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Publication
Serological markers to measure recent changes in malaria transmission - a promising tool towards malaria elimination
Book - Dissertation
Malaria, a vector-borne disease caused by a Plasmodium parasite, is one of the most deadly infectious diseases. Despite large progress in malaria control, malaria remains an important public health concern. For countries heading to elimination, evaluation and implementation of additional malaria control tools is crucial. However, follow-up of malaria prevalence and incidence using classical malariometric tools becomes challenging in low malaria transmission settings. Seroprevalence offers an alternative for evaluating malaria transmission as anti-malaria antibodies can be sufficiently long-lived to reflect current, recent or past malaria exposure. Serological markers for exposure to different Plasmodium species exist and have been recently used in a multiplex assay based on the Luminex-technology. However, interpretation of the assay results requires caution and need to take the half-life of specific antibodies into consideration.
Therefore, the main aim of this PhD thesis is to see if 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.
Our specific objectives were:
1. To implement a multiplex immunoassay and document its value as compared to other serological tests
a. By reviewing the multiplex serological technique to the immunofluorescence assay technique
b. By implementing the multiplex immunoassay for detection of antibodies against antigens of different life stages and malaria parasites.
c. By documenting the half-life of the used serological markers by analyzing sequential and cohort samples from individuals in Ratanakiri province, Cambodia.
2. To validate multiple serological markers for estimating malaria transmission
a. By evaluating changes in malaria transmission due to an intervention trial.
b. By identifying geographical clusters of malaria transmission.
In this thesis we have successfully implemented the multiplex serological assay. The method proved to be valuable for the detection of anti-malarial antibodies in human blood samples in a region with a relatively low prevalence. The assay can include multiple peptides and recombinant proteins at the same time, making it more economic, faster and more standardized compared to the classical techniques.
Moreover, this thesis has shed some light on which antibodies are good markers for current malaria exposure. The interpretation of the decrease of antibody intensity made it possible to drawn some conclusions on the half-life of the antibodies. The half-lives range from approximately six months to more than two years, depending on the serological marker used. Four out of the 20 serological markers screened might have potential to be reflective for recent exposure in low endemic areas. Further validation of these serological markers by identifying geographical clusters of malaria transmission proved the added value of some of these markers to reflect current exposure.
This study was part of a cluster randomized trial based in Cambodia that is on the verge of eliminating malaria. During this cluster randomized trial, epidemiological surveys were organized to study the efficacy of repellents as added control measure to long lasting insecticidal nets. Two study arms (a control and intervention arm) were compared based on PCR as a primary outcome and on serology and malaria incidence as secondary outcomes. The comparison between the control and intervention arm did not show any significant difference in seroprevalence for all antigens, which confirms the analyses performed earlier on PCR prevalence and malaria incidence.
In conclusion Pf.GLURP.R2 out of all different serological markers tested throughout all chapters, showed to be most informative for current infection. However, the other antigens should certainly not be ruled out, as they probably reflects transmission in the former past for which no PCR-prevalence data may be available. Further in-depth research on the serological markers and statistical modeling is required to obtain better information on ongoing malaria transmission.
Therefore, the main aim of this PhD thesis is to see if 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.
Our specific objectives were:
1. To implement a multiplex immunoassay and document its value as compared to other serological tests
a. By reviewing the multiplex serological technique to the immunofluorescence assay technique
b. By implementing the multiplex immunoassay for detection of antibodies against antigens of different life stages and malaria parasites.
c. By documenting the half-life of the used serological markers by analyzing sequential and cohort samples from individuals in Ratanakiri province, Cambodia.
2. To validate multiple serological markers for estimating malaria transmission
a. By evaluating changes in malaria transmission due to an intervention trial.
b. By identifying geographical clusters of malaria transmission.
In this thesis we have successfully implemented the multiplex serological assay. The method proved to be valuable for the detection of anti-malarial antibodies in human blood samples in a region with a relatively low prevalence. The assay can include multiple peptides and recombinant proteins at the same time, making it more economic, faster and more standardized compared to the classical techniques.
Moreover, this thesis has shed some light on which antibodies are good markers for current malaria exposure. The interpretation of the decrease of antibody intensity made it possible to drawn some conclusions on the half-life of the antibodies. The half-lives range from approximately six months to more than two years, depending on the serological marker used. Four out of the 20 serological markers screened might have potential to be reflective for recent exposure in low endemic areas. Further validation of these serological markers by identifying geographical clusters of malaria transmission proved the added value of some of these markers to reflect current exposure.
This study was part of a cluster randomized trial based in Cambodia that is on the verge of eliminating malaria. During this cluster randomized trial, epidemiological surveys were organized to study the efficacy of repellents as added control measure to long lasting insecticidal nets. Two study arms (a control and intervention arm) were compared based on PCR as a primary outcome and on serology and malaria incidence as secondary outcomes. The comparison between the control and intervention arm did not show any significant difference in seroprevalence for all antigens, which confirms the analyses performed earlier on PCR prevalence and malaria incidence.
In conclusion Pf.GLURP.R2 out of all different serological markers tested throughout all chapters, showed to be most informative for current infection. However, the other antigens should certainly not be ruled out, as they probably reflects transmission in the former past for which no PCR-prevalence data may be available. Further in-depth research on the serological markers and statistical modeling is required to obtain better information on ongoing malaria transmission.
Publication year:2016