Evidence that seasonal malaria chemoprevention with SPAQ influences blood and pre-erythrocytic stage antibody responses of Plasmodium falciparum infections in Niger

Abstract

Background: In endemic areas, children develop slowly and naturally anti-Plasmodium antibodies and become semi-immune. Seasonal Malaria Chemoprevention (SMC) with sulfadoxine-pyrimethamine + amodiaquine (SPAQ) is a new strategy to reduce malaria morbidity in West African young children. However, SMC may impact on the natural acquisition of anti-Plasmodium immunity. This paper evaluates the effect of SMC with SPAQ on antibody concentration in young children from Niger.

Methods: This research was conducted in areas benefitting from SMC since 2014 (Zinder district), without SMC (Dosso district), and with 1 year of SMC since 2016 (Gaya district). To assess the relationship between SMC and Plasmodium falciparum IgG antibody responses, the total antibody concentrations against two P. falciparum asexual stage vaccine candidate antigens, circumsporozoite protein (CSP) and glutamate-rich protein R2 (GLURP-R2), in children aged 3 to 59 months across the three areas were compared. Antibody concentrations are quantified using an enzyme-linked immunosorbent assay on the elution extracted from positive and negative malaria Rapid Diagnostic Test cassettes.

Results: The analysis concerns two hundred and twenty-nine children aged from 3 to 59 months: 71 in Zinder, 77 in Dosso, and 81 in Gaya. In Zinder (CSP = 17.5 µg/ml and GLURP-R2 = 14.3 µg/ml) median antibody concentration observed are higher than in Gaya (CSP = 7.7 µg/ml and GLURP-R2 = 6.5 µg/ml) and Dosso (CSP = 4.5 µg/ml and GLURP-R2 = 3.6 µg/ml) (p < 0.0001).

Conclusion: The research reveals some evidences which show that seasonal malaria chemoprevention with SPAQ has an effect on blood stage antibody responses and pre-erythrocytic stage of P. falciparum infections in Niger. Increased antibody titres with increased SMC/SPAQ implementation. This contradicts hypothesis that SMC/SPAQ could reduce immunity to erythrocyte and liver-stage antigens. Further studies are necessary to provide better understanding of the SMC effect on malaria immunity.

Keywords: Antibody; CSP; GLURP-R2; Immunity; P. falciparum; Seasonal malaria chemoprevention.

Fig. 1

Characteristics of samples collected. A total of 875 RDTs were collected, of which 229 were analysed and 646 were not analysed. Of 229 included in the analysis 7 were from Zinder, 77 from Dosso, and 81 from Gaya

Fig. 2

Comparison of anti-CSP IgG antibody median concentrations. Zinder district (SMC since 2014), Dosso district (No SMC) and Gaya district (SMC since 2016). Comparison of the three districts simultaneous is performed using a Median test and two by two with Mann–Whitney test. The significance limit was p < 0.05

Fig. 3

Comparison of anti-GLURP-R2 IgG antibody median concentrations. Zinder district (SMC since 2014), Dosso district (No SMC) and Gaya district (SMC since 2016). Comparison of the three districts simultaneous is performed using a Median test and two by two with Mann–Whitney test. The significance limit was p < 0.05