The role of rosette formation in pathogenesis of vivax malaria / Lee Wenn Chyau
Rosette formation is one of the unique biological phenomena that have been linked to pathobiology of malaria. It is believe to be associated with the severe outcomes of falciparum malaria. Most of the knowledge about rosetting is obtained from in-depth studies conducted on Plasmodium falciparum....
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Format: | Thesis |
Published: |
2014
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Online Access: | http://studentsrepo.um.edu.my/4579/1/Lee_WennChyau_MHA_110020_PhD_2014.pdf http://studentsrepo.um.edu.my/4579/ |
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Institution: | Universiti Malaya |
Summary: | Rosette formation is one of the unique biological phenomena that have been linked to
pathobiology of malaria. It is believe to be associated with the severe outcomes of
falciparum malaria. Most of the knowledge about rosetting is obtained from in-depth
studies conducted on Plasmodium falciparum. However, the rosetting phenomenon and
pathobiology of vivax malaria is not well studied. This research project aimed at
deciphering the unknown aspects behind rosetting phenomenon of P. vivax, and
investigating the role of rosette formation in pathobiology of vivax malaria. In total, 121
fresh P. vivax isolates, 48 cryopreserved P. vivax isolates, 122 fresh P. falciparum
isolates and 5 cryopreserved P. falciparum isolates were recruited into this research
project. A novel technique suitable for reticulocyte characterization and rosetting assay
in field setting was developed from this research project. Based on the field studies
conducted, rosette formation is common in P. vivax. However, rosetting is not
significantly correlated to clinical parameters such as reticulocyte count and
parasitaemia. Besides, cryopreservation and thawing processes affect the rosetting
capability of P. vivax isolates. Rosette formation was found to be initiated at the early
trophozoite stage of P. vivax and the rosetting development reached plateau at the end
of the erythrocytic maturation. Giant rosettes were found more frequently in P. vivax
than P. falciparum. In addition, gametocytes were found to be involved in rosette
formation. Unlike P. falciparum, the rosetting phenomenon of P. vivax is independent
of human ABO blood groups and complement receptor 1 (CR1/CD35). However,
rosetting phenomena of P. vivax and P. falciparum are dependent on the BRIC4 region
of human glycophorin C (CD236R), strongly indicating the BRIC4 region of CD236R
as another rosetting coreceptor for P. vivax and P. falciparum. On elucidating the roles
of rosette formation in pathobiology of malaria, the significantly high preference for
normocytes instead of reticulocytes in rosette formation clearly shows that rosetting is
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unlikely to assist merozoite reinvasion in vivax malaria. Furthermore, increased
rosetting rates upon exposure to anti-malaria drug compounds and human white blood
cells suggest that the rosetting phenomenon may serve as an intrinsic protective
mechanism of the malaria parasites against their environmental threats. |
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