METHODS The strips are constructed based on the same principles as a glucose strip for diabetes patients, where one drop of blood from the finger detects formate by a color change (Fig 2). Fig 2 Principles and basic structure Methanol itself is not toxic, and symptoms does not appear until a sufficient amount of formic acid/formate has been developed (approx 10mM) – this usually takes 12-24 hours after metabolism has started. Knut Erik Hovda 1 , Gaut Gadeholt 2 , Dag Jacobsen 2 1 The Norwegian CBRNE Centre of Medicine, Department of Acute Medicine, Oslo University Hospital, Oslo, Norway 2 Department of Acute Medicine, Oslo University Hospital, Oslo, Norway BACKGROUND Every year, thousands of people are poisoned by methanol, but in spite of an increasing number of outbreaks being reported by the media and sometimes the medical literature (Fig 1), this is likely only tip of the iceberg. Despite effective treatment, the lack of awareness, knowledge and especially diagnostic equipment, leaves thousands dead, blind or brain damaged. Methanol poisoning most often affects the poorest of the poor – children and adults – predominantly in the low- and middle income countries 1 . By often tearing away the young and healthy members of society, it increases the social burden. Fig 1 Reported methanol incidents recent years In addressing the methanol poisoning problem worldwide, there are several challenges: The delay from intake to symptoms, the variation of symptoms, the lack of clinical experience, the limited availability of treatment options, the overwhelming of resources/lack of capacity, and the high morbidity and mortality. Still, the lack of diagnostic equipment 2 remains one of the major problems, as it is difficult to identify and treat a poisoning if you do not know who to treat. The diagnostic alternatives are far from satisfactory most places 3 , and more or less non-existing in the low- and middle income countries where most of the poisonings actually occurs. We have therefore developed a point-of-care diagnostic tool (MeTOXÔ) for measuring formate 4 , the toxic metabolite of methanol. DISCUSSION We have developed a simple, bedside tool for diagnosing methanol poisoning and for screening metabolic acidosis of unknown origin: No laboratory equipment is needed. The sensitivity and specificity is high, it is stable, and can be disposed after use. The strip is meant as a screening tool to eliminate methanol poisoning as the cause in metabolic acidosis of unknown origin – a very common medical condition causing challenges in all health care systems. The production of MeTOXÔ Generation 1 is expected to start in 2017 as a non-for-profit for the inventors. Novel bedside diagnostics for methanol poisoning REFERENCES 1 Rostrup M et al. Plos One 2016;11:e0152676 2 Hovda KE et al.. Scand J Clin Lab Invest 2015; 75(7): 610-4 3 Kraut Ja. Clin Toxicol. 2015;53(7):589-95. 4 Hovda KE et al. J Anal Toxicol 2005; 29(6): 586-588 RESULTS The prototype is now finalized, with testing rendering a high sensitivity with an increasing color reaction with higher concentrations of formate. There were no influence on the specificity testing on any of the tested substances (i.e. no false positives). The result can be read within 2-3 minutes from a disposable strip. The shelf life is more than two years in room temperature (i.e. no cold storage or cold chain during transport is necessary). Detectable few hours after methanol metabolism (>6 hours before symptoms appears) 0 10 20 30 40 50 60 ID: R515 Disclosure MeTOXÔ is a registered product owned by Orphan Diagnostics (www.orphandiagnostics.com). Orphan Diagnostics is owned by Oslo University Hospital/Inven2 and the innovators. The innovators have given away all future income and royalties to make the product non-for-profit and thus reach the low- and middle income countries for as low cost as possible.

ID: R515 Novelbedsidediagnosticsfor methanolpoisoning...MeTOX - Bedside diagnostics for methanol poisoning Author Knut Erik Hovda Created Date 20170502125019Z

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Page 1: ID: R515 Novelbedsidediagnosticsfor methanolpoisoning...MeTOX - Bedside diagnostics for methanol poisoning Author Knut Erik Hovda Created Date 20170502125019Z

METHODSThestripsareconstructedbasedonthesameprinciplesasaglucosestripfordiabetespatients,whereonedropofbloodfromthefingerdetectsformatebyacolorchange(Fig2).

Fig2Principles andbasic structureMethanol itself isnottoxic,andsymptomsdoes notappear until asufficientamount offormic acid/formatehasbeen developed (approx 10mM)– this usuallytakes 12-24hours after metabolism hasstarted.

KnutErikHovda1,Gaut Gadeholt2,DagJacobsen2

1TheNorwegianCBRNECentreofMedicine,DepartmentofAcuteMedicine,OsloUniversityHospital,Oslo,Norway2DepartmentofAcuteMedicine,OsloUniversityHospital,Oslo,Norway

BACKGROUNDEveryyear,thousandsofpeoplearepoisonedbymethanol,butinspiteofanincreasingnumberofoutbreaksbeingreportedbythemediaandsometimesthemedicalliterature(Fig1),thisislikelyonlytipoftheiceberg.Despiteeffectivetreatment,thelackofawareness,knowledgeandespeciallydiagnosticequipment,leavesthousandsdead,blindorbraindamaged.Methanolpoisoningmostoftenaffectsthepoorestofthepoor– childrenandadults– predominantlyinthelow- andmiddleincomecountries1.Byoftentearingawaytheyoungandhealthymembersofsociety,itincreasesthesocialburden.

Fig1Reported methanol incidents recent years

Inaddressingthemethanolpoisoningproblemworldwide,thereareseveralchallenges:Thedelayfromintaketosymptoms,thevariationofsymptoms,thelackofclinicalexperience,thelimitedavailabilityoftreatmentoptions,theoverwhelmingofresources/lackofcapacity,andthehighmorbidityandmortality.Still,thelackofdiagnosticequipment2 remainsoneofthemajorproblems,asitisdifficulttoidentifyandtreatapoisoningifyoudonotknowwhototreat.Thediagnosticalternativesarefarfromsatisfactorymostplaces3,andmoreorlessnon-existinginthelow- andmiddleincomecountrieswheremostofthepoisoningsactuallyoccurs.Wehavethereforedevelopedapoint-of-carediagnostictool(MeTOXÔ)formeasuringformate4,thetoxicmetaboliteofmethanol.

DISCUSSIONWehavedevelopedasimple,bedsidetoolfordiagnosingmethanolpoisoningandforscreeningmetabolicacidosisofunknownorigin:Nolaboratoryequipmentisneeded.Thesensitivityandspecificityishigh,itisstable,andcanbedisposedafteruse.Thestripismeantasascreeningtooltoeliminatemethanolpoisoningasthecauseinmetabolicacidosisofunknownorigin– averycommonmedicalconditioncausingchallengesinallhealthcaresystems.

TheproductionofMeTOXÔ Generation1isexpectedtostartin2017asanon-for-profitfortheinventors.

Novel bedside diagnostics formethanol poisoning

REFERENCES1RostrupMetal.Plos One2016;11:e01526762HovdaKEetal..Scand JClin LabInvest2015;75(7):610-43KrautJa.ClinToxicol.2015;53(7):589-95.4HovdaKEetal. JAnalToxicol 2005;29(6):586-588

RESULTSTheprototypeisnowfinalized,withtestingrenderingahighsensitivitywithanincreasingcolorreactionwithhigherconcentrationsofformate.Therewerenoinfluenceonthespecificitytestingonanyofthetestedsubstances(i.e.nofalsepositives).Theresultcanbereadwithin2-3minutesfromadisposablestrip.Theshelflifeismorethantwoyearsinroomtemperature(i.e.nocoldstorageorcoldchainduringtransportisnecessary).

Detectable few hours aftermethanol metabolism

(>6hours before symptomsappears)

ID:R515

DisclosureMeTOXÔ isaregisteredproductownedbyOrphanDiagnostics(www.orphandiagnostics.com).OrphanDiagnosticsisownedbyOsloUniversityHospital/Inven2andtheinnovators.Theinnovatorshavegivenawayallfutureincomeandroyaltiestomaketheproductnon-for-profitandthusreachthelow- andmiddleincomecountriesforaslowcostaspossible.