Diagnosis and treatment of invasive aspergillosis

Abstract

Methods for diagnosing, treating, and monitoring the treatment of invasive aspergillosis (IA) are described. The methods can include detecting the presence of one or more volatile organic compounds (VOCs) in the breath of subjects suspected of having IA.

1 - 4 . (canceled) 
     
     
         5 . A method of detecting the presence of an  Aspergillus fumigatus, A. terreus,  or  A. calidoustus  infection in a subject, the method comprising:
 obtaining a sample comprising breath of a subject, or headspace from a culture suspected of comprising Aspergillus isolated from a subject;   determining the presence of one, two, three, or more Volatile Organic Compounds (VOCs) selected from the group consisting of camphene, alpha-pinene, beta-pinene, limonene, alpha-bergamotene, alpha-santalene, beta-elemene, acoradien, chamigrene, 1,5,9-trimethyl cyclododecatriene, 9-decene-2-one and beta-sesquiphellandrene in the sample, wherein:
 the presence of one, two, three, or more of camphene, alpha-pinene, beta-pinene, limonene, or alpha-bergamotene indicates the presence of an  A. fumigatus  infection; 
 the presence of one, two, three, or more of alpha-santalene, beta-elemene, acoradien, chamigrene, and 1,5,9-trimethyl cyclododecatriene indicates the presence of an  A. terreus  infection; and 
 the presence of one or both of 9-decene-2-one and beta-sesquiphellandrene indicates the presence of an  A. calidoustus  infection in the subject; and 
   administering a therapy comprising an azole to a subject who has an  A. fumigatus  infection or who has an  A. terrus  infection, and administering a therapy comprising amphotericin B (AMB) to a subject who has an  A. calidoustus  infection.   
     
     
         6 . The method of  claim 5 ,
 wherein the azole is voriconazole   or the amphotericin B (AMB) is D-AMB or a lipid formulation of AMB   
     
     
         7 - 9 . (canceled) 
     
     
         10 . A method of detecting the presence of an  Aspergillus fumigatus, A. terreus,  or  A. calidoustus  infection in a culture, the method comprising:
 obtaining a sample comprising gas from the headspace of the culture;   determining the presence of one, two, three, or more VOCs selected from the group consisting of camphene, alpha-pinene, beta-pinene, limonene, alpha-bergamotene, alpha-santalene, beta-elemene, acoradien, chamigrene, 1,5,9-trimethyl cyclododecatriene, 9-decene-2-one and beta-sesquiphellandrene in the sample, wherein:
 the presence of one, two, three, or more of camphene, alpha-pinene, beta-pinene, limonene, or alpha-bergamotene indicates the presence of  A. fumigatus  in the culture; 
 the presence of one, two, three, or more of alpha-santalene, beta-elemene, acoradien, chamigrene, and 1,5,9-trimethyl cyclododecatriene indicates the presence of  A. terreus  in the culture; and 
 the presence of one or both of 9-decene-2-one and beta-sesquiphellandrene indicates the presence of  A. calidoustus  infection in the culture. 
   
     
     
         11 . The method of  claim 5 , wherein determining the presence of a VOC comprises assaying the sample to detect the presence the VOC. 
     
     
         12 . The method of  claim 11 , wherein assaying the sample to detect the presence the VOC comprises using a gas chromatography (GC) or spectrometry method. 
     
     
         13 . The method of  claim 12 , wherein the spectrophotometry method is mobility spectrometry (IMS) or differential mobility spectrometry (DMS). 
     
     
         14 . The method of  claim 5 , wherein the subject is a human.\ 
     
     
         15 . The method of  claim 11 , wherein the subject is a human. 
     
     
         16 . (canceled)