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<front>
<journal-meta>
<journal-id journal-id-type="pmc">JAR</journal-id>
<journal-id journal-id-type="nlm-ta">JAR</journal-id>
<journal-id journal-id-type="publisher-id">JAR</journal-id>
<journal-title-group>
<journal-title>Journal of Animal Research</journal-title>
</journal-title-group>
<issn pub-type="ppub">2249-6629</issn>
<issn pub-type="epub">2277-940X</issn>
<publisher>
<publisher-name>Association of Mastitis</publisher-name>
<publisher-loc>India</publisher-loc>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="other">JAR-11-03-0497</article-id>
<article-id pub-id-type="doi">10.30954/2277-940X.03.2021.21</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Research Paper</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Intrinsic Risk Factors for Bovine Tropical Theileriosis in Indian Cattle: A Meta-Analysis</article-title>
</title-group>
<contrib-group><contrib contrib-type="author">
<name><surname>Bhangale</surname><given-names>Gajendra N.</given-names></name>
<xref ref-type="aff" rid="A1"/>
<xref ref-type="corresp" rid="cor001">*</xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Prakash</surname><given-names>K.C. Bhanu</given-names></name>
<xref ref-type="aff" rid="A1"/>
</contrib>
<contrib contrib-type="author">
<name><surname>Dhabale</surname><given-names>Ankush R.</given-names></name>
<xref ref-type="aff" rid="A1"/>
</contrib>
</contrib-group>
<aff id="A1">Department of Parasitology, College of Veterinary and Animal Sciences, Parbhani, MAFSU, Nagpur, INDIA</aff>
<author-notes>
<corresp id="cor001"><label>*</label>Corresponding author: GN Bhangale; E-mail: <email>gajumanu@gmail.com</email></corresp>
</author-notes>
<pub-date pub-type="ppub">
<month>06</month>
<year iso-8601-date="2021">2021</year>
</pub-date>
<volume>11</volume>
<issue>03</issue>
<fpage>497</fpage>
<lpage>503</lpage>
<history>
<date date-type="received" iso-8601-date="2021-03-26">
<day>26</day>
<month>03</month>
<year>2021</year>
</date>
<date date-type="revised" iso-8601-date="2021-04-19">
<day>19</day>
<month>04</month>
<year>2021</year>
</date>
<date date-type="accepted" iso-8601-date="2021-04-25">
<day>25</day>
<month>04</month>
<year>2021</year>
</date>
</history>
<permissions>
<copyright-statement>&#x00A9; Association of Mastitis, India</copyright-statement>
<copyright-year>2021</copyright-year>
<copyright-holder>Association of Mastitis, India</copyright-holder>
</permissions>
<self-uri content-type="pdf" xlink:href="JAR-11-03-0497.pdf"></self-uri>
<abstract>
<title>ABSTRACT</title>
<p>Meta-analysis of systematically selected studies published during 2015-2020 on the prevalence of bovine tropical theileriosis from Indian cattle was done. It was found that age, sex and breed of cattle are important risk factors to get infected with <italic>Thieleria</italic> sp. Adult cattle are found at higher risk of getting infected with BTT than the younger stocks with an odds ratio of 2.062, however as regards sex of the cattle is concerned cows are little more susceptible to BTT than bullocks / bulls with an odds ratio of 1.632. The breed factor of cattle has shown that exotic/ crossbred cattle are more prone to contract BTT with an odds ratio of 2.113. The meta-analysis showed no publication bias.</p>
<sec>
<title>HIGHLIGHTS</title>
<list list-type="bullet">
<list-item><p>Age, sex, and breed of cattle are major risk factors for Theileriosis in Indian cattle.</p></list-item>
<list-item><p>Very few studies recorded those risk factors.</p></list-item>
<list-item><p>More studies on epidemiological aspect of bovine tropical Theileriosis are needed.</p></list-item>
</list>
</sec>
</abstract>
<kwd-group>
<title>Keywords:</title>
<kwd>Theileria</kwd>
<kwd>cattle</kwd>
<kwd>risk factors</kwd>
<kwd>MetaXL</kwd>
</kwd-group>
<counts>
<fig-count count="7"/>
<table-count count="2"/>
<ref-count count="36"/>
<page-count count="7"/>
</counts>
</article-meta>
</front>
<body>
<sec id="S1">
<title/>
<p>In dairy animals vector borne haemoprotozoan diseases are of prime importance considering their impact on production and substantial economic costs ultimately upsetting the dairy enterprises. With significant morbidity and mortality in its ruminant hosts, theileriosis is a major impediment in dairy industry globally (<xref ref-type="bibr" rid="R10">Demessie and Derso, 2015</xref>). Bovine tropical Theileriosis (BTT) is a tick borne haemprotozoan disease caused by an apicomplexan parasite <italic>Theileria</italic> spp., the obligate intracellular protozoan parasite which infects domestic and wild ruminanats. The ticks of Ixodidiae family are the vectors of this protozoa and they have a complex life cycle both in vertebrate and invertebrate hosts. Amongst several species of <italic>Theileria</italic> genus that infect cattle, <italic>T. parva</italic> and <italic>T. annulata</italic> are most pathogenic and prevalent species. BTT is very lethal and debilitating hemoprotozoon disease infecting cattle which is caused by <italic>T. annulata</italic> and transmitted by <italic>Hyalomma</italic> sp ticks (<xref ref-type="bibr" rid="R26">Mans <italic>et al.</italic>, 2015</xref>). The disease is clinically characterized by high fever and enlargement of superficial lymph nodes. As per earlier estimate about 33 million Indian cattle are at risk of BTT (<xref ref-type="bibr" rid="R27">Minjauw and McLeod, 2003</xref>) and annual economic losses due to this disease approximately amounts to &#x20B9; 8426 crores in India (Narladkar, 2015).</p>
<p>As the sub-tropical climatic conditions of Indian subcontinent are extremely conducive for ticks and therefore for tick borne disease, BTT is a major disease dairy animals are exposed to in this region including India. Several earlier studies from across India reported prevalence of BTT of different extent attributed to various risk factors <italic>viz</italic>. age, sex, breed, season, management practices <italic>etc.</italic> (<xref ref-type="bibr" rid="R16">Gul <italic>et al</italic>., 2015</xref>). Various factors such as managament practices, sex, health status, nutritional deficits, breed, herd size, agro-climate (humidity, temperature) directly affects the livestock health and pose them to get this disease (<xref ref-type="bibr" rid="R15">Ghosh and Nagar 2014</xref>, Ayadi <italic>et al.,</italic> 2016). Considering its importance epidemiological studies have since long being conducted in India to estimate its spread so as to formulate effective control strategies to minimize the losses incurred by BTT.</p>
<p><bold>How to cite this article:</bold> Bhangale, G.N., Prakash, B.K.C. and Dhabale, A.R. (2021). Intrinsic risk factors for bovine tropical theileriosis in Indian cattle: A meta-analysis. <italic>J. Anim. Res.,</italic> <bold>11</bold>(3): 497-503. <bold>Source of Support:</bold> None; <bold>Conflict of Interest:</bold> None</p>
<p>The present study has detailed on animal bio-markers as the risk factors for BTT in India though meta-analysis approach based on earlier published reports.</p>
</sec>
<sec>
<title>MATERIALS AND METHODS</title>
<p>Present study is based on meta-analysis of earlier reports on risk factors for BTT in India. This meta-analysis was conducted according to criteria laid down under PRISMA Guidelines (<xref ref-type="bibr" rid="R28">Moher <italic>et al</italic>., 2009</xref>). The studies were selected for this meta-analysis were spanned over years 20152020. The studies were selected through a systematic search from online free databases viz. GoogleScholar, PubMed, IndianJournals. The keys used for this search were Theileria, Theileriosis, Bovine, Cattle, India with combinations by using Boolean words <italic>i.e.</italic> AND, OR. the criteria for selection of studies were such that the study to be selected should have reported prevalence of Theileriosis in cattle based various risk factors including age, sex and breed as the biomarkers of the cattle. The search and strategic selection based on the aforementioned criteria yielded 12 studies for final meta-analysis.</p>
<fig>
<p>Moher <italic>et al.</italic> (2009). www.prisma-statement.org</p>
<graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="JAR-11-03-0497-f001.jpg"/>
</fig>
<p>The requisite data on the BTT prevalence estimates based on risk factors were extracted from the selected studies and entered in an MS-excel sheet. Depending on the extent of heterogeneity, the random effects model and fixed effects model was employed for this meta-analysis. When heterogeneity was above 75%, random effects model was employed otherwise fixed effect model was used.</p>
<p>Risk factors for BTT as age, sex, breed was considered for this analysis and accordingly data was categorized. Studies with exact and essentially with both the number of animals tested and the number animals found positive for at least one of these factors was included in this analysis. Individual spreadsheet for data on each of the risk factors was prepared and subjected to meta-analysis. Meta-analysis was performed on MetaXL add-in with the help the command NumOR and results were presented through forest plot. Heterogeneity and publication bias were assessed and presented accordingly.</p>
<table-wrap id="t1">
<label>Table 1</label>
<caption>
<p>Characteristics of the included studies on risk factor wise prevalence of BTT in India</p>
</caption>
<graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="JAR-11-03-0497-t001.jpg"/>
</table-wrap>
</sec>
<sec>
<title>RESULTS AND DISCUSSION</title>
<p>Through the systematic search and following selection criteria amongst 87 studies reviewed from databases 12 were eligible for this meta-analysis (Fig 1). The characteristics of the selected studies and details of each are given in <xref ref-type="table" rid="t1">Table 1</xref>. Meta-analysis results are also presented in <xref ref-type="table" rid="t2">Table 2</xref> wherein the log odds ratio for each of risk factor along with heterogeneity data and publication bias accounts are given. Publication bias was presented through LFK Index and Doi plot and depicted through <xref ref-type="fig" rid="f5">Figures 5</xref>, <xref ref-type="fig" rid="f6">6</xref>, <xref ref-type="fig" rid="f7">7</xref>.</p>
<table-wrap id="t2">
<label>Table 2</label>
<caption>
<p>Results of meta-analysis of risk factors of BTT in India</p>
</caption>
<graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="JAR-11-03-0497-t002.jpg"/>
</table-wrap>
<sec>
<title>Age as a risk factor</title>
<p>Results of this meta-analysis revealed that age plays an important role in development of Theileriosis in cattle. Adult cattle are found twice at risk for BTT than the younger stocks with an odds ratio of 2.062 (95% CI 1.352 &#x2013; 3.145) which was highly significant (Q= 38.729; p=0.0) with substantial heterogeneity (I<sup>2</sup> = 476.76%). As regards age factor in the distribution of BTT these findings correspond to earlier reports by <xref ref-type="bibr" rid="R31">Panda <italic>et al.</italic> (2011)</xref>; <xref ref-type="bibr" rid="R23">Kumar (2012)</xref>; <xref ref-type="bibr" rid="R2">Agrawal (2016)</xref>; <xref ref-type="bibr" rid="R21">Kolte <italic>et al</italic>. (2017)</xref>; <xref ref-type="bibr" rid="R14">Ghosh <italic>et al</italic>. (2020)</xref>. However, several other studies contradicted these findings (<xref ref-type="bibr" rid="R32">Salih <italic>et al</italic>., 2013</xref>; <xref ref-type="bibr" rid="R35">Velusamy <italic>et al</italic>., 2014</xref>). Since adult cattle particularly cows are usually subjected to milk production, the stress due to lactation and pregnancy will be a major predisposing factor for getting BTT and other infectious disease. Additionally, higher exposure of vectors to adult cattle due to open grazing is also an important contributing factor. On the other hand, young stock which are generally raised on intensive feeding and confined housing are less prone to attack by vectors and therby vector borne diseases (<xref ref-type="bibr" rid="R5">Bhutto <italic>et al</italic>., 2010</xref>). Even earlier reports justifying the age related resistance in young stock to most of the tick borne protozoan and rickettsial diseases including <italic>T.annulata</italic> (<xref ref-type="bibr" rid="R11">Dumanli <italic>et al</italic>., 2005</xref>).</p>
<fig id="f2">
<label>Fig. 2</label>
<caption>
<p>Forest plot depicting age as a risk factor of BTT in Indian cattle</p>
</caption>
<graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="JAR-11-03-0497-f002.jpg"/>
</fig>
</sec>
<sec>
<title>Sex as a risk factor</title>
<p>Sex of cattle was found to have moderate impact to make the animal susceptible for BTT. It was estimated that cows are little more susceptible to BTT than bullocks / bulls with an odds ratio of 1.632 (95% CI 1.266 &#x2013; 2.104). However, with lower heterogeneity between studies (I<sup>2</sup> = 42.54%) this estimate was non-significant (Q = 13.923; p=0.08). These findings also corroborates with earlier reports by <xref ref-type="bibr" rid="R36">Zaman <italic>et al</italic>. (2020)</xref>. However, the rationale for such distribution may be attributed to certain intrinsic factors such as hormones may have a role to play (<xref ref-type="bibr" rid="R22">Kumar <italic>et al</italic>., 2017</xref>). As males are either culled or utilized for drought purposes as against cows which are raised longer for milk production and breeding are under persistent physiological stress due to pregnancy and/or lactation. This stress along with suppression of immunity may predispose those cows to higher risk of getting infected with BTT (<xref ref-type="bibr" rid="R18">Kamani <italic>et al</italic>., 2010</xref>, Ghosh <italic>et al.</italic>, 2018).</p>
<fig id="f3">
<label>Fig. 3</label>
<caption>
<p>Forest plot depicting sex as a risk factor of BTT in Indian cattle</p>
</caption>
<graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="JAR-11-03-0497-f003.jpg"/>
</fig>
</sec>
<sec>
<title>Breed as a risk factor</title>
<p>As being reported since long, exotic / crossbred cattle are more prone to contract BTT with an odds ratio of 2.113 (95% CI = 1.315 &#x2013; 3.396) which was even supported by several earlier evidences based on molecular studies (<xref ref-type="bibr" rid="R22">Kumar <italic>et al</italic>., 2017</xref>). Similarly, the estimates of current meta-analysis also seconded this, however there is absence of heterogeneity (I<sup>2</sup> = 0%) between the studies under this meta-analysis. The results on the basis of Q statistics (0.304; p= 0.99) are non-significant. Yet the current metaanalysis revealed that exotic and cross bred cattle are two fold at risk of getting infected with BTT than those cattle of domestic breeds. Similar trends were reported earlier by <xref ref-type="bibr" rid="R32">Salih <italic>et al</italic>., (2013)</xref>; Ghosh <italic>et al</italic>., (2018); <xref ref-type="bibr" rid="R13">Gharbi <italic>et al</italic>., (2020)</xref>. The observations of current study have strongly justified the earlier report by <xref ref-type="bibr" rid="R21">Kolte <italic>et al</italic>., (2017)</xref> wherein they have validated that germplasm of the cattle was crucial for the infection of Theileriosis and found that carrier crossbred cattle attracts more maintenance costs to the dairy enterprises. Furthermore, earlier reports also pointed out low case fatality and infection rates in local breeds while the higher morbidity and mortality in exotic and crossbred cattle (<xref ref-type="bibr" rid="R17">Jensen <italic>et al</italic>., 2007</xref>).</p>
<fig id="f4">
<label>Fig. 4</label>
<caption>
<p>Forest plot depicting breed as a risk factor of BTT in Indian cattle</p>
</caption>
<graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="JAR-11-03-0497-f004.jpg"/>
</fig>
<p>Since the 95% confidence intervals of odds ratios for all the factors under this study are more than 1 and did not include 1 (<italic>i.e.</italic> OR &#x2260;1), the effects size <italic>i.e.</italic> pooled ORs are significant at 5% level of significance.</p>
</sec>
<sec>
<title>Publication bias</title>
<p>The meta-analysis conducted for individual risk factor with selected set of studies for each of them has also tested for publication bias and presented through LFK Index and Doi plot individually. The LFK indices for each of them are in the range of 0 &#x2013; 1 which signifies no publication bias (<xref ref-type="table" rid="t2">Table 2</xref>). Also visual observation of Doi plots also seconded the absence of publication bias between the studies included for this analysis (<xref ref-type="fig" rid="f2">Figs. 2</xref>, <xref ref-type="fig" rid="f3">3</xref>, 4). No publication bias in meta-analysis of risk factors of BTT in Indian cattle was found for individual analysis conducted (<xref ref-type="bibr" rid="R4">Barendregt and Doi, 2011</xref> and <xref ref-type="bibr" rid="R19">Kanamori <italic>et al.,</italic> 2018</xref>).</p>
<fig id="f5">
<label>Fig. 5</label>
<caption>
<p>Doi plot and LFK index for publication bias in meta analysis of age as risk factor for BTT</p>
</caption>
<graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="JAR-11-03-0497-f005.jpg"/>
</fig>
<fig id="f6">
<label>Fig. 6</label>
<caption>
<p>Doi plot and LFK index for publication bias in metaanalysis of sex as risk factor for BTT</p>
</caption>
<graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="JAR-11-03-0497-f006.jpg"/>
</fig>
<fig id="f7">
<label>Fig. 7</label>
<caption>
<p>Doi plot and LFK index for publication bias in metaanalysis of breed as risk factor for BTT</p>
</caption>
<graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="JAR-11-03-0497-f007.jpg"/>
</fig>
</sec>
</sec>
<sec>
<title>CONCLUSION</title>
<p>It is herewith concluded that among the variables <italic>viz</italic>. age, sex, breed of cattle considered to be potential risk factors for BTT in Indian cattle, age and sex are found significant association with the occurrence of Theileriosis. On the other hand, even if breed of cattle has shown non-significant relation with the BTT incidence, its importance as a risk factor based on evidence from previous studies cannot be overruled. Though meta-analysis gives pooled estimates, the evidence obtained through it depends primarily on the qualities of primary studies included in it. To overcome this, further studies with appropriate sampling from each of the risk groups need to be undertaken to build a concrete evidence for better understanding of epidemiology of BTT.</p>
</sec>
</body>
<back>
<ack>
<title>ACKNOWLEDGMENTS</title>
<p>Authors express gratitude to the authorities of COVAS, Parbhani and MAFSU, Nagpur for providing necessary facilities for this study.</p>
</ack>
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