Inhaled Nitric Oxide and Cerebral Malaria: Basis of a Strategy for Buying Time for Pharmacotherapy

1Brigham and Women's Hospital, Harvard Medical School 2Institut de recherche pour le développement, France 3Epicentre Research Base, Mbarara, Uganda 4Mbarara University, Mbarara, Uganda 5Massachusetts General Hospital, Harvard Medical School.
The Pediatric Infectious Disease Journal (Impact Factor: 3.14). 07/2012; 31(12). DOI: 10.1097/INF.0b013e318266c113
Source: PubMed

ABSTRACT There are approximately 225-600 million new malaria infections worldwide annually, with severe and cerebral malaria representing major causes of death internationally. The role of nitric oxide (NO) in the host response in cerebral malaria continues to be elucidated, with numerous known functions relating to the cytokine, endovascular, and cellular responses to infection with Plasmodium falciparum. Evidence from diverse modes of inquiry suggests NO to be critical in modulating the immune response and promoting survival in patients with cerebral malaria. This line of investigation has culminated in the approval of two phase II randomized prospective clinical trials in Uganda studying the use of inhaled NO as adjuvant therapy in children with severe malaria. The strategy underlying both trials is to use the sytemic anti-inflammatory properties of inhaled NO to "buy time" for chemical anti-parasite therapy to lower the parasite load. This paper reviews the nexus of malaria and nitric oxide biology with a primary focus on cerebral malaria in humans.

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May 20, 2014