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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
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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-issamkurnalod • 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-isswrafi diagnostika; • filtvgareSe TB-isdiagnostika; • 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 vaqcinisSeqmnis mizniTbiosamedicino kvlevebis ZiriTadi amocana uaxlesi teqnologiis gamoyenebiTM.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 (acyllipids), wyalgaumtari Srisagan. mycolyl-arabino-galactan-peptidoglycan, anu mAGP (1990)
gram-dadebiTi baqteria gram-uaryofiTi baqteria mikobaqteria acyl lipids lipid bilayer lipid + LPS peptidoglycan MYCOLATE LAM arabinogalactan porins
preklinikuri kvlevebi (2005 w.) • Diamine SQ-109 • Dipiperidines(SQ-609) • arafTorirebuli qinolonebi • Synthase InhibitorFAS20013 • Translocase IInhibitors klinikuri kvlevebi • DiarylquinolineTMC207* • gatifloqsacini • moqsifloqsacini • Nitroimidazole PA-824* • Pyrrole LL-3858* * axali qimiuri Semadgenlobis preparatebi
axali TB vaqcinisSeqmnis 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 Humanisda Africanum-issapasuxod adamianis organizms gansxvavebuli imunuri reaqciebi axasiaTebT; • M. Tuberculosis Humanisda 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-isSemTxvevaSi 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, romICL-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-iskonformaciuli cvlilebiT gamowveuli fluoroscentiuli naTebiT fiqsirdeba
Molecular Beacon Mutant Sequence Wildtype Sequence Amplicon Fluorophore Loop Quencher Heat Light Molecular Beacon (off) 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;