Antibody profiles to plasmodium merozoite surface protein-1 in Cambodian adults during an active surveillance cohort with nested treatment study

Abstract

Background: In addition to evidence for a protective role of antibodies to the malaria blood stage antigen merozoite surface protein 1 (MSP1), MSP1 antibodies are also considered as a marker of past malaria exposure in sero-epidemiological studies.

Methods: In order to better assess the potential use of MSP1 serology in malaria chemoprophylaxis trials in endemic areas, an analysis for the prevalence of antibodies to both Plasmodium falciparum and Plasmodium vivax MSP142 in healthy Cambodian adults was conducted at two sites as part of an active, observational cohort evaluating the efficacy of dihydroartemisinin-piperaquine (DP) for uncomplicated malaria (ClinicalTrials.gov identifier NCT01280162).

Results: Rates of baseline sero-positivity were high (59 and 73% for PfMSP142 and PvMSP142, respectively), and titers higher in those who lived in a higher transmission area, although there was little correlation in titers between the two species. Those volunteers who subsequently went on to develop malaria had higher baseline MSP142 titers than those who did not for both species. Titers to both antigens remained largely stable over the course of the 4-6 month study, except in those infected with P. falciparum who had multiple recurrences.

Conclusion: These findings illuminate the difficulties in using MSP142 serology as either a screening criterion and/or biomarker of exposure in chemoprophylaxis studies. Further work remains to identify useful markers of malarial infection and/or immunity.

Fig. 1

Titers to P. falciparum and P. vivax MSP1₄₂ by site and clinical history. Antibody titers to P. falciparum MSP1₄₂ (a, c) and Pv MSP1₄₂ (b, d) in smear-negative volunteers at screening. a, b Titers grouped according to site: site A (n = 113) versus site B (n = 101) while c, d show titers at each site according to time since most recent malaria infection (any species): within past year, more than 1 year ago and never. c, d Also include the percent of seropositive volunteers in each timing category and site. Black line is geomean titer for each site, while the blue line represents cutoff titer for seropositivity

Fig. 2

MSP1₄₂ titers at enrollment and malaria outcome. Antibody titers to P. falciparum MSP1₄₂ (a) and Pv MSP1₄₂ (b) in smear-negative volunteers at enrollment based on the species of the first malaria infection contracted during the study or if remaining malaria negative. For PfMSP1, among three groups one-way ANOVA p = 0.0012, with Tukey’s post-test significant for P. falciparum infection compared to both P. vivax infection and no malaria. PvMSP1 titers among three groups: one-way ANOVA p < 0.0001 with Tukey’s post-test only significantly different between P. vivax titers and no malaria

Fig. 3

Longitudinal titers per species of infection and recurrence. a, c, e PfMSP titers (red); b, d, f: PvMSP1 titers (green). a Group 1 Pf titers in those seven volunteers with 2 or 3 P. falciparum or mixed P. falciparum/P. vivax infections; asterisk indicates the one volunteer with a new P. falciparum infection, not recrudescence. b Group 1 with 7 representative volunteers with P. vivax infections and P. vivax relapses only. c, d Titers in those with mono—P. falciparum infection followed by mono—P. vivax infection. e, f Titers in volunteers with mono—P. vivax infection followed by mono—P. falciparum infection. Study period is divided into approximately 2 week blocks along X axis. Geometric symbols indicate a clinic visit with serology blood draw. Those symbols in black are ones with a positive malaria blood smear. All diagnoses are by PCR-corrected blood smears

Fig. 4

Change in titers from enrollment to discharge. Antibody titers to PfMSP1₄₂ (a) and PvMSP1₄₂ (b) both at enrollment and discharge grouped by no malaria infection during the study, P. falciparum or P. vivax infection one time only and those with two or more P. falciparum or P. vivax infections