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An immune basis for malaria protection by the sickle cell trait.

Williams TN, Mwangi TW, Roberts DJ, Alexander ND, Weatherall DJ, Wambua S, Kortok M, Snow RW, Marsh K - PLoS Med. (2005)

Bottom Line: Nevertheless, the mechanism of this resistance remains the subject of considerable debate.We found that protection increased with age from only 20% in the first 2 y of life to a maximum of 56% by the age of 10 y, returning thereafter to 30% in participants greater than 10 y old.A better understanding of the underlying mechanisms might yield important insights into both these processes.

View Article: PubMed Central - PubMed

Affiliation: Kenya Medical Research Institute, Wellcome Trust Programme, Centre for Geographic Medicine Research, Coast, Kilifi District Hospital, Kilifi, Kenya. twilliams@kilifi.mimcom.net

ABSTRACT

Background: Malaria resistance by the sickle cell trait (genotype HbAS) has served as the prime example of genetic selection for over half a century. Nevertheless, the mechanism of this resistance remains the subject of considerable debate. While it probably involves innate factors such as the reduced ability of Plasmodium falciparum parasites to grow and multiply in HbAS erythrocytes, recent observations suggest that it might also involve the accelerated acquisition of malaria-specific immunity.

Methods and findings: We studied the age-specific protection afforded by HbAS against clinical malaria in children living on the coast of Kenya. We found that protection increased with age from only 20% in the first 2 y of life to a maximum of 56% by the age of 10 y, returning thereafter to 30% in participants greater than 10 y old.

Conclusions: Our observations suggest that malaria protection by HbAS involves the enhancement of not only innate but also of acquired immunity to the parasite. A better understanding of the underlying mechanisms might yield important insights into both these processes.

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Related in: MedlinePlus

The IRR for Malaria in HbAS versus HbAA Children by Age and Genotypic GroupInfants less than 3 mo old were excluded from the baseline group.
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pmed-0020128-g001: The IRR for Malaria in HbAS versus HbAA Children by Age and Genotypic GroupInfants less than 3 mo old were excluded from the baseline group.

Mentions: Overall, HbAS was almost 40% protective against mild clinical malaria (IRR = 0.62; 95% confidence interval 0.51–0.76; p < 0.001); however, protection appeared to vary with age, increasing from only 20% to almost 60% over the first 10 y of life and returning to around 30% thereafter (Table 1; Figure 1). A similar pattern was seen when data from each of the study areas were analyzed separately. Although we were not able to prove statistically an overall interaction between age and protection over the full range of ages (χ25 = 6.46; p = 0.26), the data support the strong impression of acquired protection with age.


An immune basis for malaria protection by the sickle cell trait.

Williams TN, Mwangi TW, Roberts DJ, Alexander ND, Weatherall DJ, Wambua S, Kortok M, Snow RW, Marsh K - PLoS Med. (2005)

The IRR for Malaria in HbAS versus HbAA Children by Age and Genotypic GroupInfants less than 3 mo old were excluded from the baseline group.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1140945&req=5

pmed-0020128-g001: The IRR for Malaria in HbAS versus HbAA Children by Age and Genotypic GroupInfants less than 3 mo old were excluded from the baseline group.
Mentions: Overall, HbAS was almost 40% protective against mild clinical malaria (IRR = 0.62; 95% confidence interval 0.51–0.76; p < 0.001); however, protection appeared to vary with age, increasing from only 20% to almost 60% over the first 10 y of life and returning to around 30% thereafter (Table 1; Figure 1). A similar pattern was seen when data from each of the study areas were analyzed separately. Although we were not able to prove statistically an overall interaction between age and protection over the full range of ages (χ25 = 6.46; p = 0.26), the data support the strong impression of acquired protection with age.

Bottom Line: Nevertheless, the mechanism of this resistance remains the subject of considerable debate.We found that protection increased with age from only 20% in the first 2 y of life to a maximum of 56% by the age of 10 y, returning thereafter to 30% in participants greater than 10 y old.A better understanding of the underlying mechanisms might yield important insights into both these processes.

View Article: PubMed Central - PubMed

Affiliation: Kenya Medical Research Institute, Wellcome Trust Programme, Centre for Geographic Medicine Research, Coast, Kilifi District Hospital, Kilifi, Kenya. twilliams@kilifi.mimcom.net

ABSTRACT

Background: Malaria resistance by the sickle cell trait (genotype HbAS) has served as the prime example of genetic selection for over half a century. Nevertheless, the mechanism of this resistance remains the subject of considerable debate. While it probably involves innate factors such as the reduced ability of Plasmodium falciparum parasites to grow and multiply in HbAS erythrocytes, recent observations suggest that it might also involve the accelerated acquisition of malaria-specific immunity.

Methods and findings: We studied the age-specific protection afforded by HbAS against clinical malaria in children living on the coast of Kenya. We found that protection increased with age from only 20% in the first 2 y of life to a maximum of 56% by the age of 10 y, returning thereafter to 30% in participants greater than 10 y old.

Conclusions: Our observations suggest that malaria protection by HbAS involves the enhancement of not only innate but also of acquired immunity to the parasite. A better understanding of the underlying mechanisms might yield important insights into both these processes.

Show MeSH
Related in: MedlinePlus