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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 (<a href="#Sanger-Institute--2008-."><span class="Hyperlink">Sanger Institute, 2008</span></a>). 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>
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