughbreds and 66 Standardbreds admitted to 1 of 6 veterinary teaching hospitals between 1984 and 1992 in which R equi infection was positively diagnosed. Methods: Results of physical examination, laboratory testing, and thoracic radiography were reviewed. Indices of raci...
Giguère S, Wilkie BN, Prescott JF.The ability of Rhodococcus equi to induce pneumonia in foals depends on the presence of an 85- to 90-kb plasmid. In this study, we evaluated whether plasmid-encoded products mediate virulence by modulating the cytokine response of foals. Foals infected intrabronchially with a virulence plasmid-containing strain of R. equi had similar gamma interferon (IFN-gamma) and interleukin-12 (IL-12) p35 but significantly higher IL-1beta, IL-10, IL-12 p40, and tumor necrosis factor alpha (TNF-alpha) mRNA expression in lung tissue compared to foals infected with the plasmid-cured derivative. IFN-gamma mRNA...
Cohen ND, O'Conor MS, Chaffin MK, Martens RJ.To identify farm characteristics and management practices associated with development of Rhodococcus equi pneumonia in foals. Methods: Prospective case-control study. Methods: 5230 foals on 138 breeding farms with 9136 horses. Methods: During 2003, participating veterinarians provided data from 1 or 2 farms with > or =1 foal with R equi pneumonia and unaffected farms. Data from affected and unaffected farms were compared by use of logistic regression analysis. Results: A number of variables relating to farm size and desirable management practices were significantly associated with increased od...
Morton AC, Begg AP, Anderson GA, Takai S, Lämmler C, Browning GF.Pulsed-field gel electrophoresis of restriction endonuclease-digested genomic DNA from a large collection of clinical isolates of Rhodococcus equi, an important pathogen of foals, was used to compare strain distribution between farms and over time. Forty-four strains were found among 209 isolates, with 5 of these accounting for over half the isolates and the 22 strains isolated more than once accounting for 90% of the isolates. The average genotypic diversity on each farm and in each year was found to be less than the genotypic diversity of the isolates taken as a whole, with 5.2% of the total...
Jacks S, Giguère S, Crawford PC, Castleman WL.Rhodococcus equi is a facultative intracellular pathogen that causes pneumonia in young foals but does not induce disease in immunocompetent adult horses. Clearance of R. equi depends mainly on gamma interferon (IFN-gamma) production by T lymphocytes, whereas the predominance of interleukin 4 (IL-4) is detrimental. Young foals, like neonates of many other species, are generally deficient in the ability to produce IFN-gamma. The objective of this study was to compare the cytokine profiles, as well as cell-mediated and antibody responses, of young foals to those of adult horses following intrabr...
Liu T, Nerren J, Liu M, Martens R, Cohen N.Neonates are thought to be generally deficient in production of Th-1-associated cytokines at birth, and thereby more susceptible to bacterial infections. Using neonatal foals as a model, this study examined the age-dependent maturation of both basal and stimulus-induced immune responses, as reflected by the expression of a panel of Th-1-associated and pro-inflammatory cytokines. Results showed that although the basal production of IFN-gamma and IL-6 was impaired (P<0.05) in PBMCs of neonatal foals at birth, the basal production of IL-8, IL-12(p35/p40) and IL-23(p19/p40) were either in exces...
Patton KM, McGuire TC, Fraser DG, Hines SA.The goal of this research was to examine the role of cytotoxic T lymphocytes (CTL) in the control of Rhodococcus equi and specifically to determine if R. equi-specific CD8+ CTL occurred in the blood of immune horses. Equine peripheral blood mononuclear cells stimulated with antigen-presenting cells either infected with R. equi or exposed to soluble R. equi antigen lysed R. equi-infected target cells. Lysis was decreased to background by depletion of either CD2+ or CD3+ cells, indicating that the effector cell had a T-lymphocyte, but not NK cell, phenotype. Stimulation induced an increased perc...
Hietala SK, Ardans AA, Sansome A.An enzyme-linked immunosorbant assay was developed to measure naturally occurring Corynebacterium equi specific antibody in horse serum. Antibody against C equi was demonstrated in normal adults and was passively transferred to foals. Adult levels of specific antibody were reached by 5 to 6 months of age in healthy foals. Decreased early antibody levels were demonstrated in a limited number of foals with confirmed C equi infection.
Flaminio MJ, Rush BR, Shuman W.Infectious diseases are common in foals aged 1-5 months. The objectives of this investigation were to evaluate immunologic parameters in foals from birth to weaning to establish reference values for the proportion of circulating lymphocytes that were helper (CD4+) or cytotoxic (CD8+) T cells, or B cells; to measure serum immunoglobulin (IgM and IgG) concentrations; and to compare these immunologic parameters to values in foals with naturally occurring Rhodococcus equi pneumonia and in adult horses. Peripheral blood lymphocyte subpopulations were determined by flow cytometric analysis, and seru...
