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Cytokine profiles at birth predict malaria severity during infancy
Edward Kabyemela1, Bronner P Gonçalves, D Rebecca Prevots
1MOMS Project, Seattle Biomedical Research Institute, Seattle, Washington, United States of America, and Muheza Designated District Hospital, Muheza, Tanzania.
Insights
Cytokine profiles at birth, specifically Interleukin-1 beta (IL-1β), can predict malaria risk. Higher IL-1β levels at birth are linked to lower parasite density and reduced severe malaria in children.
Area of Science:
- Immunology
- Infectious Diseases
- Pediatrics
Background:
- Severe malaria risk exhibits significant inter-individual variability, with much of this unexplained.
- Early life immune responses may play a crucial role in determining long-term susceptibility to malaria.
Purpose of the Study:
- To investigate if cytokine profiles measured at birth predict malaria parasite density and disease severity in early childhood.
- To examine the persistence of cytokine levels from birth into early childhood.
Main Methods:
- A birth cohort study in Muheza, Tanzania (N=783) measured cytokine levels (including IL-1β, TNF-α) in cord blood at birth and peripheral blood during follow-up.
- Children received regular clinical and blood smear assessments for malaria parasite density and severe disease events.
Main Results:
- Cord blood cytokine levels were positively correlated. IL-1β and TNF-α cord levels correlated with early childhood levels.
- Higher cord blood IL-1β levels were associated with approximately 40% lower malaria parasite densities.
- Elevated cord IL-1β levels significantly decreased the risk of severe malaria (aHR 0.60).
Conclusions:
- Interleukin-1 beta (IL-1β) levels at birth are a significant predictor of both future IL-1β levels and severe malaria risk.
- The protective effect of IL-1β against severe malaria may be mediated by its role in controlling parasite density through inflammatory responses.
Background:
Severe malaria risk varies between individuals, and most of this variation remains unexplained. Here, we examined the hypothesis that cytokine profiles at birth reflect inter-individual differences that persist and influence malaria parasite density and disease severity throughout early childhood.
Methods And Findings:
Cytokine levels (TNF-α, IFN-γ, IL-1β, IL-4, IL-5, IL-6 and IL-10) were measured at birth (cord blood; N=783) and during subsequent routine follow-up visits (peripheral blood) for children enrolled between 2002 and 2006 into a birth cohort in Muheza, Tanzania. Children underwent blood smear and clinical assessments every 2-4 weeks, and at the time of any illness. Cord blood levels of all cytokines were positively correlated with each other (Spearman's rank correlation). Cord levels of IL-1β and TNF-α (but not other cytokines) correlated with levels of the same cytokine measured at routine visits during early life (P < 0.05). Higher cord levels of IL-1β but not TNF-α were associated with lower parasite densities during infancy (P=0.003; Generalized Estimating Equation (GEE) method), with an average ~40% reduction versus children with low cord IL-1β levels, and with decreased risk of severe malaria during follow-up (Cox regression): adjusted hazard ratio (95% CI) 0.60 (0.39-0.92), P = 0.02.
Conclusion:
IL-1β levels at birth are related to future IL-1β levels as well as the risk of severe malaria in early life. The effect on severe malaria risk may be due in part to the effect of inflammatory cytokines to control parasite density.
