Suppression of Plasmodium falciparum by serum collected from a case of Plasmodium vivax infection

Abstract

Background: It has frequently been reported that Plasmodium vivax suppressed Plasmodium falciparum and ameliorated disease severity in patients infected with these two species simultaneously. The authors investigate the hypothesis that immunological responses stimulated by P. vivax may play a role in suppressing co-infecting P. falciparum.

Methods: Sera, taken sequentially from one of the authors (YN) during experimental infection with P. vivax, were added to in vitro cultures of P. falciparum. Cross-reactive antibodies against P. falciparum antigens, and cytokines were measured in the sera.

Results: Significant growth inhibitory effects upon P. falciparum cultures (maximally 68% inhibition as compared to pre-illness average) were observed in the sera collected during an acute episode. Such inhibitory effects showed a strong positive temporal correlation with cross-reactive antibodies, especially IgM against P. falciparum schizont extract and, to a lesser degree, IgM against Merozoite Surface Protein (MSP)-119. Interleukin (IL)-12 showed the highest temporal correlation with P. vivax parasitaemia and with body temperatures in the volunteer.

Conclusion: These results suggest the involvement by cross-reactive antibodies, especially IgM, in the interplay between plasmodial species. IL-12 may be one of direct mediators of fever induction by rupturing P. vivax schizonts, at least in some subjects. Future studies, preferably of epidemiological design, to reveal the association between cross-reactive IgM and cross-plasmodial interaction, are warranted.

Figure 1

Course of illness in the volunteer and in vitro growth inhibition on P. falciparum exhibited by the volunteer's sera. (a) Plasmodium vivax parasitaemias (percentage of infected red blood cells) determined microscopically in the volunteer are represented by a line, while detection of P. vivax by PCR is denoted by horizontal black bars. (b) Body temperatures measured at the time of phlebotomies are shown. (c) The solid line represents the average of in vitro growth inhibition obtained from four cultures, while the dotted lines represent standard errors. The broken line denotes the upper 95% confidence limit of the baseline sera. Days of high values are denoted on the symbols in this and subsequent figures. Day 0 is the day of challenge.

Figure 2

Cross-reactive antibodies against Plasmodium falciparum antigens. (a) IgM against P. falciparum schizont extract, (b) IgM against P. falciparum Merozoite Surface Protein (MSP)-1₁₉, (c) IgG against P. falciparum schizont extract, and (d) IgG against P. falciparum MSP-1₁₉. The solid line represents the concentration of IgM, or the titer of IgG as compared to the hyper-immune pooled serum (titer = 1). The broken line denotes the upper 95% confidence limit obtained from the baseline, while the mean and confidence interval in the control subjects are denoted as the vertical bar overlapping Y axis.

Figure 3

Serum cytokine levels. Concentrations of (a) IL-12, (b) IFN-γ, (c) IL-6, (d) IL-1β, (e) IL-4 (all in pg/ml) (solid lines). The broken line denotes the upper limit of 95% confidence interval obtained from the baseline, while the mean and confidence interval in the control subjects are shown as the vertical bar overlapping Y axis.