Dynamics of anti-MSP3 and Pfs230 antibody responses and multiplicity of infection in asymptomatic children from southern Ghana

Abstract

BackgroundDuring a Plasmodium infection, exposure of human host immune cells to both the asexual and the sexual stages of the parasite elicit immune responses. These responses may be protective and prevent the development of high parasitaemia and its associated clinical symptoms, or block the transmission of malaria to an uninfected person. This study aimed at examining the dynamics of naturally acquired immune responses against the asexual and sexual forms of Plasmodium falciparum as well as assessing differences in the multiplicity of infection (MOI) in asymptomatic Ghanaian children living in two communities with varying malaria transmission intensities.MethodsSchool children aged between 6 and 12 years were recruited from Obom, a high malaria prevalence setting and Abura, a low malaria prevalence setting and enrolled in monthly multiple cross sectional surveys between February and May 2015. Filter paper blood blots (DBS) as well as thick and thin blood smears were made from finger-pricked blood at each visit. Plasmodium falciparum parasite prevalence was determined by microscopy and PCR. Serum eluted from the DBS were used to assess anti-Pfs230 (sexual stage) and anti-MSP3 (asexual stage) antibody levels using indirect ELISA and DNA extracted from the DBS used to assess MOI.ResultsMalaria parasite point prevalence and MOI throughout the study was higher in Obom than Abura. The trend of parasite prevalence estimated by microscopy was similar to that determined by PCR in Obom but not in Abura. The trend of MSP3 antibody seroprevalence followed that of PCR-estimated parasite prevalence in Obom, while in Abura the trend of Pfs230 antibody seroprevalence followed that of PCR-estimated parasite prevalence.ConclusionsMicroscopy can more accurately predict changes in parasite prevalence in high transmission settings than low transmission settings. In high transmission settings, P. falciparum parasite prevalence can predict antibody seroprevalence to MSP3, whilst in low transmission settings, seroprevalence against Pfs230 may be a useful predictor of parasite prevalence.Electronic supplementary materialThe online version of this article (10.1186/s13071-017-2607-5) contains supplementary material, which is available to authorized users.

Sexual forms obtained in a continuous in vitro cultured Colombian strain of Plasmodium falciparum (FCB2)

“…Gametocyte blockade is thus considered a good target for vaccine development because it is intended to stall the disease at human-vector transmission level [6,7]. Small quantities of gametocytes circulate in infected humans' bloodstreams, being exposed to the host immune system; ookinetes could come into contact with the mosquito's immune system that includes a complement-like immune response [8][9][10]. The host's immune response gradually controls Plasmodium dispersal by reducing the amount of circulating gametocytes and limiting parasite development inside the mosquito vector, making this Plasmodium sexual stage an important biological bottleneck [11,12].…”

“…However, even with such biological control, natural response against the parasite leaves asymptomatic human parasite carriers (i.e. an important cause of transmission) [7,8]. Parasite culture and the biological study of sexual-stage parasite antigens are important for identifying and selecting effective vaccine candidates to stop this never-ending infection cycle [13].…”

Stage-specific Plasmodium falciparum immune responses in afebrile adults and children living in the Greater Accra Region of Ghana

“…Pfs230 is a gamete surface antigen [10][11][12] and marked as a transmission blocking vaccine candidate [13]. Antibodies against Pfs230 have been detected in populations naturally exposed to malaria parasites [14,15]. Such antibodies together with specific antibodies generated in small rodents have been shown to inhibit parasite development in the standard membrane-feeding assay (SMFA) considered the 'gold standard' assay for functional transmission-blocking antibodies [16][17][18].…”

“…Such antibodies together with specific antibodies generated in small rodents have been shown to inhibit parasite development in the standard membrane-feeding assay (SMFA) considered the 'gold standard' assay for functional transmission-blocking antibodies [16][17][18]. These antibodies, however, have been suggested to be very short lived, peaking during the transmission season [19] and are more prevalent in children than in adults [15].…”

“…Monitoring antibody responses in asymptomatic individuals is thus a valuable tool for monitoring the acquisition of anti-disease immunity as well as the frequency and magnitude of parasite infection [1]. A few earlier studies have characterized natural antibody responses to both asexual and sexual stage antigens, however these studies have only looked into immune responses in asymptomatic children below the age of 12 years [15] or in a symptomatic population [30]. Other studies on afebrile individuals have characterized antibody responses against sporozoite [31], asexual [32,33] or only sexual stage [34] antibody responses amongst a cohort of Ghanaians.…”