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Topic:Rhodococcus equi

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.
Intestinal and hepatic contributions to the pharmacokinetic interaction between gamithromycin and rifampicin after single-dose and multiple-dose administration in healthy foals.
Equine veterinary journal    January 8, 2018   Volume 50, Issue 4 525-531 doi: 10.1111/evj.12796
Berlin S, Wallstabe S, Scheuch E, Oswald S, Hasan M, Wegner D, Grube M, Venner M, Ullrich A, Siegmund W.Standard treatment of foals with severe abscessing lung infection caused by Rhodococcus equi using rifampicin and a macrolide antibiotic can be compromised by extensive inhibition and/or induction of drug metabolising enzymes (e.g. CYP3A4) and transport proteins (e.g. P-glycoprotein), as has been shown for rifampicin and clarithromycin. The combination of rifampicin with the new, poorly metabolised gamithromycin, a long-acting analogue of azithromycin and tulathromycin with lower pharmacokinetic interaction potential, might be a suitable alternative. Objective: To evaluate the pharmacokinetic ...
Effects of priming with cytokines on intracellular survival and replication of Rhodococcus equi in equine macrophages.
Cytokine    December 12, 2017   Volume 102 7-11 doi: 10.1016/j.cyto.2017.12.011
Berghaus LJ, Giguère S, Bordin AI, Cohen ND.Rhodococcus equi is a common cause of pneumonia in foals and an opportunistic pathogen in immunosuppressed people. The ability of R. equi to survive and replicate in macrophages is the basis of its pathogenicity. Limited knowledge about the role of cytokines in host defense against R. equi comes from studies in mice and the role of cytokines in intracellular survival of R. equi in equine macrophages is unknown. The objectives of this study were to determine the effect of priming with interferon (IFN)-γ, interleukin (IL)-1β, IL-4, IL-6, IL-10, or tumor necrosis factor (TNF)-α at various conc...
Antimicrobial Resistance in Rhodococcus equi.
Microbiology spectrum    October 21, 2017   Volume 5, Issue 5 doi: 10.1128/microbiolspec.ARBA-0004-2016
Giguère S, Berghaus LJ, Willingham-Lane JM.Pneumonia caused by remains an important cause of disease and death in foals. The combination of a macrolide (erythromycin, azithromycin, or clarithromycin) with rifampin has been the recommended treatment for foals with clinical signs of infection caused by since the early 1980s with, until recently, only rare reports of resistance. Resistance to macrolides and rifampin in isolates of cultured from horses is increasing, with isolates resistant to all macrolides and rifampin now being cultured from up to 40% of infected foals at some farms. This text reviews the available data regarding ant...
Development of a multilocus sequence typing scheme for Rhodococcus equi.
Veterinary microbiology    August 19, 2017   Volume 210 64-70 doi: 10.1016/j.vetmic.2017.08.010
Duquesne F, Houssin E, Sévin C, Duytschaever L, Tapprest J, Fretin D, Hébert L, Laugier C, Petry S.Rhodococcus equi causes pulmonary and extrapulmonary infections in animals and humans, with endemic situations and significant young foal mortality in stud farms worldwide. Despite its economic impact in the horse-breeding industry, the broad geographic and host distribution, global diversity and population structure of R. equi remain poorly characterised. In this context, we developed a multilocus sequence typing (MLST) scheme using 89 clinical and environmental R. equi of various origins and eight Rhodococcus sp. Data can be accessed at http://pubmlst.org/rhodococcus/. A clonal R. equi popul...
Seroprevalence of Rhodococcus equi in horses in Israel.
Journal of the South African Veterinary Association    June 26, 2017   Volume 88 e1-e6 doi: 10.4102/jsava.v88i0.1508
Tirosh-Levy S, Gürbilek SE, Tel OY, Keskin O, Steinman A.Rhodococcus equi is a common cause of pneumonia in foals and has extensive clinical, economic and possibly zoonotic consequences. This bacterium survives well in the environment and may be considered as normal flora of adult horses. Certain strains of this bacterium are extremely virulent in foals, and early identification and intervention is crucial for prognosis. Rhodococcus equi is endemic in many parts of the world and occasionally isolated in Israel. This study was designed to evaluate R. equi seroprevalence in adult horses in Israel to indirectly indicate the potential level of exposure ...
Differential distribution of vapA-positive Rhodococcus equi in affected and unaffected horse-breeding farms.
The Veterinary record    June 22, 2017   Volume 181, Issue 6 145 doi: 10.1136/vr.104088
Petry S, Sévin C, Fleury MA, Duquesne F, Foucher N, Laugier C, Henry-Amar M, Tapprest J.No abstract available
The antimicrobial activity of bupivacaine, lidocaine and mepivacaine against equine pathogens: An investigation of 40 bacterial isolates.
Veterinary journal (London, England : 1997)    May 10, 2017   Volume 223 27-31 doi: 10.1016/j.tvjl.2017.05.001
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...
Efficacy of Tulathromycin for the Treatment of Foals with Mild to Moderate Bronchopneumonia.
Journal of veterinary internal medicine    April 19, 2017   Volume 31, Issue 3 901-906 doi: 10.1111/jvim.14717
Rutenberg D, Venner M, Giguère S.There is conflicting data regarding the efficacy of tulathromycin for the treatment of foals with bronchopneumonia. Tulathromycin is effective for the treatment of bronchopneumonia in foals and noninferior to the combination of azithromycin and rifampin. A total of 240 foals on a farm endemic for infections caused by Rhodococcus equi. In a controlled, randomized, and double-blinded clinical trial, foals with ultrasonographic pulmonary lesions (abscess score 10-15 cm) were allocated to 3 groups: 1-tulathromycin IM q 7 days (n = 80); 2-azithromycin-rifampin, orally q24h (n = 80); or 3-untreated ...
Effects of clarithromycin, azithromycin and rifampicin on terbutaline-induced sweating in foals.
Equine veterinary journal    March 29, 2017   Volume 49, Issue 5 624-628 doi: 10.1111/evj.12677
Stieler Stewart AL, Sanchez LC, Mallicote MF, Muniz AL, Westerterp MS, Burrow JA, MacKAY RJ.Erythromycin (ERY) induces anhidrosis in foals. Azithromycin (AZI) and clarithromycin (CLA), often combined with rifampicin (RIF), are commonly used to treat Rhodococcus equi infections, but effects on sweating have not been investigated. Objective: To determine the effects of AZI, CLA and RIF on sweat responses in normal foals. Methods: Each experiment was a blinded, duplicated, six foal × three period counterbalanced within subjects design (12 foals/experiment). Methods: Antimicrobials were given orally for 5 days. In Experiment 1, ERY, AZI and CLA were given. In Experiment 2, ERY, RIF and ...
Pharmacokinetics and pulmonary distribution of gamithromycin after intravenous administration in foals.
Journal of veterinary pharmacology and therapeutics    March 19, 2017   Volume 40, Issue 4 406-410 doi: 10.1111/jvp.12402
Berlin S, Randow T, Scheuch E, Grube M, Venner M, Siegmund W.The long-acting azalide antibiotic gamithromycin is marketed for intramuscular treatment of bovine and swine infections. Off-label use in foals leads to severe local lesions likely caused by hyperosmolality of the injected solution. We provide evidence from a pharmacokinetic study in 10 warm-blooded healthy foals for intravenous bolus injection of gamithromycin diluted in distilled water to be a safe and well tolerated alternative. By intravenous dosing, markedly higher plasma exposure and better penetration into bronchoalveolar lavage cells but lower distribution into epithelial lining fluid ...
Pharmacological indices and pulmonary distribution of rifampicin after repeated oral administration in healthy foals.
Equine veterinary journal    February 25, 2017   Volume 49, Issue 5 618-623 doi: 10.1111/evj.12662
Berlin S, Kirschbaum A, Spieckermann L, Oswald S, Keiser M, Grube M, Venner M, Siegmund W.The treatment of equine lung infections by Rhodococcus equi with rifampicin is empirically based because pharmacokinetic/pharmacodynamic (PK/PD) indices and pivotal clinical outcome data are not available. Objective: To evaluate the pharmacokinetics and pulmonary distribution of rifampicin into epithelial lining fluid (ELF) and bronchoalveolar lavage cells (BALC) to predict antimicrobial activity in the lung using PK/PD indices. Methods: Controlled, randomised, two-period, crossover, repeated-dose study with an initial arm to measure disposition after i.v. administration of rifampicin. Methods...
Treatment of septic arthritis of the coxofemoral joint in 12 foals.
Veterinary surgery : VS    February 15, 2017   Volume 46, Issue 4 530-538 doi: 10.1111/vsu.12621
Barceló Oliver F, Russell TM, Uprichard KL, Neil KM, Pollock PJ.To describe the clinical signs, surgical treatment, and outcome of septic arthritis of the coxofemoral joint in foals. Methods: Retrospective clinical study. Methods: Foals (n = 12) with confirmed sepsis of the coxofemoral joint. Methods: Lameness was localized to the coxofemoral joint based on physical examination. Sepsis was confirmed by cytological analysis of synovial fluid obtained under ultrasonographic guidance, during general anesthesia or standing sedation. Intra-articular analgesia was used as an adjunct diagnostic modality in 2 foals. Surgical lavage of the affected joint was pe...
Treatment of Infections Caused by Rhodococcus equi.
The Veterinary clinics of North America. Equine practice    February 1, 2017   Volume 33, Issue 1 67-85 doi: 10.1016/j.cveq.2016.11.002
Giguère S.Pneumonia caused by Rhodococcus equi remains an important cause of disease and death in foals. The combination of a macrolide (erythromycin, azithromycin, or clarithromycin) with rifampin remains the recommended therapy for foals with clinical signs of infection caused by R equi. Most foals with small, subclinical ultrasonographic pulmonary lesions associated with R equi recover without therapy, and administration of antimicrobial agents to these subclinically affected foals does not hasten lesion resolution relative to administration of a placebo. Resistance to macrolides and rifampin in isol...
Molecular characterization of Rhodococcus equi isolates from horses in Poland: pVapA characteristics and plasmid new variant, 85-kb type V.
BMC veterinary research    January 26, 2017   Volume 13, Issue 1 35 doi: 10.1186/s12917-017-0954-2
Witkowski L, Rzewuska M, Takai S, Chrobak-Chmiel D, Kizerwetter-Świda M, Feret M, Gawryś M, Witkowski M, Kita J.Rhodococcus equi is one of the most significant bacterial pathogens affecting foals up to 6 months of age worldwide. Rhodococcosis is present in Poland however information about molecular characterization of R. equi isolates is scarce. This study describes molecular characterization of Rhodococcus equi infection on 13 horse breeding farms in Poland between 2001 and 2012. Samples were collected by tracheobronchial aspiration from pneumonic foals or during necropsy. The R. equi isolates were genotyped by plasmid profiling and pulsed-field gel electrophoresis. Results: Totally, 58 R. equi isolat...
Molecular characterization of Rhodococcus equi isolates in equines.
Veterinary world    January 5, 2017   Volume 10, Issue 1 6-10 doi: 10.14202/vetworld.2017.6-10
Javed R, Taku AK, Sharma RK, Badroo GA.The aim was to determine the occurrence of in equines and their environment in Jammu (R.S. Pura, Katra), molecular characterization and to determine the antibiotic resistance pattern of . Methods: A total of 96 nasopharyngeal swab samples were collected from equines. The organism was isolated on Columbia nalidixic acid agar containing 5% sheep blood as well as on sheep blood agar and was later confirmed by cultural characteristics and biochemical tests. Molecular detection of isolates was done by gene amplification followed by virulence associated protein A () gene amplification. Antibiogra...
TRPM2 SNP genotype previously associated with susceptibility to Rhodococcus equi pneumonia in Quarter Horse foals displays differential gene expression identified using RNA-Seq.
BMC genomics    December 5, 2016   Volume 17, Issue 1 993 doi: 10.1186/s12864-016-3345-3
McQueen CM, Whitfield-Cargile CM, Konganti K, Blodgett GP, Dindot SV, Cohen ND.Rhodococcus equi (R. equi) is an intracellular bacterium that affects young foals and immuno-compromised individuals causing severe pneumonia. Currently, the genetic mechanisms that confer susceptibility and/or resistance to R. equi are not fully understood. Previously, using a SNP-based genome-wide association study, we identified a region on equine chromosome 26 associated with culture-confirmed clinical pneumonia. To better characterize this region and understand the function of the SNP located within TRPM2 that was associated with R. equi pneumonia, we performed RNA-Seq on 12 horses repres...
Influence of Plasmid Type on the Replication of Rhodococcus equi in Host Macrophages.
mSphere    October 12, 2016   Volume 1, Issue 5 e00186-16 doi: 10.1128/mSphere.00186-16
Willingham-Lane JM, Berghaus LJ, Giguère S, Hondalus MK.The soil-dwelling, saprophytic actinomycete is a multihost, facultative intracellular pathogen of macrophages. When inhaled by susceptible foals, it causes severe bronchopneumonia. It is also a pathogen of pigs, which may develop submaxillary lymphadenitis upon exposure. isolates obtained from foals and pigs possess conjugative plasmids housing a pathogenicity island (PAI) containing a novel family of genes of unknown function called the virulence-associated protein or family. The PAI regions of the equine and swine plasmids differ in gene composition, with equine isolates possessing six ...
Clinical Assessment of a Point-of-Care Serum Amyloid A Assay in Foals with Bronchopneumonia.
Journal of veterinary internal medicine    June 14, 2016   Volume 30, Issue 4 1338-1343 doi: 10.1111/jvim.13978
Giguère S, Berghaus LJ, Miller CD.Despite the paucity of data available, stall-side serum amyloid (SAA) assays are commonly used to make diagnostic and treatment decisions in foals with bronchopneumonia. Objective: Measurement of SAA concentrations can accurately differentiate pneumonic from healthy foals. Methods: Fifty-four pneumonic foals between 3 weeks and 5 months of age were compared to 44 healthy controls. In addition, 47 foals on a farm endemic for R. equi infections were studied. Methods: Serum samples were collected from pneumonic foals at hospital admission. Foals were categorized as having pneumonia caused by R. e...
Equid herpesvirus 1 and rhodococcus equi coinfection in a foal with bronchointerstitial pneumonia.
The Journal of veterinary medical science    June 3, 2016   Volume 78, Issue 9 1511-1513 doi: 10.1292/jvms.16-0024
Perez-Ecija A, Mendoza FJ, Estepa JC, Bautista MJ, Pérez J.A 2-month-old foal with septic shock and severe respiratory distress was referred to the Veterinary Teaching Hospital. Due to poor prognosis, the foal was euthanized. Histopathology showed lesions suggestive of Rhodococcus equi infection associated with a diffuse interstitial infiltrate of foamy macrophages and syncytial cells presenting large acidophilic intranuclear inclusion bodies, fibrin exudates and hyaline membranes. Bacteriological examination from lung and respiratory exudates confirmed R. equi infection, whilst immunohistochemistry and PCR yielded a positive result for Equid herpesvi...
Plasmid Profiles of Virulent Rhodococcus equi Strains Isolated from Infected Foals in Poland.
PloS one    April 13, 2016   Volume 11, Issue 4 e0152887 doi: 10.1371/journal.pone.0152887
Kalinowski M, Grądzki Z, Jarosz Ł, Kato K, Hieda Y, Kakuda T, Takai S.Rhodococcus equi is an important bacterial pathogen in foals up to 6 months old, widespread in horse farms all over the world. It was found that only virulent R. equi strains expressing 15-17 kDa virulence-associated protein (VapA) and having large virulence plasmid of 85-90 kb containing vapA gene are pathogenic for horses. To date, 12 plasmid types have been reported in VapA positive strains from horses. There are no data concerning plasmid types of Polish field R. equi strains isolated from horses and horse farm environment. The aim of the study is to determine plasmid profiles of virulent ...
Hygienic characteristics and microbiological hazard identification in horse and donkey raw milk.
Veterinaria italiana    April 2, 2016   Volume 52, Issue 1 21-29 doi: 10.12834/VetIt.180.545.1
Colavita G, Amadoro C, Rossi F, Fantuz F, Salimei E.Today the interest toward horse (Equus caballus) and donkey (Equus asinus) milk for human consumption is receiving a renewed attention because of its particular composition, hypoallergenicity, and nutraceutical properties. The realistic perspective of global use of this aliment in balanced diets, especially for infancy and geriatrics, poses the need for a more in depth knowledge on milk hygiene and on the health status of dairy animals, as a prerequisite of consumers' safety. The aim of this paper was to review the available literature on the health and hygiene parameters as well as on the pot...
Chloroquine inhibits Rhodococcus equi replication in murine and foal alveolar macrophages by iron-starvation.
Veterinary microbiology    March 26, 2016   Volume 188 16-24 doi: 10.1016/j.vetmic.2016.03.019
Gressler LT, Bordin AI, McQueen CM, Cohen ND, de Vargas AC.Rhodococcus equi preferentially infects macrophages causing pyogranulomatous pneumonia in young foals. Both the vapA and rhbC genes are up-regulated in an iron (Fe)-deprived environment, such as that found within macrophages. Chloroquine (CQ) is a drug widely used against malaria that suppresses the intracellular availability of Fe in eukaryotic cells. The main objective of this study was to evaluate the ability of CQ to inhibit replication of virulent R. equi within murine (J774A.1) and foal alveolar macrophages (AMs) and to verify whether the mechanism of inhibition could be Fe-deprivation-d...
An Adenoviral Vector Based Vaccine for Rhodococcus equi.
PloS one    March 23, 2016   Volume 11, Issue 3 e0152149 doi: 10.1371/journal.pone.0152149
Giles C, Ndi O, Barton MD, Vanniasinkam T.Rhodococcus equi is a respiratory pathogen which primarily infects foals and is endemic on farms around the world with 50% mortality and 80% morbidity in affected foals. Unless detected early and treated appropriately the disease can be fatal. Currently, there is no vaccine available to prevent this disease. For decades researchers have endeavoured to develop an effective vaccine to no avail. In this study a novel human adenoviral vector vaccine for R. equi was developed and tested in the mouse model. This vaccine generated a strong antibody and cytokine response and clearance of R. equi was d...
Rhodococcus equi hyperimmune plasma decreases pneumonia severity after a randomised experimental challenge of neonatal foals.
The Veterinary record    March 1, 2016   Volume 178, Issue 11 261 doi: 10.1136/vr.103095
Sanz MG, Loynachan A, Horohov DW.Since a vaccine is not available against Rhodococcus equi, R equi-specific hyperimmune plasma (HIP) is commonly used, although its efficacy remains controversial. The objective of this study was to evaluate the ability of a commercially available HIP to prevent clinical rhodococcal pneumonia in neonatal foals after experimental challenge.
Oral Administration of Electron-Beam Inactivated Rhodococcus equi Failed to Protect Foals against Intrabronchial Infection with Live, Virulent R. equi.
PloS one    February 1, 2016   Volume 11, Issue 2 e0148111 doi: 10.1371/journal.pone.0148111
Rocha JN, Cohen ND, Bordin AI, Brake CN, Giguère S, Coleman MC, Alaniz RC, Lawhon SD, Mwangi W, Pillai SD.There is currently no licensed vaccine that protects foals against Rhodococcus equi-induced pneumonia. Oral administration of live, virulent R. equi to neonatal foals has been demonstrated to protect against subsequent intrabronchial challenge with virulent R. equi. Electron beam (eBeam)-inactivated R. equi are structurally intact and have been demonstrated to be immunogenic when administered orally to neonatal foals. Thus, we investigated whether eBeam inactivated R. equi could protect foals against developing pneumonia after experimental infection with live, virulent R. equi. Foals (n = 8) w...
Use of Serial Quantitative PCR of the vapA Gene of Rhodococcus equi in Feces for Early Detection of R. equi Pneumonia in Foals.
Journal of veterinary internal medicine    January 24, 2016   Volume 30, Issue 2 664-670 doi: 10.1111/jvim.13828
Madrigal RG, Shaw SD, Witkowski LA, Sisson BE, Blodgett GP, Chaffin MK, Cohen ND.Current screening tests for Rhodococcus equi pneumonia in foals lack adequate accuracy for clinical use. Real-time, quantitative PCR (qPCR) for virulent R. equi in feces has not been systematically evaluated as a screening test. Objective: The objective of this study was to evaluate the accuracy of qPCR for vapA in serially collected fecal samples as a screening test for R. equi pneumonia in foals. Methods: One hundred and twenty-five foals born in 2011 at a ranch in Texas. Methods: Fecal samples were collected concurrently with thoracic ultrasonography (TUS) screening examinations at ages 3, ...
Use of Liposomal Gentamicin for Treatment of 5 Foals with Experimentally Induced Rhodococcus equi Pneumonia.
Journal of veterinary internal medicine    December 22, 2015   Volume 30, Issue 1 322-325 doi: 10.1111/jvim.13810
Cohen ND, Giguère S, Burton AJ, Rocha JN, Berghaus LJ, Brake CN, Bordin AI, Coleman MC.Adverse effects of, and bacterial resistance to, macrolides used to treat Rhodococcus equi infections have prompted search for clinically effective alternative antimicrobials. Liposomal gentamicin (LG) is effective against R. equi in vitro and decreases tissue concentrations of R. equi in experimentally infected mice. Effectiveness of LG treatment of foals with R. equi pneumonia, however, has not been described. Objective: Liposomal gentamicin is safe and effective for treating foals with R. equi pneumonia. Methods: Ten foals with experimentally induced R. equi pneumonia. Methods: Pilot treatm...
Development and evaluation of the internal-controlled real-time PCR assay for Rhodococcus equi detection in various clinical specimens.
The Journal of veterinary medical science    December 8, 2015   Volume 78, Issue 4 543-549 doi: 10.1292/jvms.15-0516
Stefańska I, Witkowski L, Rzewuska M, Dzieciątkowski T.Rhodococcus equi is the causative agent of rhodococcosis in horses, resulting in significant morbidity and mortality in foals. This bacterium has also been isolated from a variety of animals and is being increasingly reported as a cause of infection in humans, mainly in immunosuppressed individuals. Laboratory diagnostics of R. equi infections based only on conventional microbiological methods shows low accuracy and can lead to misidentification. The objective of the study was to develop and evaluate a real-time PCR assay for direct detection of R. equi in various clinical specimens, including...
Three new serotypes of Rhodococcus equi in Prescott’s serotyping system – Short communication.
Acta veterinaria Hungarica    November 10, 2015   Volume 63, Issue 3 265-270 doi: 10.1556/004.2015.024
Makrai L, Fodor L, Hajtós I, Varga J, Dénes B.Three new serotypes were found among Rhodococcus equi strains, which could not be assigned into any of the seven serotypes of Prescott's system. Fortythree R. equi strains out of 44 previously nontypable ones isolated in Hungary could be allocated into one of the three new serotypes using the agar gel immunodiffusion (AGID) test. The three new suggested serotypes are serotype 8 (proposed reference strain: HNCMB-138003), serotype 9 (proposed reference strain: HNCMB-138004) and serotype 10 (proposed reference strain: HNCMB-138005). Hyperimmune sera produced in rabbits against the new serotypes a...
Minimum inhibitory concentrations of erythromycin and rifampin for Rhodococcus equi during the years 2007-2014.
Irish veterinary journal    October 6, 2015   Volume 68 23 doi: 10.1186/s13620-015-0051-4
Fenton CS, Buckley TC.Rhodococcus equi is a gram positive, intracellular pathogen of foals worldwide. The aim of this study was to determine whether there was an increasing resistance occurring in Rhodococcus equi towards the antibiotics rifampin and erythromycin over a seven year period. The investigation was carried out with the use of E test strips (epsilometers) for rifampin and erythromycin in order to determine the Minimum Inhibitory Concentrations (MIC) values of Rhodococcus equi to these antibiotics. Results: The main results of this study found that the mean MICs were higher for erythromycin than for rifam...