Range of Normal Neutrophil Counts in Healthy Zimbabwean Infants

Abstract

Mother-to-child HIV prevention trials in sub-Saharan Africa use the US National Institutes of Health Division of AIDS (DAIDS) grading scale to monitor hematologic toxicity. A recent study of nevirapine prophylaxis given for 6 months in breast-feeding Zimbabwean infants reported several cases of relative neutropenia in clinically well infants, raising concerns of drug toxicity. However, the DAIDS tables are based on normal blood counts for white infants, although there is evidence that black African infants may have lower absolute neutrophil counts (ANCs) than white infants. To establish normal hematologic values in black Zimbabwean infants and to quantify the apparent prevalence of relative neutropenia in this population, we evaluated HIV-uninfected healthy infants born to HIV-uninfected women at birth, 10 days, 6 weeks, 3, and 4 months of life. A physical examination and blood count were performed at each visit, and an HIV test was performed at the final visit. The ANC values were graded using the DAIDS table. A total of 145 healthy term infants satisfied the inclusion criteria. The mean ANC values for Zimbabwean infants were less than half of the corresponding standard values at all 5 time points (P < 0.0001). Using the DAIDS table in use at the time that the blood was collected, 57% of these healthy infants had relative neutropenia of any grade at birth, followed by 29% at day 10, 53% at 6 weeks, 32% at 3 months, and 37% at 4 months of life. Our data indicate that relative neutropenia exists in healthy black Zimbabwean infants. The guidelines for identifying toxicity were changed in December 2004. However, even by the new DAIDS tables, 43%, 23%, 24%, 42%, and 43% of these healthy babies had relative neutropenia at the time of the 5 visits. Future HIV prevention and treatment trials in sub-Saharan Africa should use normal hematologic values derived from African infants to avoid the overestimation of antiretroviral drug toxicity.

Cotrimoxazole Prophylaxis and Risk of Severe Anemia or Severe Neutropenia in HAART-Exposed, HIV-Uninfected Infants

“…[31]–[33] However, the findings of this study indicate that an absolute increase in severe neutropenia related to cotrimoxazole is likely to be at most 5%. In settings where either continued breastfeeding or limited access to early infant HIV diagnosis make the use of cotrimoxazole prophylaxis a consideration, these negative findings are important to inform decisions about the optimal period for prophylaxis.…”

Effect of co-trimoxazole on mortality in HIV-exposed but uninfected children in Botswana (the Mpepu Study): a double-blind, randomised, placebo-controlled trial

“…Few data exist regarding the implications of medication-induced neutropenia for child health outcomes in Africa, and normal neutrophil count ranges for African infants may be lower than ranges in the populations used in the development of the DAIDS toxicity tables. 40–43 Lastly, we detected an increase in CTX resistance among commensal E. coli stool isolates in the CTX arm; the clinical consequences of this finding are unknown.…”

Immunohaematological reference values for HIV-negative healthy adults in Botswana

“…8,13,16,17,18 These studies have also observed significant differences with values from developed countries, in haematologic parameters such as haemoglobin and absolute neutrophil, which are normally used for toxicity grading in clinical trials, and consequently have implications in patient management and the conduct of clinical trials. 18,19,20,21 A significant number of potential African volunteers are excluded from participating in vaccine trials because screening, enrollment and follow-up monitoring is mostly based on values derived from predominantly White populations. A study in Uganda 19 documented an exclusion rate of as high as 69% of vaccine clinical trial participants because of haematologic abnormalities, 83% of whom could have been included in the studies if local reference ranges were used.…”