Genome-wide association study indicates two novel resistance loci for severe malaria.

Malaria causes approximately one million fatalities per year, mostly among African children. Although highlighted by the strong protective effect of the sickle-cell trait, the full impact of human genetics on resistance to the disease remains largely unexplored. Genome-wide association (GWA) studies are designed to unravel relevant genetic variants comprehensively; however, in malaria, as in other infectious diseases, these studies have been only partly successful. Here we identify two previously unknown loci associated with severe falciparum malaria in patients and controls from Ghana, West Africa. We applied the GWA approach to the diverse clinical syndromes of severe falciparum malaria, thereby targeting human genetic variants influencing any step in the complex pathogenesis of the disease. One of the loci was identified on chromosome 1q32 within the ATP2B4 gene, which encodes the main calcium pump of erythrocytes, the host cells of the pathogenic stage of malaria parasites. The second was indicated by an intergenic single nucleotide polymorphism on chromosome 16q22.2, possibly linked to a neighbouring gene encoding the tight-junction protein MARVELD3. The protein is expressed on endothelial cells and might therefore have a role in microvascular damage caused by endothelial adherence of parasitized erythrocytes. We also confirmed previous reports on protective effects of the sickle-cell trait and blood group O. Our findings underline the potential of the GWA approach to provide candidates for the development of control measures against infectious diseases in humans.

Hemolysis scavenger proteins and renal function marker in children with sickle cell disease at steady state: A cross-sectional study.

Background and Aims: Hemolysis is a fundamental feature of sickle cell disease (SCD) contributing to the vaso-occlusive crisis of patients. The objectives of the study were to assess the link between hemolysis proteins and hematological parameters, and to validate cystatin C (CYS C) as a potent renal marker in diagnoising SCD. Method: Here, a cross-sectional study carried out at the pediatric SCD clinic of the Komfo Anokye Teaching Hospital comprised 90 SCD children (HbSC, HbSF, and HbSS). ANOVA, t-test, and Spearman's rank correlation analysis were done. Elevated proteins levels were compared to standard values; alpha-1 microglobulin (A1M) (1.8-65 µg/L), CYS C (0.1-4.5 µmol/L), and haemopexin (HPX) (500-1500 µg/mL). Results: The mean (standard deviation) age of participants was 9.830 (±0.3217) years, and 46% of them were males. From simple descriptive analysis, we observed that all but one patient had their HPX level below the reference range (<500 µg/mL). Here, A1M levels were shown to be within the appropriate reference range for all the patients except few patients. CYS C levels were also all within the required reference values. A Spearman's rank correlation test between full blood count and HPX generally suggested a weak but positive correlation; RBC (coef. = 0.2448; p = 0.0248), HGB (coef. = 0.2310; p = 0.030), hematocrit (coef. = 0.2509; p = 0.020), and platelet (coef. = 0.1545; p = 0.160). Mean corpuscular volume (coef. = -0.5645; p = 0.610) had a stronger but negative correlation with HPX. This study depicts a positive and stronger association between CYS C and HPX levels (coef. = 0.9996; p < 0.0001), validating the use of CYS C as a useful marker of renal function in persons with SCDs. Conclusion: In the present study, we show that A1M levels were normal for most of the patients, hence CYS C levels are not alarming in this study. Further, there exists a correlation between hemolysis scavenger proteins and hematological parameters.

Capillary refill time as an independent prognostic indicator in severe and complicated malaria.

OBJECTIVES: To improve algorithms for the identification of children at risk of dying of malaria in endemic areas. STUDY DESIGN: In a prospective study of 2446 children with severe and complicated malaria admitted to a tertiary referral center in Ghana, West Africa, 12 clinical and laboratory signs were evaluated as indicators of death. RESULTS: A prolonged (> 2 seconds) capillary refill time (pCRT) was identified as an independent prognostic indicator of death along with acidosis, coma, and respiratory distress. Among the clinical signs, pCRT increased the risk of dying from 4-fold to 11-fold when present in addition to coma and respiratory distress. CONCLUSIONS: The recognition of pCRT as an independent indicator of death justifies its inclusion as a defining criterion of severe and complicated malaria and improves the use of clinical examinations in the triage of patients with malaria. As pCRT has been shown to reflect circulatory disturbances in children, it should be included in upcoming studies as a possible sign to indicate the need for intravenous fluid administration.