Developing mass spectrometry tools as a surveillance tool for vector control interventions

Jonathan, Karisa (2024). Developing mass spectrometry tools as a surveillance tool for vector control interventions. PhD thesis The Open University.

DOI: https://doi.org/10.21954/ou.ro.00099853

Abstract

The gold standard methods (i.e., morphological assessment, PCR and ELISA) for measuring mosquito entomological parameters such as species identification, bloodmeal source, infection and age are limited by cost and time. Cost-effective and high-throughput entomological surveillance tools are needed. Matrix-assisted laser desorption/ionisation time of flight mass spectrometry (MALDI-TOF MS) represents such a tool. This thesis aimed to advance MALDI-TOF MS as a surveillance tool for malaria vector control interventions. My PhD objectives included: 1) to create and validate MALDI-TOF MS databases for mosquito species identification, blood meal source and infection status; 2) to compare the cost of MALDI-TOF typing compared to gold standard methods; and 3) evaluate whether MALDI-TOF can be used for monitoring a cluster randomised controlled trial investigating a malaria vector control intervention in sub-Saharan Africa.

MALDI-TOF MS databases for species identification, blood meal source and infection status were developed using An. gambiae s.l and An. funestus s.l collected along Kenya's coastal region. Individual MALDI-TOF MS spectral "fingerprints" were obtained from each mosquito's head and thorax and the abdomens of blood-engorged mosquitoes. The same mosquitoes were also processed using gold standard tests. Cost comparison analysis of the tool was evaluated using a decision-tree approach for a comparative analysis of the time and cost associated with current methods versus MALDI-TOF MS diagnostic workflows. Lastly, MALDI-TOF MS was used to analyse samples originating from the entomological monitoring of the BOHEMIA clinical trial (Broad One-Health Endectocide Based Intervention in Africa) evaluating ivermectin mass drug administration (MDA) for malaria vector control.

Overall, MALDI-TOF MS demonstrated an accuracy of 97.5% in identifying sibling species of the two main malaria vector species viz., An. gambiae s.l and An. funestus s.l and 95.3% for blood meal source identification. The cost comparison analysis revealed that the MALDI-TOF MS workflow significantly reduced costs, equating to an overall direct cost savings of 83.12 % compared to the current workflow. Lastly, in a cluster-randomised controlled trial, MALDI-TOF MS technology was successfully used to support measuring the impact evaluation of ivermectin MDA for malaria vector control.