The relationship between cross-reactive Plasmodium vivax antibody responses and P. knowlesi parasitaemia and...

Background Pre-existing antibodies to Plasmodium vivax may cross-react with P. knowlesi and influence infection outcomes. We investigated whether baseline P. vivax antibody levels affect parasitaemia and clearance in knowlesi malaria. Methods Total IgG to 21 P. vivax antigens was quantified in pre-treatment plasma from patients in three Malaysian clinical trials. Parasitaemia was assessed 6-hourly by microscopy and clearance half-life estimated. Antibody associations with P. knowlesi baseline parasitaemia and clearance were identified using regression and machine learning approaches (elastic net regression and random forests). Results Data were available for 134 patients (median age 37 years, 37% with prior malaria). Five antibodies were associated with reduced baseline P. knowlesi parasitaemia (0.75-0.90-fold lower per two-fold increase, 95% CIs ranging from 0.65-1.00). Median P. knowlesi parasite clearance half-life was 2.6 hours (IQR 2.1-3.2). Two antibodies were associated with slightly slower parasite clearance (1.04-fold increases in mean clearance half-life per two-fold antibody level). Within-group correlation analyses revealed widespread, positive antibody associations in P. knowlesi infections, with weaker but coordinated (RBP and DBP family) responses in malaria-negative endemic controls. Conclusions Cross-reactive P. vivax antibodies may partially constrain P. knowlesi parasitaemia, but functional studies are needed to clarify their role in immunity and zoonotic transmission.