EDCTP2

Call: Career Development Fellowship (CDF)

Programme: EDCTP2

Start Date: 2018-07-01

End Date: 2021-06-30

Project Code: TMA2016CDF1605

Status:  Active

European and Developing Countries Clinical Trials Partnership

Project Summary

As international efforts towards malaria elimination increase, accurate data on transmission intensity will be crucial for directing control efforts, developing and testing new interventions, as well as predicting the effects of these interventions under various conditions. However, current tools; the entomological inoculation rate, parasite infection and serological measures have limitations in either sensitivity at low-level transmission or lack the inherent ability to track short-term changes. Again changes measured by these traditional tools reflect either parasite or vector exposure but not both.  The ideal tool for tracking malaria transmission intensity should reflect both exposure to the vector, parasite infection and human immunity as well as detect short-term changes and also  be applicable at both individual and population level.

 

We have identified sporozoite and ookinete proteins which human immune response correlates with seasonal vector and parasite exposure and thus a promising ideal marker for an infectious bites. The role of infectious bite markers to detect short-term changes in malaria transmission has not been thoroughly studied. Using longitudinal community cohorts, under varying transmission levels, we will study the dynamics of antibody response to candidate biomarkers in comparison to other salivary proteins to validate infectious-bite markers. It is hoped that these biomarkers will prove to be sensitive for the identification of transmission hotspots, vulnerable populations and inform focused interventions to speed up malaria elimination.

Study Goals and Objectives

The overarching goal of the study is to validate novel malaria infectious-bite marker as a simple straightforward sero-surveillance tool to identify ‘hotspots’ and ‘hotpops’ for targeted interventions to yield maximum community-wide benefits.

 

Specific Objectives

 

  • Determine kinetic antibody response to novel infectious-bite markers, gSG6-P1, PSOP24 and CSP and to compare with newly reported up-regulated salivary gland peptides
  • To compare with parasite prevalence with parasite prevalence, and entomological indices at household levels in study populations
  • Identify micro-geographic heterogeneities in malaria transmission using ArcGIS and spatial statistics, this will test the sensitivity and the reliability of sero-surveillance in identifying hotspots for targeted control
  • To find out the role of submicroscopic infections in malaria transmission at the household levels.

Study Design

This will be three-time point longitudinal community based survey at quarterly intervals cutting across both dry and rainy season.  Serological, parasitological and entomological as well as demographic data will be collected at household level.  The study will not discriminate participants in terms of age or gender but a representation of all age groups except infants of less than 6months where maternal antibodies drive immune response rather than exposure will be excluded.  Blood samples from finger prick will be taken from an average of 4 people per household from 100 households per community.

 

Measurement of humoral responses

All test samples will be tested for anti-infectious-bite markers, CSP and anti-gSG6-P1 human IgG antibodies by ELISA using standard methodology [Badu et al 2012a]. Test sera will be serially diluted in duplicate on the plates from 1:50 to 1:64,000.  Serial dilutions will be used to fit a four-parameter curve using SoftMax Pro v4.1 (Molecular Devices).  Results will be expressed in titer values, the titer endpoint being defined as the calculated serum dilution yielding an optical density of 1.0.

Expected Outcome

The overarching goal of the study is to validate novel malaria infectious-bite marker as a simple straightforward sero surveillance tool to identify ‘hotspots’ and ‘hotpops’ for targeted interventions to yield maximum community-wide benefits. This proposal will seek to determine heterogeneity in antibody response to infectious-bites markers corresponding to exposure to infected Anopheles mosquitoes to identify restricted geographical areas (household –level) in which there is a higher level of transmission intensity.

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