Influence of host factors and parasite biomass on the severity of imported Plasmodium falciparum malaria

Abstract

Objectives: Imported malaria in France is characterized by various clinical manifestations observed in a heterogeneous population of patients such as travelers/expatriates and African migrants. In this population, host factors and parasite biomass associated with severe imported malaria are poorly known.

Methods: From data collected by the Centre National de Référence du Paludisme, we identified epidemiological, demographic and biological features including parasite biomass and anti-plasmodial antibody levels (negative, positive and strongly positive serology) associated with different disease severity groups (very severe, moderately severe, and uncomplicated malaria) in 3 epidemiological groups (travelers/expatriates, first- and second-generation migrants).

Results: Age, ethnicity, absence of prior infection with P. falciparum, antibody levels, plasma PfHRP2 levels, total and circulating parasite biomass were related to severe malaria onset. Sequestered parasite biomass tended to be increased in very severe malaria, and was strongly correlated to the antibody level of the host.

Conclusions: Prior exposure to P. falciparum is associated with high anti-plasmodial antibody levels which influence clinical presentation of imported malaria and its correlated circulating and sequestered parasite burden.

Fig 1. PfHRP2 plasma levels and parasite biomass according to clinical presentation of imported malaria.

(A) Log-transformed plasma levels of PfHRP2 in the very severe malaria (VSM), moderately severe malaria (MSM) and uncomplicated malaria (UM) sub-groups. Levels of PfHRP2 were determined on 315 D0 plasma samples by ELISA. (*) corresponds to a significant difference using ANOVA test (p<0.05) and Bonferroni’s correction (p<0.016). (B) Log-transformed estimated total parasite biomass (Ptot), estimated total circulating parasite biomass (Pcirc) and estimated sequestrated parasite biomass (Pseq) respectively in the very severe malaria (VSM) (red box plot), moderately severe malaria (MSM) (orange box plot) and uncomplicated malaria (UM) groups (white box plot). Parasite biomass was estimated for 176 patients using a mathematical approach as described [15] with quantitative plasma levels of PfHRP2 (g/L) determined by ELISA, hematocrit (%), patient body weight (kg) and parasitemia (parasites/μL) on D0 sample. Box plot represents the median [25th percentile-75th percentile] with the extreme value 10th and 90th percentile. (*) corresponds to a significant difference using ANOVA test (p<0.05) and Bonferroni’s correction (p<0.016).