Utility of the monocyte to lymphocyte ratio in diagnosing latent tuberculosis among HIV-infected individuals with a negative tuberculosis symptom screen
Latent Tuberculosis Infection (LTBI) remains a major driver of the TB epidemic, and individuals with Human Immuno-deficiency Virus (HIV) are particularly at a heightened risk of developing LTBI. However, LTBI screening among HIV-infected individuals in resource limited setting is largely based on a...
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| description | Latent Tuberculosis Infection (LTBI) remains a major driver of the TB epidemic, and individuals with Human Immuno-deficiency Virus (HIV) are particularly at a heightened risk of developing LTBI. However, LTBI screening among HIV-infected individuals in resource limited setting is largely based on a negative symptom screen, which has low specificity.
In a cross sectional diagnostic study, 115 HIV infected participants with a negative symptom screen will be consented and enrolled. They will be requested to donate 5 ml of blood for complete blood count (CBC) and interferon gamma release assay (IGRA) testing. In a nested prospective study, the 115 participants will be initiated on Tuberculosis Preventive Therapy and the CBC testing repeated after 3 months. In the analysis of study finding, the monocyte to lymphocyte ratio (MLR) will be derived from the dividend of the absolute monocyte and lymphocyte counts. The optimal MLR positivity cut-off for elevated or normal MLR will be the highest value of Youden's index, J (sensitivity + specificity-1). The MLR will be cross tabulated with the IGRA status to determine the sensitivity, specificity, negative and positive predictive values of the MLR. The area under the receiver operating characteristic (ROC) curve will be determined to give the overall diagnostic accuracy of MLR. The baseline and 3 month CBC will be used to determine the change in MLR, and a random effect logistic regression will be used to determine factors associated with the change in the MLR.
If positive results are realized from this study, the MLR could become an inexpensive alternative biomarker with potential to improve the specificity of the negative symptom screen in identifying individuals that should be targeted for TB preventive therapy. |
| doi_str_mv | 10.1371/journal.pone.0241786 |
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In a cross sectional diagnostic study, 115 HIV infected participants with a negative symptom screen will be consented and enrolled. They will be requested to donate 5 ml of blood for complete blood count (CBC) and interferon gamma release assay (IGRA) testing. In a nested prospective study, the 115 participants will be initiated on Tuberculosis Preventive Therapy and the CBC testing repeated after 3 months. In the analysis of study finding, the monocyte to lymphocyte ratio (MLR) will be derived from the dividend of the absolute monocyte and lymphocyte counts. The optimal MLR positivity cut-off for elevated or normal MLR will be the highest value of Youden's index, J (sensitivity + specificity-1). The MLR will be cross tabulated with the IGRA status to determine the sensitivity, specificity, negative and positive predictive values of the MLR. The area under the receiver operating characteristic (ROC) curve will be determined to give the overall diagnostic accuracy of MLR. The baseline and 3 month CBC will be used to determine the change in MLR, and a random effect logistic regression will be used to determine factors associated with the change in the MLR.
If positive results are realized from this study, the MLR could become an inexpensive alternative biomarker with potential to improve the specificity of the negative symptom screen in identifying individuals that should be targeted for TB preventive therapy.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0241786</identifier><identifier>PMID: 33166312</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Biology and Life Sciences ; Biomarkers ; Blood ; Blood cell count ; Cross-Sectional Studies ; Diagnosis ; Diagnostic systems ; Disease prevention ; Epidemics ; Female ; Health risks ; Health sciences ; HIV ; HIV Infections - immunology ; HIV patients ; Human immunodeficiency virus ; Humans ; Infections ; Infectious diseases ; Interferon ; Interferon-gamma Release Tests ; Latent Tuberculosis - metabolism ; Lymphocytes ; Lymphocytes - cytology ; Male ; Medical diagnosis ; Medical examination ; Medicine and Health Sciences ; Middle Aged ; Monocytes ; Monocytes - cytology ; Prospective Studies ; Public health ; Registered Report Protocol ; Regression analysis ; ROC Curve ; Sensitivity ; Tuberculosis ; Tuberculosis - immunology ; Viruses</subject><ispartof>PloS one, 2020-11, Vol.15 (11), p.e0241786-e0241786</ispartof><rights>COPYRIGHT 2020 Public Library of Science</rights><rights>2020 Mayito et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 Mayito et al 2020 Mayito et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c622t-5115d0470aaba75f2ea1df0e52329bf275839697b23753d659f8eab934df91533</citedby><cites>FETCH-LOGICAL-c622t-5115d0470aaba75f2ea1df0e52329bf275839697b23753d659f8eab934df91533</cites><orcidid>0000-0001-9611-2178</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652277/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652277/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2100,2926,23865,27923,27924,53790,53792,79371,79372</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33166312$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Hasnain, Seyed Ehtesham</contributor><creatorcontrib>Mayito, Jonathan</creatorcontrib><creatorcontrib>Meya, David B</creatorcontrib><creatorcontrib>Rhein, Joshua</creatorcontrib><creatorcontrib>Sekaggya-Wiltshire, Christine</creatorcontrib><title>Utility of the monocyte to lymphocyte ratio in diagnosing latent tuberculosis among HIV-infected individuals with a negative tuberculosis symptom screen</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Latent Tuberculosis Infection (LTBI) remains a major driver of the TB epidemic, and individuals with Human Immuno-deficiency Virus (HIV) are particularly at a heightened risk of developing LTBI. However, LTBI screening among HIV-infected individuals in resource limited setting is largely based on a negative symptom screen, which has low specificity.
In a cross sectional diagnostic study, 115 HIV infected participants with a negative symptom screen will be consented and enrolled. They will be requested to donate 5 ml of blood for complete blood count (CBC) and interferon gamma release assay (IGRA) testing. In a nested prospective study, the 115 participants will be initiated on Tuberculosis Preventive Therapy and the CBC testing repeated after 3 months. In the analysis of study finding, the monocyte to lymphocyte ratio (MLR) will be derived from the dividend of the absolute monocyte and lymphocyte counts. The optimal MLR positivity cut-off for elevated or normal MLR will be the highest value of Youden's index, J (sensitivity + specificity-1). The MLR will be cross tabulated with the IGRA status to determine the sensitivity, specificity, negative and positive predictive values of the MLR. The area under the receiver operating characteristic (ROC) curve will be determined to give the overall diagnostic accuracy of MLR. The baseline and 3 month CBC will be used to determine the change in MLR, and a random effect logistic regression will be used to determine factors associated with the change in the MLR.
If positive results are realized from this study, the MLR could become an inexpensive alternative biomarker with potential to improve the specificity of the negative symptom screen in identifying individuals that should be targeted for TB preventive therapy.</description><subject>Adult</subject><subject>Biology and Life Sciences</subject><subject>Biomarkers</subject><subject>Blood</subject><subject>Blood cell count</subject><subject>Cross-Sectional Studies</subject><subject>Diagnosis</subject><subject>Diagnostic systems</subject><subject>Disease prevention</subject><subject>Epidemics</subject><subject>Female</subject><subject>Health risks</subject><subject>Health sciences</subject><subject>HIV</subject><subject>HIV Infections - immunology</subject><subject>HIV patients</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Infections</subject><subject>Infectious diseases</subject><subject>Interferon</subject><subject>Interferon-gamma Release Tests</subject><subject>Latent Tuberculosis - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mayito, Jonathan</au><au>Meya, David B</au><au>Rhein, Joshua</au><au>Sekaggya-Wiltshire, Christine</au><au>Hasnain, Seyed Ehtesham</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Utility of the monocyte to lymphocyte ratio in diagnosing latent tuberculosis among HIV-infected individuals with a negative tuberculosis symptom screen</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2020-11-09</date><risdate>2020</risdate><volume>15</volume><issue>11</issue><spage>e0241786</spage><epage>e0241786</epage><pages>e0241786-e0241786</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Latent Tuberculosis Infection (LTBI) remains a major driver of the TB epidemic, and individuals with Human Immuno-deficiency Virus (HIV) are particularly at a heightened risk of developing LTBI. However, LTBI screening among HIV-infected individuals in resource limited setting is largely based on a negative symptom screen, which has low specificity.
In a cross sectional diagnostic study, 115 HIV infected participants with a negative symptom screen will be consented and enrolled. They will be requested to donate 5 ml of blood for complete blood count (CBC) and interferon gamma release assay (IGRA) testing. In a nested prospective study, the 115 participants will be initiated on Tuberculosis Preventive Therapy and the CBC testing repeated after 3 months. In the analysis of study finding, the monocyte to lymphocyte ratio (MLR) will be derived from the dividend of the absolute monocyte and lymphocyte counts. The optimal MLR positivity cut-off for elevated or normal MLR will be the highest value of Youden's index, J (sensitivity + specificity-1). The MLR will be cross tabulated with the IGRA status to determine the sensitivity, specificity, negative and positive predictive values of the MLR. The area under the receiver operating characteristic (ROC) curve will be determined to give the overall diagnostic accuracy of MLR. The baseline and 3 month CBC will be used to determine the change in MLR, and a random effect logistic regression will be used to determine factors associated with the change in the MLR.
If positive results are realized from this study, the MLR could become an inexpensive alternative biomarker with potential to improve the specificity of the negative symptom screen in identifying individuals that should be targeted for TB preventive therapy.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>33166312</pmid><doi>10.1371/journal.pone.0241786</doi><tpages>e0241786</tpages><orcidid>https://orcid.org/0000-0001-9611-2178</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Biology and Life Sciences Biomarkers Blood Blood cell count Cross-Sectional Studies Diagnosis Diagnostic systems Disease prevention Epidemics Female Health risks Health sciences HIV HIV Infections - immunology HIV patients Human immunodeficiency virus Humans Infections Infectious diseases Interferon Interferon-gamma Release Tests Latent Tuberculosis - metabolism Lymphocytes Lymphocytes - cytology Male Medical diagnosis Medical examination Medicine and Health Sciences Middle Aged Monocytes Monocytes - cytology Prospective Studies Public health Registered Report Protocol Regression analysis ROC Curve Sensitivity Tuberculosis Tuberculosis - immunology Viruses |
| title | Utility of the monocyte to lymphocyte ratio in diagnosing latent tuberculosis among HIV-infected individuals with a negative tuberculosis symptom screen |
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