{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T13:06:11Z","timestamp":1763816771734,"version":"3.45.0"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,5,31]],"date-time":"2025-05-31T00:00:00Z","timestamp":1748649600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000030","name":"Centers for Disease Control and Prevention","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000030","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004339","name":"Sanofi US","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004339","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Differences in absolute neutrophil count (ANC) between African and non-African populations have been reported. Neutropenia has also been reported during rifamycin use. ANC values in current tables that assign severity grades to clinical or laboratory events (National Cancer Institute Common Terminology Criteria for Adverse Events [CTCAE] and the National Institute of Allergy and Infectious Diseases Division of AIDS [DAIDS]) might not consistently be applicable among different populations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>During 2 international tuberculosis treatment trials, 337 participants received 10\u2005mg\/kg of rifampin, and 3 groups of 361, 81, and 81 participants received 10, 15, and 20\u2005mg\/kg of rifapentine, respectively, for 2 months of daily treatment. ANC was measured at baseline and after 2, 4, 6, 8, and 12 weeks of treatment. CTCAE versions 2.0\u20134.0 and DAIDS version 2.0 define neutropenia grade 3 as ANC 500\u2013999 cells\/\u03bcL and ANC 400\u2013599 cells\/\u03bcL, respectively. We analyzed factors associated with neutropenia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Baseline median ANC was lower in Black African participants than in Black non-African participants (P = .004). CTCAE-defined grade 3 or higher neutropenia occurred in 32 (28 in Africa) participants. Proportions did not differ between rifapentine doses. Only 4 events would have been reported by DAIDS criteria. All neutropenia events resolved spontaneously without interrupting treatment. Enrollment in an African country was an independent factor associated with the development of neutropenia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Differences in baseline median ANC can result in misclassification of adverse events or inappropriate clinical management. Development and use of population-specific normal values of ANC could improve guidance for research and clinical management.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/infdis\/jiaf291","type":"journal-article","created":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T07:43:42Z","timestamp":1748504622000},"page":"1128-1138","source":"Crossref","is-referenced-by-count":0,"title":["Differences in Neutrophil Counts Between African and Non-African Countries in 2 International Clinical Trials"],"prefix":"10.1093","volume":"232","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8283-1304","authenticated-orcid":false,"given":"Ruth N","family":"Moro","sequence":"first","affiliation":[{"name":"Division of HIV Prevention, Centers for Disease Control and Prevention , Atlanta, Georgia ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1783-0476","authenticated-orcid":false,"given":"John L","family":"Johnson","sequence":"additional","affiliation":[{"name":"Uganda\u2013Case Western Reserve University Research Collaboration , Kampala ,","place":["Uganda"]},{"name":"Case Western Reserve University School of Medicine , Cleveland, Ohio ,","place":["USA"]},{"name":"Department of Medicine, University Hospitals Cleveland Medical Center , Cleveland, Ohio ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neil","family":"Martinson","sequence":"additional","affiliation":[{"name":"Perinatal HIV Research Unit, University of the Witwatersrand , Johannesburg ,","place":["South Africa"]},{"name":"Johns Hopkins Center for Tuberculosis Research , School of Medicine, Baltimore, Maryland ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grace","family":"Muzanyi","sequence":"additional","affiliation":[{"name":"Uganda\u2013Case Western Reserve University Research Collaboration , Kampala ,","place":["Uganda"]},{"name":"Case Western Reserve University School of Medicine , Cleveland, Ohio ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chi-Chiu","family":"Leung","sequence":"additional","affiliation":[{"name":"Tuberculosis and Chest Service, Department of Health , Hong Kong Special Administrative Region ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kwok-Chiu","family":"Chang","sequence":"additional","affiliation":[{"name":"Tuberculosis and Chest Service, Department of Health , Hong Kong Special Administrative Region ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8717-9039","authenticated-orcid":false,"given":"Ziyaad","family":"Waja","sequence":"additional","affiliation":[{"name":"Perinatal HIV Research Unit, University of the Witwatersrand , Johannesburg ,","place":["South Africa"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8513-7342","authenticated-orcid":false,"given":"Stefan V","family":"Goldberg","sequence":"additional","affiliation":[{"name":"Division of Tuberculosis Elimination, Centers for Disease Control and Prevention , Atlanta, Georgia , , retired","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,5,31]]},"reference":[{"key":"2025112208022810300_jiaf291-B1","doi-asserted-by":"crossref","first-page":"486","DOI":"10.7326\/0003-4819-146-7-200704030-00004","article-title":"Prevalence of neutropenia in the U.S. population: age, sex, smoking status, and ethnic differences","volume":"146","author":"Hsieh","year":"2007","journal-title":"Ann Intern Med"},{"key":"2025112208022810300_jiaf291-B2","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1001\/archinte.1991.00400030063011","article-title":"Leukopenia, neutropenia, and reduced hemoglobin levels in healthy American Blacks","volume":"151","author":"Reed","year":"1991","journal-title":"Arch Intern Med"},{"key":"2025112208022810300_jiaf291-B3","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1200\/JCO.2009.24.3881","article-title":"Neutrophil count in African Americans: lowering the target cutoff to initiate or resume chemotherapy?","volume":"28","author":"Hsieh","year":"2010","journal-title":"J Clin Oncol"},{"key":"2025112208022810300_jiaf291-B4","doi-asserted-by":"crossref","first-page":"e2043","DOI":"10.1371\/journal.pone.0002043","article-title":"Baseline morbidity in 2,990 adult African volunteers recruited to characterize laboratory reference intervals for future HIV vaccine clinical trials","volume":"3","author":"Stevens","year":"2008","journal-title":"PLoS One"},{"key":"2025112208022810300_jiaf291-B5","doi-asserted-by":"crossref","first-page":"e4401","DOI":"10.1371\/journal.pone.0004401","article-title":"CLSI-derived hematology and biochemistry reference intervals for healthy adults in eastern and southern Africa","volume":"4","author":"Karita","year":"2009","journal-title":"PLoS One"},{"key":"2025112208022810300_jiaf291-B6","doi-asserted-by":"crossref","first-page":"e105089","DOI":"10.1371\/journal.pone.0105089","article-title":"Effect of seasonal variation on adult clinical laboratory parameters in Rwanda, Zambia, and Uganda: implications for HIV biomedical prevention trials","volume":"9","author":"Ruzagira","year":"2014","journal-title":"PLoS One"},{"key":"2025112208022810300_jiaf291-B7","first-page":"29","article-title":"Population-based hematologic and immunologic reference values for a healthy Ugandan population","volume":"11","author":"Lugada","year":"2004","journal-title":"Clin Diag Lab Immunol"},{"key":"2025112208022810300_jiaf291-B8","doi-asserted-by":"crossref","first-page":"e21040","DOI":"10.1371\/journal.pone.0021040","article-title":"Population-based biochemistry, immunologic and hematological reference values for adolescents and young adults in a rural population in western Kenya","volume":"6","author":"Zeh","year":"2011","journal-title":"PLoS One"},{"key":"2025112208022810300_jiaf291-B9","doi-asserted-by":"crossref","first-page":"e0123140","DOI":"10.1371\/journal.pone.0123140","article-title":"Evaluation of locally established reference intervals for hematology and biochemistry parameters in western Kenya","volume":"10","author":"Odhiambo","year":"2015","journal-title":"PLoS One"},{"key":"2025112208022810300_jiaf291-B10","doi-asserted-by":"crossref","first-page":"e97391","DOI":"10.1371\/journal.pone.0097391","article-title":"Reference values for clinical laboratory parameters in young adults in Maputo, Mozambique","volume":"9","author":"Tembe","year":"2014","journal-title":"PLoS One"},{"key":"2025112208022810300_jiaf291-B11","doi-asserted-by":"crossref","first-page":"e0165821","DOI":"10.1371\/journal.pone.0165821","article-title":"Adult hematology and clinical chemistry laboratory reference ranges in a Zimbabwean population","volume":"11","author":"Samaneka","year":"2016","journal-title":"PLoS One"},{"key":"2025112208022810300_jiaf291-B12","doi-asserted-by":"crossref","first-page":"e93919","DOI":"10.1371\/journal.pone.0093919","article-title":"Comprehensive reference ranges for hematology and clinical chemistry laboratory parameters derived from normal Nigerian adults","volume":"9","author":"Miri-Dashe","year":"2014","journal-title":"PLoS One"},{"key":"2025112208022810300_jiaf291-B13","doi-asserted-by":"crossref","first-page":"e1000360","DOI":"10.1371\/journal.pgen.1000360","article-title":"Reduced neutrophil count in people of African descent is due to a regulatory variant in the Duffy antigen receptor for chemokines gene","volume":"5","author":"Reich","year":"2009","journal-title":"PLoS Genet"},{"key":"2025112208022810300_jiaf291-B14","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1038\/ncomms1265","article-title":"The global distribution of the Duffy blood group","volume":"2","author":"Howes","year":"2011","journal-title":"Nat Commun"},{"key":"2025112208022810300_jiaf291-B15","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1182\/bloodadvances.2022007680","article-title":"White blood cell ranges and frequency of neutropenia by Duffy genotype status","volume":"7","author":"Bagheri","year":"2023","journal-title":"Blood Adv"},{"key":"2025112208022810300_jiaf291-B16","doi-asserted-by":"crossref","first-page":"607","DOI":"10.2165\/00003495-199856040-00008","article-title":"Rifapentine","volume":"56","author":"Jarvis","year":"1998","journal-title":"Drugs"},{"author":"Sanofi","key":"2025112208022810300_jiaf291-B17"},{"author":"Sanofi","key":"2025112208022810300_jiaf291-B18"},{"key":"2025112208022810300_jiaf291-B19","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.tube.2010.02.001","article-title":"Rifamycins\u2014obstacles and opportunities","volume":"90","author":"Aristoff","year":"2010","journal-title":"Tuberculosis (Edinb)"},{"key":"2025112208022810300_jiaf291-B20","doi-asserted-by":"crossref","first-page":"e30925","DOI":"10.1002\/pbc.30925","article-title":"Absolute neutrophil count clinical trial eligibility criteria for pediatric oncology phase I and phase I\/II trials by sponsorship","volume":"71","author":"Ruiz","year":"2024","journal-title":"Pediatr Blood Cancer"},{"key":"2025112208022810300_jiaf291-B21","doi-asserted-by":"crossref","first-page":"2263","DOI":"10.1056\/NEJMra1510065","article-title":"Interpreting geographic variations in results of randomized, controlled trials","volume":"375","author":"Yusuf","year":"2016","journal-title":"N Engl J Med"},{"author":"National Cancer Institute","key":"2025112208022810300_jiaf291-B22"},{"author":"National Cancer Institute","key":"2025112208022810300_jiaf291-B23"},{"author":"National Cancer Institute","key":"2025112208022810300_jiaf291-B24"},{"author":"National Institute of Allergy and Infectious Diseases","key":"2025112208022810300_jiaf291-B25"},{"author":"National Institute of Allergy and Infectious Diseases","key":"2025112208022810300_jiaf291-B26"},{"key":"2025112208022810300_jiaf291-B27","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1093\/infdis\/jis461","article-title":"Substitution of rifapentine for rifampin during intensive phase treatment of pulmonary tuberculosis: study 29 of the tuberculosis trials consortium","volume":"206","author":"Dorman","year":"2012","journal-title":"J Infect Dis"},{"key":"2025112208022810300_jiaf291-B28","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1164\/rccm.201410-1843OC","article-title":"Daily rifapentine for treatment of pulmonary tuberculosis. A randomized, dose-ranging trial","volume":"191","author":"Dorman","year":"2015","journal-title":"Am J Respir Crit Care Med"},{"author":"White House Office of Management and Budget","key":"2025112208022810300_jiaf291-B29"},{"author":"US Census Bureau. About the Topic of Race","key":"2025112208022810300_jiaf291-B30"},{"author":"White House Office of Management and Budget","key":"2025112208022810300_jiaf291-B31"},{"key":"2025112208022810300_jiaf291-B32","doi-asserted-by":"crossref","first-page":"3341","DOI":"10.1093\/hmg\/ddaa208","article-title":"The Duffy-null genotype and risk of infection","volume":"29","author":"Legge","year":"2020","journal-title":"Hum Mol Genet"},{"key":"2025112208022810300_jiaf291-B33","doi-asserted-by":"crossref","first-page":"328","DOI":"10.7326\/0003-4819-64-2-328","article-title":"Quantitative relationships between circulating leukocytes and infection in patients with acute leukemia","volume":"64","author":"Bodey","year":"1966","journal-title":"Ann Intern Med"},{"key":"2025112208022810300_jiaf291-B34","doi-asserted-by":"crossref","first-page":"e56","DOI":"10.1093\/cid\/cir073","article-title":"Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America","volume":"52","author":"Freifeld","year":"2011","journal-title":"Clin Infect Dis"},{"key":"2025112208022810300_jiaf291-B35","doi-asserted-by":"crossref","first-page":"2088","DOI":"10.1001\/jama.2023.7467","article-title":"Development of Duffy null\u2013specific absolute neutrophil count reference ranges","volume":"329","author":"Merz","year":"2023","journal-title":"JAMA"},{"key":"2025112208022810300_jiaf291-B36","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1097\/MOH.0000000000000007","article-title":"Neutrophil counts in persons of African origin","volume":"21","author":"Thobakgale","year":"2014","journal-title":"Curr Opin Hematol."},{"key":"2025112208022810300_jiaf291-B37","first-page":"625","article-title":"The genetics of benign neutropenia","volume":"13","author":"Paz","year":"2011","journal-title":"Isr Med Assoc J"},{"key":"2025112208022810300_jiaf291-B38","doi-asserted-by":"crossref","first-page":"3887","DOI":"10.1097\/MS9.0000000000001084","article-title":"Impact of anti-tuberculosis treatment on hematological parameters in newly diagnosed tuberculosis patients at Jimma town: a longitudinal prospective study","volume":"85","author":"Reta","year":"2023","journal-title":"Ann Med Surg (Lond)"},{"key":"2025112208022810300_jiaf291-B39","doi-asserted-by":"crossref","first-page":"e1003468","DOI":"10.1371\/journal.ppat.1003468","article-title":"Ethnic variation in inflammatory profile in tuberculosis","volume":"9","author":"Coussens","year":"2013","journal-title":"PLoS Pathog"},{"key":"2025112208022810300_jiaf291-B40","doi-asserted-by":"crossref","first-page":"15449","DOI":"10.1073\/pnas.1200072109","article-title":"Vitamin D accelerates resolution of inflammatory responses during tuberculosis treatment","volume":"109","author":"Coussens","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2025112208022810300_jiaf291-B41","doi-asserted-by":"crossref","first-page":"e18358","DOI":"10.1371\/journal.pone.0018358","article-title":"Geographic differences in time to culture conversion in liquid media: Tuberculosis Trials Consortium study 28. Culture conversion delayed in Africa","volume":"6","author":"MacKenzie","year":"2011","journal-title":"PLoS One"}],"container-title":["The Journal of Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jid\/advance-article-pdf\/doi\/10.1093\/infdis\/jiaf291\/63409030\/jiaf291.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jid\/article-pdf\/232\/5\/1128\/63409030\/jiaf291.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jid\/article-pdf\/232\/5\/1128\/63409030\/jiaf291.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T13:02:39Z","timestamp":1763816559000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jid\/article\/232\/5\/1128\/8154211"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,31]]},"references-count":41,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,5,31]]},"published-print":{"date-parts":[[2025,11,14]]}},"URL":"https:\/\/doi.org\/10.1093\/infdis\/jiaf291","relation":{},"ISSN":["0022-1899","1537-6613"],"issn-type":[{"type":"print","value":"0022-1899"},{"type":"electronic","value":"1537-6613"}],"subject":[],"published-other":{"date-parts":[[2025,11,15]]},"published":{"date-parts":[[2025,5,31]]}}}