ABSTRACT
The blood type of malaria patients may determine the outcome of disease. Blood group
O associates with protection, while non-O blood groups (A, B or AB) are associated
with severe malaria. Rosetting of red blood cells (RBC), which is mediated by blood
group A and other red blood cell surface molecules, is also associated with severe
disease in the two most virulent species of Plasmodium that infect humans. The
interaction of parasite ligands with blood group carbohydrates on RBC and endothelial
receptors leads to infected RBC sequestration and persistence of the parasite in the
vasculature. The objectives of this work were to study and measure the interactions
between parasite-expressed factors on the red cell surface and blood group molecules
using standard and novel methods, in both laboratory strains and field isolates of
Plasmodium falciparum. Expression levels of var and rif transcripts in laboratory
isolates selected for binding to blood group antigens were determined, while antibody
reactivity to surface antigens were investigated in these isolates. Venous blood samples
were collected from 113 children aged 12 years and below diagnosed with malaria and
resident in Hohoe, a high malaria transmission zone in the Volta Region of Ghana. The
blood type was determined for all patients, while plasma and RBCs were processed and
stored for subsequent work.
Long term blood group A and B binding variants of laboratory strains of P. falciparum
3D7, FMG and FUP parasites were successfully produced by regular panning on
immobilized blood group oligosaccharides, though the production of binding variants in
other strains (FCR3 and HB3) were not as successful. Selected parasites were found to
bind to both A and B blood group carbohydrates irrespective of the blood group antigen
used in selection. The binding isolates also showed a marked adhesion to aorta and
dermal endothelial cell (EC) lines. A novel microtiter-plate based quantitative assay to
iii
specifically measure binding of parasite infected RBC to plate-bound blood group
antigens was developed and used to determine the interaction of both laboratory and
field strains to the blood group A and B antigens. All blood group antigen-selected
isolates showed a strong propensity to form rosettes in the presence of RBC from
donors of blood type A, AB or B, in contrast to unselected isogenic isolates which did
not form rosettes under the same conditions.
The transcription levels of 58 var genes of ring stage parasites of 3D7 and FMG
selected on blood group antigens and detected by quantitative real-time polymerase
chain reaction (QPCR) showed no consistent pattern of expression between selected and
unselected parasites, though the adhesion linked genes Pf13_0003 and IT4var32b of
3D7 and FMG, respectively, had elevated levels in some selected isolates.
In conclusion, a novel plate-based assay to directly measure infected erythrocyte
adhesion to blood group antigens has been developed. Selection for long term blood
group specific parasite binding isolates was also achieved, but with no clear changes in
variant surface antigen transcript levels. Notwithstanding, an increased rosette
formation and adhesion to non-O blood antigens of selected parasites which suggest a
link to severe disease was observed. It is hoped that future investigations using field
isolates with clearer categorization of severe cases and a larger sample size would
further validate these findings. Whole genome transcriptional studies and sequencing
studies in these parasites may also specifically identify the genes and molecules
involved in adhesion. Improved knowledge in all these areas will accelerate the design
and development of targeted syndrome specific vaccines which will improve the
management of this disease.
Eastern Network, L (2021). Interaction Of Plasmodium Falciparum Antigens With Blood Group Determinants: Preferences And Link To Disease Severity. Afribary.com: Retrieved April 15, 2021, from https://afribary.com/works/interaction-of-plasmodium-falciparum-antigens-with-blood-group-determinants-preferences-and-link-to-disease-severity
Library, Eastern Network. "Interaction Of Plasmodium Falciparum Antigens With Blood Group Determinants: Preferences And Link To Disease Severity" Afribary.com. Afribary.com, 06 Apr. 2021, https://afribary.com/works/interaction-of-plasmodium-falciparum-antigens-with-blood-group-determinants-preferences-and-link-to-disease-severity . Accessed 15 Apr. 2021.
Library, Eastern Network. "Interaction Of Plasmodium Falciparum Antigens With Blood Group Determinants: Preferences And Link To Disease Severity". Afribary.com, Afribary.com, 06 Apr. 2021. Web. 15 Apr. 2021. < https://afribary.com/works/interaction-of-plasmodium-falciparum-antigens-with-blood-group-determinants-preferences-and-link-to-disease-severity >.
Library, Eastern Network. "Interaction Of Plasmodium Falciparum Antigens With Blood Group Determinants: Preferences And Link To Disease Severity" Afribary.com (2021). Accessed April 15, 2021. https://afribary.com/works/interaction-of-plasmodium-falciparum-antigens-with-blood-group-determinants-preferences-and-link-to-disease-severity