Anti-sporozoite antibodies as alternative markers for malaria transmission intensity estimation

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.

Serological markers to measure recent changes in malaria at population level in Cambodia

“…As age influences Ab-responses [11, 32], age categories were created based on the work of Kusi et al [8]. To explore whether the age categories defined were al biologically relevant in the study region, the (ln) MFI values were plotted against age (Additional file 5).…”

“…Three linear models were compared per Ag through ANOVA tests: (1) a model with time since infection as dependent variable, (2) a model with time since infection and age groups as dependent variable (without interaction and (3) with interaction). Based on the slope (=λ) of the selected model, the half-life was estimated per serological marker () [8, 41]. The 95% confidence intervals (95% CI) were estimated using the ‘confint’ function in R [28].…”

“…Traditional techniques for determining malaria transmission intensity include entomological inoculation rates (EIR) and parasite prevalence (PP) estimates [8]. However, in low transmission areas, the EIR and PP lack sensitivity, due to very low numbers of parasite-positive samples, both in mosquitoes and humans [9, 10].…”

Seroprevalence of Antibodies against Plasmodium falciparum Sporozoite Antigens as Predictive Disease Transmission Markers in an Area of Ghana with Seasonal Malaria Transmission

“…The levels of antibodies against sporozoite stage antigens are therefore expected to be relatively higher in individuals with frequent or recent exposure to infectious bites and lower in those with no recent exposure. We have previously shown in an area of very low malaria transmission that antibodies to two such sporozoite antigens, circumsporozoite protein (CSP) and cell traversal for ookinetes and sporozoites (CelTOS), indeed had relatively higher decay rates compared to the classical blood stage antigen AMA1 [10]. Reversible catalytic models based on seroprevalence of antibodies to CSP further predicted a 13-fold decrease in seroconversion rate and hence malaria transmission, an event which occurred approximately four years prior to the time of sampling in this area [10].…”

“…We have previously shown in an area of very low malaria transmission that antibodies to two such sporozoite antigens, circumsporozoite protein (CSP) and cell traversal for ookinetes and sporozoites (CelTOS), indeed had relatively higher decay rates compared to the classical blood stage antigen AMA1 [10]. Reversible catalytic models based on seroprevalence of antibodies to CSP further predicted a 13-fold decrease in seroconversion rate and hence malaria transmission, an event which occurred approximately four years prior to the time of sampling in this area [10]. The association between anti-CSP antibodies and malaria transmission intensity as estimated by such modeled cross-sectional data are consistent with similar estimates based on longitudinal data [11–14].…”