Association of ABO Blood Group and Severe Plasmodium falciparum Malaria: An Updated Meta-Analysis and Trial Sequential Analysis.

BACKGROUND

Plasmodium falciparum malaria remains a major cause of morbidity and mortality in endemic regions, with outcomes influenced by host genetic factors. The ABO blood group system has been linked to clinical severity, though findings differ regarding blood groups and severe malaria susceptibility. This analysis aims to synthesise evidence on ABO blood group's role in severe P. falciparum malaria (SM) through meta-analysis and trial sequential analysis.

MATERIALS AND

METHODS

A search was conducted across PubMed, Scopus, Embase, Web of Science and Science Direct databases on August 31, 2025, to identify case-control studies reporting ABO blood groups in SM and uncomplicated malaria (UM). All Statistical analysis was performed with CMAv4.

RESULTS

Twenty-three studies comprising 3553 SM and 6112 UM cases were analysed. Results showed higher SM risk in blood groups A (OR:1.98; p = 0.00), B (OR:1.87; p = 0.00), AB (OR:1.91; p = 0.00) and non-O (OR:1.88; p = 0.00) versus group O. These associations were confirmed in African and South Asian populations, while Melanesians showed different patterns. Non-O groups showed increased risk in adults and children. Group A was linked to severe malarial anaemia (OR:1.75, p = 0.004), while group B showed protective effects (OR:0.75, p = 0.00). SM patients had lower haemoglobin (MD = -2.23; p = 0.00), with parasite density showing no correlation with severity. TSA confirmed evidence linking ABO groups with SM and haemoglobin levels.

CONCLUSION

This meta-analysis and TSA confirm non-O blood groups as a susceptible factor for SM across ethnicities and ages. While ABO blood group is an inexpensive and widely available genetic marker, its clinical utility should be viewed as complementary rather than deterministic. However, at present, evidence does not support population-wide screening solely for malaria risk prediction. These findings improve understanding of host genetic susceptibility and may inform future research into targeted risk stratification.