Age-Related Changes in Malaria Clinical Phenotypes During Infancy Are Modified by Sickle Cell Trait.
asymptomatic parasitemia
malaria in infancy
sickle cell trait
Journal
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
ISSN: 1537-6591
Titre abrégé: Clin Infect Dis
Pays: United States
ID NLM: 9203213
Informations de publication
Date de publication:
16 11 2021
16 11 2021
Historique:
received:
12
11
2020
pubmed:
20
3
2021
medline:
23
11
2021
entrez:
19
3
2021
Statut:
ppublish
Résumé
Infants are protected against Plasmodium falciparum malaria. Mechanisms that drive this protection remain unclear due to a poor understanding of malaria clinical phenotypes during infancy. We enrolled a birth cohort of 678 infants in Busia, Uganda, an area of high malaria transmission. We followed infants through 12 months of age and quantified protection against parasitemia and clinical disease. Symptomatic malaria incidence increased from 1.2 to 2.6 episodes per person-year between 0 and <6 months and between 6 and 12 months of age, while the monthly probability of asymptomatic parasitemia given infection decreased from 32% to 21%. Sickle cell trait (HbAS) was protective against symptomatic malaria (incidence rate ratio = 0.57 comparing HbAS vs hemoglobin AA (HbAA); 95% confidence interval, 0.44-0.74; P < .001), but age modified this relationship (Pint = <0.001), with nonlinear protection that waned between 0 and 9 months of age before increasing. Increasing age was associated with higher parasite densities at the time of infection and, in infants with HbAS, a reduced ability to tolerate high parasite densities without fever. Age-dependent changes in HbAS protective efficacy in infancy were accompanied by differential loss of antiparasite and antidisease protection among HbAS and HbAA infants. This provides a framework for investigating the mechanisms that underlie infant protection against malaria. NCT02793622.
Sections du résumé
BACKGROUND
Infants are protected against Plasmodium falciparum malaria. Mechanisms that drive this protection remain unclear due to a poor understanding of malaria clinical phenotypes during infancy.
METHODS
We enrolled a birth cohort of 678 infants in Busia, Uganda, an area of high malaria transmission. We followed infants through 12 months of age and quantified protection against parasitemia and clinical disease.
RESULTS
Symptomatic malaria incidence increased from 1.2 to 2.6 episodes per person-year between 0 and <6 months and between 6 and 12 months of age, while the monthly probability of asymptomatic parasitemia given infection decreased from 32% to 21%. Sickle cell trait (HbAS) was protective against symptomatic malaria (incidence rate ratio = 0.57 comparing HbAS vs hemoglobin AA (HbAA); 95% confidence interval, 0.44-0.74; P < .001), but age modified this relationship (Pint = <0.001), with nonlinear protection that waned between 0 and 9 months of age before increasing. Increasing age was associated with higher parasite densities at the time of infection and, in infants with HbAS, a reduced ability to tolerate high parasite densities without fever.
CONCLUSIONS
Age-dependent changes in HbAS protective efficacy in infancy were accompanied by differential loss of antiparasite and antidisease protection among HbAS and HbAA infants. This provides a framework for investigating the mechanisms that underlie infant protection against malaria.
CLINICAL TRIALS REGISTRATION
NCT02793622.
Identifiants
pubmed: 33738485
pii: 6178468
doi: 10.1093/cid/ciab245
pmc: PMC8599196
doi:
Banques de données
ClinicalTrials.gov
['NCT02793622']
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1887-1895Subventions
Organisme : NICHD NIH HHS
ID : P01 HD059454
Pays : United States
Organisme : NICHD NIH HHS
ID : P01 HD059454
Pays : United States
Organisme : Bill and Melinda Gates Foundation
ID : OPP1141549
Informations de copyright
© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.
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