evidence for age-specific protection in a cross-sectional study in Guinea-Bissau

Objectives Sickle cell trait (SCT) remains poorly documented in Guinea-Bissau. We aimed to investigate SCT frequency, its geographic-ethnic distribution, and association with Plasmodium falciparum infection. Methods DNA from 601 dried whole blood samples collected in the 2017 national malaria prevalence survey underwent β-globin genotyping. SCT ( HbAS ) and HbAA distributions were examined across health regions and ethnic groups. Associations with P. falciparum , parasitemia, anemia, and fever were evaluated using chi-square and Mann–Whitney U tests and logistic regression models (IBM SPSS Statistics, Version 29). Statistical significance was set at P <0.05. Results SCT carriers (32.0%) were concentrated in the island regions and their corresponding ethnic groups. They were more likely to have microscopic P. falciparum infection than non-carriers in unstratified (odds ratio [OR] = 2.3, 95% confidence interval [CI] = 1.4-3.5) and age-stratified analyses (<5 years, OR = 2.3, 95% CI = 1.0-5.2; 15-24 years, OR = 5.0, 95% CI = 1.8-13.8). However, among infected children aged <5 years, they had lower parasitemia and higher hemoglobin levels. Conclusions SCT offered protection against severe outcomes among young children but increased microscopic infection risk among older individuals, underscoring the paradox and complexity of SCT-mediated protective mechanisms and their relevance for host-targeted malaria elimination strategies.