Alpha+ -thalassemia protects against anemia associated with asymptomatic malaria: evidence from community-based surveys in Tanzania and Kenya.
BACKGROUND
In hospital-based studies, alpha(+)-thalassemia has been found to protect against severe, life-threatening falciparum malaria. alpha(+)-Thalassemia does not seem to prevent infection or high parasite densities but rather limits progression to severe disease--in particular, severe malarial anemia. We assessed to what extent alpha(+)-thalassemia influences the association between mild, asymptomatic Plasmodium falciparum infection and hemoglobin concentration.


METHODS
The study was based on 2 community-based surveys conducted among afebrile children (0.5-8 years old; n=801) in Kenya and Tanzania.


RESULTS
Among children without inflammation (whole-blood C-reactive protein concentration <or=10 mg/L), P. falciparum infection was associated with only small reductions in hemoglobin concentration, and effects were similar across alpha-globin genotypes. By contrast, the reduction in hemoglobin concentration associated with P. falciparum infection accompanied by inflammation was larger and strongly depended on genotype (normal, -21.8 g/L; heterozygous, -16.7 g/L; and homozygous, -4.6 g/L). Relative to children with a normal genotype, this difference in effect was 5.1 g/L (95% confidence interval [CI], -1.0 to 11.1 g/L) for heterozygotes and 17.2 g/L (95% CI, 8.3 to 26.2 g/L) for homozygotes (estimates are adjusted for study site, age, height-for-age z score, and iron deficiency).


CONCLUSIONS
alpha(+)-Thalassemia limits the decline in hemoglobin concentration that is associated with afebrile infections, particularly those that are accompanied by inflammation.
Veenemans
Jacobien
J
Cell Biology and Immunology Group, Wageningen University, Wageningen, The Netherlands.
Andang'o
Pauline E A
PE
Mbugi
Erasto V
EV
Kraaijenhagen
Rob J
RJ
Mwaniki
David L
DL
Mockenhaupt
Frank P
FP
Roewer
Susanne
S
Olomi
Raimos M
RM
Shao
John F
JF
van der Meer
Jos W M
JW
Savelkoul
Huub F J
HF
Verhoef
Hans
H
D000740:Anemia / Q000517:prevention & control*; D000818:Animals; D002648:Child; D002675:Child, Preschool; D005914:Globins / Q000235:genetics; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007113:Immunity, Innate; D007223:Infant; D007630:Kenya / Q000453:epidemiology; D008288:Malaria / Q000150:complications* / Q000276:immunology*; D013636:Tanzania / Q000453:epidemiology; D017085:alpha-Thalassemia
D006454:Hemoglobins; D005914:Globins