Abstract
Procalcitonin (PCT) and C-reactive protein (CRP) may be useful to predict complicated forms of malaria. A total of 30 consecutive travelers diagnosed with Plasmodium falciparum malaria over a two-year period were included in the study. Patients with complicated Plasmodium falciparum malaria showed higher levels of parasitemia (P = 0.0001), PCT (P = 0.0018), CRP (P = 0.0005), bilirubinemia (P = 0.004), and a lower platelet count (P<0.0001) compared with patients with uncomplicated forms. PCT levels above 5 ng/mL showed the highest value of specificity (0.86) and positive predictive factor (0.67) among other parameters, and equal sensitivity (0.67) was displayed by CRP levels above 150 mg/dl. None of the patients with complicated malaria showed PCT levels within normal limits (<0.5 ng/ml). Both PCT and CRP correlated with parasitemia (P<0.001) and showed areas under ROC curve of 0.83. At multivariate analysis, only PCT was associated with an increased risk of complicated malaria (OR 8.2, IC 95% 1.2–57.2, P = 0.03). The determination of PCT on admission showed better results compared to CRP, platelet count, and bilirubinemia and can be useful in non-endemic areas for the initial clinical assessment of disease severity in travelers with Plasmodium falciparum malaria.
References
Ansar W., Habib S.K., Roy S., Mandal C., Mandal C. 2009. Unraveling the C-reactive protein complement-cascade in destruction of red blood cells: potential pathological implications in Plasmodium falciparum malaria. Celluar Physiology and Biochemistry, 23, 175–190. DOI: 10.1159/00020410610.1159/000204106Search in Google Scholar PubMed
Anstey N.M., Price R.N. 2007. Improving case definitions for severe malaria. PLoS Medicine, 4:e267 DOI: 10.1371/journal.pmed. 004026710.1371/journal.pmed.0040267Search in Google Scholar PubMed PubMed Central
Bailey J.W., Williams J., Bain B.J., Parker-Williams J., Chiodini P.L. 2013. General Haematology Task Force of the British Committee for Standards in H. Guideline: the laboratory diagnosis of malaria. General Haematology Task Force of the British Committee for Standards in Haematology. Brish Journal of Haematology, 163, 573–580. DOI:10.1111/bjh.1257210.1111/bjh.12572Search in Google Scholar PubMed
Black S., Kushner I., Samols D. 2004 C-reactive Protein. The Journal of Biological Chemistry, 279, 48487–48490. DOI: 10.1074/jbc.r40002520010.1074/jbc.R400025200Search in Google Scholar PubMed
Braun N., Marfo Y., Von Gartner C., Burchard G.D., Zipfel P.F., Browne N.E.N., Fleischer B., Broker B. 2003. CTLA-4 positive T cells in contrast to procalcitonin plasma levels discriminate between severe and uncomplicated Plasmodium falciparum malaria in Ghanaian children. Tropical Medicine and International Health, 8, 1018–1024. DOI: 10.1046/ j.1360-2276.2003.01128.x10.1046/j.1360-2276.2003.01128.xSearch in Google Scholar PubMed
Center for Disease Control and Prevention (CDC). 2015. Malaria – Diagnosis and Tratment in the US. Rapid diagnostic tests, http://www.cdc.gov/malaria/diagnosis_treatment/rdt.html. Accessed 18 November 2015Search in Google Scholar
Chiwakata C.B., Manegold C., Bonicke L., Waase I., Julch C., Diet-rich M. 2001. Procalcitonin as a parameter of disease severity and risk of mortality in patients with Plasmodium falciparum malaria. Journal of Infectious Diseases,183, 1161– 1164. DOI:10.1086/31928310.1086/319283Search in Google Scholar PubMed
Erdman L.K., Dhabangi A., Musoke C., Conroy A.L., Hawkes M., Higgins S., Rajwans N., Wolofsky K.T., Streiner D.L., Liles W.C., Cserti-Gazdewich C.M., Kain K.C. 2011. Combinations of host biomarkers predict mortality among Ugandan children with severe malaria: a retrospective case-control study. PLoS One, 6, e17440. DOI: 10.1371/journal.pone.001744010.1371/journal.pone.0017440Search in Google Scholar PubMed PubMed Central
Guide for the use of procalcitonin (PCT) in diagnosis and monitoring of sepsis. http://www.procalcitonin.com/pct-guide/pdf/200809/PCT_Guide_EN.pdf. April 2008Search in Google Scholar
Hesselink D.A., Burgerhart J.S., Bosmans-Timmerarends H., Petit P., van Genderen P.J. 2009. Procalcitonin as a biomarker for severe Plasmodium falciparum disease: a critical appraisal of a semi-quantitative point-of-care test in a cohort of travellers with imported malaria. Malaria Journal, 8, 206. DOI: 10.1186/1475-2875-8-20610.1186/1475-2875-8-206Search in Google Scholar PubMed PubMed Central
Hurt N., Smith T., Teuscher T., Tanner M. 1994. Do high levels of C-reactive protein in Tanzanian children indicate malaria morbidity. Clinical and Diagnostic Laboratory Immunology, 1, 437–444. DOI: 10.1016/0035-9203(94)90287-910.1128/cdli.1.4.437-444.1994Search in Google Scholar PubMed PubMed Central
Marnell L., Mold C., Du Clos T.W. 2005. C-reactive protein: ligands, receptors and role in inflammation. Clinical Immunology, 117, 104–111 DOI: 10.1016/j.clim.2005.08.00410.1016/j.clim.2005.08.004Search in Google Scholar PubMed
Marsh K., Forster D., Waruiru C., Mwangi I., Winstanley M., Marsh V., Newton C., Winstanley P., Warn P., Peshu N. 1995. Indicators of life-threatening malaria in African children. New England Journal of Medicine, 332,1399–1404 DOI: 10.1056/ nejm19950525332210210.1056/NEJM199505253322102Search in Google Scholar
McGuire W., D’Alessandro U., Olaleye B.O., Thomson M.C., Lange-rock P., Greenwood B.M., Kwiatkowski D. 1996. C-reactive protein and haptoglobin in the evaluation of a community-based malaria control programme. Transactions of the Royal Society of Tropical Medicine and Hygiene, 90, 10–14. DOI: 10.1016/s0035-9203(96)90461-710.1016/S0035-9203(96)90461-7Search in Google Scholar
Simon L., Gauvin F., Amre D.K., Saint-Louis P., Lacroix J. 2004. Serum procalcitonin and C-reactive protein levels as markers of bacterial infection: a systematic review and meta-analysis. Clinical Infectious Diseases, 39, 206–217 DOI: 10.1086/ 42199710.1086/421997Search in Google Scholar
Tangpukdee N., Krudsood S., Kano S., Wilairatana P. 2012. Falciparum malaria parasitemia index for predicting severe malaria. International Journal of Laboratory Hematology, 34, 320–327. DOI: 10.1111/j.1751-553X.2011.0139810.1111/j.1751-553X.2011.01398.xSearch in Google Scholar
te Witt R., van Wolfswinkel M.E., Petit P.L., van Hellemond J.J., Koelewijn R., van Belkum A., van Genderen P.J. 2010. Neopterin and procalcitonin are suitable biomarkers for exclusion of severe Plasmodium falciparum disease at the initial clinical assessment of travellers with imported malaria. Malaria Journal, 9, 255. DOI:10.1186/14752875-9-25510.1186/1475-2875-9-255Search in Google Scholar
van Genderen P.J., van der Meer I.M., Consten J., Petit P.L., van Gool T., Overbosch D. 2005. Evaluation of plasma lactate as a parameter for disease severity on admission in travelers with Plasmodium falciparum malaria. Journal of Travel Medicine, 12, 261–264. DOI: 10.2310/7060.2005.1250410.2310/7060.2005.12504Search in Google Scholar
Wacker C., Prkno A., Brunkhorst F.M., Schlattmann P. 2013. Pro-calcitonin as a diagnostic marker for sepsis: a systematic review and meta-analysis. Lancet Infectious Diseases, 13, 426–435 DOI :10.1016/s1473-3099(12)70323-710.1016/S1473-3099(12)70323-7Search in Google Scholar
Walther M., Tongren J.E., Andrews L., et al. 2005. Upregulation of TGF-beta, FOXP3, and CD4+CD25+ regulatory T cells correlates with more rapid parasite growth in human malaria infection. Immunity, 23, 287–296. DOI: 10.1016/j.immuni. 2005.08.00610.1016/j.immuni.2005.08.006Search in Google Scholar
World Health Organization. 2000. Severe falciparum malaria. Transactions of the Royal Society of Tropical Medicine and Hygiene 94, S1–S90. DOI:10.1016/s0035-9203(00)90300-610.1016/S0035-9203(00)90300-6Search in Google Scholar
World Health Organization. 2010. Guidelines for the treatment of malaria 2nd edition. Geneva: World Health Organization March 2010, 35Search in Google Scholar
Zhang R., Becnel L., Li M., Chen C., Yao Q. 2006. C-reactive protein impairs human CD14+ monocyte-derived dendritic cell differentiation, maturation and function. European Journal of Immunology, 36, 2993–3006. DOI: 10.1002/eji.20063520710.1002/eji.200635207Search in Google Scholar PubMed
Zhong W., Zen Q., Tebo J., Schlottmann K., Coggeshall M., Mortensen R.F. 1998. Effect of human C-reactive protein on chemokine and chemotactic factor-induced neutrophil chemotaxis and signaling. Journal of Immunology, 161, 2533–2540. DOI: 10.4049/jimmunol.168.3.141310.4049/jimmunol.168.3.1413Search in Google Scholar PubMed
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