Dirofilaria volatile organic compound signatures and uses thereof

Abstract

Described herein are Dirofilarial exhalant signatures and methods of detecting a Dirofilaria signature in a non-blood biological sample, such as exhalant, that can be used to detect Dirofilarial infection in a subject, such as a canine.

What is claimed is: 
     
         1 . A method of non-invasively detecting  Dirofilaria  infection in a subject, the method comprising:
 (a) detecting a  Dirofilaria  exhalant signature in an exhalant sample obtained from the subject, wherein the  Dirofilaria  exhalant signature comprises one or more volatile organic compounds (VOCs) selected from the group consisting of: an aromatic hydrocarbon, a monoterpene, a cyclopentanone, an aziridine, an alkane hydrocarbon, a phenol, a ketone, and combinations thereof,   whereby detection of a decrease or increase of one or more VOCs of the  Dirofilaria  exhalant signature as compared to a threshold value, a suitable control, or both indicates the presence or absence of  Dirofilaria  infection in the subject.   
     
     
         2 . The method of  claim 1 , further comprising
 (b) administering to a subject determined in step (a) to not have a  Dirofilaria  infection an anthelmintic effective to prevent at least the adult stage of  Dirofilaria  in the subject one or more times; or   (c) administering to a subject determined in step (a) to have a  Dirofilaria  infection a treatment effective to kill the adult stage of  Dirofilaria  in the subject one or more times, an anthelmintic effective to prevent at least the adult stage of  Dirofilaria  in the subject one or more times or both.   
     
     
         3 . The method of  claim 1 , wherein the number of VOCs in the  Dirofilaria  exhalant signature is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 15, or 15. 
     
     
         4 . The method of  claim 1 , wherein the one or more VOCs are selected from the group consisting of: ortho xylene, p-Methane-1,2,3-triol, 3,7,11-trimethyl-1-Dodecanol, 2-ethyl-Cyclohexanone, 2-mehtyl-2-(2,2,4,4,6,6-hexamethylheptyl)-Aziridine, 1,2,3,6,7,8,8a,8b-octahydro, trans-Biphenylene, 2,6,10-trimethyl- tetradecane, 5,6,6-Trimethyl-5-(3-oxobut enyl)-1-oxaspiro[2.5]octan-4-one, and 5,5-Dibutylnonane. 
     
     
         5 . The method of  claim 1 , wherein the  Dirofilaria  is  Dirofilaria immitis, Dirofilaria repens, Dirofilaria tenuis, Dirofilaria ursi, D. subdermata, D. striata,  or a  D. hongkongensis.    
     
     
         6 . The method of  claim 1 , wherein the anthelmintic effective to prevent at least the adult stage of  Dirofilaria  comprises:
 ivermectin, moxidectin, milbemycin oxime, selamectin, eprinomectin, or any combination thereof.   
     
     
         7 . The method of  claim 1 , further comprising co-administering a composition effective to prevent, treat, or both an intestinal parasite, external parasite, or both. 
     
     
         8 . The method of  claim 6 , wherein the composition effective to prevent, treat, or both an intestinal parasite, external parasite, or both is one or more compounds of one or more of the following classes benzimidazole, piperazine, depolarizing tetrahydropyrimidines, a macrocyclic lactone, neonicotinoid, phenylpyrazole, oxadiazine, pyrethrin, pyrethroid, isoxazoline, an insect growth regulator, and any combination thereof 
     
     
         9 . The method of  claim 7 , wherein the composition effective to prevent, treat, or both an intestinal parasite, external parasite, or both is selected from pyrantel, pyrantel pamoate, febantel, praziquantel, oxibendazole, piperazine, spinosad, fluralaner, afoxolaner, fipronil, sarolaner, lotilaner, lufenuron, imidacloprid, Methoprene, S-methoprene, pyriproxyfen, fenbendazole, flumethrin, selamectin, eprinomectin, indoxacarb, permethrin, nitenpyram, and any combination thereof. 
     
     
         10 . The method of  claim 1 , wherein the treatment effective to kill the adult stage of  Dirofilaria  comprises administering melarsomine to the subject. 
     
     
         11 . The method of  claim 1 , wherein the treatment effective to kill the adult stage of  Dirofilaria  comprises administering a macrocyclic lactone anthelmintic effective to kill adult 
     
     
         12 . The method of  claim 1 , wherein the subject is administered treatment effective to kill the adult stage of  Dirofilaria  and the method further comprises administering an amount of doxycycline for two or more concurrent days to the subject, and wherein the amount of doxycycline is optionally administered for about 30 days. 
     
     
         13 . The method of  claim 1 , wherein the subject is a human. 
     
     
         14 . The method of  claim 1 , wherein the subject is a non-human animal, optionally a canine. 
     
     
         15 . A device configured to collect an exhalant for analysis of volatile organic compounds (VOCs) present in the exhalant of a single non-human animal subject, comprising:
 an exhalant collector configured to actively and non-invasively collect exhalant expelled from the non-human animal subject without being placed in an orifice of the subject; and   one or more removable collection chambers, each removable collection chamber configured to hold an amount of exhalant collected and are suitable for containment of VOCs, wherein the one or more removable collection chambers are operatively coupled to the exhalant collector.   
     
     
         16 . The device of  claim 15 , wherein the exhalant collector comprises or is coupled to one or more low pressure air pumps capable of moving exhalant external to the device into the exhalant collector and into the one or more removable collection chambers. 
     
     
         17 . The device of  claim 15 , wherein the device comprises one or more one-way air valves configured to control the flow of exhalant in one direction through the device from the external environment through the exhalant collector and into and optionally through the one or more removable collection chambers. 
     
     
         18 . The device of  claim 15 , wherein the exhalant collector is a tube that is configured to be placed in effective proximity to a mouth, nose, nostrils, or a combination thereof of the subject during collection and draw exhalant into the exhalant collector, and wherein the exhalant collector is optionally a mask that is configured to cover the mouth and nose of the subj ect. 
     
     
         19 . The device of claim  23 , wherein the exhalant collector, the one or more removable collection chambers, or both comprise one or more filters, wherein at least one of the one or more filters is effective to remove environmental VOCs from exhalant collected and optionally comprises a material capable of capturing VOCs, retaining VOCs, preserving VOCs, concentrating VOCs, enriching VOCs, releasing captured VOCs, or any combination thereof from collected exhalant. 
     
     
         20 . A kit comprising:
 one or more removable collection chambers configured to use in a device of  claim 15 , wherein the one or more removable collection chambers comprise one or more filters, wherein at least one of the one or more filters is effective to remove environmental VOCs from exhalant collected and optionally comprises a material capable of capturing VOCs, retaining VOCs, preserving VOCs, concentrating VOCs, enriching VOCs, releasing captured VOCs, or any combination thereof from collected exhalant;   and instructions fixed in a tangible medium of expression wherein the instructions provide directions for using the one or more removable collection chambers to collect volatile organic compounds from an exhalant of a subject and detecting a  Dirofilaria  exhalant signature to diagnose, prognose, and/or stage a  Dirofilaria  infection in the subject.