Background: Malaria microscopy, while the gold standard for malaria diagnosis, has limitations. Efficacy estimates in drug and vaccine malaria trials are very sensitive to small errors in microscopy endpoints. This fact led to the establishment of a Malaria Diagnostics Centre of Excellence in Kisumu, Kenya. The primary objective was to ensure valid clinical trial and diagnostic test evaluations. Key secondary objectives were technology transfer to host countries, establishment of partnerships, and training of clinical microscopists.
This study was designed to directly compare the accuracy, reproducibility, and efficiency of three methods commonly used to measure blood-stage malaria parasite density from Giemsa-stained blood films. Parasites and white blood cells (WBCs) were counted in 154 thick films by two independent microscopists. Forty-six slides were read by counting parasitized red blood cells (RBCs) in the thin film. Using these same slides, parasites were again counted by two independent microscopists using an ocular grid. Overall, parasite densities were significantly lower and discrepancy between readers was higher when using the grid method compared to the WBC method, but there was no difference when compared to the RBC method. When one reader who had difficulty with the grid method was excluded, the discrepancy between readers was equivalent for the three methods. Densities and discrepancy between readers were indistinguishable when parasites were counted until 200 or 500 WBCs. Counting beyond 200 WBCs may not significantly improve parasite density measurements. Using an ocular grid directly measures parasites per volume rather than using a WBC per microliter conversion factor and eliminates the need to switch from the thick film to the thin film for high parasitemias. However, significant differences in densities measured by the grid method and the WBC method need to be evaluated.
Antiretroviral drugs cross from maternal plasma to breast milk and from breast milk to the infant in different concentrations. We measured concentrations of nelfinavir and its active metabolite (M8) in maternal plasma and breast milk from women and in dried blood spots collected from their infants at delivery and postnatal weeks 2, 6, 14, and 24 in the Kisumu Breastfeeding Study, Kisumu, Kenya. Nelfinavir-based antiretroviral regimens given to mothers as prevention of mother-to-child HIV transmission (PMTCT) do not expose the breast-feeding infant to biologically significant concentrations of nelfinavir or M8.Maternal antiretroviral medications taken during breastfeeding as prevention of mother-to-child HIV transmission (PMTCT) reduce HIV viral load in the breast milk of nursing mothers (5). Antiretrovirals cross from maternal plasma to breast milk and from breast milk to the infant in different concentrations (4,5,7,8,9,10). The Kisumu Breastfeeding study (KiBS) was a phase IIb open-label single-arm PMTCT trial of maternal triple-antiretroviral regimens administered from 34 weeks' gestation to 6 months postpartum while infants exclusively breast-fed. The study was conducted in Kisumu, Kenya, with women and their infants enrolled between July 2003 and November 2006 (11). We demonstrated in a prior KiBS substudy that nevirapine, lamivudine, and zidovudine were present in the breast milk of lactating mothers prescribed those medications and that nevirapine and lamivudine were transferred to infants via breast-feeding in biologically significant concentrations, as evidenced by the emergence of resistance to lamivudine and nevirapine, respectively, among strains of HIV infecting the infants (7, 12). However, breastfeeding HIV-infected infants from the same substudy whose mothers received nelfinavir did not develop protease inhibitor resistance (12). The aim of this study was to describe concentrations of nelfinavir and its active metabolite, hydroxy-t-butylamidenelfinavir (M8), in maternal plasma, breast milk, and infant dried blood spots collected during the administration of nelfinavir to nursing mothers. MATERIALS AND METHODSA subset of mothers participating in KiBS with a CD4 count of Ͼ250 cells/l received nelfinavir mesylate (1,250 mg twice daily; Viracept, Hoffman-La Roche Ltd, Germany) and zidovudine-lamivudine (300 mg/150 mg twice daily; Combivir, GlaxoSmithKline, United Kingdom) (11). Maternal plasma, breast milk, and infant dried blood spots were collected at delivery and postnatal weeks 2, 6, 14, and 24 from a nonrandom subset of sequentially enrolled subjects participating in a breast milk substudy (7). Nelfinavir was dispensed in pill bottles with MEMS (medication event monitoring system) caps (Aardex, Ltd., Union City, CA), which were used to determine the dosing times for the last maternal antiretroviral dose prior to sampling; timing was confirmed by pharmacy staff. Prior to analysis, plasma and breast milk specimens were stored at Ϫ70°C and dried blood spots were stored at Ϫ20°C. Included in this a...
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