A hospital-based cross-sectional study was conducted at Khartoum state to investigate the variation of antibody responses to Plasmodium falciparum 19-kDa C-terminal region of merozoite surface protein 1 antigen and the variation of human IL4 polymorphism with parasitaemia. Measurements of natural acquisition of anti- Plasmodium falciparum MSP1-19 IgG, IgG1 and IgG3 antibodies were performed using ELISA. Molecular characterization of IL4vntr polymorphism was achieved. We were able to detect a statistically significant negative correlation between parasitaemia and different age groups (r = − 0.262 and p value = 0.043) and with anti- P.f MSP1-19 IgG1 (r = − 0.418, p value = 0.047). Anti- P.f MSP1-19 IgG showed a significant difference among age groups ( p < 0.001) . Only anti- P.fMSP1-19 IgG showed a significant association with general appearance ( p value < 0.001). The mean for total anti- P.f MSP1-19 IgG3 was statistically significantly higher in females compared to males ( p value < 0.001). There was no significant difference in the distribution of human IL4 vntr genotypic and allelic frequencies between cases and control group as well as among different clinical manifestation.We concluded that IgG1 levels to MSP1-19 were found to be negatively correlated with parasitaemia and anti- PfMSP1 -19 IgG was significantly increased in ill and severely ill with age considered as a cofactor. Further studies are needed to ascertain the role of IgG and IgG1 in protection and to investigate the IgG and subclasses’ response against other antigenic markers. These findings are valuable for advancing vaccine development by providing evidence supporting merozoite antigens as targets of protective immunity in humans.