Browsing by Author "Day, P. J. Nicholas"

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    Comparing HemoCue® and Quantitative Buffy Coat® and Coulter Counter‑measured haemoglobin concentrations in African children with acute uncomplicated malaria: a Bland–Altman analysis
    (BMC, 2025) Ayuen, S. Dhol; Olupot‑Olupot, Peter; Muhindo, Rita; Onyamboko, A. Marie; Ajayi, Seun; Chimjinda, Natenapa; Taya, Chiraporn; Uyoga, Sophie; Williams, N. Thomas; Maitland, Kathryn; Fanello, Caterina; Day, P. J. Nicholas; Taylor, R. Walter; Mukaka, Mavuto
    Background: Anaemia is a deleterious consequence of malaria, and its accurate diagnosis is crucial for effective management. However, laboratory methods for measuring haemoglobin (Hb) concentration, like the Coulter Counter and the Quantitative Buffy Coat® (QBC®), are costly and not widely accessible in resource-limited settings. The pointof-care HemoCue® test is a cheaper alternative and suitable in rural areas. The study aimed to determine the level of agreement between Coulter Counter/QBC® vs. HemoCue®-measured Hb concentrations by Bland–Altman analysis. Methods: As part of a randomized, placebo-controlled trial of single low-dose primaquine in Ugandan and Congolese children with acute uncomplicated Plasmodium falciparum malaria, Hb concentrations were measured on days 0, 3, 7, and 28 using Coulter Counter (Uganda, n=1880 paired values), QBC® (DR Congo, n=1984 paired values) and HemoCue® Hb-301™. The predefined clinically acceptable limits were set at±0.5 g/dL. Results: The Bland–Altman analysis showed that the HemoCue® minus Coulter Counter mean Hb difference was − 0.15 g/dL with lower and upper limits of agreement of − 3.68 g/dL and 3.39 g/dL, respectively. Corresponding HemoCue® minus QBC® values were − 0.23 g/dL, − 1.66 g/dL and 1.22 g/dL. Linear regression of Hb concentration differences vs. mean Hb concentrations showed negative correlations: r=− 0.43 and r=− 0.34 for HemoCue® vs. Coulter Counter and HemoCue® vs. QBC®, respectively. Conclusions: Compared to Coulter and QBC®, mean HemoCue® measured Hb concentrations were lower and, compared to the Coulter or QBC® methods, had an overall tendency to measure lower Hb concentrations with increasing Hb concentrations. Upper and lower limits of agreement were wider than the predefined clinically acceptable limits of±0.5 g/dL. HemoCue® should be used with caution in settings where decisions about blood transfusions are made. Keywords Bland–Altman analysis, Haemoglobin, Anaemia, Malaria, HemoCue, Coulter Counter, QBC®
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    Single low dose primaquine to block the transmission of Plasmodium falciparum proposed stand‑alone and ACT‑adapted regimens.
    (BMC Medicine, 2025) Taylor, R. J. Walter; Olupot‑Olupot, Peter; Onyamboko, A. Marie; Chimjinda, Natenapa; Taya, Chiraporn; Pouplin, Nguyen Ngoc Julie; Williams, N. Thomas; Maitland, Kathryn; Fanello, A. Caterina; Day, P. J. Nicholas; Tarning, Joel; White, J. Nicholas; Mukaka, Mavuto
    Background: Despite the 2012 WHO recommendation to add single low dose primaquine (SLDPQ, 0.25 mg/kg body weight) to artemisinin-based combination treatments (ACTs) for blocking the transmission of artemisinin-resistant Plasmodium falciparum, there are currently no weight-based regimens founded on robust evidence. Methods: Applying published safety, transmission blocking and pharmacokinetic data, and exploring pharmacokinetic-pharmacodynamic relationships of age-based dosing of SLDPQ in African children with acute, uncomplicated Plasmodium falciparum, we derived weight-based, stand-alone, ACT-, triple ACT-, and vivax-matched regimens by following allometric dosing principles and simulating PQ exposure (area under the concentration time curve). The ACTs were dihydroartemisinin piperaquine (DHAPP), artesunate pyronaridine (ASPYR), artesunate amodiaquine (ASAQ), artesunate mefloquine (ASMQ), artemether lumefantrine (AL), and ALAQ. Tablet strengths were predefined: 2.5, 3.75, 5, 7.5, and 15 mg, and no tablet fractions were allowed. The maximum mg/kg dose was set at 0.5, and, primarily for ease of ACT co-blistering, 1 tablet=1 dose. We assessed different mg/kg doses and selected the dosing associated with a predicted median exposure closest to 1200 ng*h/mL, the exposure predicted for a 60 kg individual given 15 mg of PQ. Results: The designed 8 regimens had 4–8 dosing bands. The stand-alone, DHAPP, and ASPYR regimens contain the full line of PQ tablets and all other regimens, except AL (2.5, 7.5, 15 mg) and ALAQ (2.5, 5, 7.5, 15 mg), use 3.75 mg. The 2.5 mg tablet resulted in a maximum dose of 0.56 mg/kg for ASAQ, as this regimen starts at 4.5 kg body weight, whilst all other regimens start at 5 kg and resulted in 0.5 mg/kg. Substituting 3.75 mg with 5 mg results in maximum doses of 0.56 mg/kg (ASAQ, ASMQ) and 0.63 mg/kg (other regimens), risking greater toxicity. Across all dosing bands, 0.17−0.56 mg/kg doses predict exposures of~500−2000 ng*mL/h. Regimens with more dosing bands had less variations in exposure. Conclusions: These regimens offer flexibility for malaria control programmes and guidance for drug manufacturers wishing to co-blister SLDPQ with ACTs. The WHO should reinstate the 3.75 mg tablet for prequalification and determine which regimens should be incorporated into their treatment guidelines to advance malaria elimination. Trial registration: The trial is registered at ISRCTN, number 11594437. Keywords Primaquine, Transmission blocking, Plasmodium falciparum, Allometric dosing, Haemolysis, Glucose-6phosphate dehydrogenase deficiency