Antibody acquisition models: A new tool for serological surveillance of malaria transmission intensity

Abstract

Serology has become an increasingly important tool for the surveillance of a wide range of infectious diseases. It has been particularly useful to monitor malaria transmission in elimination settings where existing metrics such as parasite prevalence and incidence of clinical cases are less sensitive. Seroconversion rates, based on antibody prevalence to Plasmodium falciparum asexual blood-stage antigens, provide estimates of transmission intensity that correlate with entomological inoculation rates but lack precision in settings where seroprevalence is still high. Here we present a new and widely applicable method, based on cross-sectional data on individual antibody levels. We evaluate its use as a sero-surveillance tool in a Tanzanian setting with declining malaria prevalence. We find that the newly developed mathematical models produce more precise estimates of transmission patterns, are robust in high transmission settings and when sample sizes are small, and provide a powerful tool for serological evaluation of malaria transmission intensity.In order to reduce the global malaria burden and achieve control, or even elimination, robust estimates of malaria transmission intensity are required for the strategic planning, implementation and evaluation of interventions [1][2][3][4] . Efficient monitoring of malaria transmission intensity depends on tools that produce reliable estimates across a wide range of transmission settings 5,6 . Such tools should preferably integrate information about both parasite and vector populations to capture the current level of transmission intensity as well as the transmission potential in areas where parasite carriage has decreased but vector populations persist [6][7][8][9] . Traditionally, transmission intensity has been estimated by a variety of techniques such as spleen rates, parasite prevalence or entomological inoculation rates (EIR) 2 . EIR has been considered the gold standard among metrics 10 , but is expensive and labour intensive to evaluate and estimates are often imprecise (especially when transmission is low) due to marked heterogeneity of both malaria transmission and vector distribution [10][11][12] . In addition, single-time point evaluation of parasite prevalence or EIR provides limited information about past transmission intensity 13,14 . Cumulative exposure to P. falciparum, however, can be estimated by evaluation of antibody responses to P. falciparum blood-stage antigens [15][16][17] . In addition, exposure to Anopheles mosquitoes can be evaluated through antibody responses to An. gambiae salivary gland protein 6 (gSG6) [18][19][20] . Existing methods for serological evaluation of malaria transmission have largely been based on cross-sectional data on antibody prevalence and on estimation of seroconversion rates (SCR) using serocatalytic models as shown by Drakeley et al. 15 . Although SCR based estimates have been extended to evaluate temporal changes 21-23 and provide robust information about medium and long-term trends of transmission intensity, they ...

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

“…Alternatively, linear regression models are used to provide information about the antibody acquisition [13, 21]. Helb et al [13] and Yman et al [12] estimated recent P. falciparum exposure at individual (longitudinal data) and population level (cross-sectional data). Studies based on longitudinal data mainly use approaches such as linear regression models [13, 20], generalized linear models (GLM) [64], or Ab-intensity models [12] to analyse Ab profiles.…”

“…In particular, serological markers can be used as a proxy for Plasmodium transmission intensity in low endemic areas [11] where parasite carriage is reduced and vector populations persevere [12]. More specifically this corresponds to the measurement of the force of infection (FOI), reflecting a rate at which susceptible individuals acquire an infection per year in a given area [9].…”

“…Producing Abs against sporozoites or merozoites is challenging, due to the short time that sporozoites need to reach and penetrate liver cells, and for merozoites to reinvade erythrocytes. Strong Ab-responses are expressed against early blood stage Ags, which can be more useful in estimating cumulative exposure [12, 17]. Even though it is difficult to determine the half-life of Abs, some studies have already studied the Ab persistence [18–20].…”

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

“…Transmission monitoring is also important as it can inform about the appropriate timing of control interventions such as drug and vaccine trials. Mathematical models that estimate the rate of antibody seroconversion against mostly blood stage parasite antigens are gaining relevance [2,14,27,32], but a difficulty with this approach has been the identification of appropriate antigen targets since the levels of specific antibodies to these targets must reflect any changes in transmission patterns [20]. …”

“…These antibody seroprevalence models are designed to predict annual changes in seroconversion rates by averaging the patterns of seropositivity changes over an entire year [20,21,32]. This may therefore preclude the possibility of detecting changes in transmission that occur within a 12-month period for areas with seasonal disease transmission.…”