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Infection and Immunity, July 2003, p. 3682-3689, Vol. 71, No. 7
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.7.3682-3689.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Nitric Oxide Production and Mononuclear Cell Nitric Oxide Synthase Activity in Malaria-Tolerant Papuan Adults

Craig S. Boutlis,^1,2 Emiliana Tjitra,³ Helena Maniboey,^4, Mary A. Misukonis,⁵ Jocelyn R. Saunders,¹ Sri Suprianto,⁶ J. Brice Weinberg,⁵ and Nicholas M. Anstey^1,7*

International Health Program, Division of Infectious Diseases, Menzies School of Health Research,¹ Northern Territory University,² Flinders University Northern Territory Clinical School, Darwin, Northern Territory, Australia,⁷ National Institute of Health Research and Development,³ Directorate-General of Communicable Disease Control, Ministry of Health, Jakarta,⁶ Menzies School of Health Research, Jayapura Field Unit, Jayapura, Papua, Indonesia,⁴ Division of Hematology-Oncology, Department of Medicine, VA and Duke University Medical Centers, Durham, North Carolina⁵

Received 10 January 2003/ Returned for modification 21 February 2003/ Accepted 11 March 2003

Individuals living in regions of intense malaria transmission exhibit natural immunity that allows them to be without fever and other symptoms for most of the time despite frequent parasitization. Although this tolerance of parasitemia appears to be more effective in children than in adults (as evidenced by lower parasitemia fever thresholds with age), adults do exhibit a degree of tolerance but the mechanism(s) underlying this are unclear. Asymptomatic malaria-exposed children have higher levels of nitric oxide (NO) than children with severe disease, and NO has been proposed as a mediator of malarial tolerance. However, the ability of highly malaria-exposed asymptomatic adults to generate high-level basal NO is unknown, as is the relationship between NO and malaria tolerance in adults. The relationship between NO and malaria parasitemia was therefore determined in asymptomatic adults from Papua, Indonesia. Adults with Plasmodium falciparum parasitemia had markedly increased basal systemic NO production relative to aparasitemic Papuan controls, who in turn produced more NO than healthy controls from a region without malaria. Immunoglobulin E levels were universally elevated in malaria-exposed Papuan subjects, suggesting that the prevalence of intestinal parasitosis may be high and that nonmalarial infection may also contribute to high basal NO production. Basal peripheral blood mononuclear cell (PBMC) NO synthase activity was elevated in Papuans but poorly correlated with systemic NO production, suggesting that NO production in this setting arises not only from PBMCs but also from other tissue and cellular sources. NO production was associated with and may contribute to malaria tolerance in Papuan adults.

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* Corresponding author. Mailing address: Menzies School of Health Research, P.O. Box 41096, Casuarina, NT 0811, Australia. Phone: 61-8-8922-8196. Fax: 61-8-8927-5187. E-mail: anstey{at}menzies.edu.au.

Editor: W. A. Petri, Jr.

Present address: Rumah Sakit Dok II, Jl. Kesehatan, Jayapura, Papua, Indonesia.

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Infection and Immunity, July 2003, p. 3682-3689, Vol. 71, No. 7
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.7.3682-3689.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

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