Longitudinal analysis of antibody responses in symptomatic malaria cases do not mirror parasite transmission in peri-urban area of Cote d'Ivoire between 2010 and 2013

Abstract

Background: In the agenda towards malaria eradication, assessment of both malaria exposure and efficacy of anti-vectorial and therapeutic strategies is a key component of management and the follow-up of field interventions. The simultaneous use of several antigens (Ags) as serological markers has the potential for accurate evaluation of malaria exposure. Here we aimed to measure the longitudinal evolution of the background levels of immunity in an urban setting in confirmed clinical cases of malaria.

Methods: A retrospective serological cross-sectional study on was carried out using 234 samples taken from 2010 to 2013 in peri-urban sentinel facility of Cote d'Ivoire. Antibody responses to recombinant proteins or BSA-peptides, 8 Plasmodium falciparum (PfAMA1, PfMSP4, PfMSP1, PfEMP1-DBL1α1-PF13, PfLSA1-41, PfLSA3-NR2, PfGLURP and PfCSP), one P. malariae (PmCSP) and one Anopheles gambiae salivary (gSG6-P1) antigens were measured using magnetic bead-based multiplex immunoassay (MBA). Total anti- P. falciparum IgG responses against schizont lysate from african 07/03 strain (adapted to culture) and 3D7 strain was measured by ELISA.

Results: High prevalence (7-93%) and levels of antibody responses to most of the antigens were evidenced. However, analysis showed only marginal decreasing trend of Ab responses from 2010 to 2013 that did not parallel the reduction of clinical malaria prevalence following the implementation of intervention in this area. There was a significant inverse correlation between Ab responses and parasitaemia (P<10-3, rho = 0.3). The particular recruitment of asymptomatic individuals in 2011 underlined a high background level of immunity almost equivalent to symptomatic patients, possibly obscuring observable yearly variations.

Conclusion: The use of cross-sectional clinical malaria surveys and MBA can help to identify endemic sites where control measures have unequal impact providing relevant information about population immunity and possible decrease of transmission. However, when immunity is substantially boosted despite observable clinical decline, a larger cohort including asymptomatic recruitment is needed to monitor the impact of control measures on level of immunity.

Fig 1. Indicators of malaria prevention measures in Abobo from 2010 to 2013.

Longitudinal annual profiles of incidence of clinical malaria (a), percentage of population coverage by LLIN distribution (b) and number of ACT treatments distributed (c) are shown as histogram plots. These indicators illustrate the substantial increase of prevention measures from 2010 to 2013 (data from RASS 2013—Rapport Annuel des Service de Sante, Ministère de la Sante et de la Lutte contre le SIDA, Côte Ivoire).

Fig 2. Ab responses as function of presence of circulating parasites in asymptomatic group recruited in 2011.

Levels of Ab responses against schizont extract, SALSA, PF13, MSP4p20 and MSP1p19 are illustrated as boxplot for asymptomatic individuals recruited in 2011 as function of their parasite carriage ie RDT negative, RDT positive, RDT and blood smear positivity. Significant differences (Kruskal wallis test, P<0.05) are indicated by an asterisk.

Fig 3. Ab responses against strongly recognized P.falciparum antigens in age-groups from 2010 to 2013.

Profiles of antibody responses measured by ELISA or multiplex magnetic bead based fluorescence assay are plotted as mean OD ratio or Median fluorescence levels from 2010 to 2013 for individuals from 4 different age groups: < 5 years old (empty), 6-10yo (light grey), 11–15 years old (dark grey), >15 years old (black). Schizont extract and antigens strongly recognized are shown ie MSPs, SALSA and PF13.

Fig 4. Age-group profiles of Ab responses against Plasmodium and A. gambiae antigens from 2010 to 2013.

Antibody responses measured by magnetic bead based fluorescence assay are plotted as Median fluorescence levels from 2010 to 2013 for individuals from 4 different age groups: < 5 years old (empty), 6-10yo (light grey), 11–15 years old (dark grey), >15 years old (black). On this figure are plotted antibody responses to P.falciparum Ags tested not shown on Fig 3 together with P. malariae CSP and A gambiae salivary peptide gSG6.