Some babies who are exposed to malaria before birth develop a tolerant phenotype that increases their susceptibility to malaria and anemia in childhood, says a new study in the open access journal PLoS Medicine. Indu Malhotra and Christopher King (Case Western Reserve University) and colleagues studied 586 newborns residing in a malaria-holoendemic area of Kenya to age three, assessing their malaria infection, malaria-specific immune responses, and anemia, and classifying them into three groups: "sensitized" babies in which cord blood cells made activating cytokines in response to malaria antigens; "exposed, not-sensitized" babies in which cord blood cells did not make activating cytokines but made an inhibitory cytokine (IL-10); and "not-exposed" babies born to uninfected mothers.
The authors report that in the first 3 years of life, the exposed, not-sensitized newborns had a 60% greater risk of malaria infection than the unexposed group and a slightly higher risk of malaria infection than the sensitized group. They also had lower hemoglobulin levels, a sign of anemia, than the other babies. At 6 months, the T-cells of exposed, not-sensitized children were less likely to make activating cytokines in response to malaria antigens but made more IL-10 than the T-cells of the other children; malaria-specific antibody levels were similar in the three groups, say the authors.
Why some children exposed to malaria before birth become tolerant to the disease while exposure to malaria antigens "primes" the immune system of other children to respond efficiently to malaria antigens is not clear. However, these findings could have important implications for the design of malaria vaccines for use in areas where children are often exposed to malaria before birth and for the design of strategies for the prevention of malaria during pregnancy, say the authors.
"Once the significance of fetal malaria experience is better understood," the authors say, "it should translate into more effective strategies for malaria chemoprophylaxis during pregnancy."
In a related Perspective on the study, Lars Hviid (not involved in the research) states that the research by Dr. King and colleagues "adds significantly to our understanding of prenatal exposure to P. falciparum antigens" and has "obvious clinical importance." But he outlines several areas for further investigation of pregnancy-associated malaria.
Funding: The work was supported in part by United States Public Health Service grants I064687, AI054711, MH080601, AI065717 and Veterans' Affairs Research Service. The funders had no role in the study design, data collection, analysis, decision to publish or preparation of the manuscript. They did contribute to the design of the study.
Competing Interests: David Narum has declared the following competing interest: ''Narum et al., United States Patent 7,078,507 for production of recombinant EBA-175 RII protein.''
Citation: Malhotra I, Dent A, Mungai P, Wamachi A, Ouma JH, et al. (2009) Can Prenatal Malaria Exposure Produce an Immune Tolerant Phenotype?: A Prospective Birth Cohort Study in Kenya. PLoS Med 6(7): e1000116. doi:10.1371/journal.pmed.1000116
IN YOUR COVERAGE PLEASE USE THIS URL TO PROVIDE ACCESS TO THE FREELY AVAILABLE PAPER: http://medicine.plosjournals.org/perlserv/?request=get-document&doi= 1000116
PRESS-ONLY PREVIEW OF THE ARTICLE: http://www.plos.org/press/plme-06-07-king.pdf
EDITORS' SUMMARY: http://www.plos.org/press/plme-06-07-king-summary.pdf
CONTACTS:Christopher KingCase Western Reserve UniversityCenter for Global Health and Diseases2103 Cornell RdWRB 4129Cleveland, OH 44106-7286United States of America216 368- 4817216 368-4825 (fax)christopherkin@gmail.com
Related PLoS Medicine Perspective:
In a related Perspective on the study, Lars Hviid (not involved in the research) states that the research by Dr. King and colleagues "adds significantly to our understanding of prenatal exposure to P. falciparum antigens" and has "obvious clinical importance." But he outlines several areas for further investigation of pregnancy-associated malaria.
Funding: The author received no specific funding for this article.
Citation: Hviid L (2009) Unraveling the Impact of Malaria Exposure Before Birth. PLoS Med 6(7): e1000117.doi:10.1371/journal.pmed.1000117
IN YOUR COVERAGE PLEASE USE THIS URL TO PROVIDE ACCESS TO THE FREELY AVAILABLE PAPER: http://medicine.plosjournals.org/perlserv/?request=get-document&doi= 1000117
PRESS-ONLY PREVIEW OF THE ARTICLE: http://www.plos.org/press/plme-06-07-hviid.pdf
CONTACTS:
Lars HviidRigshospitaletDepartment of Infectious DiseasesM7641Blegdamsvej 9Copenhagen, 2100Denmark+45 (35) 45 79 57+45 (35) 45 76 44 (fax)lars.hviid@rh.hosp.dk
Source: Public Library of Science