Molecular and Genomic Malaria Diagnostics for Elimination and Resistance Surveillance: A Critical Narrative Review of Analytical Performance, Epidemiological Inference and Programmatic Translation
Robinson Ndifrekeabasi Itek
Department of Medical Microbiology and Parasitology, Rivers state University, Nigeria.
Evelyn Orevaoghene Onosakponome *
Department of Medical Microbiology and Parasitology, Faculty of Medical Laboratory Science, Federal University Otuoke, Bayelsa State, Nigeria.
*Author to whom correspondence should be addressed.
Abstract
Malaria control has become dependent on two technologies whose limitations are now well documented: light microscopy, which cannot reliably detect the low-density infections that sustain transmission, and antigen-detecting rapid diagnostic tests, whose principal target is being deleted from parasite populations under diagnostic selection pressure. Molecular and genomic methods have been advanced as the corrective, yet the evidence supporting their programmatic use is uneven and has not been appraised critically across the full range of purposes to which these methods are now applied. This review examines that evidence, distinguishing three tasks that are frequently conflated: detection of infection in an individual, characterisation of parasite populations for resistance surveillance, and inference about transmission, connectivity and importation. Literature was identified through structured searching of major open scholarly databases and institutional sources, supplemented by citation chaining, and appraised for design adequacy, analytical validation, representativeness and evidence–claim alignment. The synthesis indicates that analytical sensitivity is no longer the principal constraint. Nucleic acid amplification approaches routinely detect infections below one parasite per microlitre, and field-deployable isothermal and sequencing platforms now approach the performance previously confined to reference laboratories. The binding constraints lie elsewhere: near-universal reliance on a single amplification target, unstandardised pre-analytical handling, heterogeneous genotyping protocols that generate non-comparable deletion prevalence estimates, sampling frames that were designed for clinical case management rather than for population genomic inference, and a persistent gap between assay development and sustained national implementation. Evidence for non-falciparum species, particularly for relapse attribution and zoonotic transmission, remains substantially weaker than for Plasmodium falciparum. Confidence is strongest for the analytical claims and weakest for claims about programmatic impact, where controlled comparisons of surveillance strategies are almost entirely absent. Priorities include target diversification, protocol harmonisation with external quality assessment, purpose-matched sampling design, and evaluation of whether molecularly informed surveillance changes outcomes rather than merely improving measurement.
Keywords: Malaria elimination, molecular surveillance, genomic epidemiology, pfhrp2 deletion, antimalarial drug resistance, nucleic acid amplification, targeted amplicon sequencing, Plasmodium vivax