Infeksi Plasmodium Berghei Anka pada Mencit Galur Swiss Webster dan C57bl/6 Sebagai Model Malaria Serebral

  • Putri Reno Intan Badan Penelitian dan Pengembangan Kesehatan
  • Tati Febrianti Badan Penelitian dan Pengembangan Kesehatan
  • Rita Marleta Dewi Badan Penelitian dan Pengembangan Kesehatan

Abstract

Abstract

Cerebral malaria is a complication of Plasmodium falciparum infection and can cause death in humans. Plasmodium berghei ANKA (PbA) infection in C57BL/6 strain is widely used for cerebral malaria research. However, research to assess differences in brain histopathology, TNFα levels and the degree of parasitemia in Swiss websters infected with PbA are still limited. Therefore an infection with P. berghei ANKA strain was carried out on Swiss webster mice and C57BL/6 as a model of cerebral malaria. This research is a laboratory experiment with a post-test only control group design. Each experimental animal was divided into 3 groups namely PbA group (infected and given aquades), DHP (infected and given Dihidroartemisinin piperakuin), and healthy (mice not infected with PbA called aquades). Animal testing tried to examine parasitemia by microscopic counts on thin blood smear, calculation of serum TNFα levels by ELISA method and histopathology of the brain and slide microscopic examination with Haematoxylin Eosin staining conducted at the Experimental Animal Laboratory, Parasite Laboratory, Puslitbang BTDK, NIHRD; and Balitvet Pathology Laboratory by the research team. The results showed a peak percentage of parasitemia in the PbA group on day 4 for the Swiss webster strain (68.8%) and on the 5th day for the C57BL/6 strain (43.7%). The percentage of parasitemia was higher in the Swiss webster strain than in the C57BL/6 strain. TNFα levels in the Swiss webster strain (3.6 pg/ml) were higher than TNFα levels in the C57BL/6 strain (0.18 pg/ml). Histopathological changes in the brain consisting of lymphocyte cells, infiltration, macrophages, gliosis, necrosis, vacuolization and malaria parasitemia were found in both strains. The results showed that Swiss webster mice can be used as a model of cerebral malaria when seen from the clinical picture, the percentage of parasitemia, serum TNFα levels, macroscopic and microscopic brains that have similarities to the C57BL/6 strain.

Keywords: Cerebral malaria, Plasmodium berghei ANKA, Swiss webster, C57BL/6.

Abstrak

Malaria serebral merupakan salah satu komplikasi infeksi Plasmodium falciparum dan dapat menyebabkan kematian pada manusia. Infeksi Plasmodium berghei ANKA (PbA) pada mencit galur C57BL/6 banyak digunakan untuk penelitian malaria serebral. Di Indonesia, mencit Swiss webster banyak digunakan sebagai hewan coba untuk malaria, namun penelitian untuk menilai perbedaaan histopatologi otak, kadar TNFα dan derajat parasitemia pada Swiss webster yang diinfeksi PbA masih terbatas. Oleh sebab itu dilakukan infeksi P. berghei galur ANKA pada mencit Swiss webster dan C57BL/6 sebagai model malaria serebral. Penelitian ini merupakan eksperimen laboratorium dengan desain post-test only control group. Masing-masing galur hewan coba dibagi menjadi 3 kelompok yaitu kelompok PbA (diinfeksi dan diberi akuades), DHP (diinfeksi dan diberi Dihidroartemisinin piperakuin), dan sehat (mencit yang tidak diinfeksi PbA yang diberi akuades). Pengujian pada hewan coba meliputi pemeriksaan parasitemia dengan penghitungan kepadatan parasit secara mikroskopis pada ulas darah tipis, penghitungan kadar TNFα serum dengan metode ELISA serta gambaran histopatologi sediaan otak dengan pewarnaan Haematoksilin Eosin dilakukan di Laboratorium Hewan Coba, Laboratorium Parasit Puslitbang BTDK, Badan Litbangkes; dan Laboratorium Patologi Balitvet oleh tim peneliti. Hasil penelitian menunjukkan puncak persentase parasitemia kelompok PbA pada hari ke- 4 untuk galur Swiss webster (68.8%) sementara untuk galur C57BL/6 (43.7%) pada hari ke-5. Hal ini berarti bahwa puncak parasitemia lebih cepat dan tinggi terjadi pada galur Swiss webster dibandingkan pada galur C57BL/6. Demikian juga untuk kadar TNFα didapatkan bahwa pada galur Swiss webster (3.6 pg/ml) lebih tinggi dibandingkan galur C57BL/6 (0.18 pg/ml). Perubahan histopatologik otak berupa infiltrasi sel limfosit, makrofag, gliosis, nekrosis, vakuolisasi dan parasitemia malaria ditemukan pada kedua galur. Hasil penelitian menunjukkan bahwa mencit galur Swiss webster dapat dijadikan sebagai model malaria serebral.

Kata kunci: Malaria serebral, Plasmodium berghei ANKA, Swiss webster, C57BL/6.

References

World Health Organization (WHO). World Malaria Report; WHO: Geneva, Switzerland, 2017.

Harijanto PN. Malaria. Dalam: Ilmu Penyakit Dalam. Edisi Keempat. Jakarta: Fakultas Kedokteran Universitas Indonesia ; 2007

Miller LH, Shunichi U, Chien S. Alteration in The Theologic Properties of Plasmodium knowlesi Infected Red Cells. A Possible Mechanism of Cerebal Malaria. J. Clin. Invest. 1971' 50: 1451-1455

David Langlais Regina Cencic, Neda Moradin. Rocaglates as dual-targeting agents for experimental cerebral malaria. E2366– E2375|PNAS| vol. 115| no.10. www. pnas. org/cgi/doi/10. 1073/pnas. 1713000115. 2018.

Dondorp AM, Kager PA, Vreeken J, White NJ. . Abnormal Blood Flow and Red Blood Cell Deformability in Severe MalriaMalaria. Parasitol. 2000, Today. 16: 228–232

Grau GE, Fajarado L, Piquet PF, Allet B, Lamb rt PH, Vasalli P: Tumor necrosis factor (cachectin) as an essential mediator in murine malaria serebral. Science 1987; 237:12101212.

Grau GE, Pointaire G, Piquet PF, Vesin C, Rosen H, Stamenkovic I, Takei F, Vasalli P: Late administration of monoclonal antibody to leukocyte function-antigen 1 abrogates incipient murine malaria serebral. Eur J Immunol 1991; 21:2265-2267. dan

Willimann K, Matile H, Weiss NA, Imhof BA: In vivo sequestration of Plasmodium falciparum-infected human erythrocytes: a severe combined immunodeficiency mouse model for malaria serebral. J Exp Med 1995; 182:643-653

Brakes in the pathogenesis of malaria serebral. Trends Immunol. 2003; 24(9): 491- 499.

Combes V, de Souza JB, Renia L, Hunt NH, Grau GE. Malaria serebral: which parasite? Which model? Drug Disc Today. 2005; 2(2): 141-147

Institute for Laboratory Animal Research. Guide for The Care and Use of Laboratory Animals 8th ed. Washington (DC): National Academies Press; 2011.

Tsige Ketema, Moti Yohannes, Esayas Alemayehu and Argaw Ambelu. Effect of Chronic Khat (Catha edulis, Forsk) Use on Outcome of Plasmodium berghei ANKA infection in Swiss Albino Mice. BMC Infectious Diseases. 2015; 15 : 170.

Ana Cecilia A.D.O., Renato S. C., Flavio HM, et al. Up- and Down -Modulation of Liver Cytochrome P450 Activities and Associated events In Two Murine Malaria Models. Malaria Journal. 2010; 9:81.

Marcela M, Christian E, Ashraful H.Irving C. Allen (editor). Mouse models of innate immunity methods and protocols. Springer protocol, methods in molecular biology 1031. Humana press. 2013; P203-2014.

Kusmardi, Berna Elya, Tri Wahyuni, Rafika Indah P. Combination of Sambiloto (Andrographis Paniculata (Burm.F.) Nees) Extract and Sprilrulina (Arthrospira Platensis Gomont) to Prevent Anemia in Mice Infected With Plasmodium berghei ANKA. Asian Journal of Pharmaceutical and Clinical Research; 2017.Vol. 10, Issue 12.

Dirjen Pencegahan dan Pengendalian Penyakit Kementerian Kesehatan RI. Buku Saku Tatalaksana Kasus Malaria, Direktorat Jenderal Pencegahan dan Pengendalian Penyakit. Jakarta : Dirjen Penceahan dan Pengendalian Penyakit; 2018.

Norinne LQ., Onesia COL., Claudia Martins C., et al. Plasmodium berghei NK65 Induces Cerebral Leukocyte recruitment in vivo: An Intravital Microscopic Study/ Acta Tropica 120(2011) 31-39.

Yuri C. Martins, Brandi D. Freeman, Oscar B. Akide, et al. Endothelin-1 Treatment Induces an Experimental Cerebral Malaria-Like Syndrome in C57BL/6 Mice Infected With Plasmodium berghei NK65. The American Journal of Pathology. 2016; November, Vol. 186, No. 11.

C.M. Thumwood, N.H. Hunt, W.B. Cowden and I.A. Clark Antioxidants can prevent cerebral malaria in Plasmodium bergheiinfected mice. Br. J. Exp. Path. I989; 70 : 293303.

Carvalho LJ, Lenzi HL, Pelajo-Machado M, Oliveira DN, Daniel-Ribeiro CT, Ferreira-da-Cruz MF. Plasmodium berghei: cerebral malaria in CBA mice is not clearly related to plasma TNF levels or intensity of histopathological changes. Exp Parasitol. 2000; 95(1):1–7. [PubMed: 10864512].

Bauer PR, Van Der Heyde HC, Sun G, Specian RD, Granger DN. Regulation of endothelial cell adhesion molecule expression in an experimental model of cerebral malaria. Microcirculation. 2002; 9(6):463–470. [PubMed: 12483543]

Cabrales P, Zanini GM, Meays D, Frangos JA, Carvalho LJ. Murine cerebral malaria is associated with a vasospasm-like microcirculatory dysfunction, and survival upon rescue treatment is markedly increased by nimodipine. Am J Pathol. 2010; 176(3):1306– 1315. [PubMed: 20110412]

Neill A.L., Chan-Ling T. and Hunt N. H. Comparison Between Microvascular Changes InCerebral and Non- Cerebral Malaria In Mice, Using The Retinal whole-Mount technique. Parasitology. 1993; 107: 477-487. Cambridge University Press.

Published
2020-07-27
How to Cite
1.
Intan P, Febrianti T, Dewi R. Infeksi Plasmodium Berghei Anka pada Mencit Galur Swiss Webster dan C57bl/6 Sebagai Model Malaria Serebral. bpk [Internet]. 27Jul.2020 [cited 3Jul.2024];48(1). Available from: http://ejournal2.litbang.kemkes.go.id/index.php/bpk/article/view/2867
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