title: Analysis of Breath Specimens for Biomarkers of Plasmodium falciparum Infection.
abstract: Currently, the majority of diagnoses of malaria rely on a combination of the patient's clinical presentation and the visualization of parasites on a stained blood film. Breath offers an attractive alternative to blood as the basis for simple, noninvasive diagnosis of infectious diseases. In this study, breath samples were collected from individuals during controlled malaria to determine whether specific malaria-associated volatiles could be detected in breath. We identified 9 compounds whose concentrations varied significantly over the course of malaria: carbon dioxide, isoprene, acetone, benzene, cyclohexanone, and 4 thioethers. The latter group, consisting of allyl methyl sulfide, 1-methylthio-propane, (Z)-1-methylthio-1-propene, and (E)-1-methylthio-1-propene, had not previously been associated with any disease or condition. Before the availability of antimalarial drug treatment, there was evidence of concurrent 48-hour cyclical changes in the levels of both thioethers and parasitemia. When thioether concentrations were subjected to a phase shift of 24 hours, a direct correlation between the parasitemia and volatile levels was revealed. Volatile levels declined monotonically approximately 6.5 hours after initial drug treatment, correlating with clearance of parasitemia. No thioethers were detected in in vitro cultures of Plasmodium falciparum. The metabolic origin of the thioethers is not known, but results suggest that interplay between host and parasite metabolic pathways is involved in the production of these thioethers.
authors: CSIRO Food and Nutrition Flagship, Canberra.
authors: Amalia Z
authors: AZ
authors: Berna
authors: QIMR Berghofer Medical Research Institute Infectious Diseases Unit, Royal Brisbane and Women's Hospital, Brisbane.
authors: James S
authors: JS
authors: McCarthy
authors: CSIRO Digital Productivity Flagship, Sydney.
authors: Rosalind X
authors: RX
authors: Wang
authors: Research School of Biology, Australian National University, Canberra, Australia.
authors: Kevin J
authors: KJ
authors: Saliba
authors: CSIRO Food and Nutrition Flagship, Canberra.
authors: Florence G
authors: FG
authors: Bravo
authors: CSIRO Food and Nutrition Flagship, Canberra.
authors: Julie
authors: J
authors: Cassells
authors: CSIRO Food and Nutrition Flagship, Canberra.
authors: Benjamin
authors: B
authors: Padovan
authors: CSIRO Food and Nutrition Flagship, Canberra.
authors: Stephen C
authors: SC
authors: Trowell
mesh_terms: D015415:Biomarkers / Q000032:analysis*; D001944:Breath Tests; D015331:Cohort Studies; D006801:Humans; D016778:Malaria, Falciparum / Q000175:diagnosis*; D009812:Odorants / Q000032:analysis; D018512:Parasitemia; D013440:Sulfides / Q000032:analysis*; D055549:Volatile Organic Compounds / Q000032:analysis*
chemical_list: D015415:Biomarkers; D013440:Sulfides; D055549:Volatile Organic Compounds
keywords: (E)-1-methylthio-1-propene; diagnostic tool; machine learning; malaria; odors; thioethers; volatile organic compound