Hematological Indices in Malian Children Change Significantly During a Malaria Season and with Increasing Age: Implications for Malaria Epidemiological Studies

Diakité, Mahamadou; Miura, Kazutoyo; Diouf, Ababacar; Konaté, Drissa; Keita, Abdoul S.; Doumbia, S.; Diakité, Seidina A. S.; Traoré, Karim; Doumbouya, Mory; Anderson, Jennifer M.; Fairhurst, Rick M.; Long, Carole A.

doi:10.4269/ajtmh.16-0125

Cited by 4 publications

(3 citation statements)

References 23 publications

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“…This disagreement might be due to differences in the hematological profile of circulating cells between geographical areas (90). Regardless of the number of malaria episodes experienced, age and season also affect hematological indices and white blood cell subsets, including the monocyte count (91). Still, it is possible to establish reference intervals for hematological parameters that are comparable and applicable across areas with similar transmission conditions (92).…”

Section: Effect Of Malaria Parasites On Circulating Monocyte Countsmentioning

confidence: 99%

The Rough Guide to Monocytes in Malaria Infection

Ortega-Pajares

Rogerson

2018

Front. Immunol.

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While half of the world's population is at risk of malaria, the most vulnerable are still children under five, pregnant women and returning travelers. Anopheles mosquitoes transmit malaria parasites to the human host; but how Plasmodium interact with the innate immune system remains largely unexplored. The most recent advances prove that monocytes are a key component to control parasite burden and to protect host from disease. Monocytes' protective roles include phagocytosis, cytokine production and antigen presentation. However, monocytes can be involved in pathogenesis and drive inflammation and sequestration of infected red blood cells in organs such as the brain, placenta or lungs by secreting cytokines that upregulate expression of endothelial adhesion receptors. Plasmodium DNA, hemozoin or extracellular vesicles can impair the function of monocytes. With time, reinfections with Plasmodium change the relative proportion of monocyte subsets and their physical properties. These changes relate to clinical outcomes and might constitute informative biomarkers of immunity. More importantly, at the molecular level, transcriptional, metabolic or epigenetic changes can “prime” monocytes to alter their responses in future encounters with Plasmodium. This mechanism, known as trained immunity, challenges the traditional view of monocytes as a component of the immune system that lacks memory. Overall, this rough guide serves as an update reviewing the advances made during the past 5 years on understanding the role of monocytes in innate immunity to malaria.

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Section: Effect Of Malaria Parasites On Circulating Monocyte Countsmentioning

confidence: 99%

The Rough Guide to Monocytes in Malaria Infection

Ortega-Pajares

Rogerson

2018

Front. Immunol.

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“…Leukocytosis can also occur, and is associated with concurrent bacterial infection [ 7 ] and severe malaria [ 11 ]. Whilst it is known that, independent of infection, children have a higher WBC count than adults [ 17 ], other determinants of WBC count during malaria are poorly understood. For example, in Thailand, WBC counts were consistently lower at presentation in those with P. falciparum compared to those with P. vivax infection [ 18 ], yet the opposite was observed in India [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Variability in white blood cell count during uncomplicated malaria and implications for parasite density estimation: a WorldWide Antimalarial Resistance Network individual patient data meta-analysis

Wynberg¹,

Commons²,

Humphreys³

et al. 2023

Malar J

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Background The World Health Organization (WHO) recommends that when peripheral malarial parasitaemia is quantified by thick film microscopy, an actual white blood cell (WBC) count from a concurrently collected blood sample is used in calculations. However, in resource-limited settings an assumed WBC count is often used instead. The aim of this study was to describe the variability in WBC count during acute uncomplicated malaria, and estimate the impact of using an assumed value of WBC on estimates of parasite density and clearance. Methods Uncomplicated malaria drug efficacy studies that measured WBC count were selected from the WorldWide Antimalarial Resistance Network data repository for an individual patient data meta-analysis of WBC counts. Regression models with random intercepts for study-site were used to assess WBC count variability at presentation and during follow-up. Inflation factors for parasitaemia density, and clearance estimates were calculated for methods using assumed WBC counts (8000 cells/µL and age-stratified values) using estimates derived from the measured WBC value as reference. Results Eighty-four studies enrolling 27,656 patients with clinically uncomplicated malaria were included. Geometric mean WBC counts (× 1000 cells/µL) in age groups < 1, 1–4, 5–14 and ≥ 15 years were 10.5, 8.3, 7.1, 5.7 and 7.5, 7.0, 6.5, 6.0 for individuals with falciparum (n = 24,978) and vivax (n = 2678) malaria, respectively. At presentation, higher WBC counts were seen among patients with higher parasitaemia, severe anaemia and, for individuals with vivax malaria, in regions with shorter regional relapse periodicity. Among falciparum malaria patients, using an assumed WBC count of 8000 cells/µL resulted in parasite density underestimation by a median (IQR) of 26% (4–41%) in infants < 1 year old but an overestimation by 50% (16–91%) in adults aged ≥ 15 years. Use of age-stratified assumed WBC values removed systematic bias but did not improve precision of parasitaemia estimation. Imprecision of parasite clearance estimates was only affected by the within-patient WBC variability over time, and remained < 10% for 79% of patients. Conclusions Using an assumed WBC value for parasite density estimation from a thick smear may lead to underdiagnosis of hyperparasitaemia and could adversely affect clinical management; but does not result in clinically consequential inaccuracies in the estimation of the prevalence of prolonged parasite clearance and artemisinin resistance.

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“…40–60%) across all malaria transmission intensities [ 68 – 73 ], but tend to be lower in low-transmission settings [ 69 , 72 ]. Anaemia is inversely related to age in healthy individuals, asymptomatic falciparum carriers and malaria patients independent of malaria transmission intensity [ 68 , 74 , 75 ]. Table 3 shows Hb data in children aged <5 years from a community survey in the Kenyan highlands (low transmission) [ 68 ], and Table 4 shows Hb data in P. falciparum -infected patients of all ages from several African countries (database used in this analysis).…”

Section: Introductionmentioning

confidence: 99%

Single low-dose primaquine for blocking transmission of Plasmodium falciparum malaria – a proposed model-derived age-based regimen for sub-Saharan Africa

Taylor

Naw

Maitland

et al. 2018

BMC Med

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BackgroundIn 2012, the World Health Organization recommended blocking the transmission of Plasmodium falciparum with single low-dose primaquine (SLDPQ, target dose 0.25 mg base/kg body weight), without testing for glucose-6-phosphate dehydrogenase deficiency (G6PDd), when treating patients with uncomplicated falciparum malaria. We sought to develop an age-based SLDPQ regimen that would be suitable for sub-Saharan Africa.MethodsUsing data on the anti-infectivity efficacy and tolerability of primaquine (PQ), the epidemiology of anaemia, and the risks of PQ-induced acute haemolytic anaemia (AHA) and clinically significant anaemia (CSA), we prospectively defined therapeutic-dose ranges of 0.15–0.4 mg PQ base/kg for children aged 1–5 years and 0.15–0.5 mg PQ base/kg for individuals aged ≥6 years (therapeutic indices 2.7 and 3.3, respectively). We chose 1.25 mg PQ base for infants aged 6–11 months because they have the highest rate of baseline anaemia and the highest risks of AHA and CSA. We modelled an anthropometric database of 661,979 African individuals aged ≥6 months (549,127 healthy individuals, 28,466 malaria patients and 84,386 individuals with other infections/illnesses) by the Box–Cox transformation power exponential and tested PQ doses of 1–15 mg base, selecting dosing groups based on calculated mg/kg PQ doses.ResultsFrom the Box–Cox transformation power exponential model, five age categories were selected: (i) 6–11 months (n = 39,886, 6.03%), (ii) 1–5 years (n = 261,036, 45.46%), (iii) 6–9 years (n = 20,770, 3.14%), (iv) 10–14 years (n = 12,155, 1.84%) and (v) ≥15 years (n = 328,132, 49.57%) to receive 1.25, 2.5, 5, 7.5 and 15 mg PQ base for corresponding median (1st and 99th centiles) mg/kg PQ base of: (i) 0.16 (0.12–0.25), (ii) 0.21 (0.13–0.37), (iii) 0.25 (0.16–0.38), (iv) 0.26 (0.15–0.38) and (v) 0.27 (0.17–0.40). The proportions of individuals predicted to receive optimal therapeutic PQ doses were: 73.2 (29,180/39,886), 93.7 (244,537/261,036), 99.6 (20,690/20,770), 99.4 (12,086/12,155) and 99.8% (327,620/328,132), respectively.ConclusionsWe plan to test the safety of this age-based dosing regimen in a large randomised placebo-controlled trial (ISRCTN11594437) of uncomplicated falciparum malaria in G6PDd African children aged 0.5 − 11 years. If the regimen is safe and demonstrates adequate pharmacokinetics, it should be used to support malaria elimination.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-017-0990-6) contains supplementary material, which is available to authorized users.

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Hematological Indices in Malian Children Change Significantly During a Malaria Season and with Increasing Age: Implications for Malaria Epidemiological Studies

Cited by 4 publications

References 23 publications

The Rough Guide to Monocytes in Malaria Infection

The Rough Guide to Monocytes in Malaria Infection

Variability in white blood cell count during uncomplicated malaria and implications for parasite density estimation: a WorldWide Antimalarial Resistance Network individual patient data meta-analysis

Single low-dose primaquine for blocking transmission of Plasmodium falciparum malaria – a proposed model-derived age-based regimen for sub-Saharan Africa

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