Trial reportClinical infectious diseases : an official publication of the Infectious Diseases Society of America2019
A Balanced Proinflammatory and Regulatory Cytokine Signature in Young African Children Is Associated With Lower Risk of Clinical Malaria.
Trial report in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00231452 (Age of Exposure and Immunity to Malaria in Infants), which is not on this map. Cited by 12 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Age of Exposure and Immunity to Malaria in Infants
Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.
- Increased interleukin-6 levels associated with malaria infection and disease severity: a systematic review and meta-analysis.Scientific reports · 2022Pooled it
- From Traditional Use to Modern Evidence: The Medicinal Chemistry of Antimalarials from GenusMini reviews in medicinal chemistry · 2025Review
- Dynamics of osteopontin levels and correlation with parasitemia in acute malaria in Uganda and Sweden.BMC infectious diseases · 2024Article
- Article
- Mature beyond their years: young children who escape detection of parasitemia despite living in settings of intense malaria transmission.Biochemical Society transactions · 2024Review
- Review
- IL-18 and IL-18 binding protein are related to disease severity and parasitemia during falciparum malaria.BMC infectious diseases · 2021Article
- G6pd-Deficient Mice Are Protected From Experimental Cerebral Malaria and Liver Injury by Suppressing Proinflammatory Response in the Early Stage ofFrontiers in immunology · 2021Article
- AlteredFrontiers in immunology · 2021Article
- Research Advances on Health Effects of EdibleFoods (Basel, Switzerland) · 2020Review
- Plasma levels of interleukin 27 in falciparum malaria is increased independently of co-infection with HIV: potential immune-regulatory role during malaria.BMC infectious diseases · 2020Article
- Red blood cell homeostasis in children and adults with and without asymptomatic malaria infection in Burkina Faso.PloS one · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 6 institutions in 3 countries.
Funding
Abstract
backgroundThe effect of timing of exposure to first Plasmodium falciparum infections during early childhood on the induction of innate and adaptive cytokine responses and their contribution to the development of clinical malaria immunity is not well established.
methodsAs part of a double-blind, randomized, placebo-controlled trial in Mozambique using monthly chemoprophylaxis with sulfadoxine-pyrimethamine plus artesunate to selectively control timing of malaria exposure during infancy, peripheral blood mononuclear cells collected from participants at age 2.5, 5.5, 10.5, 15, and 24 months were stimulated ex vivo with parasite schizont and erythrocyte lysates. Cytokine messenger RNA expressed in cell pellets and proteins secreted in supernatants were quantified by reverse-transcription quantitative polymerase chain reaction and multiplex flow cytometry, respectively. Children were followed up for clinical malaria from birth until 4 years of age.
resultsHigher proinflammatory (interleukin [IL] 1, IL-6, tumor necrosis factor) and regulatory (IL-10) cytokine concentrations during the second year of life were associated with reduced incidence of clinical malaria up to 4 years of age, adjusting by chemoprophylaxis and prior malaria exposure. Significantly lower concentrations of antigen-specific T-helper 1 (IL-2, IL-12, interferon-γ) and T-helper 2 (IL-4, IL-5) cytokines by 2 years of age were measured in children undergoing chemoprophylaxis compared to children receiving placebo (P < .03).
conclusionsSelective chemoprophylaxis altering early natural exposure to malaria blood stage antigens during infancy had a significant effect on T-helper lymphocyte cytokine production >1 year later. Importantly, a balanced proinflammatory and anti-inflammatory cytokine signature, probably by innate cells, around age 2 years was associated with protective clinical immunity during childhood. CLINICAL TRIALS REGISTRATION: NCT00231452.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.