High-throughput molecular tests for routine surveillance of malaria potentially missed by rapid diagnostic tests

Abstract

Malaria remains one of the most common infectious diseases in the world and still a public health problem particularly in sub-Saharan Africa despite the remarkable progress made during the past decades in cutting the number of cases by around 50 %. Improvement in diagnosis and the introduction of artemisinin-based therapies have contributed substantially to this development. Currently available diagnosis tools for the identification of P. falciparum include the gold standard TBS microscopy and RDT. Despite many advantages, currently deployed RDTs have severe limitations in detecting low-density parasitemia. P. falciparum isolates lacking the hrp2 and hrp3 genes escape RDT detection posing a serious threat to the currently deployed test-treat-track approach for malaria recommended by WHO. False positive RDTs based on circulating HRP2 protein after successful asexual blood stage clearance following treatment have been described. RDTs with high sensitivity and specificity for monitoring non-falciparum species are missing. Therefore, improved diagnostic tools for rapid surveillance of malaria are essential for approaching the final aim of malaria elimination. The main goal of this PhD thesis is to develop, validate and implement novel tools and techniques for high-throughput molecular detection that will support a comprehensive surveillance of malaria by (i) measuring prevalence of P. falciparum parasites potentially escaping detection by RDTs, (ii) monitoring of kelch13 gene mutations conferring artemisinin resistance, (iii) monitoring impact of preventive treatment programs in pregnant women, (iv) understand the interaction of co-infections like HIV on P. falciparum, (v) assess the epidemiology of Plasmodium spp. co-infections with P. falciparum.