Submit or Track your Manuscript LOG-IN

Advances in Animal and Veterinary Sciences

NEW AAVS_Nexus 544

Review Article

 

Current Understanding of Rhodococcus equi Infection and its Zoonotic Implications

 

Sandip Kumar Khurana

National Research Centre on Equines, Sirsa Road, Hisar (Haryana)-125 001, India.

 

Abstract | Rhodococcus equi is a soil actinomycete responsible for severe respiratory disease in young foals leading to high mortality. The organism is also emerging as an important pathogen in immune-compromised humans. Intracellular localization of R. equi makes therapeutic management very difficult and prolonged lasting up to three months. Presently no suitable vaccine and effective serological test for early diagnosis is available. High mortality rate, non-availability of suitable diagnostic methods during early phase of infection and high cost of prolonged treatments makes it a disease of high economic importance and thus is considered among the top most disease problems affecting equine industry globally.


Keywords | Rhodococcus equi, Foals, Diagnosis, Treatment


Editor | Kuldeep Dhama, Indian Veterinary Research Institute, Uttar Pradesh, India.

Received | October 18, 2014; Revised | December 05, 2014; Accepted | December 07, 2014; Published | December 11, 2014

*Correspondence | Sandip Kumar Khurana, National Research Centre on Equines, Sirsa Road, Hisar, India; Email: sandipkk2003@yahoo.co.in

Citation | Khurana SK (2015). Current understanding of Rhodococcus equi infection and its zoonotic implications. Adv. Anim. Vet. Sci. 3(1): 1-10.

DOI | http://dx.doi.org/10.14737/journal.aavs/2015/3.1.1.10

ISSN (Online) | 2307-8316; ISSN (Print) | 2309-3331

Copyright © 2015 Khurana. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Introduction


Rhodococcus equi is a gram-positive, aerobic, non-motile, pleomorphic coccobacillus having simple nutritional requirements and forms irregular, smooth, mucoid colonies which acquire salmon pink colour in 4 to 5 days. The organism has circular chromosome of about 5 Mb, G+C content is 68.8% and may possess different plasmids (Sanger Institute, 2008). A 15-17 kDa cell surface lipoprotein known as virulence associated protein A (Vap A) is essential for virulence in foals, another cell surface lipoprotein of 20 kDa size, Vap B which is analogous to Vap A is often associated with disease in pigs and humans.


This organism is causative agent of zoonotic infections in horses, foals and some other herbivorous animals (Giguère et al., 2011a, b). R. equi mostly affects foals aged between one to four months (Tkachuksaad and Prescott, 1991; Yager et al., 1991; von Bargen and Haas, 2009). Disease occurs in adult horses rarely and in horses with severe immunodeficiency. The extra-pulmonary complications due to R. equi include enteritis often with necrosis, bone and joint infections, lymphadenopathy, diarrhoea, and abscesses in abdomen and uveitis (Giguère and Prescott, 1997). R. equi was first recovered from lung of a foal with respiratory illness as Corynebacterium equi in Sweden (Magnusson, 1923). Later, it was classified as R. equi (Goodfellow and Alderson, 1977).


R. equi is also an important emerging pathogen in immunocompromised human beings. Immunocompetent persons also rarely get infected. This infection was first recorded in human beings in a case of hepatitis in 1967. There are reports of R. equi as opportunistic pathogen in AIDS patients (Weinstock and Brown, 2002), drug therapy (Mizuno et al., 2005) and other immunosuppressive conditions (Napoleão et al., 2005).


Treatment requires prolonged combination antibiotic therapy, primarily due to intracellular localization of this pathogen. It is reported by von Bargen and Hass (2009) that this organism arrests the phagosome maturation and resultantly forms a special niche inside the host cells. Surgical intervention also becomes essential in some instances.


The disease is direct anthropozoonosis since the animals are primary reservoirs of the etiological agent (Khurana, 2014). Comparative analysis of whole cell proteins of R. equi isolates from different geographical locations in India revealed varied protein banding patterns, thus varied on molecular epidemiological basis (Khurana et al., 2014), however comparable reports are not available from other countries.


The knowledge about pathogenesis, immunity, diagnostic methods, preventive and therapeutic management approaches regarding R. equi has increased gradually, but still no effective vaccine is available apart from newer managemental challenges including appearance of multidrug resistant virulent strains of R. equi (Giguère et al., 2010; Venner et al., 2012, 2013; Burton et al., 2013; Chaffin et al., 2013). Muscatello (2012) has reviewed the details regarding management, diagnosis, treatment, immunity, pathogenesis and epidemiology of R. equi infections. Vazquez-Boland et al. (2013) have described the biology, immunological and clinical aspects of the organism in great details. The present review provides an insight into current status of equine-centric R. equi infections as well as anthropozoonotic aspects.


Etiology of Infection

 

R. equi is a gram-positive, pleomorphic coccobacillus and an intracellular pathogen of macrophages. It is catalase positive, oxidase negative and usually urease positive. The organism is known as Rhodococcus because it forms salmon pink-coloured colonies on solid media due to pigmentation. Rhodococcus species include symbionts as well as animal, human and plant pathogens (Bell et al., 1998). The organism is mainly soil bacteria having simple nutritional requirements and grows well in animal manure.


Host Range among Animals and Humans

 

R. equi primarily affects equines especially foals aged between one to four months (Prescott, 1991; Takai, 1997). Cattle (Soedarmanto et al., 1997), pigs (Mutimer and Woolcock, 1980; Soedarmanto et al., 1997), goats (Jeckel et al., 2011), camels (Kinne et al., 2011), dogs (Takai et al., 2003a), cats (Takai et al., 2003a) and human beings (Weinstock and Brown, 2002) are also affected. This organism has been isolated from a number of terrestrial and aquatic animals like crocodiles, several avian species and arthropods (Prescott, 1991). R. equi in human beings is reported as opportunistic pathogen in AIDS patients (Weinstock and Brown, 2002), drug therapy (Mizuno et al., 2005) and other immunosuppressive conditions (Napoleão et al., 2005).


Geographical Distribution

 

The disease is present worldwide with highly variable pattern (Hughes and Sulaiman, 1987). There are many endemic areas and endemic equine farms as animal manure especially horse manure is suitable for growth of this organism in soil and environment (Prescott, 1991). Disease was reported in India (Garg et al., 1985; Khurana et al., 2009; Saxena and Narwal, 2009). The prevalence of R. equi has been reported from several countries including Argentina, Australia, Canada, France, Hungary, Japan, Ireland and others (Ocampo-Sosa et al., 2007). R. equi infections have been also reported from Thailand (Asoh et al., 2003), Korea (Kim et al., 2008), USA (Weinstock and Brown, 2002; Burton et al., 2013), Denmark (Gudeta et al., 2014), Brazil (Gressler et al., 2014) and China (Liu et al., 2014).


Transmission of Disease

 

The main route of exposure is by inhalation or ingestion (Martens et al., 1982; Johnson et al., 1983a, 1983b). The organism is present in soil and enters the respiratory tract of foal through inhalation of dust having airborne bacteria. Ingestion of soil is another common mode of transmission. Naturally occurring R. equi infections are mostly chronic with varying incubation period. However, incubation period ranging from 6 to 18 days has been reported in foals with an experimental dose of 104 cfu of virulent R. equi (Barten and Embury, 1987; Wada et al., 1997).


R. equi bacteria are present in the soil of most farms in large numbers, but disease pattern varies from farm to farm. The incidence of the disease at a farm depends on the density of foals and horses at farm, climate, contamination level of organisms and virulence of the R. equi (Weinstock and Brown, 2002). Airborne R. equi bacteria are the major source of disease transmission at farms, but has direct correlation with age and immunological status of foals (Muscatello, 2009). The most susceptible age is one to four months and immunologically deficient foals are more vulnerable.


Human beings acquire infection by inhalation of airborne bacteria from dust or soil, wound or mucous membrane inoculation and from domestic animals harbouring R. equi (Weinstock and Brown, 2002). Horizontal transmission among human beings is rarely understood (Weinstock and Brown, 2002).


Symptoms and Disease Manifestations in Foals/Equine

 

The disease usually occurs in one to four month old foals (Tkachuksaad and Prescott, 1991; Yager et al., 1991; von Bargen and Haas, 2009). The highest incidence of the disease is witnessed between one and a half to three months of age. This is the period when maternal antibodies decline and antibodies produced by the foal have not developed. Infectious occur rarely in adult horses and they are more common and severe in foals due to compromised immunity (Hondalus and Mosser, 1994). Protective immunity develops in adult horses and in some foals which clears the infection (Lopez et al., 2002). The disease is insidious in nature, so requires considerable experience to detect the disease in early phases. In the beginning there are diffuse bronchial sounds, later rattling sounds develop. Pyrexia along with high respiratory rate occurs within two days. Symptoms in foals include pyrexia and respiratory distress. Chronic pus filled lung abscesses in untreated foals lead to death due to asphyxiation (Wichtel et al., 1991; Lavoie et al., 1994). The disease may spread from lungs to other organs and joints (Prescott, 1991). Ulcerative enteritis, mucosal invasion of the bacteria along with diarrhoea is usual feature in chronic cases (Bell et al., 1998; Vazquez-boland et al., 2009). Development of uveitis, anaemia and thrombocytopenia, occasionally arthritis and osteomyelitis are also seen (Giguère et al., 1999). Osteomyelitis due to R.equi infection has been described in a mature immunocompetent horse (Watts, 2014; Kilcoyne et al., 2014). Concurrent extra-pulmonary disorders are reported in about 74% foals, though pneumonia is primary clinical manifestation (Johns, 2013).


Morbidity and mortality rates were reported to be 5-17% and 40-80% respectively in foals due to R.equi (Elissalde et al., 1980).


Symptoms and Disease Manifestations in Human Beings

 

The most common manifestation of R. equi infection is pneumonia. Other manifestations include pyrexia, diarrhoea, abscessation of thyroid gland, brain, meninges and peritoneum, lymphadenitis, pericarditis, bone and joint inflammation.


Colonic polyps associated with disseminated R. equi infection were reported in a male patient with homosexual orientation (Talanin et al., 1998). Donisi et al. (1996) reported this organism from patients suffering from HIV. Kedlaya et al. (2001) reported that in R. equi infected patients, mortality rate was highest among HIV infected patients, intermediate among non-HIV infected immunocompromised patients and lowest among the immunocompetent patients. Nath et al. (2013) reported granulomatous mastitis in an immunocompetent woman due to this organism. Ferretti et al. (2011) reported dissemination of this bacterial infection in HIV patients even after application of highly active antiretroviral therapy. Brain abscess due to R. equi was reported in an immunocompetent patient who recovered after a prolonged antibiotic therapy (Corne et al., 2002). A case of endophthalmitis was reported in a 9 year old patient (Ebersole and Paturzo, 1988). R. equi infection was reported in a kidney transplant recipient who ultimately died after several relapses within a year (Menon et al., 2012). Speck et al. (2008) reported a mass in lungs due to R. equi infection in a kidney transplant recipient. Guyssens et al. (2010) reported invasive infections with this organism, a pulmonary form and another with brain abscess, both in immunocompromised patients.


Chronic R. equi infection has been reported in 47% of patients with HIV, whereas in patients with non-HIV associated immunocompromised conditions it was reported to be 17% (Verville et al., 1994). Discontinuation of antibiotics may commonly lead to relapse of R. equi infection. Most common site of extra pulmonary relapse is the central nervous system.


An overall mortality rate of about 25% has been reported in these infections (Cornish et al., 1999; Harvey and Sunstrum.1991). Long-term subsidence of disease manifestations have been reported especially in HIV patients (Vladusic et al., 2006).


Capdevila et al. (1997) reported that in HIV patients with R. equi pneumonia, the mortality rate only attributable to R. equi was limited to 15% only.


Prevalence of R.equi infections has been reported three times in men as compared to women with no racial difference (Kedlaya et al., 2001). The high mortality rate in these infections is attributed to lack of early diagnosis, misdiagnosis, insidious nature of disease and requirement of specific and prolonged antibiotic therapy.


Diagnostic procedures

 

Diagnosis in Foals

Firstly diagnosis at most farms is practically made on the basis of clinical symptoms. Confirmation of the disease is dependent on history of occurrence of disease on a farm or endemicity at the farm.

 

These infections are routinely diagnosed by cultural examination, colonial characteristics, staining characteristics and biochemical tests. R.equi grows well on simple solid bacteriological media. Mucoid, tear drop like colonies appear in about two days which coalesce. The salmon pink coloured pigment appears later which deepens in colour over a period of time.

 

Nakazawa et al. (1987) developed an agar gel diffusion test for screening of R.equi in foals at farms. Giguère et al. (2003) evaluated performance of various ELISAs for detection of antibodies to R.equi. However there was poor performance of these assays.

 

In India, only a few reports are available in the literature which include diagnosis of this infection by post mortem examination (Garg et al., 1985; Saxena and Narwal, 2009) and isolation of organism from clinical samples collected from infected foals (Khurana et al., 2009).

 

Since conventional cultural methods cumbersome and time consuming, molecular techniques are desired for early diagnosis to save the foals.

 

PCR assays are employed for detection R. equi infection, which are rapid, sensitive and specific (Sellon et al., 2001; Arriaga et al., 2002; Ladro´n et al., 2003; Pusterla et al., 2007; Letek et al., 2008). The virulence of R. equi is associated with plasmids encoding virulence-associated proteins predominantly protein A (VapA) or protein B (VapB) (Letek et al., 2008; Takai et al., 1991b). Avirulent R. equi have no virulence associated plasmids and are widely distributed in horse premises (Wada et al., 1997). Careful standardization and meticulous optimization is essential for detection of plasmids in R. equi isolates (Takai et al., 1991a; Makrai et al., 2002). A PCR-based assay that differentiates between strains of R. equi with or without plasmid and also discriminates between vapA and vapB plasmid is very valuable (Oldfield et al., 2004; Ocampo-Sosa et al., 2007; Monego et al., 2009).

 

Pathogenesis of R. equi infections is different in humans than from horses. Makrai et al. (2002) showed that 88% of the isolates of R. equi in foals have VapA, which is also reported about 20-25% human isolates. Pig R. equi isolates demonstrate VapB. The isolates of VapA origin are highly virulent, whereas that of VapB origin are of intermediate virulence. About 75% of human isolates expressed VapB (Takai et al., 2003b). IcgA is a factor identified in R. equi that negatively affects its intracellular replication and is another pathogenicity island-encoded protein which has a role in intracellular growth of this organism (Wang et al., 2014). Mc Queen et al. (2014) have identified a region on chromosome 26 associated with R. equi pneumonia in foals based on single nucleotide polymorphism (SNP) and copy number variant (CNV) genome-wide association studies as an evidence that genetic factors might be contributing towards occurrence of R. equi pneumonia in foals.

 

Another PCR assay of R. equi based on ChoE gene which encodes for cholesterol oxidase, is a rapid, sensitive, specific and reliable identification method (Ladro´n et al., 2003).

 

A combination of cultural examination along with PCR based assay is considered valuable for its diagnosis.

 

Differential Diagnosis

The pneumonic form should be differentiated from viral respiratory infections due to rhinovirus, herpesvirus and influenza virus, Streptococcus zooepidemicus, parasitic pneumonia by migrating stages of Parascaris equorum and Pneumocystis cariniia.

 

Diarrhoea should be differentiated from infection due to Salmonella sp., parasitism due to cyathostomes and antibiotic induced diarrhoea. Joint infection should be differentiated from septic arthritis due to Streptococcus zooepidemicus, Salmonella sp. and some other bacteria.

 

Prevention and control strategies

 

Prevention in Equines and Foals

Regular and proper cleaning of foal sheds, proper and frequent disposal of manure along with dust control results in reducing the levels of bacteria effectively, and hence the incidence of R. equi infection. Quaternary ammonium compounds (QACs), hypochlorites, chlorhexidine, iodophors and phenolic compounds are effective for control of R. equi on farms (Dwyer, 1995). Till date, no suitable vaccination is available due to several complicated immunological reasons including occurrence of diseases at a very early stage of life, poor humoral response and intracellular localization of this organism. If foals are administered antibiotics during the first 15 days of life, infection may be reduced to some extent as this is most probable period of infection.

 

Some recent studies are exploring suitable vaccine against this organism. Administration of hyperimmune plasma to foals during the first few days and then again at 3 weeks of age is reported to reduce the incidence and severity of the disease. A recent study has shown that the immunization of pregnant mares with R. equi vaccine candidate having aqueous medium based nanoparticle mineral oil adjuvinated inactive bacterin and VapA along with administration of anti- R. equi hyperimmune plasma in foals may be effective in protection of foals from R. equi infection (Erganis et al. 2014). Bordin et al. (2014) have studied the immunogenicity of an electron beam inactivated R. equi vaccine in foals. They could demonstrate that electron beam inactivates R. equi without affecting cell wall integrity and it was found to be immunogenic in foals when administered enterally. However, till date no effective vaccine is commercially available.

Another method of preventing the disease is simply its early detection. 

 

Treatment in Foals/Equines

The prognosis of R. equi pneumonia is poor even after prolonged treatment. Erythromycin along with rifampin are antibiotics of choice (Hilldge, 1987; Sweeney, 1987). Rifampin is paired with some macrolides for treatment of foals (Giguère et al., 2004). These drug combinations are effective, but have side effects of serious nature. Treatment durations vary from two to eight week. Therapeutic management of the pathogen is complicated due to its intracellular localization making it necessary to administer prolonged treatments, sometimes even more than three months with no guaranteed outcome of successful treatment (Muscatello et al., 2007; Prescott et al., 2010).

 

Treatment in Human beings

Use of combination antibiotics is recommended. Rifampin-erythromycin, rifampin-minocycline, erythromycin-minocycline, imipenem-amikacin have been reported as effective combinations under in vitro conditions (Nordmann et al., 1992). In a case report by Scotton et al., (2000), a meningitis patient was successfully treated with levofloxacin. Munoz et al. (2008) reported successful treatment with linezolid in pulmonary R.equi infection. However use of single antibiotic is not recommended for treatment of systemic R. equi infections.

 

Pulmonary infections require a prolonged course of treatment lasting more than two months. A shorter course of treatment is suggested in immunocompetent patients. Some local R. equi infections also require a shorter course. Early and accurate diagnosis along with proper antibiotic therapy is a key to prevent the relapses in R. equi infections. Local R. equi infections and infections in immunocompetent children have fair chances of successful treatment.

 

Emergence of Antibiotic Resistance

Anderson et al. (1997) demonstrated a highly significant resistance to rifampicin in R. equi attributable to monooxygenase like sequence. Mutations in rpoB gene leading to rifampicin resistance have been reported (Asoh et al., 2013; Liu et al., 2014). Rifampicin resistance has also been reported by other authors (Burton et al., 2013; Goldstein, 2014). Macrolide resistance in R. equi has also been reported (Burton et al., 2013; Liu et al., 2014). A glycopeptides resistance operon vanO having potential implications in R. equi therapy has been described (Gudeta et al., 2014). Cohen (2014) has warned about the challenges of emergence of resistance to macrolide due to non-availability of effective alternative for R. equi therapeutics.

 

Rifampicin along with macrolide is drug of choice for effective treatment of R. equi infections. Therefore emergence of resistance against these antibiotics poses a serious challenge in therapeutic management and there is an urgent need for judicious use of antibiotics.

 

Future outlook

 

There are no suitable serological tests for early and accurate mass screening diagnosis due to complex immunological status of the infection. Suitable vaccination is also not there due to of similar reasons. This organism is very versatile and goes across species. Since the organism resides intracellularly, treatment with conventional antibiotics is not successful. Emergence of multi drug resistant strains is also an upcoming challenge which needs to be researched and tackled suitably. There seems to be a need for early and accurate diagnostic tests so that both foals and human patients may be saved. At present molecular diagnostic tools are available but these are required at grass root level for human patients and in field for foals and other animals. There is a need for development of suitable vaccines especially for foals, but age at which the disease occurs coupled with its complex immunological nature makes the proposition very difficult. Preventing disease by proper management and sanitation at farms is very important. Special care and hygiene for immunocompromised humans is also very essential.

 

References

  • Anderson SJ, Quan S, Gowan B, Dabbs ER (1997). Monooxygenase like sequence of Rhodococcus equi gene conferring increased resistance to rifampin by inactivating this antibiotic. Antimicrob. Agents Chemother. 41(1): 218-221.
  • Arriaga JM, Cohen ND, Derr JN, Chaffin MK, Martens RJ (2002). Detection of Rhodococcus equi by polymerase chain reaction using species-specific non-proprietary primers. J. Vet. Diagn. Invest. 14(4): 347-353.
  • Asoh N, Watanabe H, Fines-Guyon M, Watanabe K, Oishi K, Kositsakulchai W, Sanchai T, Kunsuikmengrai K, Kahintapong S, Khanawa B, Tharavichitkul P, Sirisanthana T, Nagatake T (2013). Emergence of rifampin-resistant Rhodococcus equi with several types of mutations in rpoB gene among AIDS patients in northern Thailand. J. Clin. Microbiol. 41(6): 2337-2340.
  • Barten MD, Embury DH (1987). Studies of the pathogenesis of Rhodococcus equi infections in foals. Aust. Vet. J. 64(11): 332-339.
  • Bell KS, Philp JC, Aw DW, Christofi N (1998). The genus Rhodococcus. J. Appl. Microbiol. 85(2): 195-210.
  • Bordin AI, Pillai SD, Brake C, Bagley KB, Bourquin JR, Coleman M, Oliveira FN, Mwangi W, Mc Murray DN, Love CC, Fillipe MJB, Cohen ND (2014). Immunogenicity of an electron beam inactivated Rhodococcus equi vaccine in neonatal foals. PLoS ONE. 9(8): e105367.doi:10.1371/journal.pone.0105367.
  • Burton AJ, Giguère S, Sturgill TL , Berghaus LJ, Slovis NM, Whitman JL, Levering C, Kuskie KR, Cohen ND (2013). Macrolide-and Rifampin-Resistant Rhodococcus equi on a Horse Breeding Farm, Kentucky, USA. Emerg. Infect. Dis. 19(2): 282-285.
  • Capdevila JA, Bujan S, Gavalda J, Ferrer A, Pahissa A (1997). Rhodococcus equi pneumonia in patients infected with the human immunodeficiency virus. Report of 2 cases and review of the literature. Scand. J. Infect. Dis. 29(6): 535-541.
  • Chaffin MK, Cohen ND, Blodgett GP, Syndergaard M (2013). Do haematologic and ultrasonographic methods predict clinically apparent Rhodococcus equi in foals? Proceedings of the American College of Veterinary Internal Medicine Annual Forum; June 13-15, 2013; Seattle, WA.
  • Cohen ND (2014). Rhodococcus equi foal pneumonia. Vet. Clin. Equine. 30(3): 609-622.
  • Corne P, Rajeebally I, Jonquet O (2002). Rhodococcus equi brain abscess in an immunocompetent patient. Scand. J. Infect. Dis. 34(4): 300-302.
  • Cornish N, Washington JA (1999). Rhodococcus equi infections: clinical features and laboratory diagnosis. Curr. Clin. Top. Infect. Dis. 19: 198-215.
  • Donisi A, Suardi MG, Casari S, longo M, Cadeo GP, Carosi G (1996). Rhodococcus equi infection in HIV-infected patients. AIDS. 10(4): 359-362.
  • Dwyer RM (1995). Disinfecting equine facilities. Rev. Sci. Tech. Off. Int. Epiz.14 (2): 403-418.
  • Ebersole LL, Paturzo JL (1988). Endophthalmitis caused by Rhodococcus equi Prescott serotype 4. J. Clin. Microbiol. 26(6): 1221-1222.
  • Elissalde GS, Renshaw HW, Walberg JA (1980). Corynebacterium equi: An interhost review with emphasis on the foal. Comp. Immunol. Microbiol. Infect. Dis. 3(4): 433-445.
  • Erganis O, Sayin Z, Hadimli HH, Sakmanoglu A, Pinakara Y, Ozdemir O, Maden M (2014). The effectiveness of anti- R. equi hyperimmune plasma against R. equi challenge in thoroughbred Arabian foals of mares vaccinated with R. equi vaccine. Scientific World J. Article ID 480732, http://dx.doi.org/10.1155/2014/480732
  • Ferretti F, Boschini A, Iabichino C, Gerevini S, De Nardi P, Guffanti M, Balconi G, Lazzarin A, Cinque P (2011). Disseminated Rhodococcus equi infection in HIV infection despite high antiretroviral therapy. BMC Infect. Dis. 11: 343.
  • Garg DN, Manchanda VP, Chandramani NK (1985). Etiology of post-natal foal mortality. Ind. J. Comp. Microbiol. Immunol. Infect. Dis. 6(1): 29-35.
  • Giguère S, Prescott JF (1997). Clinical manifestations, diagnosis, treatment, and prevention of Rhodococcus equi infections in foals. Vet. Microbiol. 56: 313-334.
  • Giguère S, Hondalus MK, Yager JA, Darrah P, Mosser DM, Prescott JF (1999). Role of the 85 Kb plasmid and plasmid encoded virulence protein A in intracellular survival and virulence of R.equi. Infect. Immun. 67(7): 3548-3557.
  • Giguère S, Hernandez J, Gaskin J, Prescott JF, Takai S, Miller C (2003). Performance of five serological assays for diagnosis of Rhodococcus equi in foals. Clin. Diagn. Lab. Immunol. 10(2): 241-245.
  • Giguère S, Jacks S, Roberts GD, Hernandez J, Long MT, Ellis C (2004). Retrospective comparison of azithromycin, clarithromycin, and erythromycin for the treatment of foals with Rhodococcus equi pneumonia. J. Vet. Intern. Med. 18(4): 568-573.
  • Giguère S, Lee E, Williams E, Cohen ND, Chaffin MK, Halbert N, Martens RJ, Franklin RP, Clark CC, Slovis NM (2010). Determination of the prevalence of antimicrobial resistance to macrolide antimicrobials or rifampin in Rhodococcus equi isolates and treatment outcome in foals infected with antimicrobial-resistant isolates of R. equi. J. Am. Vet. Med. Assoc. 237(1): 74-81.
  • Giguère S, Cohen ND, Keith Chaffin M, Hines SA, Hondalus MK, Prescott JF, Slovis NM (2011a). Rhodococcus equi: Clinical Manifestations, Virulence, and Immunity. J. Vet. Intern. Med. 25(6): 1221-1230.
  • Giguère S, Cohen ND, Keith Chaffin M, Slovis NM, Hondalus MK, Hines SA, Prescott JF (2011b). Diagnosis, Treatment, Control, and Prevention of Infections Caused by Rhodococcus equi in Foals. J. Vet. Intern. Med. 25(6): 1209-1220.
  • Goldstein BP (2014). Resistance to rifampicin: a review. J. Antibiot. 67(9): 625-630.
  • Goodfellow M, Alderson G (1977). The actinomycete-genus Rhodococcus: A home for “rhodochrous complex”. J. Gen. Microbiol. 100(1): 99-122.
  • Gressler LT, de Vargas AC, da Costa MM, Potter L, da Silveira BP, Sangioni LA, de Avila Botton S (2014). Genotypic and phenotypic detection of efflux pump in Rhodococcus equi. Braz. J. Microbiol. 45(2): 661-665.
  • Gudeta DD, Moodley A, Borotolaia V, Guardabassi L (2014). vanO, a new glycopeptides resistance operon in environmental Rhodococcus equi isolates. Antimicrob. Agents Chemother. 58(3): 1768-1770.
  • Guyssens V, Vandekerckhove L, Colle I, De Rudder P, Blots S, Vogelaers D (2010). Invasive infection with Rhodococcus equi- two case reports and review of literature. Acta. Clin. Belg. 65(4): 271-275.
  • Harvey RL, Sunstrum JC (1991). Rhodococcus equi infection in patients with and without human immunodeficiency virus infection. Rev. Infect. Dis. 13(1): 139-145.
  • Hondalus MK, Mosser DM (1994). Survival and replication of Rhodococcus equi in macrophages. Infect. Immun. 62(10): 4167-4175.
  • Hilldge CJ (1987). Use of erythromycin–rifampin combination in treatment of Rhodococcus equi pneumonia. Vet. Microbiol. 14: 337-342.
  • Hughes KL, Sulaiman I (1987). The ecology of Rhodococcus equi and physicochemical influences on growth. Vet. Microbiol. 14(3): 241-250.
  • Jeckel S, Holmes P, King S, Whatmore AM, Kirkwood I (2011). Disseminated Rhodococcus equi infection in goats in the UK. Vet. Rec. 169(2): 56.
  • Johns I (2013) Management of Rhodococcus equi pneumonia in foals. Vet. Med. Res. Rep. 4: 49-59.
  • Johnson JA, Prescott JF, Markham KJ (1983a). The pathology of experimental Corynebacterium equi in foals following intrabrochial challenge. Vet. Path. 20(4): 440-449.
  • Johnson JA, Prescott JF, Markham KJ (1983b). The pathology of experimental Corynebacterium equi in foals following intragastric challenge. Vet Path. 20(4): 450-459.
  • Kedlaya I, Ing MB, Wong SS (2001). Rhodococcus equi infections in immunocompetent hosts: case report and review. Clin. Infect. Dis. 32(3): E 39-46.
  • Khurana SK, Malik P, Virmani N, Singh BR (2009). Prevalence of Rhodococcus equi infection in foals. Ind. J. Vet. Res. 18(1): 20-22.
  • Khurana SK (2014). Rhodococcus equi infection. In: SR Garg, ed. Zoonoses: bacterial Diseases. Daya Publishing House. New Delhi. India. Pp. 390-401.
  • Khurana SK, Kanu Priya, Singh N, Singha H, Punia S (2014). Comparative analysis of whole cell proteins of Rhodococcus equi isolates using SDS-PAGE. Int. J. Bioassays. 3(3): 1803-1805.
  • Kilcoyne I, Nieto J, Vaughan B (2014). Tibial osteomielitis caused by Rhodococcus equi in a mature horse. Equine Vet. Edu. 26(6): 283-287.
  • Kim SJ, Yook SY, Hwang JS, You M, Jun M (2008). Rhodococcus equi pneumonia in foals in Gyeonggi-do and characterization of isolates from lesions and environment. Korean J. Vet. Res. 48(2): 139-143.
  • Kinne J, Madarame H, Takai S, Jose S, Wernery U (2011). Disseminated Rhodococcus equi infection in dromedary camels (Camelus dromedarius). Vet. Microbiol. 149(1-2): 269-272.
  • Ladro´n N, Ferna´ndez M, Agu¨ero J, Zo¨rn BG, Va´zquez-Boland JA, Navas J (2003). Rapid identification of Rhodococcus equi by a PCR assay targeting the choE gene. J. Clin. Microbiol. 41(7): 3241–3245.
  • Lavoie JP, Fiset L, Laverty S (1994). Review of 40 Cases of Lung Abscesses in Foals and Adult Horses. Equine Vet. J. 26(5), 348-352.
  • Letek M, Ocampo-Sosa AA, Sanders M, Fogarty U, Buckley T, Leadon DP, Gonza´lez P, Scortti M, Meijer WG, Parkhill J, Bentley S, Va´zquez-Boland JA (2008). Evolution of the Rhodococcus equi vap pathogenicity island seen through comparison of host-associated vapA and vapB virulence plasmids. J. Bacteriol. 190: 5797-5805.
  • Liu H, Wang Y, Yan J, Wang C, He H (2014). Appearance of multidrug-resistant virulent Rhodococcus equi clinical isolates obtained in China. J. Clin. Microbiol. 52(2): 703.
  • Lopez AM, Hines MT, Palmer GH, Alperin DC, Hines SA (2002). Identification of pulmonary T-lymphocyte and serum antibody isotype responses associated with protection against Rhodococcus. Clin. Diagn. Lab. Immunol. 9(6): 1270-1276.
  • Makrai L, Takai S, Tamura M, Tsukamoto A, Sekimoto R, Sasaki Y, Kakuda T, Tsubaki S, Varga J, Fodor L, Solymosi N, Major A (2002). Characterization of virulence plasmid types in Rhodococcus equi isolates from foals, pigs, humans and soil in Hungary. Vet. Microbiol. 88(4): 377-384.
  • Magnusson H (1923). Spezifische infektiose Pneumonie beim Fohlen. Ein neuer Eiterreger beim Pferd. Arch. Wiss. Prakt. Tierhelkd. 50: 22-38.
  • Martens RJ, Fiske RA, Renshaw HW (1982). Experimental subacute foal pneumonia inducible by aerosol administration of Corynebacterium equi. Equine Vet. J. 14(2): 111-116.
  • Mc Queen CM, Doan R, Dindot SV, Bourquin JR, Zlatev ZZ, Chaffin MK, Blodgett GP, Ivanov I (2014). Identification of genetic loci associated with Rhodococcus equi susceptibility in foals. PLoS ONE 9(6): e98710.doi: 10.1371/journal.pone.0098710
  • Menon V, Gottlib T, Gallagher M, Cheong EL (2012). Persistent Rhodococcus equi infection in a renal transplant patient: case report and review of literature. Transpl. Infect. Dis. 14(6): E 126-133.
  • Mizuno Y, Sato F, Sakamoto M, Yoshikawa K, Yoshida M, Shiba K, Onodera S, Matsuura R, Takai SJ (2005).VapB-positive Rhodococcus equi infection in an HIV-infected patient in Japan. J. Infect. Chemother. 11(1): 37-40.
  • Monego F, Maboni F, Krewer C, Vargas A, Costa M, Loreto E (2009). Molecular characterization of Rhodococcus equi from horse-breeding farms by means of multiplex PCR for the vap gene family. Curr. Microbiol. 58(4): 399-403.
  • Munoz P, Palomo J, Guinea J, Yanez J, Gianella M, Bouza E (2008). Relapsing Rhodococcus equi infection in a heart transplant recipient successfully treated with long-term linezolid. Diagn. Microbiol. Infect. Dis. 60(2):197-199.
  • Muscatello G, Leadon DP, Klay M, Ocampo-Sosa A, Lewis DA, Fogarty U, Buckley T, Gilkerson JR, Meijer WG, Vazquez-Boland JA (2007). Rhodococcus equi infection in foals: the science of rattles. Equine Vet. J. 39(5): 470-478.
  • Muscatello G (2009). Detection of virulent Rhodococcus in exhaled air samples from naturally infected foals. J. Clin. Microbiol. 47(3): 734-737.
  • Muscatello G (2012). Rhodococcus equi pnemonia in the foals- Part 1: Pathogenesis and Epidemiology. Vet. J. 192(1): 20-26.
  • Mutimer MD, Woolcock JB (1980). Corynebacterium equi in cattle and pigs. Tijdschr. Diergeneeskd. 105: 25-27.
  • Nakazawa M, Isayama Y, Kashiwazaki M, Yasui T (1987). Diagnosis of Rhodococcus equi infoals by agar gel diffusion test with protein antigen. Vet. Microbiol. 41(7): 3241-3245.
  • Napoleão F, Damasco P V, Camello T C, do Vale M D, de Andrade A F, Hirata R Jr, de Mattos-Guaraldi A L (2005). Pyogenic liver abscess due to Rhodococcus equi in an immunocompetent host. J. Clin. Microbiol. 43: 1002-1004.
  • Nath SR, Mathew AP, Mohan A, Anila KR (2013). Rhodococcus equi granulomatous mastitis in an immuno-competent patient - A case report. J. Med. Microbiol. 62(pt 8): 1253-1255.
  • Nordmann P, Kerestedjian J J, Ranco E (1992). Therapy of Rhodococcus equi disseminated infections in nude mice. Antimicrob. Agents Chemother. 36(6): 1244-1248.
  • Ocampo-Sosa AA, Lewis DA, Navas J, Quigley F, Callejo R, Scortti M, Leadon DP, Fogarty U, Va´zquez-Boland JA (2007). Molecular epidemiology of Rhodococcus equi based on traA, vapA, and vapB virulence plasmid markers. J. Infect. Dis. 196(5): 763-769.
  • Oldfield C, Bonella H, Renwick L, Dodson HI, Alderson G, Goodfellow M (2004). Rapid determination of vapA/vapB genotype in Rhodococcus equi using a differential polymerase chain reaction method. Antonie Van Leeuwenhoek. 85(4): 317-326.
  • Prescott JF (1991). Rhodococcus equi an animal and human pathogen. Clin. Microbiol. Rev. 4(1): 20-34.
  • Prescott JF, Meijer WG, Vazquez-Boland JA (2010). Rhodococcus In: L Gyles JFP, J.G. Songer, C Theon, eds. Pathogenesis of Bacterial Infections in Animals: Wiley-Blackwell. Pp. 149-166.
  • Pusterla N, Wilson WD, Mapes S, Leutenegger CM (2007). Diagnostic evaluation of real-time PCR in the detection of Rhodococcus equi in faeces and nasopharyngeal swabs from foals with pneumonia. Vet. Rec. 161(8): 272-275.
  • Sanger Institute (2008). The sequence data were produced by the Rhodococcus equi Sequencing Group at the Sanger Institute.
  • Saxena V, Narwal PS (2009). Rhodococcus equi infection in foals. J. Remount Vet. Corps. 48: 27-31.
  • Sellon DC, Besser TE, Vivrette SL, McConnico RS (2001). Comparison of nucleic acid amplification, serology, and microbiologic culture for diagnosis of Rhodococcus equi pneumonia in foals. J. Clin. Microbiol. 39(4): 1289-1293.
  • Scotton PG, Tonon E, Giobbia M, Gallucci M, Rigoli R, Vaglia (2000). Rhodococcus equi nosocomial meningitis cured by levofloxacin and shunt removal. Clin. Infect. Dis. 30(1): 223-224.
  • Soedarmanto I, Oliveira R, Lammler C, Durrling H (1997). Identification and epidemiological relationship of Rhodococcus equi isolated from cases of lymphadenitis in cattle. Zentrabl. Bakteriol. Parasitenkd. Infektkrankh. Hyg. Abt. 1 Orig. 286(4): 457-466.
  • Speck D, Koneth I, Diethelm M, Binet I (2008). A pulmonary mass caused by Rhodococcus equi infection in a renal transplant recipient. Nat. Clin. Pract. Nephrol. 4: 398-403.
  • Sweeney CR, Sweeney RW, Divers TJ (1987). Rhodococcus equi pneumonia in 48 foals: response to antimicrobiol therapy. Vet. Microbiol. 14(3): 329-336.
  • Talanin NY, Donabedian H, Kaw M, Kaw M, O’Donnell ED, Zaher A (1998). Colonic polyps and disseminated infection associated with Rhodococcus equi in a patient with AIDS. Clin. Infect. Dis. 26(5): 1241-1242. 
  • Takai S, Koike K, Ohbushi S, Izumi C, Tsubaki S (1991a). Identification of 15-to 17-kilodalton antigens associated with virulent Rhodococcus equi. J. Clin. Microbiol. 29(11): 439-443.
  • Takai S, Sekizaki T, Ozawa T, Sugawara T, Watanabe Y, Tsubaki S (1991b). Association between a large plasmid and 15- to 17-Kilodalton antigen in virulent Rhodococcus equi. Infect. Immun. 59(3): 4056-4060.
  • Takai S (1997). Epidemiology of Rhodococcus equi infections: a review. Vet. Microbiol. 56(3-4): 167-176.
  • Takai S, Martens RJ, Julian A, Garcia RM, Rodrigues DF, Sasaki Y, Inuzuka K, Kakuda T, Tsubaki S, Prescott JF (2003a). Virulence of Rhodococcus equi isolated from cats and dogs. J. Clin. Microbiol. 41(9): 4468-4470.
  • Takai S, Tharavichitkul P, Takarn P, Khantawa B, Tamura M, Tsukamoto A,Takayama S,Yamatoda N, Kimura A, Sasaki Y, Kakuda T,Tsukaki S, Maneekarn N, Sirisanthana T, Kirikae T (2003b). Molecular epidemiology of Rhodococcus equi of intermediate virulence isolated from patients with and without acquired immune deficiency syndrome in Chiang Mai, Thailand. J. Infect. Dis. 88(11):1717-1723.
  • Tkachuksaad O, Prescott J (1991). Rhodococcus equi Plasmids -Isolation and partial characterization. J. Clin. Microbiol. 29(12): 2696-2700.
  • Vazquez-Boland JA, Prescott JF, Meijer WG, Leadon DP, Hines SA (2009). Rhodococcus comes of age. Equine Vet. J. 41(1). 93-95.
  • Vazquez-Boland JA, Giguère S, Hapeshi H, Mc Arthur I, Anastasi E, Valero-rello A (2013). Rhodococcus equi: The many facets of pathogenic actinomycete. Vet. Microbiol. 167(1-2): 9-33.
  • Venner M, Rodiger A, Lammer M, Giguère S (2012). Failure of antimicrobial therapy to accelerate spontaneous healing of subclinical pulmonary abscesses on a farm with endemic infections caused by Rhodococcus equi. Vet. J. 192(3): 293-298.
  • Venner M, Astheimer K, Lammer M, Giguère S (2013). Efficacy of mass anti-microbial treatment of foals with subclinical pulmonary abscesses associated with Rhodococcus equi. J. Vet. Intern. Med. 27(1): 171-176.
  • Verville TD, Huycke MM, Greenfield RA, Fine DP, Kuhls Tl, Slater LN (1994). Rhodococcus equi infections of humans. 12 cases and a review of the literature. Medicine (Baltimore). 73(3): 119-132.
  • Vladusic I, Krajinovic V, Begovac J (2006). Long term survival after Rhodococcus equi pneumonia in a patient with human immunodeficiency virus infection in the era of highly active antiretroviral therapy: case report and review. Acta. Med. Croatica. 60(3): 259-63.
  • von Bargen K, Haas A (2009). Molecular and infection biology of the horse pathogen Rhodococcus. FEMS Microbiol. Rev. 33(5); 870-891.
  • Wada R, Kamada M, Anzai T, Nakanishi A, Kanemaru T, Takai S, Tsubaki S (1997). Pathogenicity and virulence of Rhodococcus equi in foals following intratracheal challenge. Vet. Microbiol. 56: 301-312.
  • Wang X, Coulson GB, Miranda- Casoluengo AA, Miranda- Casoluengo R, Hondalus MK, Meijer WG (2014). IcgA is a virulence factor of Rhodococcus equi that modulates intracellular growth. Infect. Immunity. 82(5): 1793-1800.
  • Watts A (2014). Osteomyelitis caused by Rhodococcus equi infection in the horse. Equine Vet. Educ. 26(6): 287.
  • Weinstock DM, Brown AE (2002). Rhodococcus equi: An emerging pathogen. Clin. Infect. Dis. 34(10): 1379-1385.
  • Wichtel MG, Anderson KL, Johnson TV, Nathan U, Smith L (1991). Influence of age on neutrophil function in foals. Equine Vet. J. 23(6): 466-469.
  • Yager JA, Prescott CA, Kramar DP, Hannah H, Balson GA, Croy B.A (1991). The effect of experimental infection with Rhodococcus equi on immunodeficient mice. Vet. Microbiol. 28(4): 363-376.
  • Advances in Animal and Veterinary Sciences

    November

    Vol. 12, Iss. 11, pp. 2062-2300

    Featuring

    Click here for more

    Subscribe Today

    Receive free updates on new articles, opportunities and benefits


    Subscribe Unsubscribe