An Immune Basis for Malaria Protection by the Sickle Cell Trait

BACKGROUND: Malaria resistance by the sickle cell trait (genotype HbAS) has served as the prime example of genetic selection for over half a century. Nevertheless, the mechanism of this resistance remains the subject of considerable debate. While it probably involves innate factors such as the reduced ability of Plasmodium falciparum parasites to grow and multiply in HbAS erythrocytes, recent observations suggest that it might also involve the accelerated acquisition of malaria-specific immunity. METHODS AND FINDINGS: We studied the age-specific protection afforded by HbAS against clinical malaria in children living on the coast of Kenya. We found that protection increased with age from only 20% in the first 2 y of life to a maximum of 56% by the age of 10 y, returning thereafter to 30% in participants greater than 10 y old. CONCLUSIONS: Our observations suggest that malaria protection by HbAS involves the enhancement of not only innate but also of acquired immunity to the parasite. A better understanding of the underlying mechanisms might yield important insights into both these processes

Mechanical Properties of Sisal/Cattail Hybrid-Reinforced Polyester Composites

Due to environmental and energy conservation concerns, a thrust towards low-cost lightweight materials has resulted in renewed interest in the development of sustainable materials that can replace nonbiodegradable and environmentally unfriendly materials in reinforced composites. In this study, mechanical properties of a hybrid composite consisting of polyester resin reinforced with a blend of sisal and cattail fibres were evaluated. The composite was fabricated using a hand lay-up technique at varying hybrid fibre weight fractions (5 to 25 wt%) while maintaining a constant fibre blend ratio of 50/50. Composites were also prepared at a constant fibre weight fraction of 20% while varying the fibre blend ratio between 0 and 100%. Fabricated composites were then characterised in terms of flexural, tensile, compressive, and impact strengths following ASTM and ISO standards. Results showed that, at a constant fibre blend ratio of 50/50, there was increase in the mechanical properties as the fibre weight fraction increased from 5 to 20%. At a constant fibre weight fraction (20%), a positive improvement in flexural, tensile, and compressive properties was registered as the fibre blend ratio varied between 0 and 75% with optimal values at a sisal/cattail ratio of 75/25. The current study suggests that blending sisal and cattail fibres for production of polyester composites yields hybrid composites with enhanced mechanical properties

Negative epistasis between the malaria-protective effects of α+-thalassemia and the sickle cell trait

The hemoglobinopathies, disorders of hemoglobin structure and production, protect against death from malaria1. In sub-Saharan Africa, two such conditions occur at particularly high frequencies: presence of the structural variant hemoglobin S and alpha+-thalassemia, a condition characterized by reduced production of the normal alpha-globin component of hemoglobin. Individually, each is protective against severe Plasmodium falciparum malaria2, 3, 4, but little is known about their malaria-protective effects when inherited in combination. We investigated this question by studying a population on the coast of Kenya and found that the protection afforded by each condition inherited alone was lost when the two conditions were inherited together, to such a degree that the incidence of both uncomplicated and severe P. falciparum malaria was close to baseline in children heterozygous with respect to the mutation underlying the hemoglobin S variant and homozygous with respect to the mutation underlying alpha+-thalassemia. Negative epistasis could explain the failure of alpha+-thalassemia to reach fixation in any population in sub-Saharan Africa

Parasite Densities by Clinical Status and α ⁺-Thalassaemia Genotype

<p>Geometric mean parasite densities are shown with 95% CIs. Data on symptomless parasitaemia reflect 59 measurements on normal (αα/αα) children, 100 on heterozygotes (−α/αα), and 23 on homozygotes (−α/−α) for α⁺-thalassaemia. The equivalent figures for mild, hospital, and severe malaria are described in <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0030158#pmed-0030158-t001" target="_blank">Tables 1</a> and <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0030158#pmed-0030158-t002" target="_blank">2</a>. Between-genotype differences were tested using linear regression both with and without adjustments for age, season, and within-patient clustering. No significant differences were found. </p

Haemoglobin Concentrations at Steady State and During Episodes of Clinical P. falciparum Malaria

<p>Values are means (with standard errors). 1 g/dl = 10 g/l Data for steady state, all malaria admissions, and severe malaria admissions derive from the birth cohort study. Severe malaria was defined as described in the text. Study participants (and genotypes) numbered as follows: steady state <i>n</i> = 2,104 (αα/αα, 739; −α/αα, 1,017; −α/−α, 348); all malaria admissions <i>n</i> = 434 (αα/αα, 174; −α/αα, 196; −α/−α, 64); and severe malaria admissions <i>n</i> = 146 (αα/αα, 67; −α/αα, 55; −α/−α, 24). Data for uncomplicated malaria derive from the mild disease cohort study. Data for αα/αα reflect 420 measurements in 96 study participants; for −α/αα are from 701 in 149; and for −α/−α are from 212 in 56. Amongst children in steady state, mean difference (β) = −2.6 g/l (95% CI, −4.1,−1.1; <i>p</i> = 0.001) and −5.6 (−7.8,− 3.8; <i>p</i> < 0.001) for −α/αα and −α/−α, respectively. The equivalent β values for uncomplicated malaria were −3.2 (−5.6,−7.7; <i>p</i> = 0.010) and −6.8 (−10,−3.4; <i>p</i> < 0.001); for hospital-admitted malaria were 8.4 (2.8,14.1; <i>p</i> = 0.003) and 0.97 (0.29,1.65; <i>p</i> = 0.005); and for severe malaria were 1.08 (−0.10,2.25; <i>p</i> = 0.072) and 13.8 (0.60,26.9; <i>p</i> = 0.041). These figures were adjusted for age (as continuous) and sex, and for potential within-person clustering where children contributed more than one data point. </p

Evaluation of Recurrent Parasitemia after Artemether-Lumefantrine Treatment for Uncomplicated Malaria in Children in Western Kenya

From April 2005 to April 2006, a phase 2 malaria vaccine trial in Kenya enrolled 400 children aged 12–47 months. Each received mixed supervised and unsupervised artemether-lumefantrine for uncomplicated malaria, using a standard six-dose regimen, by weight. Children were followed for detection of parasitemia and clinical malaria. A median of two negative malaria blood films occurred during every recurrent parasitemia (RP) episode, suggesting reinfection over late recrudescence. Median time to RP after starting artemether-lumefantrine was 37 days (36–38). Of 2,020 evaluable artemether-lumefantrine treatments, there were no RPs in 99% by day 14, 71% by day 28, and 41% by day 42. By World Health Organization standards, 71% of treatment courses had adequate responses. Although recrudescence in some cannot be ruled out, our cohort had a shorter median time to RP compared with other artemether-lumefantrine treatment studies. This underscores patient counseling on completing all treatment doses for optimal protection from RP

Negative epistasis between the malaria-protective effects of alpha (+) thalassaemia and the sickle cell trait [MIM-TW-395505]

The hemoglobinopathies, disorders of hemoglobin structure and production, protect against death from malaria. In sub-Saharan Africa, two such conditions occur at particularly high frequencies: presence of the structural variant hemoglobin S and alpha(+)-thalassemia, a condition characterized by reduced production of the normal alpha-globin component of hemoglobin. Individually, each is protective against severe Plasmodium falciparum malaria, but little is known about their malaria-protective effects when inherited in combination. We investigated this question by studying a population on the coast of Kenya and found that the protection afforded by each condition inherited alone was lost when the two conditions were inherited together, to such a degree that the incidence of both uncomplicated and severe P. falciparum malaria was close to baseline in children heterozygous with respect to the mutation underlying the hemoglobin S variant and homozygous with respect to the mutation underlying alpha(+)-thalassemia. Negative epistasis could explain the failure of alpha(+)-thalassemia to reach fixation in any population in sub-Saharan Africa