Anyona, Samuel Bonuke (2006) Pitting of Malaria Parasites with Formation of Spherocytes and Alpha Thalassemia in Children Living in Malaria Holoendemic Lake Victoria Basin. Masters thesis, Kenyatta University.
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Anyona Samuel Bonuke Pitting of Malaria Parasites with Formation of Spherocytes and Alpha Thalassemia in Children Living in Malaria Holoendemic Lake Victoria Basin.pdf - Accepted Version Restricted to Repository staff only Download (46MB) | Request a copy |
Abstract
Widespread red blood cell (RBC) membrane abnormalities, spherocytosis and microcytic hypochromia were detected in blood smears of children enrolled in a case control study that was conducted in New Nyanza Provincial General Hospital, Western Kenya between May and November 1998. Microcytic hypochromia was attributed to nutritional iron deficiency, which was confirmed by low serum ferritin levels. The other likely cause of microcytic hypochromia in the population studied is homozygote state for deletion form of alpha + thalassemia (a + thal), In its heterozygous form, the common African a + thal trait is protective against severe malaria and would therefore be expected to be prevalent in the malaria holoendemic region of Lake Victoria basin. Widespread spherocytosis was speculated to reflect removal of malarial parasites from infected RBC with a concurrent removal of RBC membrane through a process analogous to "pitting" of intraerythrocytic inclusion bodies, such as Heinz bodies. The study sought to determine: 1) the prevalence of a + thal in children enrolled in the case control study as a way of assessing the contribution of this trait to maintenance of microcytic hypochromia as well as evaluate any association between carrier state and severity of disease. 2) Whether interaction of P. falciparum infected RBCs (iRBC) with human macrophages could lead to pitting and spherocyte formation. In order to determine the prevalence of a + thal in the study population, DNA samples were prepared from EDT A blood obtained from cases of severe malarial anemia (SA) defined as children with asexual P. falciparum parasitemia and a hemoglobin of :s 5 g/dL and two age and gender matched controls: symptomatic controls (SC) who had symptoms of uncomplicated malaria and asymptomatic controls (AC). From each group, 25 DNA samples were randomly selected and evaluated for presence of a + thaI by polymerase chain reaction (PCR) techniques. The data shows that a +thaI is prevalent, occurring in 29.33% (95% CI 19.38-40.98) of the study population, commonly present in heterozygous state. Analysis using allele frequency data for a globin genes show high prevalence of a + thalasssemia allele (-a) in AC and SC groups: 28% and 20% respectively, with severe anemia group having -a allele frequency of 10%. Inter-group comparison revealed a significant difference in -a allele distribution between SA and AC groups, suggesting that children with normal a globin allele (aa) had a much higher risk of developing severe malarial anemia as compared to carriers of a+ thaI allele (-a); Odds Ratio (OR) 3.5: 95% CI 1.15-10.63, P = 0.02. Further, an in vitro model was developed to examine the phenomenon of pitting and spherocyte formation during interaction of infected RBCs with human macrophages. Interaction of infected RBC and tumor necrosis factor-alpha (TNF-a) activated macrophages led to pitting (14 % ± 1.31 % macrophages with engulfed trophozoites) as opposed to erythrophagocytosis (5.3 % ± 0.95 %, P < 0.01). Following interaction, 26.9 % ± 8.1 % of the RBCs were spherocytes as shown by flow cytometric reduction in eosin-5-maleimide (EMA) binding which detects RBC membrane band 3. In conclusion, the data shows that a + thal is prevalent, occurring as heterozygote trait or homozygous state. Overall, carriers of a + thaI were afforded protection against severe P. falciparum malarial anemia. In vitro data confirm that spherocytes can be formed as a result of pitting of malarial parasites from infected RBC. It was speculated that in malaria holoendemic areas where prevalence of asexual stage parasites approach 100% in children, pitting might produce high spherocytic rates.
| Item Type: | Thesis (Masters) |
|---|---|
| Subjects: | R Medicine > RB Pathology |
| Divisions: | Africana |
| Depositing User: | Tim Khabala |
| Date Deposited: | 07 Jun 2017 10:30 |
| Last Modified: | 07 Jun 2017 10:30 |
| URI: | http://thesisbank.jhia.ac.ke/id/eprint/1758 |
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