Plasma concentration of parasite DNA as a measure of disease severity in falciparum malaria.

Mallika Imwong,Amir Seni,Ilse C E Hendriksen,Arjen M Dondorp,George Mtove,Nicholas P J Day,Charles J Woodrow,Saroj Mishra,Samwel Gesase,Nicholas J White,Kajal D Chhaganlal,Hans Verhoef,Sanjib Mohanty,Jacobien Veenemans,M Abul Faiz

doi:10.1093/infdis/jiu590

Abstract

In malaria-endemic areas, Plasmodium falciparum parasitemia is common in apparently healthy children and severe malaria is commonly misdiagnosed in patients with incidental parasitemia. We assessed whether the plasma Plasmodium falciparum DNA concentration is a useful datum for distinguishing uncomplicated from severe malaria in African children and Asian adults. P. falciparum DNA concentrations were measured by real-time polymerase chain reaction (PCR) in 224 African children (111 with uncomplicated malaria and 113 with severe malaria) and 211 Asian adults (100 with uncomplicated malaria and 111 with severe malaria) presenting with acute falciparum malaria. The diagnostic accuracy of plasma P. falciparum DNA concentrations in identifying severe malaria was 0.834 for children and 0.788 for adults, similar to that of plasma P. falciparum HRP2 levels and substantially superior to that of parasite densities (P < .0001). The diagnostic accuracy of plasma P. falciparum DNA concentrations plus plasma P. falciparum HRP2 concentrations was significantly greater than that of plasma P. falciparum HRP2 concentrations alone (0.904 for children [P = .004] and 0.847 for adults [P = .003]). Quantitative real-time PCR measurement of parasite DNA in plasma is a useful method for diagnosing severe falciparum malaria on fresh or archived plasma samples.

Highlights

Severe falciparum malaria is a major cause of childhood death in sub-Saharan Africa, where it is a common diagnosis in severely ill children
Because P. falciparum HRP2 is released at the time of schizont rupture, we investigated the hypothesis that
We assessed the diagnostic performance of plasma P. falciparum DNA concentration, alone and combined with plasma P. falciparum HRP2 concentration and parasitemia, to distinguish between uncomplicated and strictly defined severe malaria in African children and Asian adults

Summary

Introduction

Severe falciparum malaria is a major cause of childhood death in sub-Saharan Africa, where it is a common diagnosis in severely ill children. 1128 JID 2015:211 (1 April) Imwong et al plasma concentrations of DNA (reflecting liberated merozoites and degraded parasites) might reflect the cumulative parasite burden and, the severity of disease in falciparum malaria. Several studies have documented the presence of P. falciparum DNA in plasma or serum [7,8,9] but have not examined the relationship between plasma P. falciparum DNA concentrations and malaria severity. We reasoned that DNA released into the plasma by schizont rupture or degradation of sequestered parasites might be a better measure of the previously sequestered biomass and, disease severity than peripheral parasitemia. We assessed the diagnostic performance of plasma P. falciparum DNA concentration, alone and combined with plasma P. falciparum HRP2 concentration and parasitemia, to distinguish between uncomplicated and strictly defined severe malaria in African children and Asian adults

Methods

Results

Conclusion