A new paper by GHTM researchers has been published in the International Journal of Infectious Diseases. The paper provides new evidence that protection against malaria from sickle cell trait (SCT) is strongly age-dependent in Guinea-Bissau.
Prevalence and geographic-ethnic distribution of SCT and its association with P. falciparum infection, fever, and anemia in children
Malaria remains a major global health issue, particularly in sub-Saharan Africa, which accounts for over 95% of cases worldwide. The interaction between humans and the Plasmodium parasite has driven the selection of genetic traits such as hemoglobin variants (HbC, HbS), thalassemias, and enzyme deficiencies, which can influence malaria susceptibility.
Sickle cell disorder, caused by the HbS mutation, is a leading genetic condition in Africa. While homozygous individuals (HbSS) often suffer severe disease and high childhood mortality, heterozygous carriers (HbAS) are generally healthy and gain protection against severe Plasmodium falciparum malaria. However, the effects of sickle cell trait (SCT) on asymptomatic or submicroscopic infections remain unclear.
Led by Ronise Silva and Ana Paula Arez (VBD-GHTM Research Group) and Márcia Medeiros (IHC-GHTM Research Group), in collaboration with Amabélia Rodrigues from the Bandim Health Project, this study assessed the prevalence and geographic-ethnic distribution of SCT and its association with P. falciparum infection, fever, and anemia in children. The study analysed β-globin genotypes from 601 dried blood samples collected during the 2017 National Malaria Prevalence Survey. SCT carriers represented 32% of participants, with the highest concentrations found in island regions and their corresponding ethnic groups.
“The results demonstrate a striking paradox: although SCT carriers under five years of age had lower parasitaemia and higher haemoglobin levels when infected with Plasmodium falciparum, SCT was strongly associated with an increased risk of microscopic infection, particularly in older individuals (15–24 years)”
A key finding was the higher prevalence of SCT in the island regions and among their predominant ethnic groups, areas that also report the highest Plasmodium falciparum burden. This supports the malaria hypothesis, which proposes that SCT is maintained at higher frequencies in regions with intense malaria transmission because of its protective effect. Cultural and geographic isolation between islands and the mainland may further enhance this distribution pattern.
Regarding infection dynamics, SCT carriers aged 15–24 years were more likely to have microscopic infections, although this pattern reversed in older adults. Importantly, despite this apparent susceptibility, SCT children under five showed significantly lower parasitemia, supporting established evidence that SCT reduces parasite density through mechanisms such as impaired parasite growth and decreased cytoadherence of infected erythrocytes. These mechanisms may also explain the higher detectability of parasites in SCT carriers, improving diagnosis and potentially reducing progression to severe disease.
The study also found fewer submicroscopic infections among SCT carriers, consistent with some previous findings and ethnic patterns in Guinea-Bissau, though not statistically significant. Differences with other studies may reflect population structure, sampling design, and local malaria transmission intensity.
Although SCT was not associated with overall anemia prevalence, children under five with microscopic infections had higher hemoglobin levels and were protected from moderate-to-severe anemia. This aligns with previous work showing that SCT mitigates malaria-associated hemolysis and its hematological consequences.
Overall, this study provides the first nationwide analysis of the sickle cell trait (SCT) in Guinea-Bissau, revealing important geographic, ethnic, and clinical patterns. The authors highlighted the complex and age-specific nature of SCT in human malaria immunity, demonstrating that host genetic traits can simultaneously provide protection against severe outcomes while maintaining transmission potential. The findings reinforce the need to consider age, genetics, and local context when designing host-targeted malaria elimination strategies.
This publication strengthens GHTM’s contribution to the understanding of host–parasite interactions in West Africa, building on the organisation’s long-standing scientific collaboration with the Bandim Health Project in Guinea-Bissau.
To read the full article in the International Journal of Infectious Diseases, please follow the link below: