School-Based Serosurveys to Assess the Validity of Using Routine Health Facility Data to Target Malaria Interventions in the Central Highlands of Madagascar

Abstract

Background In low-malaria-transmission areas of Madagascar, annual parasite incidence (API) from routine data has been used to target indoor residual spraying at sub-district commune levels. To assess validity of this approach, we conducted school-based serological surveys and health facility (HF) data quality assessments in seven districts to compare API to “gold-standard” commune-level serological measures. Methods At two primary schools in each of 93 communes, 60 students were randomly selected along with parents and teachers. Capillary blood was drawn for rapid diagnostic tests (RDTs) and serology. Multiplex bead-based immunoassays to detect antibodies to five Plasmodium falciparum antigens were conducted, and finite mixture models used to characterize seronegative and seropositive populations. Reversible catalytic models generated commune-level annual seroconversion rates (SCRs). HF register data were abstracted to assess completeness and accuracy. Results RDT positivity from 12,770 samples was 0.5%. Seroprevalence to tested antigens ranged from 17.9% (MSP-1) to 59.7% (PF13). Median commune-level SCR was 0.0108 (range: 0.001, 0.075). Compared to SCRs, API identified 71% (95% CI: 51%, 87%) of the 30% highest-transmission communes; sensitivity declined at lower levels. Routine data accuracy did not substantially affect API performance. Conclusions API performs reasonably well at identifying higher-transmission communes, but sensitivity declined at lower transmission levels.

Plasmodium falciparumserology: A comparison of two protein production methods for analysis of antibody responses by protein microarray

“…Despite the lack of a clearly defined relationship between antigen-matched targets from opposing expression systems, we remain confident that microarrays utilising IVTT or purified recombinant proteins are able to produce compelling and biologically relevant data. Indeed, our data show age-dependent trends in antibody responses (typical of highly endemic populations [1][2][3]) irrespective of expression system (Supplementary figure 2), lending weight to the applicability of either methodology in serological assays [33][34][35][36][37][38][39][40][41][42][43][44][45][46].…”

Antibody Profile Comparison against MSP1 Antigens of Multiple Plasmodium Species in Human Serum Samples from Two Different Brazilian Populations Using a Multiplex Serological Assay

“…Studies for the detection of antibodies against Plasmodium MSP1 proteins are increasingly used to map geographical distributions, seroprevalence and transmission intensities of malaria infection [22][23][24]. The C-terminal portion of the merozoite surface protein 1 (MSP1 19 ) is a promising candidate for the malaria vaccine, as it is highly immunogenic [25,26], therefore being extensively analyzed as an immunological target in many studies [23,[25][26][27][28].…”

Identification of factors associated with residual malaria transmission using school-based serological surveys in settings pursuing elimination

“…Additionally, capillary blood was collected for all children in microvette tubes (Microvette 500 Z-Gel; Sarstedt) for later serological analyses. Collected samples were transported to Institut Pasteur de Madagascar’s immunology laboratory in Antananarivo and stored at − 20 °C until used [ 11 ].…”

“…In 2014, a cross-sectional school-based survey was carried out in seven districts of the CHL and surrounding Fringes areas to better characterize malaria transmission via use of serological markers of P. falciparum exposure [ 11 ]. Results showed that the ability of annual parasite incidence estimates using health facility routine data of malaria-confirmed patients by RDT to characterize malaria transmission declined at lower transmission levels as compared with a serological approach [ 11 ].…”

“…In 2014, a cross-sectional school-based survey was carried out in seven districts of the CHL and surrounding Fringes areas to better characterize malaria transmission via use of serological markers of P. falciparum exposure [ 11 ]. Results showed that the ability of annual parasite incidence estimates using health facility routine data of malaria-confirmed patients by RDT to characterize malaria transmission declined at lower transmission levels as compared with a serological approach [ 11 ]. Using this dataset, this study expands on the previous analyses and aims (1) to characterize the spatial heterogeneity of malaria transmission intensity and to detect hotspots of both P. falciparum infection prevalence and PfAMA1 antibody (Ab) seroprevalence in CHL and surrounding Fringes; and (2) to identify sociodemographic, climatic, and environmental associated factors with such heterogeneity in malaria infection and exposure.…”