Malaria is caused by an obligate, intracellular protozoan parasite of the genus Plasmodium. Of the four species that infect humans (Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale and Plasmodium malariae), P. falciparum is responsible for virtually all deaths [¹]. The virulence of P. falciparum has been associated with the capacity of the infected RBCs to adhere to uninfected RBCs, leading to rosetting of cells [²,³]. Previous studies have implicated the ABO blood group type in rosetting [⁴]. Blood group antigens A and B are trisaccharides attached to a variety of glycoproteins and glycolipids on the surface of erythrocytes, and these trisaccharides are thought to act as receptors for rosetting on uninfected erythrocytes and bind to parasite rosetting ligands such as PfEMP-1 and sequestrin [⁵,⁶]. However, blood group antigens A and B are not expressed in blood group O individuals. As a result, rosettes formed by blood group O are suggested to be smaller and easily disrupted than rosettes formed by blood group A, B or AB erythrocytes [⁷,⁸]. The present study aimed to show whether blood group types are associated with the risk of severe P. falciparum malaria infection in three Ethiopian malaria endemic localities.

The demonstration that the cases of severe malaria were less likely to be of blood group O than other blood groups is in agreement with the report of Pathirana et al [¹] from Sri Lanka, and the findings of this study substantiated earlier reports that blood group O individuals are less prone to come down with severe malaria as compared to those with other blood groups. The finding of greater infant length, placental weight and low placental parasite count among blood group O mother compared with non-group O in the Gambia [¹²] also supports the hypothesis that group O individuals may have survival advantage in severe falciparum malaria infection. Furthermore, according to study made on 489 malaria patients in Zimbabwe, comma was three times more common among group A individuals compared with non-A, and this study suggested that group O malaria patients tend to have mild disease and less clinical outcome than blood group A individuals [¹³]. The mechanism by which blood group O confers some protection against severe malaria compared to blood groups A, B, and AB is not fully understood. However, lower rosette formation by pRBCs of group O as shown by some studies [¹⁴,³] have established that parasitized erythrocytes form rosettes more readily with RBCs of either A, B, or AB blood groups than with those belonging to blood group O. Also, it is well established that this parasite-triggered RBC rosette formation is associated with the severity of clinical disease [³].

In the present study, there was high percentage of blood group A and low percentage of group O individuals in the severe malaria category than in the uncomplicated malaria and health controls. This was in consistence with the study in Sri Lanka [¹], where there was low percentage of blood group O (23.8%) individuals as compared to the uncomplicated malaria (47.9%) and healthy controls (49.2%) and higher percentage of blood group A severe malaria (32.5%) patients. A study conducted on 200 malaria patients in Gabon also showed that, among all blood group A individuals, 71% had severe malaria and only 22% had mild malaria, and among all blood group O cases 46% had severe malaria and 54% had mild malaria [¹⁵].

In contrast to the observation of Rowe et al [¹⁶], the present study did not reveal individuals with severe malaria to have significantly higher parasite count than patients with uncomplicated malaria. This finding can be explained by the fact that in severe falciparum malaria infection, parasitized erythrocytes at schizont stage are known to be sequestered in tissue capillaries and may results in falsely low parasite count in the peripheral blood. Therefore, the severity of infection with falciparum malaria may have been greater in this study than that reported by Rowe et al [¹⁶].

In the present study, it was also been shown that individuals with severe malaria had lower haemoglobin concentration than those with uncomplicated malaria. Rowe et al [¹⁶] also provided a strong evidence in Mali that, venous blood haemoglobin concentration was lower in severe malaria patients than those with uncomplicated malaria or healthy controls. The basis for malaria mediated anaemia has been elucidated by several investigators [[²,¹⁶], and [¹⁷]]. Carlson et al [²] and Rowe et al [¹⁶] suggested that the virulence of P. falciparum is associated with the capacity of the infected RBC to adhere to uninfected RBC, a process known as rosetting. Hotez et al [¹⁷] also suggested that malaria cause anaemia by distraction of both parasitized and non-parasitized red blood cells. Therefore, the difference in mean haemoglobin concentration between the severe malaria and uncomplicated malaria or healthy control cases may be due to existance of increased distruction of red blood cells or higher rosetting in severe malaria patients.

The present study does not adjusted for the effect of other determinants such as genetic polymorphisms that might play key roles in the severity of falciparum infection, so that the effect of these factors could not be discussed in this paper.

The study revealed that on the basis of the three criteria used to determine severity of falciparum malaria, patients with blood group O were less prone to severe malaria as compared to patients with other blood groups. However, since ABO blood group can also affect the severity of P. falciparum malaria by mechanisms other than rosetting, further studies of rosette formation with Ethiopian strains of P. falciparum could be useful to test the role of rosette formation in disease severity.

The authors declare that they have no competing interests.

ZT was involved in all aspects of the project, data collection, analysis, interpretation and determined haemoglobin concentrations and in writing of the manuscript. BP has made a contribution in the design, data interpretation, work supervision and in critically revising the manuscript. All authors read and approved the manuscript.

We are very grateful to the study participants for their cooperation and the health management and working staff of Awash, Metehara and Ziway Malaria Centre. The study was financially supported by SIDA/SAREC project to Prof. Beyene Petros through the office of Graduate program and Research, Addis Ababa University.