CytoAstra, LLC — Department of Health and Human Services STTR Phase I: NIAID

Description

Summary Malaria continues to be a global health prioritywith almost half of the world s populationbillionat risk and arounddeaths each yearOvertreatment is caused by lack of diagnosis and contributes to resistancea huge threat as illustrated by artemisinin resistance in Southeast AsiaLittle progress has been made in the novel methods to diagnose malarialet alone in reliably identifying asymptomatically infected individualswhich is of utmost importance for the current elimination agendaMost current malaria tests have poor sensitivity at low levels of parasitemiain routine practice it is usually well aboveorparasitesLThat high a level is insufficient to detect the large reservoir of asymptomatic individualsThe goal of this proposal is to develop an innovative multicolor malaria detector using malaria specific in vivo photoacousticPAflow cytometryPAFCplatform for the earlynoninvasiveneedle freeno blood draw and thus no contamination concernlabel freeno injection of any reagent into the bloodrapida few secondsand safeno pain or skin damagediagnosis of malariaThis technology is based on PA detection of the malaria crystalhemozoinwithin circulating infected red blood cellsRBCsdirectly in the bloodstreamTranscutaneous irradiation of hand vessels with a low pulse energy laser leads to the microscopic local heating of hemozoin accompanied by thermoacoustic generation of acoustic wavesrecorded with an ultrasound transducer attached to the skinThe high acoustic resolution and high speed multicolor PAFC can detect and identity hemozoin in deeplargehigh flow rate blood vessels to provide the earliest and fastest malaria diagnosis withinseconds at an unprecedented parasitemia threshold as low asiRBCs mLThis istimes better than existing clinical malaria testsThis goal will be achieved through two interconnected specific aimsDevelop new malaria specific PAFC diagnostic device prototypeDetermine the efficacy of PAFC devices for label free detection of iRBCs in a preclinical mouse modelThe PAFC device will not be affected by hand movement or skin pigmentationThis malaria specific PAFC technology can be used to identify asymptomatic malaria infected individuals in a short time through gentle contact of the PA probe with the intact skinThe PAFC device can be a unique tool for malaria elimination by identifying asymptomatically infected humanswhich allows targeted interventions with appropriate treatmentOverallthis method will contribute substantially to allow treatment only for those who truly are infectedwhile avoiding unnecessary and inappropriate overtreatment of other febrile illnesses PROJECT NARRATIVE Malaria continues to be a global health prioritycausingdeaths per yearReliable diagnosis is crucial to target those truly having malaria and avoid overtreatmentand consequently resistance to antimalarial drugsThis proposal aims to develop an innovative diagnostic technology for the detection of malaria parasites at an unprecedentedfold lower detection limit as compared to current testsThe method is robustnoninvasiveneedle freeno blood drawing or contamination concernlabel freeno injection of any reagents into the bloodrapida few secondseasy to useandno pain or skin damagelow costThis unmatched diagnostic performance will significantly improve appropriate treatment and importantlywill be an invaluable tool for malaria elimination allowing clinicians to identify and target low grade asymptomatically infected individuals