Skip to main content
Top
Published in: Malaria Journal 1/2013

Open Access 01-12-2013 | Research

Clinical relevance of different biomarkers in imported plasmodium falciparum malaria in adults: a case control study

Authors: Sabine Stauga, Andreas Hahn, Norbert W Brattig, Johanna Fischer-Herr, Stephan Baldus, Gerd D Burchard, Jakob P Cramer

Published in: Malaria Journal | Issue 1/2013

Login to get access

Abstract

Background

For rapid initiation of anti-malarial treatment and prevention of complications, early diagnosis and risk stratification is important in patients with Plasmodium falciparum malaria. Routine laboratory values do not correlate well with disease severity. The aim of this study was to determine the diagnostic and prognostic value of several biomarkers related to inflammation; endothelial and cardiac dysfunction; coagulation, and haemolysis in imported P. falciparum malaria.

Methods

In a prospective case-control study, 79 adult travellers with both uncomplicated and complicated P. falciparum malaria were included between 2007 and 2011. Forty-one healthy subjects were included as controls. Blood samples were obtained within 24 hours after first consultation to assess routine laboratory values as well as markers related to inflammation (PAPP-A, copeptin, CRP), endothelial activation (MPO, elastase-2, endothelin-1, sICAM-1, sVCAM-1), cardiac function (NT-proBNP, MR-proANP), coagulation (fibrinogen, D-dimers, platelet count), and haemolysis (LDH). Prognostic performance was assessed using the receiver operating characteristic curve (area under the curve = AUROC).

Results

Twelve (15.2%) patients had severe P. falciparum malaria. In the patient group, significant thrombocytopaenia was found, all other markers but PAPP-A were significantly elevated. Diagnostic performance was best for CRP with an AUROC of 1.00, followed by MPO (0.99), D-dimers (0.98), elastase-2 (0.98), and sICAM-1 (0.98). Biomarker levels did not correlate well with disease severity.

Conclusion

The combination of travel history, fever prior to blood sampling, and CRP serum levels above or below 10.8 mg/l upon hospital admission, best discriminated between malaria patients and control persons. None of the biomarkers studied predicted the presence or the development of malaria complications, neither at the time of admission, nor during hospitalization.
Appendix
Available only for authorised users
Literature
1.
go back to reference Murray CJ, Rosenfeld LC, Lim SS, Andrews KG, Foreman KJ, Haring D, Fullman N, Naghavi M, Lozano R, Lopez AD: Global malaria mortality between 1980 and 2010: a systematic analysis. Lancet. 2012, 379: 413-431. 10.1016/S0140-6736(12)60034-8.CrossRefPubMed Murray CJ, Rosenfeld LC, Lim SS, Andrews KG, Foreman KJ, Haring D, Fullman N, Naghavi M, Lozano R, Lopez AD: Global malaria mortality between 1980 and 2010: a systematic analysis. Lancet. 2012, 379: 413-431. 10.1016/S0140-6736(12)60034-8.CrossRefPubMed
2.
go back to reference WHO: World Malaria Report. 2011, Geneva, Switzerland: World Health Organization, 2011- WHO: World Malaria Report. 2011, Geneva, Switzerland: World Health Organization, 2011-
3.
go back to reference WHO: Malaria. WHO International Travel and Health 2011. 2011, Geneva, Switzerland: World Health Organization, 144-167. WHO: Malaria. WHO International Travel and Health 2011. 2011, Geneva, Switzerland: World Health Organization, 144-167.
4.
go back to reference Askling HH, Bruneel F, Burchard G, Castelli F, Chiodini PL, Grobusch MP, Lopez-Velez R, Paul M, Petersen E, Popescu , Ramharter M, Schlagenhauf P: Management of imported malaria in Europe. Malar J. 2012, 11: 328-10.1186/1475-2875-11-328.PubMedCentralCrossRefPubMed Askling HH, Bruneel F, Burchard G, Castelli F, Chiodini PL, Grobusch MP, Lopez-Velez R, Paul M, Petersen E, Popescu , Ramharter M, Schlagenhauf P: Management of imported malaria in Europe. Malar J. 2012, 11: 328-10.1186/1475-2875-11-328.PubMedCentralCrossRefPubMed
5.
go back to reference Olliaro P: Editorial commentary: mortality associated with severe Plasmodium falciparum malaria increases with age. Clin Infect Dis. 2008, 47: 158-160. 10.1086/589288.CrossRefPubMed Olliaro P: Editorial commentary: mortality associated with severe Plasmodium falciparum malaria increases with age. Clin Infect Dis. 2008, 47: 158-160. 10.1086/589288.CrossRefPubMed
6.
go back to reference von Seidlein L, Olaosebikan R, Hendriksen IC, Lee SJ, Adedoyin OT, Agbenyega T, Nguah SB, Bojang K, Deen JL, Evans J, Fanello CI, Gomes E, Pedro AJ, Kahabuka C, Karema C, Kivaya E, Maitland K, Mokuolu OA, Mtove G, Mwanga-Amumpaire J, Nadjm B, Nansumba M, Ngum WP, Onyamboko MA, Reyburn H, Sakulthaew T, Silamut K, Tshefu AK, Umulisa N, Gesase S, Day NP, White NJ, Dondorp AM: Predicting the clinical outcome of severe falciparum malaria in african children: findings from a large randomized trial. Clin Infect Dis. 2012, 54: 1080-1090. 10.1093/cid/cis034.PubMedCentralCrossRefPubMed von Seidlein L, Olaosebikan R, Hendriksen IC, Lee SJ, Adedoyin OT, Agbenyega T, Nguah SB, Bojang K, Deen JL, Evans J, Fanello CI, Gomes E, Pedro AJ, Kahabuka C, Karema C, Kivaya E, Maitland K, Mokuolu OA, Mtove G, Mwanga-Amumpaire J, Nadjm B, Nansumba M, Ngum WP, Onyamboko MA, Reyburn H, Sakulthaew T, Silamut K, Tshefu AK, Umulisa N, Gesase S, Day NP, White NJ, Dondorp AM: Predicting the clinical outcome of severe falciparum malaria in african children: findings from a large randomized trial. Clin Infect Dis. 2012, 54: 1080-1090. 10.1093/cid/cis034.PubMedCentralCrossRefPubMed
7.
go back to reference Bruneel F, Tubach F, Corne P, Megarbane B, Mira JP, Peytel E, Camus C, Schortgen F, Azoulay E, Cohen Y, Georges H, Meybeck A, Hyvernat H, Trouillet JL, Fenroy E, Nicolet L, Roy C, Durand R, Le Bras J, Wolff M: Severe imported falciparum malaria: a cohort study in 400 critically ill adults. PLoS One. 2010, 5: e13236-10.1371/journal.pone.0013236.PubMedCentralCrossRefPubMed Bruneel F, Tubach F, Corne P, Megarbane B, Mira JP, Peytel E, Camus C, Schortgen F, Azoulay E, Cohen Y, Georges H, Meybeck A, Hyvernat H, Trouillet JL, Fenroy E, Nicolet L, Roy C, Durand R, Le Bras J, Wolff M: Severe imported falciparum malaria: a cohort study in 400 critically ill adults. PLoS One. 2010, 5: e13236-10.1371/journal.pone.0013236.PubMedCentralCrossRefPubMed
9.
go back to reference WHO: Severe falciparum malaria. Trans R Soc Trop Med Hyg. 2000, 94: 1-18. WHO: Severe falciparum malaria. Trans R Soc Trop Med Hyg. 2000, 94: 1-18.
10.
go back to reference McShane LM, Altman DG, Sauerbrei W, Taube SE, Gion M, Clark GM: Reporting recommendations for tumor marker prognostic studies (REMARK). J Natl Cancer Inst. 2005, 97: 1180-1184. 10.1093/jnci/dji237.CrossRefPubMed McShane LM, Altman DG, Sauerbrei W, Taube SE, Gion M, Clark GM: Reporting recommendations for tumor marker prognostic studies (REMARK). J Natl Cancer Inst. 2005, 97: 1180-1184. 10.1093/jnci/dji237.CrossRefPubMed
11.
go back to reference Casals-Pascual C, Kai O, Cheung JO, Williams S, Lowe B, Nyanoti M, Williams TN, Maitland K, Molyneux M, Newton CR, Peshu N, Watt SM, Roberts DJ: Suppression of erythropoiesis in malarial anemia is associated with hemozoin in vitro and in vivo. Blood. 2006, 108: 2569-2577. 10.1182/blood-2006-05-018697.CrossRefPubMed Casals-Pascual C, Kai O, Cheung JO, Williams S, Lowe B, Nyanoti M, Williams TN, Maitland K, Molyneux M, Newton CR, Peshu N, Watt SM, Roberts DJ: Suppression of erythropoiesis in malarial anemia is associated with hemozoin in vitro and in vivo. Blood. 2006, 108: 2569-2577. 10.1182/blood-2006-05-018697.CrossRefPubMed
12.
go back to reference Tonstad S, Cowan JL: C-reactive protein as a predictor of disease in smokers and former smokers: a review. Int J Clin Pract. 2009, 63: 1634-1641. 10.1111/j.1742-1241.2009.02179.x.PubMedCentralCrossRefPubMed Tonstad S, Cowan JL: C-reactive protein as a predictor of disease in smokers and former smokers: a review. Int J Clin Pract. 2009, 63: 1634-1641. 10.1111/j.1742-1241.2009.02179.x.PubMedCentralCrossRefPubMed
13.
go back to reference Castelli GP, Pognani C, Meisner M, Stuani A, Bellomi D, Sgarbi L: Procalcitonin and C-reactive protein during systemic inflammatory response syndrome, sepsis and organ dysfunction. Crit Care. 2004, 8: R234-242. 10.1186/cc2877.PubMedCentralCrossRefPubMed Castelli GP, Pognani C, Meisner M, Stuani A, Bellomi D, Sgarbi L: Procalcitonin and C-reactive protein during systemic inflammatory response syndrome, sepsis and organ dysfunction. Crit Care. 2004, 8: R234-242. 10.1186/cc2877.PubMedCentralCrossRefPubMed
14.
go back to reference Uusitalo-Seppala R, Koskinen P, Leino A, Peuravuori H, Vahlberg T, Rintala EM: Early detection of severe sepsis in the emergency room: diagnostic value of plasma C-reactive protein, procalcitonin, and interleukin-6. Scand J Infect Dis. 2011, 43: 883-890. 10.3109/00365548.2011.600325.CrossRefPubMed Uusitalo-Seppala R, Koskinen P, Leino A, Peuravuori H, Vahlberg T, Rintala EM: Early detection of severe sepsis in the emergency room: diagnostic value of plasma C-reactive protein, procalcitonin, and interleukin-6. Scand J Infect Dis. 2011, 43: 883-890. 10.3109/00365548.2011.600325.CrossRefPubMed
15.
go back to reference Struck J, Morgenthaler NG, Bergmann A: Copeptin, a stable peptide derived from the vasopressin precursor, is elevated in serum of sepsis patients. Peptides. 2005, 26: 2500-2504. 10.1016/j.peptides.2005.04.019.CrossRefPubMed Struck J, Morgenthaler NG, Bergmann A: Copeptin, a stable peptide derived from the vasopressin precursor, is elevated in serum of sepsis patients. Peptides. 2005, 26: 2500-2504. 10.1016/j.peptides.2005.04.019.CrossRefPubMed
16.
go back to reference Nickel CH, Bingisser R, Morgenthaler NG: The role of copeptin as a diagnostic and prognostic biomarker for risk stratification in the emergency department. BMC Med. 2012, 10: 7-10.1186/1741-7015-10-7.PubMedCentralCrossRefPubMed Nickel CH, Bingisser R, Morgenthaler NG: The role of copeptin as a diagnostic and prognostic biomarker for risk stratification in the emergency department. BMC Med. 2012, 10: 7-10.1186/1741-7015-10-7.PubMedCentralCrossRefPubMed
17.
go back to reference von Haehling S, Papassotiriou J, Morgenthaler NG, Hartmann O, Doehner W, Stellos K, Wurster T, Schuster A, Nagel E, Gawaz M, Bigalke B: Copeptin as a prognostic factor for major adverse cardiovascular events in patients with coronary artery disease. Int J Cardiol. 2012, 162: 27-32. 10.1016/j.ijcard.2011.12.105.CrossRefPubMed von Haehling S, Papassotiriou J, Morgenthaler NG, Hartmann O, Doehner W, Stellos K, Wurster T, Schuster A, Nagel E, Gawaz M, Bigalke B: Copeptin as a prognostic factor for major adverse cardiovascular events in patients with coronary artery disease. Int J Cardiol. 2012, 162: 27-32. 10.1016/j.ijcard.2011.12.105.CrossRefPubMed
18.
go back to reference van Wolfswinkel ME, Hesselink DA, Hoorn EJ, de Rijke YB, Koelewijn R, van Hellemond JJ, van Genderen PJ: Copeptin does not accurately predict disease severity in imported malaria. Malar J. 2012, 11: 6-10.1186/1475-2875-11-6.PubMedCentralCrossRefPubMed van Wolfswinkel ME, Hesselink DA, Hoorn EJ, de Rijke YB, Koelewijn R, van Hellemond JJ, van Genderen PJ: Copeptin does not accurately predict disease severity in imported malaria. Malar J. 2012, 11: 6-10.1186/1475-2875-11-6.PubMedCentralCrossRefPubMed
19.
go back to reference Shikani HJ, Freeman BD, Lisanti MP, Weiss LM, Tanowitz HB, Desruisseaux MS: Cerebral malaria: we have come a long way. Am J Pathol. 2012, 181: 1484-1492. 10.1016/j.ajpath.2012.08.010.PubMedCentralCrossRefPubMed Shikani HJ, Freeman BD, Lisanti MP, Weiss LM, Tanowitz HB, Desruisseaux MS: Cerebral malaria: we have come a long way. Am J Pathol. 2012, 181: 1484-1492. 10.1016/j.ajpath.2012.08.010.PubMedCentralCrossRefPubMed
20.
go back to reference Boehme MW, Werle E, Kommerell B, Raeth U: Serum levels of adhesion molecules and thrombomodulin as indicators of vascular injury in severe Plasmodium falciparum malaria. Clin Investig. 1994, 72: 598-603.CrossRefPubMed Boehme MW, Werle E, Kommerell B, Raeth U: Serum levels of adhesion molecules and thrombomodulin as indicators of vascular injury in severe Plasmodium falciparum malaria. Clin Investig. 1994, 72: 598-603.CrossRefPubMed
21.
go back to reference Ho M, White NJ: Molecular mechanisms of cytoadherence in malaria. Am J Physiol. 1999, 276 (6 Pt 1): C1231-1242.PubMed Ho M, White NJ: Molecular mechanisms of cytoadherence in malaria. Am J Physiol. 1999, 276 (6 Pt 1): C1231-1242.PubMed
22.
go back to reference Stankovic S, Asanin M, Majkic-Singh N, Ignjatovic S, Mihailovic M, Nikolajevic I, Mrdovic I, Matic D, Savic L, Marinkovic J, Ostojic M, Vasiljevic Z: The usefulness of myeloperoxidase in prediction of in-hospital mortality in patients with ST-segment elevation myocardial infarction treated by primary percutaneous coronary intervention. Clin Lab. 2012, 58: 125-131.PubMed Stankovic S, Asanin M, Majkic-Singh N, Ignjatovic S, Mihailovic M, Nikolajevic I, Mrdovic I, Matic D, Savic L, Marinkovic J, Ostojic M, Vasiljevic Z: The usefulness of myeloperoxidase in prediction of in-hospital mortality in patients with ST-segment elevation myocardial infarction treated by primary percutaneous coronary intervention. Clin Lab. 2012, 58: 125-131.PubMed
23.
go back to reference Maruyama Y, Lindholm B, Stenvinkel P: Inflammation and oxidative stress in ESRD–the role of myeloperoxidase. J Nephrol. 2004, 17 (Suppl 8): S72-76.PubMed Maruyama Y, Lindholm B, Stenvinkel P: Inflammation and oxidative stress in ESRD–the role of myeloperoxidase. J Nephrol. 2004, 17 (Suppl 8): S72-76.PubMed
24.
go back to reference Kothari N, Keshari RS, Bogra J, Kohli M, Abbas H, Malik A, Dikshit M, Barthwal MK: Increased myeloperoxidase enzyme activity in plasma is an indicator of inflammation and onset of sepsis. J Crit Care. 2011, 26 (435): e431-437. Kothari N, Keshari RS, Bogra J, Kohli M, Abbas H, Malik A, Dikshit M, Barthwal MK: Increased myeloperoxidase enzyme activity in plasma is an indicator of inflammation and onset of sepsis. J Crit Care. 2011, 26 (435): e431-437.
25.
go back to reference Karahocagil MK, Aslan M, Ceylan MR, Cikman A, Sunnetcioglu M, Kucukoglu ME, Taskin A: Serum myeloperoxidase activity and oxidative stress in patients with acute brucellosis. Clin Biochem. 2012, 45: 733-736. 10.1016/j.clinbiochem.2012.03.017.CrossRefPubMed Karahocagil MK, Aslan M, Ceylan MR, Cikman A, Sunnetcioglu M, Kucukoglu ME, Taskin A: Serum myeloperoxidase activity and oxidative stress in patients with acute brucellosis. Clin Biochem. 2012, 45: 733-736. 10.1016/j.clinbiochem.2012.03.017.CrossRefPubMed
26.
go back to reference Borato DC, Parabocz GC, Ribas SR, Kalva-Filho CA, Borba LM, Ito CA, Bail L, dos Santos FA, Vellosa JC: Changes of metabolic and inflammatory markers in HIV infection: glucose, lipids, serum Hs-CRP and myeloperoxidase. Metabolism. 2012, 61: 1353-1360. 10.1016/j.metabol.2012.03.003.CrossRefPubMed Borato DC, Parabocz GC, Ribas SR, Kalva-Filho CA, Borba LM, Ito CA, Bail L, dos Santos FA, Vellosa JC: Changes of metabolic and inflammatory markers in HIV infection: glucose, lipids, serum Hs-CRP and myeloperoxidase. Metabolism. 2012, 61: 1353-1360. 10.1016/j.metabol.2012.03.003.CrossRefPubMed
27.
go back to reference Dollery CM, Owen CA, Sukhova GK, Krettek A, Shapiro SD, Libby P: Neutrophil elastase in human atherosclerotic plaques: production by macrophages. Circulation. 2003, 107: 2829-2836. 10.1161/01.CIR.0000072792.65250.4A.CrossRefPubMed Dollery CM, Owen CA, Sukhova GK, Krettek A, Shapiro SD, Libby P: Neutrophil elastase in human atherosclerotic plaques: production by macrophages. Circulation. 2003, 107: 2829-2836. 10.1161/01.CIR.0000072792.65250.4A.CrossRefPubMed
28.
go back to reference Gando S, Hayakawa M, Sawamura A, Hoshino H, Oshiro A, Kubota N, Jesmin S: The activation of neutrophil elastase-mediated fibrinolysis is not sufficient to overcome the fibrinolytic shutdown of disseminated intravascular coagulation associated with systemic inflammation. Thromb Res. 2007, 121: 67-73. 10.1016/j.thromres.2007.02.010.CrossRefPubMed Gando S, Hayakawa M, Sawamura A, Hoshino H, Oshiro A, Kubota N, Jesmin S: The activation of neutrophil elastase-mediated fibrinolysis is not sufficient to overcome the fibrinolytic shutdown of disseminated intravascular coagulation associated with systemic inflammation. Thromb Res. 2007, 121: 67-73. 10.1016/j.thromres.2007.02.010.CrossRefPubMed
29.
go back to reference Dietmann A, Lackner P, Helbok R, Spora K, Issifou S, Lell B, Reindl M, Kremsner PG, Schmutzhard E: Opposed circulating plasma levels of endothelin-1 and C-type natriuretic peptide in children with Plasmodium falciparum malaria. Malar J. 2008, 7: 253-10.1186/1475-2875-7-253.PubMedCentralCrossRefPubMed Dietmann A, Lackner P, Helbok R, Spora K, Issifou S, Lell B, Reindl M, Kremsner PG, Schmutzhard E: Opposed circulating plasma levels of endothelin-1 and C-type natriuretic peptide in children with Plasmodium falciparum malaria. Malar J. 2008, 7: 253-10.1186/1475-2875-7-253.PubMedCentralCrossRefPubMed
30.
go back to reference Wenisch C, Wenisch H, Wilairatana P, Looareesuwan S, Vannaphan S, Wagner O, Graninger W, Schonthal E, Rumpold H: Big endothelin in patients with complicated Plasmodium falciparum malaria. J Infect Dis. 1996, 173: 1281-1284. 10.1093/infdis/173.5.1281.CrossRefPubMed Wenisch C, Wenisch H, Wilairatana P, Looareesuwan S, Vannaphan S, Wagner O, Graninger W, Schonthal E, Rumpold H: Big endothelin in patients with complicated Plasmodium falciparum malaria. J Infect Dis. 1996, 173: 1281-1284. 10.1093/infdis/173.5.1281.CrossRefPubMed
31.
go back to reference Ehrhardt S, Wichmann D, Hemmer CJ, Burchard GD, Brattig NW: Circulating concentrations of cardiac proteins in complicated and uncomplicated Plasmodium falciparum malaria. Trop Med Int Health. 2004, 9: 1099-1103. 10.1111/j.1365-3156.2004.01303.x.CrossRefPubMed Ehrhardt S, Wichmann D, Hemmer CJ, Burchard GD, Brattig NW: Circulating concentrations of cardiac proteins in complicated and uncomplicated Plasmodium falciparum malaria. Trop Med Int Health. 2004, 9: 1099-1103. 10.1111/j.1365-3156.2004.01303.x.CrossRefPubMed
32.
go back to reference Herr J, Mehrfar P, Schmiedel S, Wichmann D, Brattig NW, Burchard GD, Cramer JP: Reduced cardiac output in imported Plasmodium falciparum malaria. Malar J. 2011, 10: 160-10.1186/1475-2875-10-160.PubMedCentralCrossRefPubMed Herr J, Mehrfar P, Schmiedel S, Wichmann D, Brattig NW, Burchard GD, Cramer JP: Reduced cardiac output in imported Plasmodium falciparum malaria. Malar J. 2011, 10: 160-10.1186/1475-2875-10-160.PubMedCentralCrossRefPubMed
Metadata
Title
Clinical relevance of different biomarkers in imported plasmodium falciparum malaria in adults: a case control study
Authors
Sabine Stauga
Andreas Hahn
Norbert W Brattig
Johanna Fischer-Herr
Stephan Baldus
Gerd D Burchard
Jakob P Cramer
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2013
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/1475-2875-12-246

Other articles of this Issue 1/2013

Malaria Journal 1/2013 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.