Neutrophil Counts in Healthy South African Infants: Implications for Enrollment and Adverse Event Grading in Clinical Trials in an African Setting
Anthonet Koen, Lisa Jose, Shabir A Madhi, Alan Fix, Stanley Cryz, Michelle J Groome, Anthonet Koen, Lisa Jose, Shabir A Madhi, Alan Fix, Stanley Cryz, Michelle J Groome
Abstract
Absolute neutrophil counts are used to assess eligibility and safety during clinical trials but the toxicity grading scale used can affect enrollment and reporting of adverse events. During a trial investigating a parenteral rotavirus vaccine in South Africa, we excluded otherwise healthy infants without HIV infection from participation owing to neutropenia.
Trial registration: ClinicalTrials.gov: NCT02109484.
Keywords: DAIDS, Division of AIDS; SRC, Safety Review Committee.
© 2019 The Author(s).
Figures
References
- Muturi-Kioi V., Lewis D., Launay O., Leroux-Roels G., Anemona A., Loulergue P. Neutropenia as an adverse event following vaccination: results from randomized clinical trials in healthy adults and systematic review. PloS One. 2016;11:e0157385.
- Denic S., Narchi H., Al Mekaini L.A., Al-Hammadi S., Al Jabri O.N., Souid A.K. Prevalence of neutropenia in children by nationality. BMC Hematol. 2016;16:15.
- Hsieh M.M., Everhart J.E., Byrd-Holt D.D., Tisdale J.F., Rodgers G.P. Prevalence of neutropenia in the U.S. population: age, sex, smoking status, and ethnic differences. Ann Intern Med. 2007;146:486–492.
- Ortiz M.V., Meier E.R., Hsieh M.M. Identification and clinical characterization of children with benign ethnic neutropenia. J Pediatr Hematol Oncol. 2016;38:e140–e143.
- Groome M.J., Koen A., Fix A., Page N., Jose L., Madhi S.A. Safety and immunogenicity of a parenteral P2-VP8-P[8] subunit rotavirus vaccine in toddlers and infants in South Africa: a randomised, double-blind, placebo-controlled trial. Lancet Infect Dis. 2017;17:843–853.
- US Department of Health and Human Services, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Division of AIDS Division of AIDS table for grading the severity of adult and pediatric adverse events, version 1.0. [updated August 2009]
- US Department of Health and Human Services. National Institutes of Health. National Institute of Allergy and Infectious Diseases, Division of AIDS Division of AIDS (DAIDS) table for grading the severity of adult and pediatric adverse events, version 2.0. [November 2014]
- Lau E., Brophy J., Samson L., Kakkar F., Campbell D.M., Yudin M.H. Nevirapine pharmacokinetics and safety in neonates receiving combination antiretroviral therapy for prevention of vertical HIV transmission. J Acquir Immune Defic Syndr. 2017;74:493–498.
- Haddy T.B., Rana S.R., Castro O. Benign ethnic neutropenia: what is a normal absolute neutrophil count? J Lab Clin Med. 1999;133:15–22.
- Thobakgale C.F., Ndung'u T. Neutrophil counts in persons of African origin. Curr Opinion Hematol. 2014;21:50–57.
- Lawrie D., Coetzee L.M., Becker P., Mahlangu J., Stevens W., Glencross D.K. Local reference ranges for full blood count and CD4 lymphocyte count testing. S Afr Med J. 2009;99:243–248.
- Wells J., Shetty A.K., Stranix L., Falkovitz-Halpern M.S., Chipato T., Nyoni N. Range of normal neutrophil counts in healthy Zimbabwean infants: implications for monitoring antiretroviral drug toxicity. J Acquir Immune Defic Syndr. 2006;42:460–463.
- Buchanan A.M., Muro F.J., Gratz J., Crump J.A., Musyoka A.M., Sichangi M.W. Establishment of haematological and immunological reference values for healthy Tanzanian children in Kilimanjaro Region. Trop Med Int Health. 2010;15:1011–1021.
- Cunningham C.K., Wara D.W., Kang M., Fenton T., Hawkins E., McNamara J. Safety of 2 recombinant human immunodeficiency virus type 1 (HIV-1) envelope vaccines in neonates born to HIV-1-infected women. Clin Infect Dis. 2001;32:801–807.
- Lugada E.S., Mermin J., Kaharuza F., Ulvestad E., Were W., Langeland N. Population-based hematologic and immunologic reference values for a healthy Ugandan population. Clin Diagn Lab Immunol. 2004;11:29–34.
- Lawrie D., Payne H., Nieuwoudt M., Glencross D.K. Observed full blood count and lymphocyte subset values in a cohort of clinically healthy South African children from a semi-informal settlement in Cape Town. S Afr Med J. 2015;105:589–595.
- Karita E., Ketter N., Price M.A., Kayitenkore K., Kaleebu P., Nanvubya A. CLSI-derived hematology and biochemistry reference intervals for healthy adults in eastern and southern Africa. PloS One. 2009;4:e4401.
Source: PubMed