Skip to main content
Log in

Hemodynamic Analysis of Microcirculation in Malaria Infection

  • Published:
Annals of Biomedical Engineering Aims and scope Submit manuscript


Malaria-infected red blood cells (IRBCs) show various changes in mechanical properties. IRBCs lose their deformability and develop properties of cytoadherence and rosetting. To clarify how these changes advance microvascular occlusion, we need qualitative and quantitative information on hemodynamics in malaria infection, including the interaction among IRBCs, healthy RBCs, and endothelial cells. We developed a numerical model of blood flow with IRBCs based on conservation laws of fluid dynamics. The deformability and adhesive property of IRBCs were simply modeled using springs governed by Hook’s law. Our model could express the basic behavior of IRBCs, including the rolling motion due to cytoadhesive interaction with endothelial cells and complex interaction with healthy RBCs. We confirmed that these types of interactions significantly increase the flow resistance, particularly when knobs develop.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6

Similar content being viewed by others


  1. Chotivanich K. T., A. M. Dondorp, N. J. White, K. Peters, J. Vreeken, P. A. Kager, R. Udomsangpetch 2000. The resistance to physiological shear stresses of the erythrocytic rosettes formed by cells infected with Plasmodium falciparum. Ann. Trop. Med. Parasitol. 94, 219–226. 10.1080/00034980050006384

    Article  PubMed  CAS  Google Scholar 

  2. Dao M., C. T. Lim, S. Suresh 2003. Mechanics of the human red blood cell deformed by optical tweezers. J. Mech. Phys. Solids 51, 2259–2280. 10.1016/j.jmps.2003.09.019

    Article  Google Scholar 

  3. Dondorp A. M., P. A. Kager, J. Vreeken, N. J. White 2000. Abnormal blood flow and red blood cell deformability in severe malaria. Parasitol. Today 16, 228–232. 10.1016/S0169-4758(00)01666-5

    Article  PubMed  CAS  Google Scholar 

  4. Dzwinel W., K. Boryczko, D. A. Yuen 2003. A discrete-particle model of blood dynamics in capillary vessels. J. Colloid Interface Sci. 258, 163–173. 10.1016/S0021-9797(02)00075-9

    Article  PubMed  CAS  Google Scholar 

  5. Heise M., S. Schmidt, U. Krüger, R. Rückert, S. Rösler, P. Neuhaus, U. Settmacher 2004. Flow pattern and shear stress distribution of distal end-to-side anastomoses. A comparison of the instantaneous velocity fields obtained by particle image velocimetry. J. Biomech. 37, 1043–1051. 10.1016/j.jbiomech.2003.11.030

    Article  PubMed  Google Scholar 

  6. Ho M., N. J. White 1999. Molecular mechanisms of cytoadherence in malaria. Am. J. Physiol. Cell Physiol. 276, 1231–1242

    Google Scholar 

  7. Jeong J. H., Y. Sugii, M. Minamiyama, H. Takeuchi, K. Okamoto 2007. Interaction between liposomes and RBC in microvessels in vivo. Microvasc. Res. 73, 39–47. 10.1016/j.mvr.2006.05.001

    Article  PubMed  CAS  Google Scholar 

  8. Kaul D. K., E. F. Roth, R. L. Nagel, R. J. Howard, S. M. Handunnetti 1991. Rosetting of Plasmodium falciparum-infected red blood cells with uninfected red blood cells enhances microvascular obstruction under flow conditions. Blood 78, 812–819

    PubMed  CAS  Google Scholar 

  9. Koshizuka S., Y. Oka 1996. Moving-particle semi-implicit method for fragmentation of incompressible fluid. Nucl. Sci. Eng. 123, 421–434

    CAS  Google Scholar 

  10. Lima R., S. Wada, S. Tanaka, M. Takeda, T. Ishikawa, K. Tsubota, Y. Imai, T. Yamaguchi 2007. In vitro confocal micro-PIV measurements of blood flow in a square microchannel: the effect of the haematocrit on instantaneous velocity profiles. J. Biomech. 40, 2752–2757. 10.1016/j.jbiomech.2007.01.012

    Article  PubMed  Google Scholar 

  11. Liu Y., W. K. Liu 2006. Rheology of red blood cell aggregation by computer simulation. J. Comput. Phys. 220, 139–154. 10.1016/

    Article  Google Scholar 

  12. Miller L. H., D. I. Baruch, K. Marsh, O. K. Doumbo 2002. The pathogenic basis of malaria. Nature 415, 673–679. 10.1038/415673a

    Article  PubMed  CAS  Google Scholar 

  13. Miyazaki H., T. Yamaguchi 2003. Formation and destruction of primary thrombi under the influence of blood flow and von Willebrand factor analyzed by a discrete element method. Biorheology 40, 265–272

    PubMed  CAS  Google Scholar 

  14. Mori D., K. Yano, K. Tsubota, T. Ishikawa, S. Wada, T. Yamaguchi (2008) Simulation of platelet adhesion and aggregation regulated by fibrinogen and von Willebrand factor. Thromb. Haemost. 99(1):108–115

    PubMed  CAS  Google Scholar 

  15. Nagao E., O. Kaneko, J. A. Dvorak 2000. Plasmodium falciparum-infected erythrocytes: qualitative and quantitative analyses of parasite-induced knobs by atomic force microscopy. J. Struct. Biol. 130, 34–44. 10.1006/jsbi.2000.4236

    Article  PubMed  CAS  Google Scholar 

  16. Pasloske B. L., R. J. Howard 2000. Malaria, the red cell, and the endothelium. Annu. Rev. Med. 45, 283–295. 10.1146/

    Article  Google Scholar 

  17. Shelby J. P., J. White, K. Ganesan, P. K. Rathod, D. T. Chiu 2003. A microfluidic model for single-cell capillary obstruction by Plasmodium falciparum-infected erythrocytes. Proc. Natl. Acad. Sci. USA 100, 14618–14622. 10.1073/pnas.2433968100

    Article  PubMed  CAS  Google Scholar 

  18. Silamut K., N. H. Phu, C. Whitty, G. D. H. Turner, K. Louwrier, N. T. H. Mai, J. A. Simpson, T. T. Hien, N. J. White 1999. A quantitative analysis of the microvascular sequestration of malaria parasites in the human brain. Am. J. Pathol. 155, 395–410

    PubMed  CAS  Google Scholar 

  19. Suresh S., J. Spatz, J. P. Mills, A. Micoulet, M. Dao, C. T. Lim, M. Beil, T. Seufferlein 2005. Connection between single-cell biomechanics and human disease states: gastrointestinal cancer and malaria. Acta Biomater. 1, 15–30. 10.1016/j.actbio.2004.09.001

    Article  PubMed  CAS  Google Scholar 

  20. Tsubota K., S. Wada, T. Yamaguchi 2006. Particle method for computer simulation of red blood cell motion in blood flow. Comput. Methods Programs Biomed. 83, 139–146. 10.1016/j.cmpb.2006.06.005

    Article  PubMed  Google Scholar 

  21. Tsubota K., S. Wada, T. Yamaguchi 2006. Simulation study on effects of hematocrit on blood flow properties using particle method. J. Biomech. Sci. Eng. 1, 159–170. 10.1299/jbse.1.159

    Article  Google Scholar 

  22. Wada S., R. Kobayashi 2003. Numerical simulation of various shape changes of a swollen red blood cell by decrease of its volume. Trans. JSME 69A:14–21 (in Japanese)

    Google Scholar 

  23. Yipp B. G., S. Anand, T. Schollaardt, K. D. Patel, S. Looareesuwan, M. Ho 2000. Synergism of multiple adhesion molecules in mediating cytoadherence of Plasmodium falciparum-infected erythrocytes to microvascular endothelial cells under flow. Blood 96, 2292–2298

    PubMed  CAS  Google Scholar 

Download references


This study was made possible by the following grants: the “Revolutionary Simulation Software (RSS21)” project, supported by the next-generation IT program of the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Grants-in-Aid for Scientific Research from MEXT, and JSPS Scientific Research in Priority Areas (768) “Biomechanics at Micro- and Nano-scale Levels” and Scientific Research(A) No.16200031 “Mechanism of the Formation, Destruction, and Movement of Thrombi Responsible for Ischemia of Vital Organs”.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Yohsuke Imai.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kondo, H., Imai, Y., Ishikawa, T. et al. Hemodynamic Analysis of Microcirculation in Malaria Infection. Ann Biomed Eng 37, 702–709 (2009).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: