| dc.description.abstract | Sickle cell trait has been observed to have a similar distribution pattern as malaria in the malaria holoendemic areas of the tropics. This minored distribution pattern between malaria and sickle cell trait has been attributed to the relative protection conferred by the sickle cell trait against severe manifestations of malaria namely; cerebral malaria and severe anaemia. The mechanism of protection is not well understood but other studies have shown that this may be partly due to enhanced immune response and poor parasite growth in HbAS individuals compared to those with HbAA. The Complement Receptor 1 (CRI/CD35) and Decay Accelerating Factor (DAFICD55) are complement regulatory proteins (CRPs) that play an important role in the protection of red blood cells (RBCs) from complement mediated destruction and clearance of immune complexes (ICs) that occur during malaria and their acquired deficiencies have been associated with severe P. falciparum malaria. In this study, it was hypothesized that sickle cell trait could be associated with increased expression of CRI and CD55 leading to increased rate of clearance of immune complexes from the circulation and resistance to complement desposition. If this was true, then this could partially explain why people with HbAS are protected from severe malarial anaemia. The mean parasite density in participants who were well but parasitaemic was compared in participants with HbAS and HbAA, using cytofluorometric techniques, the level of CRl and CD55 expression, immune complex binding capacity, and susceptibility to complement activation under normal and reduced
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oxygen conditions ofRBCs from the same individuals.
The study design was a nested case-control study. It was part of a large cross-sectional study entitled "Erythrocyte Immune Complex Binding Capacity and Complement Sensitivity in Populations with Different Malaria Risks". The inclusion criteria were healthy male and females ages 0 to 45 years who were residents of Kombewa Division of Kisumu West District. The potential participants were assessed for any acute or chronic illness which could interfere with the parameters under investigation. In cases of an acute illness, they were treated and asked to come again for re-evaluation. At re-evaluation, they were enrolled when they were fully recovered. Haemoglobin electrophoresis was
carried on blood from all participants. Individuals who were less than 16 years and had HbAS were identified and matched by age (± 2 months or ± 2 years for those below or more than 8 years, respectively) at a ratio of 1: 1 or 1:2 with those with HbAA and these formed the nested case control study.
Many conditions including malaria, advanced HIV infection, and various other chronic conditions can alter the level of red cell complement regulatory proteins. Participants with features of malnutrition, possibility of HIV infection as manifested by weight loss, thrush, or diffuse adenopathy; severe anaemia (Haemoglobin :S 5.0 g/dl); bacterial infection such as pneumonia; malignancy; and blood transfusion within 3 months preceding the study were excluded from the study. Those who had malaria and other minor ailments were treated and reviewed in 2 weeks.
In total, 402 participants were screened of which 342 were found eligible and enrolled. Of the participants who were enrolled, 280 had haemoglobin AA, 60 had haemoglobin AS and 2 had haemoglobin SS. Three (3) participants had inadequate blood draw and were excluded from the study. For the nested case control study 47 HbAS individuals aged 0-16 years were matched to 70 individuals with HbAA of similar age.
Results:
In asymptomatic individuals in the community without any signs of an acute or clinically obvious chronic illness and who are-malaria parasite positive, the mean parasite count/uL for HbAS [4064.0 (95% CI 1858.0 - 6270.0)] was significantly lower than for the HbAA [11,067.9 (95% CI 7616.0 - 14520.0)]. P = 0.001. This confirmed the hypothesis that HbAS individuals are indeed protected from high density parasitaemia.
The lowest level of haemoglobin in this study was observed in the > 12 -24
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months age cohort and this corresponded to the age when these children have the
highest mean parasite counts. This may explain the high prevalence of anaemia in this age group.
The mean CR1 copy numbers per red blood cell was higher in the HbAS group than in the HbAA group, this difference was however not statistically significant (P = 0.250). This was also true under reduced oxygen saturation (P = OAOO).
Between the age of96 to 192 months, the CR1 copy numbers per erythrocyte was significantly higher in the HbAS than in the HbAA participants, (P = 0.009).
There were no significant differences in the mean CD55 antibody binding capacity between RBCs of individuals with HbAS and those with HbAA. Under reduced oxygen saturation, mean CD55 antibody binding capacity for the HbAS red blood cells were higher than for HbAA red blood cell but this again did not reach statistical significance (P = 0.058).
The mean immune complex binding capacity for the HbAS cells was higher than HbAA cells both under normal and reduced oxygen saturation (P = 0.017 and 0.003 respectively).
The mean immune complex binding capacity was lowest in the 7 - 12 months age group for both HbAS and HbAA; however, the overall picture showed that HbAS individuals had higher immune complex binding capacity than HbAA in all the
age groups.
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In general, there was a weak positive correlation between the immune complex binding capacity and the age group r (117) = 0.198, P = 0.034.
Although the % C3b deposition was similar in both HbAS and HbAA cells under normal and reduced oxygen saturation, the highest incidence of % C3b deposition was in the 6 to < 12 and 12 to < 24 months age group and lowest in the 0-6 month's age group for both the HbAS and HbAA.
Conclusion:
The mean Ck.I copy numbers increase in HbAS between the ages of after 96 - 192 months is significantly higher than in the HbAA. This may be a contributing factor to the protective effects of HbAS from getting severe manifestations of malaria especially in the older age group.
The mean immune complex binding capacity for the HbAS cells was significantly higher than HbAA cells both before and after deoxygenation.
Recommendations
Do a study to relate the complement regulatory protein machinery with percentage HbS content of the cell since the HbS content varies from 20 - 45% | en |
