Nitric Oxide Production and Nitric Oxide Synthase Activity in Malaria-Exposed Papua New Guinean Children and Adults Show Longitudinal Stability and No Association with Parasitemia
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Date
2004
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Infection and immunity.
Abstract
Individuals in areas of intense malaria transmission exhibit resistance (or tolerance) to levels of parasitemia
in their blood that would normally be associated with febrile illness in malaria-naïve subjects. The resulting
level of parasitemia associated with illness (the pyrogenic threshold) is highest in childhood and lowest in
adulthood. Clinical parallels between malarial and bacterial endotoxin tolerance have led to the supposition
that both share common physiological processes, with nitric oxide (NO) proposed as a candidate mediator. The
hypotheses that NO mediates tolerance and blood stage parasite killing in vivo were tested by determining its
relationship to age and parasitemia cross-sectionally and longitudinally in a population of 195 children and
adults from Papua New Guinea encountering intense malaria exposure. Despite pharmacological clearance of
asymptomatic parasitemia, NO production and mononuclear cell NO synthase (NOS) activity were remarkably
stable within individuals over time, were not influenced by parasitemia, and varied little with age. These results
contrast with previous smaller cross-sectional studies. Baseline NO production and NOS activity did not
protect against recurrent parasitemia, consistent with previous data suggesting that NO does not have
antiparasitic effects against blood stage infection in vivo. The NO indices studied were markedly higher in
specimens from study subjects than in samples from Australian controls, and NOS activity was significantly
associated with plasma immunoglobulin E levels, consistent with induction of NO by chronic exposure to other
infections and/or host genetic factors. These results suggest that NO is unlikely to mediate killing of blood
stage parasites in this setting and is unlikely to be the primary mediator in the acquisition or maintenance of
malarial tolerance.
Description
Keywords
Malaria, Child and adult, Papua New Guinean
Citation
Boutlis, C.S., Weinberg, J.B., Baker, J., Bockarie, M.J., Mgone, C.S., Cheng, Q. and Anstey, N.M., 2004. Nitric oxide production and nitric oxide synthase activity in malaria-exposed Papua New Guinean children and adults show longitudinal stability and no association with parasitemia. Infection and immunity, 72(12), pp.6932-6938.