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TB uaxlesi kvlevebis mimarTulebebi neli solomonia VII seminari, 15 seqtemberi, 2009 2006-2015 wlebis TB globaluri gegmis prioritetuli mimarTuleba TB kvlevebis inicireba, xelSewyoba da koordinirebaa TB uaxlesi kvlevebi msoflios masStabiT mimdinareobs Stop TB partnership-is, WHO-s, USAIDS-is, NIH-is xelmZRvanelobiT bil da milenda geitsebis fondis, klintonis sainiciativo jgufis, msoflios yvela qveynis ministerialis mxardaWeriT msoflios masStabiT mimdinare TB kvlevebis ZiriTadi mimarTulebebia axali TB preparatebis Seqmna (GATB); upiratesad MDR/XDR-TB da LTBI-is samkurnalod ukve arsebul preparatebTan maTi maqsimalurad efeqturi kombinaciebis SemuSaveba; moklevadiani (2 Tviani, an naklebi xangrZlivobis) samkurnalo reJimis SemuSaveba. 5 wliani kvlevebis gakveTili: ukve arsebuli antibaqteriuli preparatebis TB-is sawinaaRmdegod gamoyeneba naklebad efeqturia; aucilebelia arsebiTad axali qimiuri Semadgenlobis preparatis Seqmna. daavadebis eliminaciis mizniT axali efeqturi TB vaqcinis Seqmna (AERAS); diagnostikis axali, swrafi, iafi meTodebis danergva (FIND); LTBI diagnostika (sazogadoebis aqtiuri skriningisaTvis); MDR/XDR-TB-is swrafi diagnostika; filtvgareSe TB-is diagnostika; TB pacientebis klinikuri mdgomareobis Semfasebeli diagnostikuri saSualebebis da biomarkerebis srulyofa. bavSvTa TB-is, da HIV/AIDS-TB koinfeqciis marTvis gaumjobeseba mkvlevarTa koordinirebuli muSaobis xelSewyoba; uaxlesi kvlevis SedegebiT informireba; Tanamedrove samecniero literaturiT uzrunvelyofa; mkvlevarTa satreningo sistemis srulyofa. axali TB preparatis da vaqcinis Seqmnis mizniT biosamedicino kvlevebis ZiriTadi amocana uaxlesi teqnologiis gamoyenebiT M.tuberculosis struqturuli; paTomorfologiuri; genetikuri; imunologiuri Taviseburebebis Seswavlaa. struqturul TaviseburebebSi ZiriTadi aqcenti keTdeba plazmuri membranis Semdeg ganlagebul peptidoglikanuri (peptidoglycan) agebulebis mesrisebur, elastiur Sreze da samSrian garsze, romelic Sedgeba: arabino-galaqtanis (arabino-galactan) Sris; cximovani mJavebisagan (Mycolic Acid) Semdgari farTe, mJavagamZle Sris; parafinis magvari organuli nivTierebebisa da cilovani SenaerTisgan Semdgari (acyl lipids), wyalgaumtari Srisagan. mycolyl-arabino-galactan-peptidoglycan, anu mAGP (1990) gram-dadebiTi baqteria lipid bilayer peptidoglycan mikobaqteria gram-uaryofiTi baqteria acyl lipids lipid + LPS porins MYCOLATE LAM arabinogalactan sensitiuri TB-is mkurnaloba I rigis preparatebiT MDR-TB-is mkurnaloba II rigis preparatebiT Semcirebuli arCevani XDR-TB-is mkurnalobisas preparatebi, romlebzeac mimdinareobs kvlevebi preklinikuri kvlevebi (2005 w.) Diamine SQ-109 Dipiperidines (SQ-609) arafTorirebuli qinolonebi Synthase Inhibitor FAS20013 Translocase I Inhibitors klinikuri kvlevebi Diarylquinoline TMC207* gatifloqsacini moqsifloqsacini Nitroimidazole PA-824* Pyrrole LL-3858* * axali qimiuri Semadgenlobis preparatebi axali TB vaqcinis Seqmnis mizniT stiven ridma (1995-2002) gamoyo mikobaqteriis ori sxvadasxva jgufis cila, romlebic iwveven mexsierebis ujredebis gaaqtivebas da axdenen gaxangrZlivebuli specifiuri imunuri pasuxis inducirebas; genuri inJineriis da dnm-is rekombinaciuri teqnologiis gamoyenebiT ridma Seqmna am konkretuli cilebis sinTezze pasuxismgebeli xelovnuri geni da Semdeg moaxdina TviTon cilis sinTezi; problema Seqmna damxmare qimiurma preparatma, ukve arsebuli ar muSaobs specifiuri ujreduli pasuxis dros; 2004 wlidan klinikuri kvlevebi mimdinareobs Mtb 72f-ze. viliam jakobsma xelovnurad daTrguna mikobaqteriis 2 geni, romlebic pasuxismgebelni arian makrofagis SigniT mTvlemare formis SenarCunebaze da organizmSi arsebobis da gamravlebis unarze. daasnebovna Tagvebi atenuirebuli mutanti mikobaqteriebiT da TCD+4 limfocitis deficitis pirobebSic gamoiwvia maT organizmSi gaxangrZlivebuli adeqvaturi specifiuri imunuri pasuxi. am principiT Seqmnili atenuirebuli vaqcina savaraudod gamoyenebas hpovebs imunodeficitur pacientebSi. aris mcdeloba axali vaqcina Seiqmnas BCG-s da M. tuberculosis Humanis/an transplantalogiaSi gamoyenebad rapamicinis autofagis safuZvelze, jerjerobiT klinikuri kvlevebi ar dawyebula. axali vaqcinis Seqmnas aseve SeiZleba safuZvlad daedos kvleva, romelic adasturebs, rom M. Tuberculosis Humanis da Africanum-is sapasuxod adamianis organizms gansxvavebuli imunuri reaqciebi axasiaTebT; • M. Tuberculosis Humanis da Africanum-is transmisiis da adamianis inficirebis xarisxi msgavsia, magram afrikuli tipis SemTxvevaSi aqtiuri TB SedarebiT iSviaTad viTardeba; • paTogen-specifiuri faqtorebi, kerZod virulentobaze (ESAT-6 antigeni) pasuxismgebeli Rv3879c geni gansazRvravs M. Tuberculosis Africanum-is SemTxvevaSi aqtiuri tuberkulozis ganviTarebis nakleb albaTobas. mikobaqteriis unars makrofagis SigniT da mis gareT xangrZlivad SeinarCunos sicocxlisunarianoba mis mier ferment isocitrate lyase (ICL)-s gamomuSaveba ganapirobebs devid raselis kvleviT dadasturda, rom tuberkulomaSi (granulomaSi) moqceuli mTvlemare mikobaqteriis metaboluri meqanizmi gadaewyoba da iwyebs ferment isocitrate lyase (ICL) gamomuSavebas, romelic aucilebelia makrofagis SigniT mikobaqteriis arsebobisaTvis; jon makkineim Seqmna mutanti mikobaqteria, romelic am ferments ver gamoimuSavebs da daasnebovna Tagvi. mikobaqteria mTvlemare formaSi gadasvlis nacvlad daiRupa, anu gaxangrZlivebuli imuniteti ar Camoyalibda. aRmoCnda, rom ICL-is gamomuSavebaze pasuxismgebelia 2 geni da misi gamomuSaveba aqtiuri mikobaqteriis mier filtvis qsovilSic xdeba. adamianis organizmi ICL-s ar gamoimuSavebs, anu misi inhibireba makroorganizmisaTvis problemebs ar Seqmnis MDR-TB swrafi diagnostikis axali meTodi Molecular Beacon nacxiT dadebiT SemTxvevebSi myisierad aRmoaCens H da R-is mimarT rezistentobas; amcirebs TB-is araadeqvaturi mkurnalobis SemTxvevebs, empiriuli samkurnalo reJimis SerCevis aucileblobas; drouli diagnostirebiT amcirebs MDR-TB-is transmisiis xarisxs; iZleva MDR-TB-is standartuli mkurnalobis droulad dawyebis saSualebas. rezistentoba Molecular Beacon-is konformaciuli cvlilebiT gamowveuli fluoroscentiuli naTebiT fiqsirdeba Molecular Beacon Mutant Sequence Wildtype Sequence Amplicon Fluorophore Loop Quencher Heat Molecular Beacon (off) Light Hybrid (Molecular Beacon - On) 2003 wels NIAID-Tan kolaboraciaSi samxreT koreis III donis biousafrTxoebis laboratoriaSi (BSL-3) Catarda kvleva: rezistentobis warmoqmnis da ganviTarebis Seswavlis mizniT Segrovda 600-ze meti pirveladi da meoradi rezistentobis MDR/XDR-TB pacientis da maTi Stamebis genomi da Sedarda baqteriuli da adamianis urTierTqmedebis genetikuri variantebi; rezistentul Stamebze metronidazolis efeqturobis dadgenis mizniT aseve Catarda kvlevebi, romlis drosac klinikuri dinamika CT monacemebiT fasdeboda; gmadlobT yuradRebisaTvis