Hubungan Trombositopenia, Parasitemia serta Mediator Pro dan Anti Inflamasi pada Infeksi Malaria, Timika 2010
Abstract
Abstract
Trombocytopenia is related with severity of malaria. Parasitaemia and immune system have important roles for the reactions that occur in malaria infections including thrombocytopenia. Therefore, we conducted a study to determine the association between thrombocytopenia, parasitaemia and cytokines in Plasmodium falciparum and P.vivax. This was a cross-sectional and hospital based study at Mitra Masyarakat Hospital,Timika, Papua, in 2010. Subjects were all age groups with uncomplicated malaria. On admission, characteristics subjects were recorded, parasitaemia was calculated by using microscope, platelets were measured by Hematology analyzer (Sysmex), and cytokines were measured by Multiplex Flow Cytometry Assay (Luminex).Thrombocytopenia was defined if platelet count <150,000/mm . Cytokines were presented in ratio of TNFα/IL10, IFNγ/IL10, and IL12/IL10. The association thrombocytopenia, parasitaemia and cytokines were determined by logistic multivariate analysis. A total 76 subjects were recruited, 51.3% infected with P. falciparum and 48.7% infected with P. vivax infection. The mean age of subjects was 15 (range: 5 – 55) years and 82.9% with thrombocytopenia (platelet range:18958-341123/mm ). The geometric mean of parasitemia was 3393 (43–412503) /mm , while the median of ratios TNFα/IL10, IFN γ/IL10 and IL12/IL10 were 1.05; 0.99; and 0.99, respectively. Bivariate anaylsis showed that trombocytopenia was associated with low level of TNFα/IL10 (p=0.015) and IL12/IL10 (0.020). The multivariate anaysis data also showed a relationship between thrombocytopenia and ratio of TNFα/IL10 with adjusted OR of 7,33 (95%CI: 1,5–35,8), p=0.014. Thrombocytopenia is associated with low ratio of TNFα/IL10 in patients with uncomplicated infection of P. falciparum and P.vivax.
Abstrak
Trombositopenia berhubungan dengan tingkat keparahan malaria. Parasitemia dan sistem kekebalan tubuh memiliki peran penting pada manifestasi infeksi malaria termasuk trombositopenia. Oleh karenanya penelitian ini bertujuan untuk menentukan hubungan antara trombositopenia, parasitemia, dan sitokin pada Plasmodium falciparum dan P.vivax. Disain studi adalah potong lintang, dilaksanakan di Rumah Sakit Mitra Masyarakat, Timika, Papua pada tahun 2010. Subjek penelitian adalah semua kelompok umur dengan malaria tanpa komplikasi. Pada perekrutan, karakteristik subjek akan dicatat, parasitemia dihitung dengan mikroskop, trombosit diukur dengan Hematology analyzer (Sysmex) dan sitokin diukur dengan Multiplex Flow Cytometry Assay (Luminex). Trombositopenia didefinisikan jika jumlah trombosit < 150.000 mm . Sitokin yang dipaparkan adalah rasio TNFα/IL10, IFNγ/IL10, dan IL12/IL10. Hubungan trombositopenia, parasitemia, dan sitokin ditentukan dengan analisis multivariat logistik. Sebanyak 76 subjek malaria mono-infeksi direkrut, 51,3% terinfeksi P. falciparum dan 48,7% P. vivax. Rata-rata umur subjek adalah 15 (kisaran : 5-55) tahun dan 82,9% dengan trombositopenia (kisaran : 18.958-341.123/ mm 3 3 ). Rerata geometrik parasitemia adalah 3393 (43-412503)/mm , sedangkan median masing–masing rasio TNFα/IL10, IFNγ/IL10 dan IL12/IL10 yaitu 1,05, 0,99; dan 0,99. Analsis bivariat menunjukkan bahwa trombositopenia berhubungan dengan rendahnya tingkat TNFα/IL10 (p = 0,015) dan tingginya rasio IL12/ IL10 (p=0,020). Hasil analisis multivariat menunjukkan adanya hubungan antara trombositopenia dan rasio TNFα/IL10 rendah (< 1,05) dengan OR: 7,33 (95% CI: 1,5-35,8), p = 0,014. Trombositopenia dikaitkan dengan rendahnya rasio TNFα/ IL10 pada pasien infeksi dari P. falciparum dan P. vivax tanpa komplikasi.
References
Sekhon SS, Roy V. Thrombocytopenia in adults: a practical approach to evaluation and management. Southern Medical Journal. 2006;99(5):491.
Lacerda MVG, Mourão MPG, Coelho HCC, Santos JB. Thrombocytopenia in malaria: who cares? Memorias do Instituto Oswaldo Cruz. 2011;106:52-63.
Angulo I, Fresno M. Cytokines in the pathogenesis of and protection against malaria. Clinical and diagnostic laboratory immunology. 2002;9(6):1145-52.
Rodrigues-da-Silva RN, Lima-Junior JdC, Antas PRZ, Baldez A, Storer FL, Santos F, et al. Alterations in cytokines and haematological parameters during the acute and convalescent phases of Plasmodium falciparum and Plasmodium vivax infections. Memorias do Instituto Oswaldo Cruz. 2014;109(2):154-62.
Couper KN, Blount DG, Riley EM. IL10: the master regulator of immunity to infection. The Journal of Immunology. 2008;180(9):5771-7.
Casals-Pascual C, Kai O, Newton CR, Peshu N, Roberts DJ. Thrombocytopenia in falciparum malaria is associated with high concentrations of IL-10. The American journal of tropical medicine and hygiene. 2006;75(3):434-6.
Raza A, Khan MS, Ghanchi NK, Raheem A, Beg MA. Tumour necrosis factor, interleukin-6 and interleukin-10 are possibly involved in Plasmodium vivax-associated thrombocytopaenia in southern Pakistani population. Malaria journal. 2014;13(1):323.
Hanisch BR, Bangirana P, Opoka RO, Park GS, John CC. Thrombocytopenia May Mediate Disease Severity in Plasmodium falciparum Malaria Through Reduced Transforming Growth Factor Beta-1 Regulation of Proinflammatory and Antiinflammatory
Cytokines. The Pediatric infectious disease journal. 2015;34(7):783-8.
Goncalves RM, Scopel KK, Bastos MS, Ferreira MU. Cytokine balance in human malaria: does Plasmodium vivax elicit more inflammatory responses than Plasmodium falciparum? PLoS One. 2012;7(9):e44394.
Wassmer SC, Taylor T, MacLennan CA, Kanjala M, Mukaka M, Molyneux ME, et al. Platelet-induced clumping of Plasmodi um falciparum-infected erythrocytes from Malawian patients with cerebral malaria— possible modulation in vivo by thrombo cytopenia. Journal of Infectious Diseases. 2008;197(1):72-8.
Hasugian AR, Wibowo H, Tjitra E. Hubungan kadar hemoglobin dengan respon sitokin proinflamasi dan antiinflamasi pada penderita infeksi Plasmodium falciparum dan Plasmodium vivax di Timika, Papua tahun 2010. Media Litbang Kesehatan. 2012;1:6-17.
Carvalho BO, Lopes SC, Nogueira PA, Orlandi PP, Bargieri DY, Blanco YC, et al. On the cytoadhesion of Plasmodium vivax– infected erythrocytes. Journal of Infectious Diseases. 2010;202(4):638-47.
Saravu K, Docherla M, Vasudev A, Shastry B. Thrombocytopenia in vivax and falciparum malaria: an observational study of 131 patients in Karnataka, India. Annals of Tropical Medicine & Parasitology. 2011;105(8):593-8.
Gupta NK, Bansal SB, Jain UC, Sahare K. Study of thrombocytopenia in patients of malaria. Tropical parasitology. 2013;3(1):58.
Shaikh QH, Ahmad SM, Abbasi A, Malik SA, Sahito AA, Munir S. Thrombocytopenia in malaria. J Coll Physicians Surg Pak. 2009;19(11):708-10.
Artavanis-Tsakonas K, Riley EM. Innate Immune Response to Malaria: Rapid induction of IFN-y from Human NK Cells by Live Plasmodium falciparum-infected Erythrocytes. J Immunol. 2002;169:295663.
Park J-W, Park S-H, Yeom J-S, Huh A-J, Cho Y-K, Ahn J-Y, et al. Serumc ytokine proles in patients with Plasmodium vivax malaria : a comparison between those who presented with and without thrombocytopenia. AnnalsofTropicalMedicine&Parasitology ,Vol97,No4,339–344(2003). 2003.
de Mast Q, Groot E, Lenting PJ, de Groot PG, McCall M, Sauerwein RW, et al. Thrombocytopenia and release of activated von Willebrand Factor during early Plasmodium falciparum malaria. Journal of Infectious Diseases. 2007;196(4):622-8.
Muley A, Lakhani J, Bhirud S, Patel A. Thrombocytopenia in Plasmodium vivax malaria: How significant? Journal of tropical medicine. 2014;2014.
Khan SJ, Abbass Y, Marwat MA. Thrombocytopenia as an indicator of malaria in adult population. Malaria research and treatment. 2012;2012.
Arshad AR. Thrombocytopenia in malaria: can platelet counts differentiate malaria from other infections? Journal of the College of Physicians and Surgeons Pakistan. 2015;25(1):31-4.
Jadhav U, Patkar V, Kadam N. Thrombocytopenia in malaria—correlation with type and severity of malaria. JAPI. 2004;52(615):8.
