Abstract

BackgroundReported malaria cases continue to decline globally, and this has been attributed to strategic implementation of multiple malaria control tools. Gains made would however need to be sustained through continuous monitoring to ensure malaria elimination and eradication. Entomological inoculation rate (EIR) is currently the standard tool for transmission monitoring but this is not sensitive enough, especially in areas of very low transmission. Transmission estimation models based on seroconversion rates (λ) of antibodies to Plasmodium falciparum blood stage antigens are gaining relevance. Estimates of λ, which is the measure of transmission intensity, correlate with EIR but are limited by long-term persistence of antibodies to blood stage antigens. Seroprevalence of antibodies to sporozoite antigens may be better alternatives since these antigens usually have shorter immune exposure times. The aim of this study was to develop transmission estimation models based on the seroprevalence of antibodies to two P. falciparum sporozoite antigens (CSP, CelTOS) and compare with models based on the classical blood stage antigen AMA1.MethodsAntibody levels in archived plasma from three cross-sectional surveys conducted in 2009 in a low transmission area of Southern Ghana were assessed by indirect ELISA. Seroprevalence of antibodies against CSP, CelTOS and AMA1 were fitted to reversible catalytic models to estimate λ and corresponding seroreversion rates (ρ) for each antibody.ResultsOf the three models developed, the anti-CSP model predicted a 13-fold decrease in λ four years prior to the time of sampling (2009). Anti-AMA1 antibodies formed at a four-fold greater rate compared to that of anti-CelTOS antibodies, and anti-CSP antibodies during the period of decreased λ. In contrast, anti-AMA1 antibodies decayed at a five-fold slower rate relative to that of anti-CSP antibodies while anti-AMA1 and anti-CelTOS antibody decay rates were not significantly different. Anti-CSP antibodies were relatively short-lived as they formed at an 11.6-fold slower rate relative to their decay during the period of decreased λ.ConclusionsThese features of anti-CSP antibodies can be exploited for the development of models for predicting seasonal, short-term changes in transmission intensity in malaria-endemic areas, especially as the elimination phase of malaria control is approached.

Highlights

  • Reported malaria cases continue to decline globally, and this has been attributed to strategic implementation of multiple malaria control tools

  • Decay rate for anti-circumsporozoite protein (CSP) antibodies was about 11.6-fold greater than the rate at which the same antibodies formed after the time of predicted change in λ. These observations collectively suggest that anti-sporozoite antibodies, especially those against CSP, are formed at a relatively slow rate and decay at a faster rate compared to anti-apical membrane antigen 1 (AMA1) antibodies in individuals from low transmission areas

  • This study has demonstrated the potential of sporozoite antigens, especially CSP, as important markers for assessing changes in malaria transmission intensity

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Summary

Introduction

Reported malaria cases continue to decline globally, and this has been attributed to strategic implementation of multiple malaria control tools. Entomological inoculation rate (EIR) is currently the standard tool for transmission monitoring but this is not sensitive enough, especially in areas of very low transmission. The risk of infection is directly related to the intensity of transmission, which has traditionally been estimated by entomological inoculation rates (EIR) or by parasite prevalence estimates using light microscopy [2,3]. These methods have inherent limitations; EIR estimation is usually laborious, time-consuming, requires very large mosquito samples for robust estimates and has been found to be less accurate in low transmission areas [4,5]. There is, a need for less laborious tools with improved reliability and sensitivity for estimating malaria transmission intensity

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