PUTATIVE, SECRETED OOKINETE PROTEIN (PSOP24) PEPTIDES AS A MARKER OF INFECTIOUS BITES AND MALARIA TRANSMISSION ASSESSMENT

ABSTRACT

As reported malaria cases continue to decline, heterogeneity in transmission will become more pronounced and thus more sensitive tools would be required to identify micro-geographic areas of higher risk for targeted interventions. Sero-positivity against antigens expressed at different stages of the parasite life cycle and proteins in the mosquito saliva cocktail have gained relevance as transmission monitoring tool. However, the persistent nature of blood stage antigens and the possible use of Circumsporozoite protein (CSP) as a vaccine has necessitated the search for additional markers that can measure even subtle differences in malaria transmission. Seropositive against antibodies to synthetic peptides of a ookinete stage marker may be a better alternative since it may show contact to an infectious vector. Thus, the study sought to evaluate further and possibly validate PSOP24 as an infectious bite marker of malaria transmission. Synthetic peptides of PSOP24 were designed to cover the most immunogenic epitopes based on several bioinformatic models. Total IgG antibody response to three of the peptides (PSOP24- 374, PSOP24-375 and PSOP24-377), CSP and gSG6-P1 were then determined using an indirect ELISA protocol to antibody eluates from two communities 2 Km apart with low malaria transmission during the dry and wet seasons. Malaria parasites were detected in study participants by both microscopy and molecular techniques. In this study, a 2-fold decrease in IgG responses to peptides PSOP24-374 and PSOP24-375 was observed between the dry and wet season (p < 0.005), whereas a 2-fold increase in IgG response to PSOP24-377 and the vector-antigen gSG6-P1 was observed between the same sample collection periods (p < 0.0001). However, CSP showed no significant difference between the seasons when compared. Spatial variation between the study communities also show a 1 fold increase in IgG response to PSOP24-375 while a 2 fold and 1 fold decrease in IgG response to XII PSOP24-374 and PSOP24-377 from Ayeigbekorpe to Odumase was observed during the dry season. In the wet season, Odumase had high median IgG responses to PSOP24-374, PSOP24- 377 and CSP than Ayigbekorpe while median IgG response to gSG6-P1 was high in Ayigbekorpe than in Odumase. Also, the study found greater proportion (36.4%) of submicroscopic infections in individuals in Odumase compared to Ayeigbekorpe during the dry season (p=0.02) while this trend was reversed during the wet season. Generally, there were less multiple infections per individual, described as the multiplicity of infection between the study communities and also between the sample collection times with majority of participants harboring single alleles of the 3D7 strain. This data shows a high antibody response particularly to PSOP24-377 that was similar to gSG6- P1, corresponding to the different transmissions in the study communities, hence can be exploited as additional marker for assessing transmission in low transmission settings.