Sickle Cell Trait and the Risk of<i>Plasmodium falciparum</i>Malaria and Other Childhood Diseases

Williams, Thomas N.; Mwangi, Tabitha; Wambua, Sammy; Nast, Alexander; Kortok, Moses; Snow, Robert W.; Marsh, Kevin

doi:10.1086/430744

Cited by 289 publications

(287 citation statements)

References 48 publications

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“…The protective effect of group O was seen when the severe malaria cases were compared with either the uncomplicated malaria controls or the healthy controls ( Table 2). The level of protection afforded by group O [severe malaria cases versus uncomplicated malaria controls, odds ratio (OR) 0.34, 95% confidence interval (CI) 0.19-0.61, P Ͻ 0.0005 for group O versus the non-O blood groups] is equivalent to that seen for a rosette-reducing CR1 deficiency polymorphism in Papua New Guinea (4) and is slightly lower than the protection against severe malaria conferred by HbS heterozygosity in previous studies (80-90% protection) (30,31). The above statistical analysis was carried out on severe malaria cases composed of patients with a spectrum of clinical syndromes (see Materials and Methods).…”

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confidence: 76%

Blood group O protects against severe Plasmodium falciparum malaria through the mechanism of reduced rosetting

Rowe¹,

Handel²,

Thera³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Malaria has been a major selective force on the human population, and several erythrocyte polymorphisms have evolved that confer resistance to severe malaria. Plasmodium falciparum rosetting, a parasite virulence phenotype associated with severe malaria, is reduced in blood group O erythrocytes compared with groups A, B, and AB, but the contribution of the ABO blood group system to protection against severe malaria has received little attention. We hypothesized that blood group O may confer resistance to severe falciparum malaria through the mechanism of reduced rosetting. In a matched case-control study of 567 Malian children, we found that group O was present in only 21% of severe malaria cases compared with 44 -45% of uncomplicated malaria controls and healthy controls. Group O was associated with a 66% reduction in the odds of developing severe malaria compared with the non-O blood groups (odds ratio 0.34, 95% confidence interval 0.19 -0.61, P < 0.0005, severe cases versus uncomplicated malaria controls). In the same sample set, P. falciparum rosetting was reduced in parasite isolates from group O children compared with isolates from the non-O blood groups (P ‫؍‬ 0.003, Kruskal-Wallis test). Statistical analysis indicated a significant interaction between host ABO blood group and parasite rosette frequency that supports the hypothesis that the protective effect of group O operates through the mechanism of reduced P. falciparum rosetting. This work provides insights into malaria pathogenesis and suggests that the selective pressure imposed by malaria may contribute to the variable global distribution of ABO blood groups in the human population.ABO ͉ erythrocyte ͉ pathogenesis ͉ rosette formation ͉ virulence

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confidence: 76%

Blood group O protects against severe Plasmodium falciparum malaria through the mechanism of reduced rosetting

Rowe¹,

Handel²,

Thera³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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265

253

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“…The most widely known examples of this are the retention of the sickle cell and thalassemia traits: in Kenyan children from Kilifi, sickle-cell trait protects against severe malaria with an odds ratio of 0.17 (31), whereas heterozygous and homozygous alpha thalassemia confer a protective effect with odds ratios of 0.57 and 0.73, respectively (32). With an odds ratio of 0.56, homozygous FcγRIIb T232 has a similar protective effect against malaria to heterozygous thalassaemia, and thus, it could explain the higher MAF of FcγRIIb T232 seen in Africans and Southeast Asians.…”

Section: Discussionmentioning

confidence: 99%

A defunctioning polymorphism in FCGR2B is associated with protection against malaria but susceptibility to systemic lupus erythematosus

Willcocks

Carr

Niederer

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease more prevalent in people of African and Asian origin than Caucasian origin. FcγRIIb is an inhibitory Fc receptor with a critical role in immune regulation. Mouse data suggest that FcγRIIb deficiency increases susceptibility to autoimmune disease but protects against infection. We show that a SNP in human FCGR2B that abrogates receptor function is strongly associated with susceptibility to SLE in both Caucasians and Southeast Asians. The minor allele of this SNP is more common in Southeast Asians and Africans, populations from areas where malaria is endemic, than in Caucasians. We show that homozygosity for the minor allele is associated with substantial protection against severe malaria in an East African population (odds ratio = 0.56; P = 7

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“…[15][16][17][18] Although the multiple independent origins of the HbS mutation have been questioned recently, [19] the SCD mutation is classically associated with five region-defined β-globin gene haplotypes, Benin, Bantu or Central African (CAR), Cameroon, Senegal and Indian-Arab, [20][21][22][23] four of which are from Africa and associated with malaria incidence. [24] Because of the low incidence of malaria, the incidence of SCD in South Africa (SA) is equally extremely low; the HbS allele can be found in some indigenous SA ethnic groups (Venda and Shangaan) at an approximated frequency of 0.2%. [25][26] However, this is changing with the socioeconomically motivated influx of immigrants from other African countries, especially those within the equatorial malaria-endemic belt, resulting in a 300 -400% increase in new cases of SCD over the past 10 years at Red Cross War Memorial Children's Hospital (RCWMCH) in Cape Town, SA.…”

Section: Researchmentioning

confidence: 99%

Burden, genotype and phenotype profiles of adult patients with sickle cell disease in Cape Town, South Africa

et al. 2017

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Background. An exponential increase in the number of sickle cell disease (SCD) patients in paediatric services in Cape Town, South Africa, has been reported. The trend in adult/adolescent services has not been investigated. Objectives. To evaluate epidemiological trends of SCD and the profile of patients affected by SCD attending the Haematology Clinic at Groote Schuur Hospital (GSH), Cape Town. Methods. (i)A retrospective review of the number of SCD patients over the past 20 years; (ii) a cross-sectional analysis of clinical and haematological characteristics of SCD patients; and (iii) molecular analysis of the haemoglobin S mutation, the haplotype in the β-globinlike genes cluster, the 3.7 kb α-thalassaemia gene deletion and 19 selected single-nucleotide polymorphisms (SNPs) associated with fetal haemoglobin (HbF) levels. Results. From 1995 to 2016, 81 adolescent/adult patients with SCD were registered, mostly originating from other African countries (n=61, 75.3%). There was an increase of over 200% in new cases (n=47) during the last quarter of the two decades investigated. Data from 34 of 58 regular attendees (58.6%) were analysed. The mean age of the patients was 26.1 years (standard deviation (SD) 9.8), and 70.6% were male. With the exception of four patients with sickle/β-thalassaemia, all the patients had SCD (haemoglobin SS). The co-inheritance of a single 3.7 kb α-globin deletion was found in 42.3% of cases (n=11). The Bantu haplotype was the most observed (65.4% of chromosomes). Most HbF-promoting SNPs were not associated with variable levels of haematological indices. Conclusions.There is an increasing burden of adult SCD patients at GSH. National health and academic institutions need to adapt policies and healthcare professional training accordingly. S Afr Med RESEARCH Methods Ethical approvalThe study was performed in accordance with the Declaration of Helsinki and with the approval of the Faculty of Health Sciences Human Research Ethics Committee, University of Cape Town (HREC ref. no. 132/2010). Informed and written consent was obtained from adult participants (≥18 years), and for one patient aged 15 years informed consent was obtained from the guardian with assent from the participant. PatientsThe Haematology Clinic runs weekly every Wednesday. Most patients are seen at least once a month, and clinically stable patients every 3 months, with the exception of crisis-related hospitalisation.A retrospective review of the number of SCD patients attending the clinic over the past 20 years and a cross-sectional analysis of patients who regularly attend the clinic were performed. Clinical events and haematological indices were retrospectively collected from hospital records. The haematological measures were those reported at the first visit to the hospital. Molecular methods DNA extractionDNA was isolated from the peripheral blood using the AllPrep DNA/RNA/miRNA universal kit (Qiagen, USA) according to the manufacturer's instructions. GenotypingHbS mutation and β-globin haplotypes Polymerase chain reac...

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Sickle Cell Trait and the Risk ofPlasmodium falciparumMalaria and Other Childhood Diseases

Abstract: The present data are useful in that they confirm the mechanisms by which HbAS confers protection against malaria and shed light on the relationships between HbAS, malaria, and other childhood diseases.

Cited by 289 publications

References 48 publications

Blood group O protects against severe Plasmodium falciparum malaria through the mechanism of reduced rosetting

Blood group O protects against severe Plasmodium falciparum malaria through the mechanism of reduced rosetting

A defunctioning polymorphism in FCGR2B is associated with protection against malaria but susceptibility to systemic lupus erythematosus

Burden, genotype and phenotype profiles of adult patients with sickle cell disease in Cape Town, South Africa

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