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			<p class="Type-of-Article"><span class="CharOverride-1">Review Article</span></p>
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			<p class="title- ParaOverride-1">Current Understanding of <span class="CharOverride-2">Rhodococcus equi</span> Infection and its Zoonotic Implications</p>
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			<p class="Authors"><span class="CharOverride-3">Sandip Kumar Khurana</span></p>
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			<p class="Affiliations">National Research Centre on Equines, Sirsa Road, Hisar (Haryana)-125 001, India.</p>
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			<p class="Abstract ParaOverride-1"><span class="CharOverride-4">Abstract</span> | <span class="Emphasis">Rhodococcus equi</span><span class="Emphasis CharOverride-5"> 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 </span><span class="Emphasis">R. equi</span> <span class="Emphasis CharOverride-5">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.  </span></p>
			<p class="Abstract ParaOverride-1"><span class="CharOverride-4">Keywords </span>| <span class="Emphasis">Rhodococcus equi, </span><span class="Emphasis CharOverride-5">Foals, Diagnosis, Treatment</span></p>
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			<p class="Editor----Citation"><span class="CharOverride-8">Editor</span><span class="CharOverride-9"> | Kuldeep Dhama, Indian</span> Veterinary Research Institute, Uttar Pradesh, India.</p>
			<p class="Editor----Citation"><span class="CharOverride-4">Received</span> | October 18, 2014; <span class="CharOverride-4">Revised</span> | December 05, 2014; <span class="CharOverride-4">Accepted</span> | December 07, 2014; <span class="CharOverride-4">Published</span> | December 11, 2014&#9;&#9;</p>
			<p class="Editor----Citation"><span class="CharOverride-4">*Correspondence </span>| Sandip Kumar Khurana, National Research Centre on Equines, Sirsa Road, Hisar, India; <span class="CharOverride-4">Email:</span> sandipkk2003@yahoo.co.in</p>
			<p class="Editor----Citation"><span class="CharOverride-4">Citation</span> | Khurana SK (2015). Current understanding of <span class="CharOverride-10">Rhodococcus equi</span> infection and its zoonotic implications. Adv. Anim. Vet. Sci. 3(1): 1-10.  </p>
			<p class="Editor----Citation"><span class="CharOverride-8">DOI</span><span class="CharOverride-9"> | http://dx.doi.org/10.14737/journal.aavs/2015/3.1.1.10</span></p>
			<p class="Editor----Citation"><span class="Editor---Citation CharOverride-4" lang="en-US">ISSN </span><span class="Editor---Citation CharOverride-4" lang="en-US">(</span><span class="Editor---Citation CharOverride-4" lang="en-US">Online</span><span class="Editor---Citation CharOverride-4" lang="en-US">)</span><span class="Editor---Citation" lang="en-US"> | </span><span class="Editor---Citation" lang="en-US">2307-8316; </span><span class="Editor---Citation CharOverride-4" lang="en-US">ISSN </span><span class="Editor---Citation CharOverride-4" lang="en-US">(Print)  | </span><span lang="en-US">2309-3331</span></p>
			<p class="Editor----Citation"><span class="CharOverride-8">Copyright </span><span class="CharOverride-9">© 2015 </span>Khurana.<span class="CharOverride-9"> 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.</span></p>
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			<p class="Heading-1--Introduction----">Introduction</p>
			<p class="Caps-on-First-Para ParaOverride-1"><span class="_idGenDropcap-1">R</span><span class="Emphasis">hodococcus </span><span class="Emphasis CharOverride-12">equi</span><span class="Emphasis"> </span>is a gram-positive, aerobic, non-motile, pleomorphic coccobacillus having simple nutritional <span class="CharOverride-5">r</span><span class="CharOverride-13">equi</span><span class="CharOverride-5">re</span>ments 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.  <span class="Emphasis"> </span></p>
			<p class="Body-Text ParaOverride-1"><span class="Emphasis CharOverride-5">This organism</span> is causative agent of zoonotic infections in horses, foals and some other herbivorous animals (<span class="Hyperlink">Giguère et al., 2011a, b</span>). <span class="CharOverride-10">R. equi</span> mostly affects foals aged between one to four months (<a href="#Tkachuksaad-O--Prescott-J--1991-"><span class="Hyperlink">Tkachuksaad and Prescott, 1991</span></a>; <a href="#Yager-JA--Prescott-CA--Kramar-DP--Hannah-H--Balson-GA--Croy-B.A--1991-."><span class="Hyperlink">Yager et al., 1991</span></a>; <a href="#von-Bargen-K--Haas-A--2009-."><span class="Hyperlink">von Bargen and Haas, 2009</span></a>). Disease occurs in adult horses rarely and in horses with severe immunodeficiency. The extra-pulmonary complications due to <span class="CharOverride-10">R. equi </span>include enteritis often with necrosis, bone and joint infections, lymphadenopathy, diarrhoea, and abscesses in abdomen and uveitis (<a href="#Gigu-re-S--Prescott-JF--1997-"><span class="Hyperlink">Giguère and Prescott, 1997</span></a>). <span class="Emphasis">R. equi</span> was first recovered from lung of a foal with respiratory illness as <span class="Emphasis">Corynebacterium equi</span><span class="Emphasis CharOverride-5"> in Sweden</span><span class="Emphasis"> </span><span class="Emphasis CharOverride-5">(</span><a href="#Magnusson-H--1923-."><span class="Hyperlink">Magnusson, 1923</span></a>). Later, it was classified as <span class="CharOverride-10">R. equi</span> (<a href="#Goodfellow-M--Alderson-G--1977-."><span class="Hyperlink">Goodfellow and Alderson, 1977</span></a>). </p>
			<p class="Body-Text ParaOverride-1"><span class="Emphasis">R. equi</span> 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 <span class="Emphasis">R. equi</span> as opportunistic pathogen in AIDS patients (<a href="#Weinstock-DM--Brown-AE--2002"><span class="Hyperlink">Weinstock and Brown, 2002</span></a>), drug therapy (<a href="#Mizuno-Y--Sato-F---Sakamoto-M---Yoshikawa-K---Yoshida-M---Shiba-K---Onodera-S--Matsuura-R---Takai-SJ"><span class="Hyperlink">Mizuno et al., 2005</span></a>) and other immunosuppressive conditions (<a href="#Napole-o-F--Damasco--P-V--Camello--T-C--do-Vale--M-D--de-Andrade--A-F--Hirata--R-Jr--de-Mattos-Guara"><span class="Hyperlink">Napoleão et al., 2005</span></a>). </p>
			<p class="Body-Text ParaOverride-1">Treatment requires prolonged combination antibiotic therapy, primarily due to intracellular localization of this pathogen. It is reported by von <a href="#Barten-MD--Embury-DH--1987-"><span class="Hyperlink">Bargen and Hass (2009)</span></a> that this organism<span class="Emphasis CharOverride-5"> arrests the phagosome maturation and resultantly forms a special niche inside the host cells. </span>Surgical intervention also becomes essential in some instances. </p>
			<p class="Body-Text ParaOverride-1">The disease is direct anthropozoonosis since the animals are primary reservoirs of the etiological agent (<a href="#Khurana-SK--2014-.-Rh"><span class="Hyperlink">Khurana, 2014</span></a>). Comparative analysis of whole cell proteins of<span class="Emphasis"> R. equi </span><span class="Emphasis CharOverride-5">isolates from different geographical locations in India revealed varied protein banding patterns, thus varied on molecular epidemiological basis</span><span class="Emphasis"> </span>(<a href="#Khurana-SK--Kanu-Priya--Singh-N--Singha-H--Punia-S--2014-."><span class="Hyperlink">Khurana et al., 2014</span></a>), however comparable reports are not available from other countries.</p>
			<p class="Body-Text ParaOverride-1">The knowledge about pathogenesis, immunity, diagnostic methods, preventive and therapeutic management approaches regarding <span class="Emphasis">R. equi </span><span class="Emphasis CharOverride-5">has increased gradually, but still no effective vaccine is available apart from newer managemental challenges including appearance of multidrug resistant virulent strains of </span><span class="Emphasis">R. equi </span><span class="Emphasis CharOverride-5">(</span><a href="#Gigu-re-S--Lee-E--Williams-E--Cohen-ND--Chaffin-MK--Halbert-N--Martens-RJ--Franklin-RP--Clark-CC--Sl"><span class="Hyperlink">Gigu</span><span class="Hyperlink CharOverride-14" lang="en-US">è</span><span class="Hyperlink">re et al., 2010</span></a>; <a href="#Venner-M--Rodiger-A--Lammer-M--Gigu-re-S--2012-."><span class="Hyperlink">Venner et al., 2012</span></a><span class="Emphasis CharOverride-5">, </span><a href="#Venner-M--Astheimer-K--Lammer-M--Gigu-re-S--2013-."><span class="Hyperlink">2013</span></a><span class="Emphasis CharOverride-5">; </span><a href="#Burton-AJ--Gigu-re-S--Sturgill-TL---Berghaus-LJ--Slovis-NM--Whitman-JL--Levering-C--Kuskie-KR--Cohen"><span class="Hyperlink">Burton et al., 2013</span></a>; <a href="#Chaffin-MK--Cohen-ND--Blodgett-GP--Syndergaard-M--2013-"><span class="Hyperlink">Chaffin et al., 2013</span></a>). <a href="#Muscatello-G--2012-.-R"><span class="Hyperlink">Muscatello (2012)</span></a> has reviewed the details regarding management, diagnosis, treatment, immunity, pathogenesis and epidemiology of <span class="Emphasis">R. equi i</span><span class="Emphasis CharOverride-5">nfections. Vazquez-</span><a href="#Bordin-AI--Pillai-SD--Brake-C--Bagley-KB--Bourquin-JR--Coleman-M--Oliveira-FN--Mwangi-W--Mc-Murray-D"><span class="Hyperlink">Boland et al. (2013)</span></a><span class="Emphasis CharOverride-5"> 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</span><span class="Emphasis"> R. equi </span><span class="Emphasis CharOverride-5">infections as well as anthropozoonotic aspects.</span></p>
			<p class="Heading-1--Introduction----">Etiology of Infection<span class="Emphasis CharOverride-2"> </span></p>
			<p class="Body-Text ParaOverride-1"><span class="Emphasis">R. equi</span> is a gram-positive, pleomorphic coccobacillus and an intracellular pathogen of macrophages.<span class="Emphasis"> </span><span class="Emphasis CharOverride-5">It</span> is catalase positive, oxidase negative and usually urease positive. The organism is known as <span class="Emphasis">Rhodococcus</span> because it forms salmon pink-coloured colonies on solid media due to pigmentation. <span class="CharOverride-10">Rhodococcus</span> species include symbionts as well as animal, human and plant pathogens (<a href="#Bell-KS--Philp-JC--Aw-DW--Christofi-N--1998-"><span class="Hyperlink">Bell et al., 1998</span></a>). The organism is mainly soil bacteria having simple nutritional requirements and grows well in animal manure.</p>
			<p class="Heading-1--Introduction----">Host Range among Animals and Humans</p>
			<p class="Body-Text ParaOverride-1"><span class="CharOverride-10">R. equi</span> primarily affects equines especially foals aged between one to four months (<a href="#Prescott-JF--1991-"><span class="Hyperlink">Prescott, 1991</span></a>; <a href="#Takai-S--Martens-RJ--Julian-A--Garcia-RM--Rodrigues-DF--Sasaki-Y--Inuzuka-K--Kakuda-T--Tsubaki-S--Pr"><span class="Hyperlink">Takai, 1997</span></a>). Cattle (<a href="#Soedarmanto-I--Oliveira-R--Lammler-C--Durrling-H--1997-."><span class="Hyperlink">Soedarmanto et al., 1997</span></a>), pigs (<a href="#Mutimer-MD--Woolcock-JB--1980-.-C"><span class="Hyperlink">Mutimer and Woolcock, 1980</span></a>; <a href="#Soedarmanto-I--Oliveira-R--Lammler-C--Durrling-H--1997-."><span class="Hyperlink">Soedarmanto et al., 1997</span></a>), goats (<a href="#Jeckel-S--Holmes-P--King-S--Whatmore-AM--Kirkwood-I--2011-."><span class="Hyperlink">Jeckel</span><span class="Hyperlink CharOverride-10"> </span><span class="Hyperlink">et al., 2011</span></a>), camels (<a href="#Kinne-J--Madarame-H--Takai-S--Jose-S--Wernery-U--2011-."><span class="Hyperlink">Kinne et al., 2011</span></a>), dogs (<a href="#Takai-S--Tharavichitkul-P--Takarn-P--Khantawa-B--Tamura-M--Tsukamoto-A-Takayama-S-Yamatoda-N--Kimura"><span class="Hyperlink">Takai et al., 2003a</span></a>), cats (<a href="#Takai-S--Tharavichitkul-P--Takarn-P--Khantawa-B--Tamura-M--Tsukamoto-A-Takayama-S-Yamatoda-N--Kimura"><span class="Hyperlink">Takai et al., 2003a</span></a>) and human beings (<a href="#Weinstock-DM--Brown-AE--2002"><span class="Hyperlink">Weinstock and Brown, 2002</span></a>) are also affected. This organism has been isolated from a number of terrestrial and aquatic animals like crocodiles, several avian species and arthropods (<a href="#Prescott-JF--Meijer-WG--Vazquez-Boland-JA--2010-."><span class="Hyperlink">Prescott, 1991</span></a>). <span class="Emphasis">R. equi</span> in human beings is reported as opportunistic pathogen in AIDS patients (<a href="#Weinstock-DM--Brown-AE--2002"><span class="Hyperlink">Weinstock and Brown, 2002</span></a>), drug therapy (<a href="#Mizuno-Y--Sato-F---Sakamoto-M---Yoshikawa-K---Yoshida-M---Shiba-K---Onodera-S--Matsuura-R---Takai-SJ"><span class="Hyperlink">Mizuno et al., 2005</span></a>) and other immunosuppressive conditions (<a href="#Napole-o-F--Damasco--P-V--Camello--T-C--do-Vale--M-D--de-Andrade--A-F--Hirata--R-Jr--de-Mattos-Guara"><span class="Hyperlink">Napoleão et al., 2005</span></a>).</p>
			<p class="Heading-1--Introduction----">Geographical Distribution</p>
			<p class="Body-Text ParaOverride-1">The disease is present worldwide with highly variable pattern (<a href="#Hughes-KL--Sulaiman-I--1987-.-The-ecology-of-Rhodococcus-equi-and-physicochemical-influences-on"><span class="Hyperlink">Hughes and Sulaiman, 1987</span></a>). 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 (<a href="#Prescott-JF--1991-"><span class="Hyperlink">Prescott, 1991</span></a>). Disease was reported in India (<a href="#Garg-DN--Manchanda-VP--Chandramani-NK--1985-"><span class="Hyperlink">Garg et al., 1985</span></a>; <a href="#Khurana-SK--Malik-P--Virmani-N--Singh-BR--2009-."><span class="Hyperlink">Khurana et al., 2009</span></a>; <a href="#Saxena-V--Narwal-PS--2009-."><span class="Hyperlink">Saxena and Narwal, 2009</span></a>). The prevalence of <span class="Emphasis">R. equi </span><span class="Emphasis CharOverride-5">has been reported from several countries including Argentina, Australia, Canada, France, Hungary, Japan, Ireland and others (</span><a href="#Ocampo-Sosa-AA--Lewis-DA--Navas-J--Quigley-F--Callejo-R--Scortti-M--Leadon-DP--Fogarty-U--Va-zquez-B"><span class="Hyperlink">Ocampo-Sosa et al., 2007</span></a><span class="Emphasis CharOverride-5">).</span> <span class="Emphasis">R. equi </span><span class="Emphasis CharOverride-5">infections have been also reported from Thailand (</span><a href="#Asoh-N--Watanabe-H--Fines-Guyon-M--Watanabe-K--Oishi-K--Kositsakulchai-W--Sanchai-T--Kunsuikmengrai"><span class="Hyperlink">Asoh et al., 2003</span></a><span class="Emphasis CharOverride-5">), Korea (</span><a href="#Kim-SJ--Yook-SY--Hwang-JS--You-M--Jun-M--2008-"><span class="Hyperlink">Kim et al., 2008</span></a><span class="Emphasis CharOverride-5">), USA (</span><a href="#Weinstock-DM--Brown-AE--2002"><span class="Hyperlink">Weinstock and Brown, 2002</span></a><span class="Emphasis CharOverride-5">; </span><a href="#Burton-AJ--Gigu-re-S--Sturgill-TL---Berghaus-LJ--Slovis-NM--Whitman-JL--Levering-C--Kuskie-KR--Cohen"><span class="Hyperlink">Burton et al., 2013</span></a><span class="Emphasis CharOverride-5">), Denmark (</span><a href="#Gudeta-DD--Moodley-A--Borotolaia-V--Guardabassi-L--2014-.-vanO--a-new-glycopeptides-resistance-opero"><span class="Hyperlink">Gudeta et al., 2014</span></a><span class="Emphasis CharOverride-5">), Brazil (</span><a href="#Gressler-LT--de-Vargas-AC--da-Costa-MM--Potter-L--da-Silveira-BP--Sangioni-LA--de-Avila-Botton-S--20"><span class="Hyperlink">Gressler et al., 2014</span></a><span class="Emphasis CharOverride-5">) and China (</span><a href="#Liu-H--Wang-Y--Yan-J--Wang-C--He-H--2014-."><span class="Hyperlink">Liu et al., 2014</span></a><span class="Emphasis CharOverride-5">).</span></p>
			<p class="Heading-1--Introduction----">Transmission of Disease </p>
			<p class="Body-Text ParaOverride-1">The main route of exposure is by inhalation or ingestion (<a href="#Martens-RJ--Fiske-RA--Renshaw-HW--1982"><span class="Hyperlink">Martens</span><span class="Hyperlink CharOverride-4"> </span><span class="Hyperlink">et al., 1982</span></a>; <a href="#Johnson-JA--Prescott-JF--Markham-KJ--1983a-."><span class="Hyperlink">Johnson et al., 1983a</span></a>, <a href="#Johnson-JA--Prescott-JF--Markham-KJ--1983b-.-Th"><span class="Hyperlink">1983b</span></a>). The organism<span class="CharOverride-10"> </span>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 <span class="Emphasis">R. equi </span><span class="Emphasis CharOverride-5">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 </span><span class="CharOverride-16">10</span><span class="CharOverride-17">4</span><span class="Emphasis CharOverride-5"> cfu of virulent </span><span class="Emphasis">R. equi </span><span class="Emphasis CharOverride-5">(</span><a href="#Barten-MD--Embury-DH--1987-"><span class="Hyperlink">Barten and Embury, 1987</span></a><span class="Emphasis CharOverride-5">; </span><a href="#Wada-R--Kamada-M--Anzai-T--Nakanishi-A--Kanemaru-T--Takai-S--Tsubaki-S--1997-."><span class="Hyperlink">Wada et al., 1997</span></a><span class="Emphasis CharOverride-5">). </span></p>
			<p class="Body-Text ParaOverride-1"><span class="CharOverride-10">R. equi</span> 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 <span class="CharOverride-10">R. equi</span> (<a href="#Weinstock-DM--Brown-AE--2002"><span class="Hyperlink">Weinstock and Brown, 2002</span></a>). Airborne <span class="CharOverride-10">R. equi</span> bacteria are the major source of disease transmission at farms, but has direct correlation with age and immunological status of foals (<a href="#Muscatello-G--2009-."><span class="Hyperlink">Muscatello, 2009</span></a>). The most susceptible age is one to four months and immunologically deficient foals are more vulnerable. </p>
			<p class="Body-Text ParaOverride-1">Human beings acquire infection by inhalation of airborne bacteria from dust or soil, wound or mucous membrane inoculation and from domestic animals harbouring <span class="CharOverride-10">R. equi</span> (<a href="#Weinstock-DM--Brown-AE--2002"><span class="Hyperlink">Weinstock and Brown, 2002</span></a>). Horizontal transmission among human beings is rarely understood (<a href="#Weinstock-DM--Brown-AE--2002"><span class="Hyperlink">Weinstock and Brown, 2002</span></a>).</p>
			<p class="Body-Text ParaOverride-1">  </p>
			<p class="Heading-1--Introduction----">Symptoms and Disease Manifestations in Foals/Equine</p>
			<p class="Body-Text ParaOverride-1">The disease usually occurs in one to four month old foals (<a href="#Tkachuksaad-O--Prescott-J--1991-"><span class="Hyperlink">Tkachuksaad and Prescott, 1991</span></a>; <a href="#Yager-JA--Prescott-CA--Kramar-DP--Hannah-H--Balson-GA--Croy-B.A--1991-."><span class="Hyperlink">Yager et al., 1991</span></a>; <a href="#von-Bargen-K--Haas-A--2009-."><span class="Hyperlink">von Bargen and Haas, 2009</span></a>). 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 (<a href="#Hondalus-MK--Mosser-DM--1994-."><span class="Hyperlink">Hondalus and Mosser, 1994</span></a>). Protective immunity develops in adult horses and in some foals which clears the infection<span class="CharOverride-10"> </span>(<a href="#Lopez-AM--Hines-MT--Palmer-GH--Alperin-DC--Hines-SA--2002-."><span class="Hyperlink">Lopez et al., 2002</span></a>). 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 (<a href="#Wichtel-MG--Anderson-KL--Johnson-TV--Nathan-U--Smith-L--1991-."><span class="Hyperlink">Wichtel et al., 1991</span></a>; <a href="#Lavoie-JP--Fiset-L--Laverty-S--1994"><span class="Hyperlink">Lavoie et al., 1994</span></a>). The disease may spread from lungs to other organs and joints (<a href="#Prescott-JF--1991-"><span class="Hyperlink">Prescott, 1991</span></a>). Ulcerative enteritis, mucosal invasion of the bacteria along with diarrhoea is usual feature in chronic cases (<a href="#Bell-KS--Philp-JC--Aw-DW--Christofi-N--1998-"><span class="Hyperlink">Bell et al., 1998</span></a>; <a href="#Vazquez-Boland-JA--Gigu-re-S--Hapeshi-H--Mc-Arthur-I--Anastasi-E--Valero-rello-A--2013-"><span class="Hyperlink">Vazquez-boland et al., 2009</span></a>). Development of uveitis, anaemia and thrombocytopenia, occasionally arthritis and osteomyelitis are also seen (<a href="#Gigu-re-S--Hondalus-MK--Yager-JA--Darrah-P--Mosser-DM--Prescott-JF--1999-"><span class="Hyperlink">Giguère et al., 1999</span></a>). Osteomyelitis due to <span class="CharOverride-10">R.equi </span>infection has been described in a mature immunocompetent horse (<a href="#Watts-A--2014-"><span class="Hyperlink">Watts, 2014</span></a>; <a href="#Kilcoyne-I--Nieto-J--Vaughan-B--2014-"><span class="Hyperlink">Kilcoyne et al., 2014</span></a>).<span class="CharOverride-10"> </span>Concurrent extra-pulmonary disorders are reported in about 74% foals, though pneumonia is primary clinical manifestation (<a href="#Johns-I--2013--Management-of-R"><span class="Hyperlink">Johns, 2013</span></a>).  </p>
			<p class="Body-Text ParaOverride-1">Morbidity and mortality rates were reported to be 5-17% and 40-80% respectively in foals due to <span class="CharOverride-10">R.equi </span>(<a href="#Elissalde-GS--Renshaw-HW--Walberg-JA--1980-"><span class="Hyperlink">Elissalde</span><span class="Hyperlink CharOverride-4"> </span><span class="Hyperlink">et al., 198</span></a>0).</p>
			<p class="Heading-1--Introduction----">Symptoms and Disease Manifestations in Human Beings </p>
			<p class="Body-Text ParaOverride-1">The most common manifestation of <span class="Emphasis">R. equi</span> infection is pneumonia<span class="Emphasis">.</span> Other manifestations include pyrexia, diarrhoea, abscessation of thyroid gland, brain, meninges and peritoneum, lymphadenitis, pericarditis, bone and joint inflammation. </p>
			<p class="Body-Text ParaOverride-1">Colonic polyps associated with disseminated <span class="Emphasis">R. equi</span> infection were reported in a male patient with homosexual orientation (<a href="#Talanin-NY--Donabedian-H--Kaw-M--Kaw-M--O-Donnell-ED--Zaher-A--1998-.-C"><span class="Hyperlink">Talanin et al., 1998</span></a>). <a href="#Donisi-A--Suardi-MG--Casari-S--longo-M--Cadeo-GP--Carosi-G--1996-"><span class="Hyperlink">Donisi et al. (1996)</span></a> reported this organism from patients suffering from HIV. <a href="#Kedlaya-I--Ing-MB--Wong-SS--2001-."><span class="Hyperlink">Kedlaya et al. (2001)</span></a> reported that in <span class="Emphasis">R. equi</span> infected patients, mortality rate was highest among HIV infected patients, intermediate among non-HIV infected immunocompromised patients and lowest among the immunocompetent patients. <a href="#Nath-SR--Mathew-AP--Mohan-A--Anila-KR--2013-."><span class="Hyperlink">Nath et al. (2013)</span></a> reported<span class="Emphasis CharOverride-5"> granulomatous mastitis in an immunocompetent woman due to this organism. </span><a href="#Ferretti-F--Boschini-A--Iabichino-C--Gerevini-S--De-Nardi-P--Guffanti-M--Balconi-G--Lazzarin-A--Cinq"><span class="Hyperlink">Ferretti et al. (2011)</span></a><span class="Emphasis CharOverride-5"> reported dissemination of this bacterial infection in HIV patients even after application of highly active antiretroviral therapy. Brain abscess due to</span><span class="Emphasis"> R. equi </span><span class="Emphasis CharOverride-5">was reported in an immunocompetent patient who recovered after a prolonged antibiotic therapy (</span><a href="#Corne-P--Rajeebally-I--Jonquet-O--2002-"><span class="Hyperlink">Corne et al., 2002</span></a><span class="Emphasis CharOverride-5">). A case of endophthalmitis was reported in a 9 year old patient (</span><a href="#Ebersole-LL--Paturzo-JL--1988-"><span class="Hyperlink">Ebersole</span><span class="Hyperlink"> and Paturzo, 1988</span></a><span class="Emphasis CharOverride-5">). </span><span class="Emphasis">R. equi</span> infection was reported in a kidney transplant recipient who ultimately died after several relapses within a year (<a href="#Menon-V--Gottlib-T--Gallagher-M--Cheong-EL--2012-."><span class="Hyperlink">Menon et al., 2012</span></a>). <a href="#Speck-D--Koneth-I--Diethelm-M--Binet-I--2008-."><span class="Hyperlink">Speck et al. (2008)</span></a> reported a mass in lungs due to <span class="Emphasis">R. equi</span> infection in a kidney transplant recipient. <a href="#Guyssens-V--Vandekerckhove-L--Colle-I--De-Rudder-P--Blots-S--Vogelaers-D--2010-."><span class="Hyperlink">Guyssens</span><span class="Hyperlink CharOverride-4"> </span><span class="Hyperlink">et al. (2010) </span></a>reported invasive infections with this organism<span class="Emphasis CharOverride-5">, a pulmonary form and another with brain abscess, both in immunocompromised patients.</span></p>
			<p class="Body-Text ParaOverride-1">Chronic <span class="Emphasis">R. equi</span> 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% (<a href="#Verville-TD--Huycke-MM--Greenfield-RA--Fine-DP--Kuhls-Tl--Slater-LN--1994-"><span class="Hyperlink">Verville et al., 1994</span></a>). Discontinuation of antibiotics may commonly lead to relapse of <span class="Emphasis">R. equi </span><span class="Emphasis CharOverride-5">infection</span>. Most common site of extra pulmonary relapse is the central nervous system. </p>
			<p class="Body-Text ParaOverride-1">An overall mortality rate of about 25% has been reported in these infections (<a href="#Cornish-N--Washington-JA--1999-"><span class="Hyperlink">Cornish et al.,</span><span class="Hyperlink CharOverride-10"> </span><span class="Hyperlink">1999</span></a>; <a href="#Harvey-RL--Sunstrum-JC--1991-"><span class="Hyperlink">Harvey and Sunstrum.1991</span></a>). Long-term subsidence of disease manifestations have been reported especially in HIV patients (<a href="#Vladusic-I--Krajinovic-V--Begovac-J--2006-."><span class="Hyperlink">Vladusic et al., 2006</span></a>). </p>
			<p class="Body-Text ParaOverride-1"><a href="#Capdevila-JA--Bujan-S--Gavalda-J--Ferrer-A--Pahissa-A--1997-"><span class="Hyperlink">Capdevila et al.</span><span class="Hyperlink CharOverride-10"> </span><span class="Hyperlink">(1997)</span></a> reported that in HIV patients with <span class="Emphasis">R. equi</span> pneumonia, the mortality rate only attributable to <span class="Emphasis">R. equi</span> was limited to 15% only.</p>
			<p class="Body-Text ParaOverride-1">Prevalence of <span class="Emphasis">R.equi</span> infections has been reported three times in men as compared to women with no racial difference (<a href="#Kedlaya-I--Ing-MB--Wong-SS--2001-."><span class="Hyperlink">Kedlaya et al., 2001</span></a>). The high mortality rate in these<span class="Emphasis CharOverride-5"> infections is attributed to lack of early diagnosis, misdiagnosis, insidious nature of disease and r</span><span class="Emphasis">equi</span><span class="Emphasis CharOverride-5">rement of specific and prolonged antibiotic therapy.</span></p>
			<p class="Heading-1--Introduction----">Diagnostic procedures</p>
			<p class="Heading-2--History-in-MM-">Diagnosis in Foals</p>
			<p class="Body-Text ParaOverride-1">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.</p>
			<p class="Body-Text ParaOverride-1">These infections are routinely diagnosed by cultural examination, colonial characteristics, staining characteristics and biochemical tests. <span class="Emphasis">R.equi</span> 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. </p>
			<p class="Body-Text ParaOverride-1"><a href="#Nakazawa-M--Isayama-Y--Kashiwazaki-M--Yasui-T--1987-."><span class="Hyperlink">Nakazawa et al. (1987)</span></a> developed an agar gel diffusion test for screening of <span class="Emphasis">R.equi </span><span class="Emphasis CharOverride-5">in foals at farms. </span><a href="#Gigu-re-S--Hernandez-J--Gaskin-J--Prescott-JF--Takai-S--Miller-C--2003-"><span class="Hyperlink">Giguère et al. (2003)</span></a><span class="Emphasis CharOverride-5"> evaluated performance of various ELISAs for detection of antibodies to</span><span class="Emphasis"> R.equi. </span><span class="Emphasis CharOverride-5">However there was poor performance of these assays.</span></p>
			<p class="Body-Text ParaOverride-1">In India, only a few reports are available in the literature which include diagnosis of this<span class="CharOverride-10"> </span>infection by post mortem examination (<a href="#Garg-DN--Manchanda-VP--Chandramani-NK--1985-"><span class="Hyperlink">Garg et al., 1985</span></a>; <a href="#Saxena-V--Narwal-PS--2009-."><span class="Hyperlink">Saxena and Narwal, 2009</span></a>) and isolation of organism from clinical samples collected from infected foals (<a href="#Khurana-SK--Malik-P--Virmani-N--Singh-BR--2009-."><span class="Hyperlink">Khurana et al., 2009</span></a>). </p>
			<p class="Body-Text ParaOverride-1">Since conventional cultural methods cumbersome and time consuming, molecular techniques are desired for early diagnosis to save the foals.</p>
			<p class="Body-Text ParaOverride-1">PCR assays <span class="Hyperlink">are</span> employed for detection <span class="CharOverride-10">R. equi</span> infection, which are rapid, sensitive and specific (<a href="#Sellon-DC--Besser-TE--Vivrette-SL--McConnico-RS--2001-."><span class="Hyperlink">Sellon et al., 2001</span></a>; <a href="#Arriaga-JM--Cohen-ND--Derr-JN--Chaffin-MK--Martens-RJ--2002-"><span class="Hyperlink">Arriaga et al., 2002</span></a>; <a href="#Ladro-n-N--Ferna-ndez-M--Agu-ero-J--Zo-rn-BG--Va-zquez-Boland-JA--Navas-J---2003-."><span class="Hyperlink">Ladro´n et al., 2003</span></a>; <a href="#Pusterla-N--Wilson-WD--Mapes-S--Leutenegger-CM--2007-."><span class="Hyperlink">Pusterla et al., 2007</span></a>; <a href="#Letek-M--Ocampo-Sosa-AA--Sanders-M--Fogarty-U--Buckley-T--Leadon-DP--Gonza-lez-P--Scortti-M--Meijer"><span class="Hyperlink">Letek et al., 2008</span></a>). The virulence of <span class="CharOverride-10">R. equi</span> is associated with plasmids encoding virulence-associated proteins predominantly protein A (VapA) or protein B (VapB) (<a href="#Letek-M--Ocampo-Sosa-AA--Sanders-M--Fogarty-U--Buckley-T--Leadon-DP--Gonza-lez-P--Scortti-M--Meijer"><span class="Hyperlink">Letek et al., 2008</span></a>; <a href="#Takai-S--Koike-K--Ohbushi-S--Izumi-C--Tsubaki-S--1991a-."><span class="Hyperlink">Takai et al., 1991b</span></a>). Avirulent <span class="CharOverride-10">R. equi</span> have no virulence associated plasmids and are widely distributed in horse premises (<a href="#Wada-R--Kamada-M--Anzai-T--Nakanishi-A--Kanemaru-T--Takai-S--Tsubaki-S--1997-."><span class="Hyperlink">Wada et al., 1997</span></a>). Careful standardization and meticulous optimization is essential for detection of plasmids in <span class="CharOverride-10">R. equi</span> isolates (<a href="#Takai-S--Koike-K--Ohbushi-S--Izumi-C--Tsubaki-S--1991a-."><span class="Hyperlink">Takai et al., 1991a</span></a>; <a href="#Makrai-L--Takai-S--Tamura-M--Tsukamoto-A--Sekimoto-R--Sasaki-Y--Kakuda-T--Tsubaki-S--Varga-J--Fodor"><span class="Hyperlink">Makrai et al., 2002</span></a>). A PCR-based assay that differentiates between strains of <span class="CharOverride-10">R. equi</span> with or without plasmid and also discriminates between <span class="CharOverride-10">vap</span>A and <span class="CharOverride-10">vap</span>B plasmid is very valuable (<a href="#Oldfield-C--Bonella-H--Renwick-L--Dodson-HI--Alderson-G--Goodfellow-M--2004-."><span class="Hyperlink">Oldfield et al., 2004</span></a>; <a href="#Ocampo-Sosa-AA--Lewis-DA--Navas-J--Quigley-F--Callejo-R--Scortti-M--Leadon-DP--Fogarty-U--Va-zquez-B"><span class="Hyperlink">Ocampo-Sosa et al., 2007</span></a>; <a href="#Monego-F--Maboni-F--Krewer-C--Vargas-A--Costa-M--Loreto-E--2009-"><span class="Hyperlink">Monego et al., 2009</span></a>).</p>
			<p class="Body-Text ParaOverride-1">Pathogenesis of <span class="Emphasis">R. equi</span> infections is different in humans than from horses. <a href="#Makrai-L--Takai-S--Tamura-M--Tsukamoto-A--Sekimoto-R--Sasaki-Y--Kakuda-T--Tsubaki-S--Varga-J--Fodor"><span class="Hyperlink">Makrai et al. (2002)</span></a> showed that 88% of the isolates of <span class="CharOverride-10">R. equi</span> in foals have VapA, which is also reported about 20-25% human isolates. Pig <span class="CharOverride-10">R. equi</span> 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 (<a href="#Takai-S--Martens-RJ--Julian-A--Garcia-RM--Rodrigues-DF--Sasaki-Y--Inuzuka-K--Kakuda-T--Tsubaki-S--Pr"><span class="Hyperlink">Takai et al., 2003b</span></a>). IcgA is a factor identified in <span class="Emphasis">R. equi t</span><span class="Emphasis CharOverride-5">hat negatively affects its intracellular replication and is another pathogenicity island-encoded protein which has a role in intracellular growth of this organism (</span><a href="#Wang-X--Coulson-GB--Miranda--Casoluengo-AA--Miranda--Casoluengo-R--Hondalus-MK--Meijer-WG--2014-."><span class="Hyperlink">Wang et al., 2014</span></a><span class="Emphasis CharOverride-5">). </span><a href="#Mc-Queen-CM--Doan-R--Dindot-SV--Bourquin-JR--Zlatev-ZZ--Chaffin-MK--Blodgett-GP--Ivanov-I--2014-.-I"><span class="Hyperlink">Mc Queen et al. (2014)</span></a><span class="Emphasis CharOverride-5"> have identified a region on chromosome 26 associated with </span><span class="CharOverride-10">R. equi</span> 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 <span class="CharOverride-10">R. equi</span> pneumonia in foals.</p>
			<p class="Body-Text ParaOverride-1">Another PCR assay of <span class="CharOverride-10">R. equi</span> based on C<span class="CharOverride-10">hoE</span> gene which encodes for cholesterol oxidase, is a rapid, sensitive, specific and reliable<span class="CharOverride-19"> </span>identification method (<a href="#Ladro-n-N--Ferna-ndez-M--Agu-ero-J--Zo-rn-BG--Va-zquez-Boland-JA--Navas-J---2003-."><span class="Hyperlink">Ladro´n et al., 2003</span></a>).</p>
			<p class="Body-Text ParaOverride-1">A combination of cultural examination along with PCR based assay is considered valuable for its diagnosis.</p>
			<p class="Heading-2--History-in-MM-">Differential Diagnosis</p>
			<p class="Body-Text ParaOverride-1">The pneumonic form should be differentiated from viral respiratory infections due to rhinovirus, herpesvirus and influenza virus, <span class="CharOverride-10">Streptococcus zooepidemicus</span>, parasitic pneumonia by migrating stages of <span class="CharOverride-10">Parascaris equorum</span> and <span class="CharOverride-10">Pneumocystis carinii</span>a.</p>
			<p class="Body-Text ParaOverride-1">Diarrhoea should be differentiated from infection due to <span class="CharOverride-10">Salmonella</span> sp., parasitism due to cyathostomes and antibiotic induced diarrhoea. Joint infection should be differentiated from septic arthritis due to <span class="CharOverride-10">Streptococcus zooepidemicus</span>,<span class="CharOverride-10"> Salmonella</span> sp. and some other bacteria.</p>
			<p class="Heading-1--Introduction----">Prevention and control strategies</p>
			<p class="Heading-2--History-in-MM-">Prevention in Equines and Foals</p>
			<p class="Body-Text ParaOverride-1">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 <span class="Emphasis">R. equi </span><span class="Emphasis CharOverride-5">infection</span>. Quaternary ammonium compounds (QACs), hypochlorites, chlorhexidine, iodophors and phenolic compounds are effective for control of <span class="CharOverride-10">R. equi</span> on farms (<a href="#Dwyer-RM--1995-"><span class="Hyperlink">Dwyer, 1995</span></a>). 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. </p>
			<p class="Body-Text ParaOverride-1">     </p>
			<p class="Body-Text ParaOverride-1">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 <span class="CharOverride-10">R. equi</span> vaccine candidate having aqueous medium based nanoparticle mineral oil adjuvinated inactive bacterin and VapA along with administration of anti-<span class="CharOverride-10"> R. equi</span> hyperimmune plasma in foals may be effective in protection of foals from <span class="CharOverride-10">R. equi</span> infection (<a href="#Erganis-O--Sayin-Z--Hadimli-HH--Sakmanoglu-A--Pinakara-Y--Ozdemir-O--Maden-M--2014-"><span class="Hyperlink">Erganis et al. 2014</span></a>). <a href="#Bordin-AI--Pillai-SD--Brake-C--Bagley-KB--Bourquin-JR--Coleman-M--Oliveira-FN--Mwangi-W--Mc-Murray-D"><span class="Hyperlink">Bordin et al. (2014)</span></a> have studied the immunogenicity of an electron beam inactivated <span class="CharOverride-10">R. equi</span> vaccine in foals. They could demonstrate that electron beam inactivates <span class="CharOverride-10">R. equi</span> 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.</p>
			<p class="Body-Text ParaOverride-1">     </p>
			<p class="Body-Text ParaOverride-1">Another method of preventing the disease is simply its early detection.&#160;</p>
			<p class="Heading-2--History-in-MM-">Treatment in Foals/Equines</p>
			<p class="Body-Text ParaOverride-1"> The prognosis of <span class="CharOverride-10">R. equi</span> pneumonia is poor even after prolonged treatment. Erythromycin along with rifampin are antibiotics of choice (<a href="#Hilldge-CJ--1987-.-Us"><span class="Hyperlink">Hilldge, 1987</span></a>; <a href="#Sweeney-CR--Sweeney-RW--Divers-TJ--1987-."><span class="Hyperlink">Sweeney, 1987</span></a>). Rifampin is paired with some macrolides for treatment of foals (<a href="#Gigu-re-S--Jacks-S--Roberts-GD--Hernandez-J--Long-MT--Ellis-C--2004-"><span class="Hyperlink">Giguère et al., 2004</span></a>). 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 (<a href="#Muscatello-G--Leadon-DP--Klay-M--Ocampo-Sosa-A--Lewis-DA--Fogarty-U--Buckley-T--Gilkerson-JR--Meijer"><span class="Hyperlink">Muscatello et al., 2007</span></a>; <a href="#Prescott-JF--Meijer-WG--Vazquez-Boland-JA--2010-."><span class="Hyperlink">Prescott</span><span class="Hyperlink CharOverride-4"> </span><span class="Hyperlink">et al., 2010</span></a>). </p>
			<p class="Heading-2--History-in-MM-">Treatment in Human beings</p>
			<p class="Body-Text ParaOverride-1">Use of combination antibiotics is recommended. Rifampin-erythromycin, rifampin-minocycline, erythromycin-minocycline, imipenem-amikacin have been reported as effective combinations under <span class="CharOverride-10">in vitro</span> conditions (<a href="#Nordmann-P--Kerestedjian-J-J--Ranco-E--1992-."><span class="Hyperlink">Nordmann et al., 1992</span></a>). In a case report by <a href="#Scotton-PG--Tonon-E--Giobbia-M--Gallucci-M--Rigoli-R--Vaglia--2000-."><span class="Hyperlink">Scotton et al., (2000)</span></a>, a meningitis patient was successfully treated with levofloxacin. <a href="#Munoz-P--Palomo-J--Guinea-J--Yanez-J--Gianella-M--Bouza-E--2008-."><span class="Hyperlink">Munoz et al. (2008)</span></a> reported successful treatment with linezolid in pulmonary <span class="Emphasis">R.equi</span> infection. However use of single antibiotic is not recommended for treatment of systemic <span class="Emphasis">R. equi</span> infections.</p>
			<p class="Body-Text ParaOverride-1">Pulmonary infections r<span class="CharOverride-10">equi</span>re a prolonged course of treatment lasting more than two months. A shorter course of treatment is suggested in immunocompetent patients. Some local <span class="Emphasis">R. equi</span> infections also require a shorter course. Early and accurate diagnosis along with proper antibiotic therapy is a key to prevent the relapses in<span class="Emphasis"> R. equi</span> infections. Local <span class="Emphasis">R. equi</span> infections and infections in immunocompetent children have fair chances of successful treatment.</p>
			<p class="Heading-2--History-in-MM-">Emergence of Antibiotic Resistance</p>
			<p class="Body-Text ParaOverride-1"><a href="#Anderson-SJ--Quan-S--Gowan-B--Dabbs-ER--1997-"><span class="Hyperlink">Anderson et al. (1997)</span></a> demonstrated a highly significant resistance to rifampicin in <span class="Emphasis">R. equi </span><span class="Emphasis CharOverride-5">attributable to monooxygenase like sequence. Mutations in rpoB gene leading to rifampicin resistance have been reported (</span><a href="#Asoh-N--Watanabe-H--Fines-Guyon-M--Watanabe-K--Oishi-K--Kositsakulchai-W--Sanchai-T--Kunsuikmengrai"><span class="Hyperlink">Asoh et al., 2013</span></a><span class="Emphasis CharOverride-5">; </span><a href="#Liu-H--Wang-Y--Yan-J--Wang-C--He-H--2014-."><span class="Hyperlink">Liu et al., 2014</span></a><span class="Emphasis CharOverride-5">). Rifampicin resistance has also been reported by other authors (</span><a href="#Burton-AJ--Gigu-re-S--Sturgill-TL---Berghaus-LJ--Slovis-NM--Whitman-JL--Levering-C--Kuskie-KR--Cohen"><span class="Hyperlink">Burton et al., 2013</span></a><span class="Emphasis CharOverride-5">; </span><a href="#Goldstein-BP--2014-"><span class="Hyperlink">Goldstein, 2014</span></a><span class="Emphasis CharOverride-5">). Macrolide resistance in</span><span class="Emphasis"> R. equi </span><span class="Emphasis CharOverride-5">has also been reported (</span><a href="#Burton-AJ--Gigu-re-S--Sturgill-TL---Berghaus-LJ--Slovis-NM--Whitman-JL--Levering-C--Kuskie-KR--Cohen"><span class="Hyperlink">Burton et al., 2013</span></a><span class="Emphasis CharOverride-5">; </span><a href="#Liu-H--Wang-Y--Yan-J--Wang-C--He-H--2014-."><span class="Hyperlink">Liu et al., 2014</span></a><span class="Emphasis CharOverride-5">). A glycopeptides resistance operon vanO having potential implications in </span><span class="Emphasis">R. equi </span><span class="Emphasis CharOverride-5">therapy has been described (</span><a href="#Gudeta-DD--Moodley-A--Borotolaia-V--Guardabassi-L--2014-.-vanO--a-new-glycopeptides-resistance-opero"><span class="Hyperlink">Gudeta et al., 2014</span></a><span class="Emphasis CharOverride-5">). </span><a href="#Cohen-ND--2014-"><span class="Hyperlink">Cohen (2014)</span></a><span class="Emphasis CharOverride-5"> has warned about the challenges of emergence of resistance to macrolide due to non-availability of effective alternative for </span><span class="Emphasis">R. equi</span> <span class="Emphasis CharOverride-5">therapeutics</span><span class="Emphasis">.</span></p>
			<p class="Body-Text ParaOverride-1"><span class="Emphasis CharOverride-5">Rifampicin along with macrolide is drug of choice for effective treatment of </span><span class="Emphasis">R. equi</span> infections. Therefore emergence of resistance against these antibiotics poses a serious challenge in therapeutic management<span class="Emphasis CharOverride-5"> and there is an urgent need for judicious use of antibiotics.</span></p>
			<p class="Body-Text ParaOverride-1"><span class="CharOverride-4">&#9;</span></p>
			<p class="Heading-1--Introduction----"><a id="x.344"></a><a id="x.347"></a><a id="x.350"></a>Future outlook </p>
			<p class="Body-Text ParaOverride-1">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.</p>
			<p class="Heading-1--Introduction----"><a id="x.353"></a>References</p>
			<ul>
				<li class="References ParaOverride-2" lang="en-US"><a id="Anderson-SJ--Quan-S--Gowan-B--Dabbs-ER--1997-"></a>Anderson SJ, Quan S, Gowan B, Dabbs ER (1997). Monooxygenase like sequence of <span class="CharOverride-10">Rhodococcus equi</span> gene conferring increased resistance to rifampin by inactivating this antibiotic. Antimicrob. Agents Chemother. 41(1): 218-221.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Arriaga-JM--Cohen-ND--Derr-JN--Chaffin-MK--Martens-RJ--2002-"></a>Arriaga JM, Cohen ND, Derr JN, Chaffin MK, Martens RJ (2002). Detection of <span class="CharOverride-10">Rhodococcus equi </span>by polymerase chain reaction using species-specific non-proprietary primers. J. Vet. Diagn. Invest.  14(4): 347-353.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Asoh-N--Watanabe-H--Fines-Guyon-M--Watanabe-K--Oishi-K--Kositsakulchai-W--Sanchai-T--Kunsuikmengrai"></a>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 <span class="CharOverride-10">Rhodococcus equi</span> with several types of mutations in <span class="CharOverride-10">rpo</span>B gene among AIDS patients in northern Thailand. J. Clin. Microbiol. 41(6): 2337-2340.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Barten-MD--Embury-DH--1987-"></a>Barten MD, Embury DH (1987). Studies of the pathogenesis of<span class="CharOverride-10"> Rhodococcus equi</span> infections in foals. Aust. Vet. J. 64(11): 332-339.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Bell-KS--Philp-JC--Aw-DW--Christofi-N--1998-"></a>Bell KS, Philp JC, Aw DW, Christofi N (1998). The genus <span class="CharOverride-10">Rhodococcus</span>. J. Appl. Microbiol. 85(2): 195-210.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Bordin-AI--Pillai-SD--Brake-C--Bagley-KB--Bourquin-JR--Coleman-M--Oliveira-FN--Mwangi-W--Mc-Murray-D"></a>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 <span class="CharOverride-10">Rhodococcus equi</span> vaccine in neonatal foals. PLoS ONE. 9(8): e105367.doi:10.1371/journal.pone.0105367.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Burton-AJ--Gigu-re-S--Sturgill-TL---Berghaus-LJ--Slovis-NM--Whitman-JL--Levering-C--Kuskie-KR--Cohen"></a>Burton AJ, Giguère S, Sturgill TL , Berghaus LJ, Slovis NM, Whitman JL, Levering C, Kuskie KR, Cohen ND (2013). Macrolide-and Rifampin-Resistant <span class="CharOverride-10">Rhodococcus equi</span> on a Horse Breeding Farm, Kentucky, USA. Emerg. Infect. Dis. 19(2): 282-285.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Capdevila-JA--Bujan-S--Gavalda-J--Ferrer-A--Pahissa-A--1997-"></a>Capdevila JA, Bujan S, Gavalda J, Ferrer A, Pahissa A (1997). <span class="CharOverride-10">Rhodococcus equi</span> pneumonia in patients infected with the human immunodeficiency virus. Report of 2 cases and review of the literature. <span class="Emphasis CharOverride-5">Scand. J. Infect. Dis</span>. 29(6): 535-541. </li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Chaffin-MK--Cohen-ND--Blodgett-GP--Syndergaard-M--2013-"></a>Chaffin MK, Cohen ND<span lang="en-GB">, Blodgett GP, Syndergaard M (2013). Do haematologic and ultrasonographic methods predict clinically apparent </span><span class="CharOverride-10" lang="en-GB">Rhodococcus equi</span><span lang="en-GB"> in foals? Proceedings of the American College of Veterinary Internal Medicine Annual Forum; June 13-15, 2013; Seattle, WA.</span></li>
				<li class="References ParaOverride-2" lang="en-US"><span lang="en-GB"><a id="Cohen-ND--2014-"></a>Cohen ND (2014). </span><span class="CharOverride-10" lang="en-GB">Rhodococcus equi</span><span lang="en-GB"> foal pneumonia. Vet. Clin. Equine. 30(3): 609-622.</span></li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Corne-P--Rajeebally-I--Jonquet-O--2002-"></a>Corne P, Rajeebally I, Jonquet O (2002). <span class="CharOverride-10">Rhodococcus equi</span> brain abscess in an immunocompetent patient.<span class="apple-converted-space CharOverride-13">&#160;</span><span class="Emphasis CharOverride-5">Scand. J. Infect. Dis</span>. 34(4): 300-302.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Cornish-N--Washington-JA--1999-"></a>Cornish N, Washington JA (1999). <span class="CharOverride-10">Rhodococcus equi</span> infections: clinical features and laboratory diagnosis. <span class="Emphasis CharOverride-5">Curr. Clin. Top. Infect. Dis</span>. 19: 198-215.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Donisi-A--Suardi-MG--Casari-S--longo-M--Cadeo-GP--Carosi-G--1996-"></a>Donisi A, Suardi MG, Casari S, longo M, Cadeo GP, Carosi G (1996). <span class="CharOverride-10">Rhodococcus equi </span>infection in HIV-infected patients.<span class="apple-converted-space CharOverride-13">&#160;</span><span class="Emphasis CharOverride-5">AIDS</span>. 10(4): 359-362.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Dwyer-RM--1995-"></a>Dwyer RM (1995). Disinfecting <span class="CharOverride-10">equi</span>ne facilities. Rev. Sci. Tech. Off. Int. Epiz.14 (2): 403-418.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Ebersole-LL--Paturzo-JL--1988-"></a>Ebersole LL, Paturzo JL (1988). Endophthalmitis caused by <span class="CharOverride-10">Rhodococcus equi</span> Prescott serotype 4.<span class="apple-converted-space CharOverride-13">&#160;</span><span class="Emphasis CharOverride-5">J. Clin. Microbiol</span>. 26(6): 1221-1222.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Elissalde-GS--Renshaw-HW--Walberg-JA--1980-"></a>Elissalde GS, Renshaw HW, Walberg JA (1980). <span class="CharOverride-10">Corynebacterium</span> <span class="CharOverride-10">equi</span>: An interhost review with emphasis on the foal. Comp. Immunol. Microbiol. Infect. Dis. 3(4): 433-445.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Erganis-O--Sayin-Z--Hadimli-HH--Sakmanoglu-A--Pinakara-Y--Ozdemir-O--Maden-M--2014-"></a>Erganis O, Sayin Z, Hadimli HH, Sakmanoglu A, Pinakara Y, Ozdemir O, Maden M (2014). The effectiveness of anti-<span class="CharOverride-10"> R. equi</span> hyperimmune plasma against <span class="CharOverride-10">R. equi</span> challenge in thoroughbred Arabian foals of mares vaccinated with <span class="CharOverride-10">R. equi</span> vaccine. Scientific World J. Article ID 480732, http://dx.doi.org/10.1155/2014/480732</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Ferretti-F--Boschini-A--Iabichino-C--Gerevini-S--De-Nardi-P--Guffanti-M--Balconi-G--Lazzarin-A--Cinq"></a>Ferretti F, Boschini A, Iabichino C, Gerevini S, De Nardi P, Guffanti M, Balconi G, Lazzarin A, Cinque P (2011). Disseminated <span class="CharOverride-10">Rhodococcus equi</span> infection in HIV infection despite high antiretroviral therapy. BMC <span class="Emphasis CharOverride-5">Infect. Dis. 11</span><span class="Emphasis CharOverride-5">: 343</span><span class="Emphasis">.</span></li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Garg-DN--Manchanda-VP--Chandramani-NK--1985-"></a>Garg DN, Manchanda VP, Chandramani NK (1985). Etiology of post-natal foal mortality. Ind.  J. Comp. Microbiol. Immunol. Infect. Dis. 6(1): 29-35.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Gigu-re-S--Prescott-JF--1997-"></a>Giguère S, Prescott JF (1997). Clinical manifestations, diagnosis, treatment, and prevention of <span class="CharOverride-10">Rhodococcus equi </span>infections in foals. Vet. Microbiol. 56: 313-334.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Gigu-re-S--Hondalus-MK--Yager-JA--Darrah-P--Mosser-DM--Prescott-JF--1999-"></a>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 <span class="CharOverride-10">R.equi</span>. Infect. Immun. 67(7): 3548-3557.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Gigu-re-S--Hernandez-J--Gaskin-J--Prescott-JF--Takai-S--Miller-C--2003-"></a>Giguère S, Hernandez J, Gaskin J, Prescott JF, Takai S, Miller C (2003). Performance of five serological assays for diagnosis of <span class="CharOverride-10">Rhodococcus equi</span> in foals. Clin. Diagn. Lab. Immunol. 10(2): 241-245. </li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Gigu-re-S--Jacks-S--Roberts-GD--Hernandez-J--Long-MT--Ellis-C--2004-"></a>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 <span class="CharOverride-10">Rhodococcus equi</span> pneumonia. <span class="Emphasis CharOverride-5">J. Vet. Intern. Med</span>. 18(4): 568-573.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Gigu-re-S--Lee-E--Williams-E--Cohen-ND--Chaffin-MK--Halbert-N--Martens-RJ--Franklin-RP--Clark-CC--Sl"></a>Giguère S, Lee E, Williams E,<span class="apple-converted-space CharOverride-13">&#160;</span>Cohen ND,<span class="apple-converted-space CharOverride-13">&#160;</span>Chaffin MK,<span class="apple-converted-space CharOverride-13">&#160;</span>Halbert N,<span class="apple-converted-space CharOverride-13">&#160;</span>Martens RJ,<span class="apple-converted-space CharOverride-13">&#160;</span>Franklin RP,<span class="apple-converted-space CharOverride-13">&#160;</span>Clark CC,<span class="apple-converted-space CharOverride-13">&#160;</span>Slovis NM (2010). Determination of the prevalence of antimicrobial resistance to macrolide antimicrobials or rifampin in <span class="CharOverride-10">Rhodococcus equi</span> isolates and treatment outcome in foals infected with antimicrobial-resistant isolates of <span class="CharOverride-10">R. equi</span>. J. Am. Vet. Med. Assoc. 237(1): 74-81. </li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Gigu-re-S--Cohen-ND--Keith-Chaffin-M--Hines-SA--Hondalus-MK--Prescott-JF--Slovis-NM--2011a-"></a>Giguère S, Cohen ND, Keith Chaffin M, Hines SA, Hondalus MK, Prescott JF, Slovis NM (2011a). <span class="CharOverride-10">Rhodococcus equi</span>: Clinical Manifestations, Virulence, and Immunity. <span class="Emphasis CharOverride-5">J. Vet. Intern. Med</span>. 25(6): 1221-1230. </li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Gigu-re-S--Cohen-ND--Keith-Chaffin-M--Slovis-NM--Hondalus-MK--Hines-SA--Prescott-JF--2011b-."></a>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 <span class="CharOverride-10">Rhodococcus equi</span> in Foals. <span class="Emphasis CharOverride-5">J. Vet. Intern. Med</span>. 25(6): 1209-1220.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Goldstein-BP--2014-"></a>Goldstein BP (2014). Resistance to rifampicin: a review. J. Antibiot. 67(9): 625-630.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Goodfellow-M--Alderson-G--1977-."></a>Goodfellow M, Alderson G (1977). The actinomycete-genus <span class="CharOverride-10">Rhodococcus</span>: A home for “rhodochrous complex”. J. Gen. Microbiol. 100(1): 99-122.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Gressler-LT--de-Vargas-AC--da-Costa-MM--Potter-L--da-Silveira-BP--Sangioni-LA--de-Avila-Botton-S--20"></a>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 <span class="CharOverride-10">Rhodococcus equi</span>. Braz. J. Microbiol. 45(2): 661-665.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Gudeta-DD--Moodley-A--Borotolaia-V--Guardabassi-L--2014-.-vanO--a-new-glycopeptides-resistance-opero"></a>Gudeta DD, Moodley A, Borotolaia V, Guardabassi L (2014). <span class="CharOverride-10">van</span>O, a new glycopeptides resistance operon in environmental <span class="CharOverride-10">Rhodococcus equi</span> isolates. Antimicrob. Agents Chemother. 58(3): 1768-1770.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Guyssens-V--Vandekerckhove-L--Colle-I--De-Rudder-P--Blots-S--Vogelaers-D--2010-."></a>Guyssens V, Vandekerckhove L, Colle I, De Rudder P, Blots S, Vogelaers D (2010). Invasive infection with <span class="CharOverride-10">Rhodococcus equi</span>- two case reports and review of literature. Acta. Clin. Belg. 65(4): 271-275.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Harvey-RL--Sunstrum-JC--1991-"></a>Harvey RL, Sunstrum JC (1991). <span class="CharOverride-10">Rhodococcus equi</span> infection in patients with and without human immunodeficiency virus infection. <span class="Emphasis CharOverride-5">Rev. Infect. Dis</span>. 13(1): 139-145.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Hondalus-MK--Mosser-DM--1994-."></a>Hondalus MK, Mosser DM (1994). Survival and replication of <span class="CharOverride-10">Rhodococcus equi</span> in macrophages. Infect. Immun. 62(10): 4167-4175. </li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Hilldge-CJ--1987-.-Us"></a>Hilldge CJ (1987). Use of erythromycin–rifampin combination in treatment of <span class="CharOverride-10">Rhodococcus equi </span>pneumonia. Vet. Microbiol. 14: 337-342. </li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Hughes-KL--Sulaiman-I--1987-.-The-ecology-of-Rhodococcus-equi-and-physicochemical-influences-on"></a>Hughes KL, Sulaiman I (1987). The ecology of <span class="CharOverride-10">Rhodococcus equi </span>and physicochemical influences on growth. Vet. Microbiol. 14(3): 241-250. </li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Jeckel-S--Holmes-P--King-S--Whatmore-AM--Kirkwood-I--2011-."></a>Jeckel S, Holmes P, King S, Whatmore AM, Kirkwood I (2011). Disseminated <span class="CharOverride-10">Rhodococcus equi</span> infection in goats in the UK. Vet. Rec<span class="CharOverride-10">.</span> 169(2): 56.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Johns-I--2013--Management-of-R"></a>Johns I (2013) Management of<span class="CharOverride-10"> Rhodococcus equi</span> pneumonia in foals. Vet. Med. Res. Rep. 4: 49-59. </li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Johnson-JA--Prescott-JF--Markham-KJ--1983a-."></a>Johnson JA, Prescott JF, Markham KJ (1983a). The pathology of experimental <span class="CharOverride-10">Corynebacterium equi</span> in foals following intrabrochial challenge. Vet. Path. 20(4): 440-449.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Johnson-JA--Prescott-JF--Markham-KJ--1983b-.-Th"></a>Johnson JA, Prescott JF, Markham KJ (1983b). The pathology of experimental <span class="CharOverride-10">Corynebacterium equi</span> in foals following intragastric challenge. Vet Path. 20(4): 450-459.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Kedlaya-I--Ing-MB--Wong-SS--2001-."></a>Kedlaya I, Ing MB, Wong SS (2001). <span class="CharOverride-10">Rhodococcus equi</span> infections in immunocompetent hosts: case report and review.<span class="apple-converted-space CharOverride-13">&#160;</span><span class="Emphasis CharOverride-5">Clin. Infect. Dis</span>. 32(3): E 39-46.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Khurana-SK--Malik-P--Virmani-N--Singh-BR--2009-."></a>Khurana SK, Malik P, Virmani N, Singh BR (2009). Prevalence of <span class="CharOverride-10">Rhodococcus equi</span> infection in foals<span class="CharOverride-10">. </span> Ind. J. Vet. Res. 18(1): 20-22.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Khurana-SK--2014-.-Rh"></a>Khurana SK (2014). <span class="CharOverride-10">Rhodococcus equi</span> infection<span class="CharOverride-10">. </span> In: SR Garg, ed. Zoonoses: bacterial Diseases. Daya Publishing House. New Delhi. India. Pp. 390-401.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Khurana-SK--Kanu-Priya--Singh-N--Singha-H--Punia-S--2014-."></a>Khurana SK, Kanu Priya, Singh N, Singha H, Punia S (2014). Comparative analysis of whole cell proteins of <span class="CharOverride-10">Rhodococcus equi</span> isolates using SDS-PAGE<span class="CharOverride-10">. </span> Int. J. Bioassays. 3(3): 1803-1805.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Kilcoyne-I--Nieto-J--Vaughan-B--2014-"></a>Kilcoyne I, Nieto J, Vaughan B (2014). Tibial osteomielitis caused by <span class="CharOverride-10">Rhodococcus equi</span> in a mature horse. <span class="CharOverride-10">Equi</span>ne Vet.  Edu. 26(6): 283-287.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Kim-SJ--Yook-SY--Hwang-JS--You-M--Jun-M--2008-"></a>Kim SJ, Yook SY, Hwang JS, You M, Jun M (2008). <span class="CharOverride-10">Rhodococcus equi</span> pneumonia in foals in Gyeonggi-do and characterization of isolates from lesions and environment. Korean J. Vet. Res. 48(2): 139-143.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Kinne-J--Madarame-H--Takai-S--Jose-S--Wernery-U--2011-."></a>Kinne J, Madarame H, Takai S, Jose S, Wernery U (2011). Disseminated <span class="CharOverride-10">Rhodococcus equi</span> infection in dromedary camels (Camelus dromedarius). Vet. Microbiol. 149(1-2): 269-272.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Ladro-n-N--Ferna-ndez-M--Agu-ero-J--Zo-rn-BG--Va-zquez-Boland-JA--Navas-J---2003-."></a>Ladro´n N, Ferna´ndez M, Agu¨ero J, Zo¨rn BG, Va´zquez-Boland JA, Navas J  (2003). Rapid identification of <span class="CharOverride-10">Rhodococcus equi </span>by a PCR assay targeting the <span class="CharOverride-10">choE </span>gene. J. Clin. Microbiol. 41(7): 3241–3245.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Lavoie-JP--Fiset-L--Laverty-S--1994"></a>Lavoie JP, Fiset L, Laverty S (1994). Review of 40 Cases of Lung Abscesses in Foals and Adult Horses. Equine Vet. J.<span class="CharOverride-10"> </span>26(5), 348-352.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Letek-M--Ocampo-Sosa-AA--Sanders-M--Fogarty-U--Buckley-T--Leadon-DP--Gonza-lez-P--Scortti-M--Meijer"></a>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 <span class="CharOverride-10">Rhodococcus equi vap </span>pathogenicity island seen through comparison of host-associated <span class="CharOverride-10">vapA </span>and <span class="CharOverride-10">vapB </span>virulence plasmids. J. Bacteriol. <span class="CharOverride-10"> </span>190: 5797-5805.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Liu-H--Wang-Y--Yan-J--Wang-C--He-H--2014-."></a>Liu H, Wang Y, Yan J, Wang C, He H (2014). Appearance of multidrug-resistant virulent<span class="CharOverride-10"> Rhodococcus equi</span> clinical isolates obtained in China. J. Clin. Microbiol. 52(2): 703.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Lopez-AM--Hines-MT--Palmer-GH--Alperin-DC--Hines-SA--2002-."></a>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 <span class="CharOverride-10">Rhodococcus</span>. Clin.<span class="CharOverride-10"> </span>Diagn. Lab. Immunol.<span class="CharOverride-10"> </span>9(6): 1270-1276.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Makrai-L--Takai-S--Tamura-M--Tsukamoto-A--Sekimoto-R--Sasaki-Y--Kakuda-T--Tsubaki-S--Varga-J--Fodor"></a>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 <span class="CharOverride-10">Rhodococcus equi</span> isolates from foals, pigs, humans and soil in Hungary. <span class="Emphasis CharOverride-5">Vet. Microbiol</span>. 88(4): 377-384. </li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Magnusson-H--1923-."></a>Magnusson H (1923). Spezifische infektiose Pneumonie beim Fohlen. Ein neuer Eiterreger beim Pferd. Arch. Wiss. Prakt. Tierhelkd. 50: 22-38. </li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Martens-RJ--Fiske-RA--Renshaw-HW--1982"></a>Martens RJ, Fiske RA, Renshaw HW (1982). Experimental subacute foal pneumonia inducible by aerosol administration of<span class="CharOverride-10"> Corynebacterium equi</span>. <span class="CharOverride-10">Equi</span>ne Vet. J. 14(2): 111-116.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Mc-Queen-CM--Doan-R--Dindot-SV--Bourquin-JR--Zlatev-ZZ--Chaffin-MK--Blodgett-GP--Ivanov-I--2014-.-I"></a>Mc Queen CM, Doan R, Dindot SV, Bourquin JR, Zlatev ZZ, Chaffin MK, Blodgett GP, Ivanov I (2014). Identification of genetic loci associated with <span class="CharOverride-10">Rhodococcus equi</span> susceptibility in foals. PLoS ONE 9(6): e98710.doi: 10.1371/journal.pone.0098710</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Menon-V--Gottlib-T--Gallagher-M--Cheong-EL--2012-."></a>Menon V, Gottlib T, Gallagher M, Cheong EL (2012). Persistent<span class="CharOverride-10"> Rhodococcus equi</span> infection in a renal transplant patient: case report and review of literature. Transpl. Infect. Dis. 14(6): E 126-133.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Mizuno-Y--Sato-F---Sakamoto-M---Yoshikawa-K---Yoshida-M---Shiba-K---Onodera-S--Matsuura-R---Takai-SJ"></a>Mizuno Y, Sato F,  Sakamoto M,  Yoshikawa K,  Yoshida M,  Shiba K,  Onodera S, Matsuura R,  Takai SJ (2005).VapB-positive <span class="CharOverride-10">Rhodococcus equi</span> infection in an HIV-infected patient in Japan. J. Infect. Chemother. 11(1): 37-40.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Monego-F--Maboni-F--Krewer-C--Vargas-A--Costa-M--Loreto-E--2009-"></a>Monego F, Maboni F, Krewer C, Vargas A, Costa M, Loreto E (2009). Molecular characterization of <span class="CharOverride-10">Rhodococcus equi</span> from horse-breeding farms by means of multiplex PCR for the vap gene family. Curr. Microbiol. 58(4): 399-403. </li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Munoz-P--Palomo-J--Guinea-J--Yanez-J--Gianella-M--Bouza-E--2008-."></a>Munoz P, Palomo J, Guinea J, Yanez J, Gianella M, Bouza E (2008). Relapsing <span class="CharOverride-10">Rhodococcus equi</span> infection in a heart transplant recipient successfully treated with long-term linezolid. <span class="Emphasis CharOverride-5">Diagn. Microbiol. Infect. Dis</span>. 60(2):197-199.</li>
				<li class="References ParaOverride-2" lang="en-US"> <a id="Muscatello-G--Leadon-DP--Klay-M--Ocampo-Sosa-A--Lewis-DA--Fogarty-U--Buckley-T--Gilkerson-JR--Meijer"></a>Muscatello G, Leadon DP, Klay M, Ocampo-Sosa A, Lewis DA, Fogarty U, Buckley T, Gilkerson JR, Meijer WG, Vazquez-Boland JA (2007). <span class="CharOverride-10">Rhodococcus equi </span>infection in foals: the science of rattles. Equine Vet. J.<span class="CharOverride-10"> </span>39(5): 470-478. </li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Muscatello-G--2009-."></a>Muscatello G (2009). Detection of virulent <span class="CharOverride-10">Rhodococcus </span>in exhaled air samples from naturally infected foals. J. Clin. Microbiol.<span class="CharOverride-10"> </span>47(3): 734-737. </li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Muscatello-G--2012-.-R"></a>Muscatello G (2012). <span class="CharOverride-10">Rhodococcus equi </span>pnemonia<span class="CharOverride-10"> </span>in the foals- Part 1: Pathogenesis and Epidemiology. Vet. J.<span class="CharOverride-10"> </span>192(1): 20-26. </li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Mutimer-MD--Woolcock-JB--1980-.-C"></a>Mutimer MD, Woolcock JB (1980). <span class="CharOverride-10">Corynebacterium equi</span> in cattle and pigs. Tijdschr. Diergeneeskd. 105: 25-27.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Nakazawa-M--Isayama-Y--Kashiwazaki-M--Yasui-T--1987-."></a>Nakazawa M, Isayama Y, Kashiwazaki M, Yasui T (1987). Diagnosis of <span class="CharOverride-10">Rhodococcus equi</span> infoals by agar gel diffusion test with protein antigen. Vet. Microbiol. 41(7): 3241-3245.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Napole-o-F--Damasco--P-V--Camello--T-C--do-Vale--M-D--de-Andrade--A-F--Hirata--R-Jr--de-Mattos-Guara"></a>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 <span class="CharOverride-10">Rhodococcus equi</span> in an immunocompetent host. J. Clin. Microbiol. 43: 1002-1004.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Nath-SR--Mathew-AP--Mohan-A--Anila-KR--2013-."></a>Nath SR, Mathew AP, Mohan A, Anila KR (2013). <span class="CharOverride-10">Rhodococcus equi</span> granulomatous mastitis in an immuno-competent patient - A case report.<span class="apple-converted-space CharOverride-13">&#160;</span><span class="Emphasis CharOverride-5">J. Med. Microbiol</span>. 62(pt 8): 1253-1255.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Nordmann-P--Kerestedjian-J-J--Ranco-E--1992-."></a>Nordmann P, Kerestedjian J J, Ranco E (1992). Therapy of   <span class="CharOverride-10">Rhodococcus equi</span> disseminated infections in nude mice. Antimicrob. Agents Chemother. 36(6): 1244-1248.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Ocampo-Sosa-AA--Lewis-DA--Navas-J--Quigley-F--Callejo-R--Scortti-M--Leadon-DP--Fogarty-U--Va-zquez-B"></a>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 <span class="CharOverride-10">Rhodococcus equi</span> based on <span class="CharOverride-10">traA, vapA, </span>and <span class="CharOverride-10">vapB </span>virulence plasmid markers. J. Infect. Dis. 196(5): 763-769.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Oldfield-C--Bonella-H--Renwick-L--Dodson-HI--Alderson-G--Goodfellow-M--2004-."></a>Oldfield C, Bonella H, Renwick L, Dodson HI, Alderson G, Goodfellow M (2004). Rapid determination of vapA/vapB genotype in <span class="CharOverride-10">Rhodococcus equi</span> using a differential polymerase chain reaction method. Antonie Van Leeuwenhoek. 85(4): 317-326.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Prescott-JF--1991-"></a>Prescott JF (1991). <span class="CharOverride-10">Rhodococcus equi</span> an animal and human pathogen. Clin. Microbiol. Rev. 4(1): 20-34.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Prescott-JF--Meijer-WG--Vazquez-Boland-JA--2010-."></a>Prescott JF, Meijer WG, Vazquez-Boland JA (2010). <span class="CharOverride-10">Rhodococcus</span> In: L Gyles JFP, J.G. Songer, C Theon, eds. Pathogenesis of Bacterial Infections in Animals: Wiley-Blackwell. Pp. 149-166.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Pusterla-N--Wilson-WD--Mapes-S--Leutenegger-CM--2007-."></a>Pusterla N, Wilson WD, Mapes S, Leutenegger CM (2007). Diagnostic evaluation of real-time PCR in the detection of <span class="CharOverride-10">Rhodococcus equi </span>in faeces and nasopharyngeal swabs from foals with pneumonia. Vet. Rec. 161(8): 272-275.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Sanger-Institute--2008-."></a>Sanger Institute (2008). The sequence data were produced by the <span class="CharOverride-10">Rhodococcus equi</span> Sequencing Group at the Sanger Institute. </li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Saxena-V--Narwal-PS--2009-."></a>Saxena V, Narwal PS (2009). <span class="CharOverride-10">Rhodococcus equi</span> infection in foals. J. Remount Vet. Corps. 48: 27-31.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Sellon-DC--Besser-TE--Vivrette-SL--McConnico-RS--2001-."></a>Sellon DC, Besser TE, Vivrette SL, McConnico RS (2001). Comparison of nucleic acid amplification, serology, and microbiologic culture for diagnosis of <span class="CharOverride-10">Rhodococcus equi </span>pneumonia in foals. J. Clin. Microbiol. 39(4): 1289-1293.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Scotton-PG--Tonon-E--Giobbia-M--Gallucci-M--Rigoli-R--Vaglia--2000-."></a>Scotton PG, Tonon E, Giobbia M, Gallucci M, Rigoli R, Vaglia (2000). <span class="CharOverride-10">Rhodococcus equi </span>nosocomial meningitis cured by levofloxacin and shunt removal. <span class="Emphasis">Clin. Infect. Dis</span><span class="CharOverride-10">.</span> 30(1): 223-224.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Soedarmanto-I--Oliveira-R--Lammler-C--Durrling-H--1997-."></a>Soedarmanto I, Oliveira R, Lammler C, Durrling H (1997). Identification and epidemiological relationship of <span class="CharOverride-10">Rhodococcus equi</span> isolated from cases of lymphadenitis in cattle. Zentrabl. Bakteriol. Parasitenkd. Infektkrankh. Hyg. Abt. 1 Orig. 286(4): 457-466.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Speck-D--Koneth-I--Diethelm-M--Binet-I--2008-."></a>Speck D, Koneth I, Diethelm M, Binet I (2008). A pulmonary mass caused by <span class="CharOverride-10">Rhodococcus equi</span> infection in a renal transplant recipient. Nat. Clin. Pract. Nephrol. 4: 398-403.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Sweeney-CR--Sweeney-RW--Divers-TJ--1987-."></a>Sweeney CR, Sweeney RW, Divers TJ (1987). <span class="CharOverride-10">Rhodococcus equi </span>pneumonia in 48 foals: response to antimicrobiol therapy. Vet. Microbiol. 14(3): 329-336.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Talanin-NY--Donabedian-H--Kaw-M--Kaw-M--O-Donnell-ED--Zaher-A--1998-.-C"></a>Talanin NY, Donabedian H, Kaw M,<span class="Heading-2-Char CharOverride-22"> </span><span class="Emphasis">Kaw M</span>, O’Donnell ED, Zaher A (1998). Colonic polyps and disseminated infection associated with <span class="CharOverride-10">Rhodococcus equi</span> in a patient with AIDS.<span class="apple-converted-space CharOverride-13">&#160;</span><span class="Emphasis CharOverride-5">Clin. Infect. Dis</span>. 26(5): 1241-1242.<span class="apple-converted-space CharOverride-13">&#160;</span></li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Takai-S--Koike-K--Ohbushi-S--Izumi-C--Tsubaki-S--1991a-."></a>Takai S, Koike K, Ohbushi S, Izumi C, Tsubaki S (1991a). Identification of 15-to 17-kilodalton antigens associated with virulent <span class="CharOverride-10">Rhodococcus equi. </span>J. Clin. Microbiol. 29(11): 439-443. </li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Takai-S--Sekizaki-T--Ozawa-T--Sugawara-T--Watanabe-Y--Tsubaki-S--1991b-."></a>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 <span class="CharOverride-10">Rhodococcus equi. </span>Infect. Immun. 59(3): 4056-4060.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Takai-S--1997-."></a>Takai S (1997). Epidemiology of <span class="CharOverride-10">Rhodococcus equi</span> infections: a review. Vet. Microbiol. 56(3-4): 167-176.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Takai-S--Martens-RJ--Julian-A--Garcia-RM--Rodrigues-DF--Sasaki-Y--Inuzuka-K--Kakuda-T--Tsubaki-S--Pr"></a>Takai S, Martens RJ, Julian A, Garcia RM, Rodrigues DF, Sasaki Y, Inuzuka K, Kakuda T, Tsubaki S, Prescott JF (2003a). Virulence of <span class="CharOverride-10">Rhodococcus equi</span> isolated from cats and dogs. J. Clin. Microbiol. 41(9): 4468-4470.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Takai-S--Tharavichitkul-P--Takarn-P--Khantawa-B--Tamura-M--Tsukamoto-A-Takayama-S-Yamatoda-N--Kimura"></a>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 <span class="CharOverride-10">Rhodococcus equi</span> of intermediate virulence isolated from patients with and without acquired immune deficiency syndrome in Chiang Mai, Thailand. <span class="Emphasis CharOverride-5">J. Infect. Dis</span>. 88(11):1717-1723.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Tkachuksaad-O--Prescott-J--1991-"></a>Tkachuksaad O, Prescott J (1991). <span class="CharOverride-10">Rhodococcus equi </span>Plasmids -Isolation and partial characterization. J. Clin. Microbiol. 29(12): 2696-2700.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Vazquez-Boland-JA--Prescott-JF--Meijer-WG--Leadon-DP--Hines-SA--2009-"></a>Vazquez-Boland JA, Prescott JF, Meijer WG, Leadon DP, Hines SA (2009). <span class="CharOverride-10">Rhodococcus </span>comes of age. Equine Vet. J. 41(1). 93-95.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Vazquez-Boland-JA--Gigu-re-S--Hapeshi-H--Mc-Arthur-I--Anastasi-E--Valero-rello-A--2013-"></a>Vazquez-Boland JA, Giguère S, Hapeshi H, Mc Arthur I, Anastasi E, Valero-rello A (2013). <span class="CharOverride-10">Rhodococcus equi</span>: The many facets of pathogenic actinomycete. Vet. Microbiol. 167(1-2): 9-33.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Venner-M--Rodiger-A--Lammer-M--Gigu-re-S--2012-."></a>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 <span class="CharOverride-10">Rhodococcus equi</span>. Vet. J. 192(3): 293-298.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Venner-M--Astheimer-K--Lammer-M--Gigu-re-S--2013-."></a>Venner M, Astheimer K, Lammer M, Giguère S (2013). Efficacy of mass anti-microbial treatment of foals with subclinical pulmonary abscesses associated with<span class="CharOverride-10"> Rhodococcus equi</span>. J. Vet. Intern. Med. 27(1): 171-176.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Verville-TD--Huycke-MM--Greenfield-RA--Fine-DP--Kuhls-Tl--Slater-LN--1994-"></a>Verville TD, Huycke MM, Greenfield RA, Fine DP, Kuhls Tl, Slater LN (1994). <span class="CharOverride-10">Rhodococcus equi</span> infections of humans. 12 cases and a review of the literature. <span class="Emphasis CharOverride-5">Medicine (Baltimore)</span>. 73(3): 119-132.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Vladusic-I--Krajinovic-V--Begovac-J--2006-."></a>Vladusic I, Krajinovic V, Begovac J (2006). Long term survival after <span class="CharOverride-10">Rhodococcus equi </span>pneumonia in a patient with human immunodeficiency virus infection in the era of highly active antiretroviral therapy: case report and review. <span class="Emphasis CharOverride-5">Acta. Med. Croatica</span>. 60(3): 259-63.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="von-Bargen-K--Haas-A--2009-."></a>von Bargen K, Haas A (2009). Molecular and infection biology of the horse pathogen Rhodococcus. FEMS Microbiol. Rev.<span class="CharOverride-10"> </span>33(5); 870-891.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Wada-R--Kamada-M--Anzai-T--Nakanishi-A--Kanemaru-T--Takai-S--Tsubaki-S--1997-."></a>Wada R, Kamada M, Anzai T, Nakanishi A, Kanemaru T, Takai S, Tsubaki S (1997). Pathogenicity and virulence of <span class="CharOverride-10">Rhodococcus equi</span> in foals following intratracheal challenge. <span class="jrnl">Vet. Microbiol.</span> 56: 301-312.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Wang-X--Coulson-GB--Miranda--Casoluengo-AA--Miranda--Casoluengo-R--Hondalus-MK--Meijer-WG--2014-."></a>Wang X, Coulson GB, Miranda- Casoluengo AA, Miranda- Casoluengo R, Hondalus MK, Meijer WG (2014). IcgA is a virulence factor of <span class="CharOverride-10">Rhodococcus equi</span> that modulates intracellular growth. Infect. Immunity. 82(5): 1793-1800.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Watts-A--2014-"></a>Watts A (2014). Osteomyelitis caused by <span class="CharOverride-10">Rhodococcus equi</span> infection in the horse. Equine Vet. Educ. 26(6): 287. </li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Weinstock-DM--Brown-AE--2002"></a>Weinstock DM, Brown AE (2002). <span class="CharOverride-10">Rhodococcus equi</span>: An emerging pathogen. Clin. Infect. Dis. 34(10): 1379-1385.</li>
				<li class="References ParaOverride-2" lang="en-US"><a id="Wichtel-MG--Anderson-KL--Johnson-TV--Nathan-U--Smith-L--1991-."></a>Wichtel MG, Anderson KL, Johnson TV, Nathan U, Smith L (1991). Influence of age on neutrophil function in foals. Equine Vet. J.<span class="CharOverride-4"> </span>23(6): 466-469.</li>
				<li class="References ParaOverride-2" lang="en-US"><span lang="en-GB"><a id="Yager-JA--Prescott-CA--Kramar-DP--Hannah-H--Balson-GA--Croy-B.A--1991-."></a>Yager JA, Prescott CA, Kramar DP, Hannah H, Balson GA, Croy B.A (1991). The effect of experimental infection with</span><span class="apple-converted-space CharOverride-13" lang="en-GB">&#160;</span><span class="CharOverride-10" lang="en-GB">Rhodococcus equi</span><span class="apple-converted-space CharOverride-12" lang="en-GB">&#160;</span><span lang="en-GB">on immunodeficient mice. Vet. Microbiol. 28(4): 363-376.</span></li>
			</ul>
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