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

Abstract

BackgroundSerological markers for exposure to different Plasmodium species have recently been used in multiplex immunoassays based on the Luminex technology. However, interpretation of the assay results requires consideration of the half-life of specific antibodies against these markers. Therefore, the aim of the present study was to document the half-life of malaria specific serological makers, as well as assessing the sensitivity of these markers to pick up recent changes in malaria exposure.MethodsA recently developed multiplex immunoassay was used to measure the intensity of antibody (Ab) responses against 19 different Plasmodium specific antigens, covering different human malaria parasites and two vector saliva antigens. Therefore, 8439 blood samples from five cross-sectional surveys in Ratanakiri, Cambodia, were analysed. These involve a random selection from two selected surveys, and an additional set of blood samples of individuals that were randomly re-sampled three, four or five times. A generalized estimating equation model and linear regression models were fitted on log transformed antibody intensity data.ResultsResults showed that most (17/21) Ab-responses are higher in PCR positive than PCR negative individuals. Furthermore, these antibody-responses follow the same upward trend within each age group. Estimation of the half-lives showed differences between serological markers that reflect short- (seasonal) and long-term (year round) transmission trends. Ab levels declined significantly together with a decrease of PCR prevalence in a group of malaria endemic villages.ConclusionFor Plasmodium falciparum, antibodies against LSA3.RE, GLURP and Pf.GLURP.R2 are most likely to be a reflexion of recent (range from 6 to 8 months) exposure in the Mekong Subregion. PvEBP is the only Plasmodium vivax Ag responding reasonably well, in spite of an estimated Ab half-life of more than 1 year. The use of Ab intensity data rather dichotomizing the continuous Ab-titre data (positive vs negative) will lead to an improved approach for serological surveillance.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-016-1576-z) contains supplementary material, which is available to authorized users.

Genetic diversity in twoPlasmodium vivaxprotein ligands for reticulocyte invasion

“…These studies have shown that antibodies against the region II domain of the PvEBP were commonly detected in sera from individuals in malaria endemic settings such as in Cambodia or in Solomon Islands/Papua New Guinea. In Cambodia, humoral immune response to PvEBP was found to be higher and longer lasting compared to PvDBP, making this marker a better candidate to monitor P. vivax infections [43]. Moreover, Franca et al, in Papua New Guinea identified a significant association between reduced risk of clinical vivax malaria and levels of antibodies against PvEBP [44].…”

Evaluating malaria programmes in moderate- and low-transmission settings: practical ways to generate robust evidence

“…Surveys may also capture malaria infections external to the public health system through biomarker data (polymerase chain reaction (PCR) and serological analyses), and febrile illnesses reported by survey participants [24,25]. In low-transmission settings, surveys increasingly include molecular methods such as PCR to detect low-density Plasmodium infections which may be missed by rapid diagnostic test (RDT) [26], or include serological methods which assess both recent and historical exposure to Plasmodium and can be used to estimate changes in transmission over time [27][28][29].…”

Practical example of multiple antibody screening for evaluation of malaria control strategies

“…The P. falciparum schizont extract (SE) of the 07/03 Dielmo strain was prepared and used in Indirect ELISA as described [31,32]. The multiplex bead-based assay (MBA) using covalent coupled antigen (MSP1p19) or BSA-peptide (LSA1 41 ) to carboxylated magnetic Luminex beads was done as described [33][34][35][36]. In the cohort from Senegal, antibody responses to an additional six antigens were measured using the multiplex Luminex assay: circumsporozoite protein (CSP); liver-stage antigen 3 (LSA-3); glutamate-rich protein (GLURP); sporozoite and liver stage antigen (Salsa); erythrocyte associated antigen PF13 from membrane protein 1 (PfEMP1/PF13); and apical membrane antigen 1 (AMA-1) [32][33][34][35][36].…”

“…The multiplex bead-based assay (MBA) using covalent coupled antigen (MSP1p19) or BSA-peptide (LSA1 41 ) to carboxylated magnetic Luminex beads was done as described [33][34][35][36]. In the cohort from Senegal, antibody responses to an additional six antigens were measured using the multiplex Luminex assay: circumsporozoite protein (CSP); liver-stage antigen 3 (LSA-3); glutamate-rich protein (GLURP); sporozoite and liver stage antigen (Salsa); erythrocyte associated antigen PF13 from membrane protein 1 (PfEMP1/PF13); and apical membrane antigen 1 (AMA-1) [32][33][34][35][36]. A pool of sera from immune adults from Dielmo and a pool of European and African non-immune sera (20 Senegalese individuals confirmed as negative IgG response to P. falciparum schizont extract) were included in each assay as positive and naïve controls and normalization control, respectively.…”