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Diagnosing severe falciparum malaria in parasitaemic African children: a prospective evaluation of plasma PfHRP2 measurement

Hendriksen, Ilse C. E., Mwanga-Amumpaire, Juliet, von Seidlein, Lorenz, Mtove, George, White, Lisa J., Olaosebikan, Rasaq, Lee, Sue J., Tshefu, Antoinette K., Woodrow, Charles, Amos, Ben, Karema, Corine, Saiwaew, Somporn, Maitland, Kathryn, Gomes, Ermelinda, Pan-Ngum, Wirichada, Gesase, Samwel, Silamut, Kamolrat, Reyburn, Hugh, Joseph, Sarah, Chotivanich, Kesinee, Fanello, Caterina, Day, Nicholas P. J., White, Nicholas J. and Dondorp, Arjen M. (2012). Diagnosing severe falciparum malaria in parasitaemic African children: a prospective evaluation of plasma PfHRP2 measurement. PLoS Medicine,9(8 - Article No. e1001297).

Document type: Journal Article
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IRMA ID bsmithxPUB91
Title Diagnosing severe falciparum malaria in parasitaemic African children: a prospective evaluation of plasma PfHRP2 measurement
Author Hendriksen, Ilse C. E.
Mwanga-Amumpaire, Juliet
von Seidlein, Lorenz
Mtove, George
White, Lisa J.
Olaosebikan, Rasaq
Lee, Sue J.
Tshefu, Antoinette K.
Woodrow, Charles
Amos, Ben
Karema, Corine
Saiwaew, Somporn
Maitland, Kathryn
Gomes, Ermelinda
Pan-Ngum, Wirichada
Gesase, Samwel
Silamut, Kamolrat
Reyburn, Hugh
Joseph, Sarah
Chotivanich, Kesinee
Fanello, Caterina
Day, Nicholas P. J.
White, Nicholas J.
Dondorp, Arjen M.
Journal Name PLoS Medicine
Publication Date 2012
Volume Number 9
Issue Number 8 - Article No. e1001297
ISSN 1549-1676   (check CDU catalogue  open catalogue search in new window)
Scopus ID 2-s2.0-84865535789
Total Pages 10
Place of Publication United States
Publisher Public Library of Science
HERDC Category C1 - Journal Article (DIISR)
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 log10 plasma PfHRP2 and risk of death. Mortality increased 20% per log10 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 malaria-attributable disease as opposed to other severe illnesses in parasitaemic African children.

Keywords Plasma PfHRP2
falciparum malaria
parasitaemic Afican children
Plasmodium falciparum
DOI http://dx.doi.org/10.1371/journal.pmed.1001297   (check subscription with CDU E-Gateway service for CDU Staff and Students  check subscription with CDU E-Gateway in new window)
Additional Notes This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. http://creativecommons.org/licenses/by/3.0/


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