Publication:
Diagnosing Severe Falciparum Malaria in Parasitaemic African Children: A Prospective Evaluation of Plasma PfHRP2 Measurement

Issued Date

2012-08-01

Resource Type

Article

ISSN

15491676
15491277

DOI

10.1371/journal.pmed.1001297

Other identifier(s)

2-s2.0-84865535789

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

PLoS Medicine. Vol.9, No.8 (2012)

Suggested Citation

Ilse C.E. Hendriksen, Juliet Mwanga-Amumpaire, Lorenz von Seidlein, George Mtove, Lisa J. White, Rasaq Olaosebikan, Sue J. Lee, Antoinette K. Tshefu, Charles Woodrow, Ben Amos, Corine Karema, Somporn Saiwaew, Kathryn Maitland, Ermelinda Gomes, Wirichada Pan-Ngum, Samwel Gesase, Kamolrat Silamut, Hugh Reyburn, Sarah Joseph, Kesinee Chotivanich, Caterina I. Fanello, Nicholas P.J. Day, Nicholas J. White, Arjen M. Dondorp Diagnosing Severe Falciparum Malaria in Parasitaemic African Children: A Prospective Evaluation of Plasma PfHRP2 Measurement. PLoS Medicine. Vol.9, No.8 (2012). doi:10.1371/journal.pmed.1001297 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/14722

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Title

Diagnosing Severe Falciparum Malaria in Parasitaemic African Children: A Prospective Evaluation of Plasma PfHRP2 Measurement

Author(s)

Ilse C.E. Hendriksen
 Juliet Mwanga-Amumpaire
 Lorenz von Seidlein
 George Mtove
 Lisa J. White
 Rasaq Olaosebikan
 Sue J. Lee
 Antoinette K. Tshefu
 Charles Woodrow
 Ben Amos
 Corine Karema
 Somporn Saiwaew
 Kathryn Maitland
 Ermelinda Gomes
 Wirichada Pan-Ngum
 Samwel Gesase
 Kamolrat Silamut
 Hugh Reyburn
 Sarah Joseph
 Kesinee Chotivanich
 Caterina I. Fanello
 Nicholas P.J. Day
 Nicholas J. White
 Arjen M. Dondorp

Other Contributor(s)

Mahidol University
 University of Oxford
 Mbarara University of Science and Technology
 Menzies School of Health Research
 National Institute for Medical Research Tanga
 Medical Research Council Laboratories Gambia
 Kingasani Research Centre
 Teule Hospital
 Ministry of Health
 Kenya Medical Research Institute
 Hospital Central da Beira
 London School of Hygiene & Tropical Medicine
 Medical Research Council

Abstract

Background: In African children, distinguishing severe falciparum malaria from other severe febrile illnesses with coincidental Plasmodium falciparum parasitaemia is a major challenge. P. falciparum histidine-rich protein 2 (PfHRP2) is released by mature sequestered parasites and can be used to estimate the total parasite burden. We investigated the prognostic significance of plasma PfHRP2 and used it to estimate the malaria-attributable fraction in African children diagnosed with severe malaria. Methods and Findings: Admission plasma PfHRP2 was measured prospectively in African children (from Mozambique, The Gambia, Kenya, Tanzania, Uganda, Rwanda, and the Democratic Republic of the Congo) aged 1 month to 15 years with severe febrile illness and a positive P. falciparum lactate dehydrogenase (pLDH)-based rapid test in a clinical trial comparing parenteral artesunate versus quinine (the AQUAMAT trial, ISRCTN 50258054). In 3,826 severely ill children, Plasmadium falciparum PfHRP2 was higher in patients with coma (p = 0.0209), acidosis (p < 0.0001), and severe anaemia (p < 0.0001). Admission geometric mean (95%CI) plasma PfHRP2 was 1,611 (1,350-1,922) ng/mL in fatal cases (n = 381) versus 1,046 (991-1,104) ng/mL in survivors (n = 3,445, p < 0.0001), without differences in parasitaemia as assessed by microscopy. There was a U-shaped association between log 10 plasma PfHRP2 and risk of death. Mortality increased 20% per log 10 increase in PfHRP2 above 174 ng/mL (adjusted odds ratio [AOR] 1.21, 95%CI 1.05-1.39, p = 0.009). A mechanistic model assuming a PfHRP2-independent risk of death in non-malaria illness closely fitted the observed data and showed malaria-attributable mortality less than 50% with plasma PfHRP2≤174 ng/mL. The odds ratio (OR) for death in artesunate versus quinine-treated patients was 0.61 (95%CI 0.44-0.83, p = 0.0018) in the highest PfHRP2 tertile, whereas there was no difference in the lowest tertile (OR 1.05; 95%CI 0.69-1.61; p = 0.82). A limitation of the study is that some conclusions are drawn from a mechanistic model, which is inherently dependent on certain assumptions. However, a sensitivity analysis of the model indicated that the results were robust to a plausible range of parameter estimates. Further studies are needed to validate our findings. Conclusions: Plasma PfHRP2 has prognostic significance in African children with severe falciparum malaria and provides a tool to stratify the risk of "true" severe malar ia-attributable disease as opposed to other severe illnesses in parasitaemic African children. Please see later in the article for the Editors' Summary. © 2012 Hendriksen et al.

Keyword(s)

Medicine

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https://repository.li.mahidol.ac.th/handle/20.500.14594/14722

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