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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

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


Sensitiuri tb is mkurnaloba i rigis preparatebit
sensitiuri TB-is mkurnaloba I rigis preparatebiT


Mdr tb is mkurnaloba ii rigis preparatebit
MDR-TB-is mkurnaloba II rigis preparatebiT


Semcirebuli arcevani xdr tb is mkurnalobisas
Semcirebuli arCevani XDR-TB-is mkurnalobisas



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 xangrZlivad SeinarCunos sicocxlisunarianoba mis mier ferment 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 xangrZlivad SeinarCunos sicocxlisunarianoba mis mier ferment

Mutant Sequence

Wildtype Sequence

Amplicon

Fluorophore

Loop

Quencher

Heat

Light

Molecular

Beacon (off)

Hybrid (Molecular Beacon - On)


2003 wels xangrZlivad SeinarCunos sicocxlisunarianoba mis mier ferment 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

gmadlobT xangrZlivad SeinarCunos sicocxlisunarianoba mis mier ferment yuradRebisaTvis