ArticleInfection and immunity1999
Therapy with a combination of low doses of interleukin 12 and chloroquine completely cures blood-stage malaria, prevents severe anemia, and induces immunity to reinfection.
Article in Infection and immunity, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
20 citing papers in PubMed, 2 syntheses or guidelines pooled it, 47 citations in OpenAlex.
- Low Interleukin-12 Levels concerning Severe Malaria: A Systematic Review and Meta-Analysis.International journal of environmental research and public health · 2022Pooled it
- A meta-analysis of the effectiveness of albendazole compared with metronidazole as treatments for infections with Giardia duodenalis.PLoS neglected tropical diseases · 2010Pooled it
- Host candidate gene polymorphisms and associated clearance of P. falciparum amodiaquine and fansidar resistance mutants in children less than 5 years in Cameroon.Pathogens and global health · 2014Trial
- Prevalence of malaria, prevention measures, and main clinical features in febrile children admitted to the Franceville Regional Hospital, Gabon.Parasite (Paris, France) · 2016Article
- IL12Rβ1: the cytokine receptor that we used to know.Cytokine · 2015Review
- Sequential Plasmodium chabaudi and Plasmodium berghei infections provide a novel model of severe malarial anemia.Infection and immunity · 2012Article
- Antibodies to malaria vaccine candidates are associated with chloroquine or sulphadoxine/pyrimethamine treatment efficacy in children in an endemic area of Burkina Faso.Malaria journal · 2012Article
- Parasitostatic effect of maslinic acid. II. Survival increase and immune protection in lethal Plasmodium yoelii-infected mice.Malaria journal · 2011Article
- Severe malarial anemia: innate immunity and pathogenesis.International journal of biological sciences · 2011Review
- Polymorphisms in genes of interleukin 12 and its receptors and their association with protection against severe malarial anaemia in children in western Kenya.Malaria journal · 2010Article
- A replication study of the association between the IL12B promoter allele CTCTAA and susceptibility to cerebral malaria in Thai population.Malaria journal · 2009Article
- Patent filarial infection modulates malaria-specific type 1 cytokine responses in an IL-10-dependent manner in a filaria/malaria-coinfected population.Journal of immunology (Baltimore, Md. : 1950) · 2009Article
- Concepts of immunostimulation to increase antiparasitic drug action.Parasitology research · 2003Review
- Relationship between plasma Interleukin-12 (IL-12) and IL-18 levels and severe malarial anemia in an area of holoendemicity in western Kenya.Clinical and diagnostic laboratory immunology · 2003Article
- A promoter polymorphism in the gene encoding interleukin-12 p40 (IL12B) is associated with mortality from cerebral malaria and with reduced nitric oxide production.Genes and immunity · 2002Article
- Cytokines in the pathogenesis of and protection against malaria.Clinical and diagnostic laboratory immunology · 2002Review
- Antimalarial drugs clear resistant parasites from partially immune hosts.Antimicrobial agents and chemotherapy · 2001Article
- Early nonspecific immune responses and immunity to blood-stage nonlethal Plasmodium yoelii malaria.Infection and immunity · 2000Article
- Low interleukin-12 activity in severe Plasmodium falciparum malaria.Infection and immunity · 2000Article
- Macrophage migration inhibitory factor release by macrophages after ingestion of Plasmodium chabaudi-infected erythrocytes: possible role in the pathogenesis of malarial anemia.Infection and immunity · 2000Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The immunoregulatory cytokine interleukin 12 (IL-12) induces host resistance against experimental malaria. In this study, we tested the feasibility of using IL-12 in combination with chloroquine (CQ) to rescue susceptible A/J mice from lethal blood-stage Plasmodium chabaudi AS infection. Combined treatment with low doses of CQ and IL-12 resulted in a >15-fold reduction in the parasite load and 100% survival of A/J mice with established infections. Compared to control mice, which succumbed to severe anemia, CQ-plus-IL-12-treated mice had significantly higher early- and late-stage erythroid-cell progenitors in the bone marrow and spleen, resulting in significantly higher hematocrits, erythrocyte counts, and percentages of reticulocytes. Production of parasite-specific gamma interferon (IFN-gamma) by splenocytes from these mice was upregulated >20-fold relative to controls in parallel with enhanced IFN-gamma mRNA expression. Further, enhanced responsiveness to IL-12 and increased downstream IFN-gamma production in CQ-plus-IL-12-treated mice was evident from increased mRNA expression for the beta1 and beta2 subunits of IL-12 receptor in the splenocytes. Moreover, this combined therapy induced higher levels of anti-malaria antibodies than did CQ alone as well as sterile immunity against reinfection. Because IL-12 can be used at low doses and is effective even in established infections, it may be feasible to use this immunochemotherapeutic approach in human malaria.
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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.