Differences in Neutrophil Counts Between African and non-African Countries in two International Clinical Trials

Ruth N Moro; John L Johnson; Neil Martinson; Grace Muzanyi; Chi-Chiu Leung; Kwok-Chiu Chang; Ziyaad Waja; Stefan V Goldberg

doi:10.1093/infdis/jiaf291

Differences in Neutrophil Counts Between African and non-African Countries in two International Clinical Trials

J Infect Dis. 2025 May 31:jiaf291. doi: 10.1093/infdis/jiaf291. Online ahead of print.

Authors

Ruth N Moro¹, John L Johnson^{2

3}, Neil Martinson^{4

5}, Grace Muzanyi^{2

3}, Chi-Chiu Leung⁶, Kwok-Chiu Chang⁶, Ziyaad Waja⁴, Stefan V Goldberg¹

Affiliations

¹ Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
² Uganda-Case Western Reserve University Research Collaboration, Kampala, Uganda.
³ Case Western Reserve University School of Medicine and University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA.
⁴ Perinatal HIV Research Unit (PHRU), University of the Witwatersrand, Johannesburg, South Africa.
⁵ Johns Hopkins University Center for TB Research, Baltimore, Maryland, USA.
⁶ The Hong Kong Tuberculosis, Chest and Heart Diseases Association, Hong Kong, China.

PMID: 40447276
DOI: 10.1093/infdis/jiaf291

Abstract

Background: 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 (The 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.

Methods: During two international tuberculosis treatment trials, 337 participants received rifampin, and three groups of 361, 81, and 81 participants received 10, 15, and 20 mg/kg of rifapentine, respectively, for two months of daily treatment. ANC was measured at baseline, and after 2, 4, 6, 8, and 12 weeks of treatment. CTCAE versions 2.0-4.0 and DAIDS version 2.0 define neutropenia grade 3 as ANC 500-999/mm3 and ANC 400-599/mm3, respectively. We analyzed factors associated with neutropenia.

Results: Baseline median ANC was lower in Black African participants than in Black non-African participants (p=0.004). CTCAE-defined ≥Grade 3 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.

Discussion: 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.

Keywords: Africa; absolute neutrophil count; ethnic leukopenia; neutropenia; tuberculosis.

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