Plasma Concentration of Parasite DNA as a Measure of Disease Severity in Falciparum Malaria

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.

[1]  K. Silamut,et al.  Defining Falciparum-Malaria-Attributable Severe Febrile Illness in Moderate-to-High Transmission Settings on the Basis of Plasma PfHRP2 Concentration , 2012, The Journal of infectious diseases.

[2]  C. Karema,et al.  Sequence variation does not confound the measurement of plasma PfHRP2 concentration in African children presenting with severe malaria , 2012, Malaria Journal.

[3]  C. Karema,et al.  Diagnosing Severe Falciparum Malaria in Parasitaemic African Children: A Prospective Evaluation of Plasma PfHRP2 Measurement , 2012, PLoS medicine.

[4]  M. Molyneux,et al.  Plasma concentrations of parasite histidine-rich protein 2 distinguish between retinopathy-positive and retinopathy-negative cerebral malaria in Malawian children. , 2012, The Journal of infectious diseases.

[5]  P. Alonso,et al.  A direct comparison of real time PCR on plasma and blood to detect Plasmodium falciparum infection in children , 2012, Malaria Journal.

[6]  Bruce Russell,et al.  A rapid and robust tri-color flow cytometry assay for monitoring malaria parasite development , 2011, Scientific reports.

[7]  J. Baker,et al.  Transcription and Expression of Plasmodium falciparum Histidine-Rich Proteins in Different Stages and Strains: Implications for Rapid Diagnostic Tests , 2011, PloS one.

[8]  J. Laine,et al.  Fatal Outcome in Bacteremia is Characterized by High Plasma Cell Free DNA Concentration and Apoptotic DNA Fragmentation: A Prospective Cohort Study , 2011, PloS one.

[9]  C. Ockenhouse,et al.  Development of a Highly Sensitive Genus-Specific Quantitative Reverse Transcriptase Real-Time PCR Assay for Detection and Quantitation of Plasmodium by Amplifying RNA and DNA of the 18S rRNA Genes , 2011, Journal of Clinical Microbiology.

[10]  Kamolrat Silamut,et al.  Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial , 2010, The Lancet.

[11]  M. Perkins,et al.  A Large Proportion of P. falciparum Isolates in the Amazon Region of Peru Lack pfhrp2 and pfhrp3: Implications for Malaria Rapid Diagnostic Tests , 2010, PloS one.

[12]  S. Letendre,et al.  Malaria diagnosis by a polymerase chain reaction-based assay using a pooling strategy. , 2009, The American journal of tropical medicine and hygiene.

[13]  M. Molyneux,et al.  High Pneumococcal DNA Loads Are Associated With Mortality in Malawian Children With Invasive Pneumococcal Disease , 2007, The Pediatric infectious disease journal.

[14]  Susan Lewallen,et al.  Malarial retinopathy: a newly established diagnostic sign in severe malaria. , 2006, The American journal of tropical medicine and hygiene.

[15]  P. Savelkoul,et al.  New developments in the diagnosis of bloodstream infections. , 2004, The Lancet. Infectious diseases.

[16]  Wenjiang J. Fu,et al.  Differentiating the pathologies of cerebral malaria by postmortem parasite counts , 2004, Nature Medicine.

[17]  Jonathan E. Allen,et al.  Genome sequence of the human malaria parasite Plasmodium falciparum , 2002, Nature.

[18]  E. Bischoff,et al.  Three multigene families in Plasmodium parasites: facts and questions. , 2002, International journal for parasitology.

[19]  D. Roberts,et al.  Detection of Plasmodium falciparum DNA in Plasma , 2001, Annals of the New York Academy of Sciences.

[20]  N. White,et al.  A controlled trial of artemether or quinine in Vietnamese adults with severe falciparum malaria. , 1996, The New England journal of medicine.

[21]  M. Mannik,et al.  Blood clearance kinetics and liver uptake of mononucleosomes in mice. , 1996, Journal of immunology.

[22]  Y. Lo,et al.  Rapid clearance of fetal DNA from maternal plasma. , 1999, American journal of human genetics.