Effect of the ABO blood group on susceptibility to severe malaria: A systematic review and meta-analysis

Abstract

Understanding how ABO blood group interacts with Plasmodium falciparum (P. falciparum) infection may facilitate development of antimalarial treatments and vaccines. This study systematically summarizes information on the relationship of ABO blood group with severe P. falciparum infection, level of parasitemia and haemoglobin. A total of 1923 articles were retrieved from five databases. After removal of duplicates, and two levels of screening, 21 articles were selected for inclusion in the meta-analysis. A meta-analysis of the studies showed an increased odds of severe P. falciparum infection among individuals with blood group A, B, AB or non-O compared with blood group O. However, the difference in the level of P. falciparum parasitemia was not significant among individuals with blood group A or non-O compared with blood group O. The difference in haemoglobin level among P. falciparum infected individuals was also not significant between those with blood group A, B or AB versus those with blood group O.

Introduction

Malaria continues to threaten the lives of millions of people in the world for several decades and remains a major cause of mortality in tropical and subtropical countries. Globally, 212 million malaria cases and an estimated 429,000 deaths were attributed to the disease in 2015 [1]. >90% of these cases and deaths occur in sub-Saharan Africa (SSA) [2]. The majority of malaria cases and related deaths in SSA are caused by Plasmodium falciparum (P. falciparum) infection [3, 4].

There are several mechanisms through which environmental and socio-economic conditions affect malaria transmission in endemic regions [[5], [6], [7]]. For example, climate affects the development of Plasmodium parasites and Anopheles mosquitoes, and socio-economic factors affect the chance of contact of the mosquitoes with humans [[7], [8], [9]]. However, the ability of the Plasmodium parasite to enter, survive and multiply within the human body is dependent upon the immune status and genetic makeup of the host [10, 11]. As a result, clinical outcomes related with malaria and survival from the disease following infection could vary with genetic status of the host [12].

Severe malaria is characterized by an excessive invasion of red blood cells (RBC) and sequestration in the microvasculature of parasitized RBC (pRBC) because of their binding to the vascular endothelium and to RBC (rosetting), processes that collectively bring about the blockage of the blood-flow, oxygen delivery and ultimately death of the human host [13]. One of the genetic factors implicated in susceptibility of humans for severe P. falciparum infection is the ABO blood group [13]. Several studies have investigated the molecular nature of the interaction between ABO blood group and P. falciparum primarily concerning the binding of pRBC to RBC [[13], [14], [15], [16]], but importantly the ABO blood group antigens are equally expressed on the vascular endothelium and on serum-proteins suggesting also their involvement in the causation of severe malaria [17]. Although several previous epidemiological studies showed an increased severity of P. falciparum infection among individuals with blood group A and decreased severity of P. falciparum infection among individuals with blood group O [15, 18, 19], and genomic wide association studies (GWAS) suggest that blood group O protects against severe disease [[20], [21], [22]], but some studies reported lack of relationship of ABO blood group with severe P. falciparum malaria in humans [23, 24]. Still some studies reported increased severity of P. falciparum infection among individuals with blood group B or AB rather than with blood group A, and findings on the strength of relationship of blood group A with severe falciparum infection are inconsistent [25]. Moreover, findings on the effect of ABO blood group on P. falciparum parasitemia level and related reduction on haemoglobin level remain heterogeneous [[26], [27], [28]].

Understanding how the ABO blood group interacts with P. falciparum malaria will provide insights on the pathogenesis of falciparum malaria and provide direction for basic research that may help development of novel antimalarial treatments and vaccines. Specifically, investigating the genetic basis that reduces susceptibility to severe P. falciparum infection may lead the formulation of personalized strategies designed to prevent deaths due to severe P. falciparum infection.

Panda et al. [29] conducted a meta-analysis that involved six studies to understand the nature of relationship between ABO blood type and severe P. falciparum infection. However, all the six studies included in the meta-analysis were limited to case-control studies published before 2011. There are literature published before 2011 that examine the effect of ABO blood group upon severe P. falciparum infection following different designs. Moreover, a large number of studies, reporting data on the relationship of ABO blood group with severe P. falciparum malaria have been published since 2011. The objective of this study was therefore to systematically summarize literature on the relationship of ABO blood group with severity of disease, level of parasitemia, and reduction in haemoglobin level.