Serological markers to measure recent changes in malaria transmission: a promising tool towards malaria elimination


Despite large progress in malaria control, malaria remains a public health concern. For countries heading to elimination, evaluation and implementation of additional control tools is crucial. However, follow-up of malaria prevalence and incidence using classical malariometric tools becomes challenging in low transmission settings. Sero-prevalence offers an alternative for evaluating malaria transmission as anti-malaria antibodies can be sufficiently long-lived to reflect current, recent or past exposure. Serological markers from different Plasmodium species exist and have been recently used in a multiplex assay based on the Luminex-technology.

The aim of this thesis is whether a multiplex immunoassay has additional value in monitoring (ongoing) malaria transmission at community level, and thereby detecting changes in malaria transmission intensity due to seasonality or interventions in a hypo-endemic transmission setting.

In this thesis we have successfully implemented a multiplex immunoassay that proved its value when detecting anti-malarial antibodies in human blood samples in a low-endemic area. It can include multiple peptides and recombinant proteins simultaneously, making it more economic, faster and standardized compared to classical techniques. Moreover, half-life estimates have shed some light on which antibodies are good markers for current malaria exposure. Half-lives range from approximately six months to more than two years, depending on the serological marker. Further validation in identifying geographical clusters of malaria transmission showed that four out of 20 serological markers might have potential in reflecting current exposure.

This study was part of a cluster randomized trial based in Cambodia that is on the verge of eliminating malaria. During this trial, the efficacy of repellents as added control measure to long lasting insecticidal nets was studied. Two study arms (control and intervention arm) were compared based on PCR (primary outcome), serology and malaria incidence (secondary outcomes). However, no differences in sero-prevalence were observed, which confirms the outcomes obtained with PCR prevalence and malaria incidence.

In conclusion Pf.GLURP.R2, showed to be most informative for current infection. However, the other antigens should not be ruled out, as they probably reflect transmission in the further past. Further in-depth research on serological markers and statistical modeling is required to obtain better information on ongoing malaria transmission.