{"id":7001,"date":"2020-08-16T13:30:23","date_gmt":"2020-08-16T10:30:23","guid":{"rendered":"http:\/\/blog.ulubat.org\/?p=7001"},"modified":"2020-12-26T17:31:32","modified_gmt":"2020-12-26T14:31:32","slug":"tifo-ve-asi-calismalari","status":"publish","type":"post","link":"https:\/\/blog.ulubat.org\/index.php\/genel\/tifo-ve-asi-calismalari\/","title":{"rendered":"Tifo ve A\u015f\u0131 \u00c7al\u0131\u015fmalar\u0131"},"content":{"rendered":"\n
\"\"
(Tifo bakterisi. G\u00f6rsel Kayna\u011f\u0131: Festa\/Shutterstock<\/a>)<\/figcaption><\/figure>\n\n\n\n

Giri\u015f<\/p>\n\n\n\n

Tifo, Salmonella Typhi <\/em>bakterisinin yol a\u00e7t\u0131\u011f\u0131\nenterik bir enfeksiyondur. Kontamine olmu\u015f yiyecek ve i\u00e7eceklerin\nt\u00fcketilmesiyle bula\u015f\u0131r. Sadece insanlara bula\u015f\u0131r ve idrar ve d\u0131\u015fk\u0131yla at\u0131l\u0131r.\nBelirtileri ate\u015f, kuru \u00f6ks\u00fcr\u00fck, ba\u015f a\u011fr\u0131s\u0131, anoreksi, n\u00f6rolojik problemler,\nkab\u0131zl\u0131k, ishal ve v\u00fccudun \u00e7e\u015fitli yerlerinde ortaya \u00e7\u0131kan a\u011fr\u0131lard\u0131r. Ayr\u0131ca\nkaraci\u011fer ve dalak b\u00fcy\u00fcmesi de olabilir. Kardiyovask\u00fcler sistemde (%1-5), merkezi\nsinir sisteminde (%3-35), solunumda (%1-86), kemik ve eklemlerde (%1),\nhepatobilier (%1-26) ve genito\u00fcriner sistemde (<%1) komplikasyonlar\n\u00e7\u0131kabilir. S\u0131tma ve Tif\u00fcs gibi hastal\u0131klara benzedi\u011fi i\u00e7in tan\u0131s\u0131 zordur. G\u00fcney\nve G\u00fcneydo\u011fu Asya ile Afrika \u00fclkelerinde yayg\u0131nd\u0131r. Bir\u00e7ok ilaca kar\u015f\u0131\ndiren\u00e7lidir. K\u00fcresel bir hastal\u0131k olmakla birlikte her y\u0131l 25 milyon insana\nbula\u015fmaktad\u0131r ve bunlar\u0131n en az 200 bini hayat\u0131n\u0131 kaybetmektedir. Tayvan\nHastal\u0131k Kontrol Merkezi\u2019nin bir analizinde Tayvan sakinleri ve \u00fclkeye gelen Tifo\nhastas\u0131 yolcular aras\u0131nda S. Typhi <\/em>k\u00f6keninde\nbir fark g\u00f6r\u00fclmemi\u015ftir. Sebebi tifonun yayg\u0131n oldu\u011fu endemik \u00fclkelerden (G\u00fcney\nve G\u00fcneydo\u011fu Asya) gelen g\u00f6\u00e7menlerin veya yolcular\u0131n daha \u00f6nceden Tayvan\u2019a\nyerle\u015fip burada pandemi olu\u015fturmas\u0131 olabilir.<\/p>\n\n\n\n

Tifo\u2019ya endemik b\u00f6lgeler\nd\u0131\u015f\u0131nda Avrupa ve Amerika\u2019da da rastlan\u0131r. \u00d6rne\u011fin 2016 y\u0131l\u0131nda \u0130spanya\u2019da Tifo\u2019ya\n33 ki\u015fi yakalanm\u0131\u015ft\u0131r. Bunun nedeni yine endemik \u00fclkelerden gelen yolculard\u0131r. <\/p>\n\n\n\n

T\u00fcrkiye\u2019de de Tifo\nvakalar\u0131 g\u00f6r\u00fclm\u00fc\u015ft\u00fcr. Ancak 2005 y\u0131l\u0131nda hastal\u0131\u011f\u0131n b\u00f6lgeler aras\u0131nda yay\u0131l\u0131\u015f\u0131\ndengesizdir. Vakalar\u0131n %83,2\u2019si G\u00fcneydo\u011fu Anadolu\u2019da g\u00f6r\u00fclm\u00fc\u015ft\u00fcr. <\/p>\n\n\n\n

Tifo ne kadar k\u00fcresel bir\nsa\u011fl\u0131k sorunu haline gelse de son birka\u00e7 y\u0131l i\u00e7inde morbiditesi artarken\nmortalitesi d\u00fc\u015fm\u00fc\u015ft\u00fcr. 3-44 ya\u015f aral\u0131\u011f\u0131nda a\u015f\u0131 yap\u0131lan hastalar\u0131n %40-90\u2019\u0131 iki\ny\u0131l i\u00e7inde iyile\u015fmektedir. Ancak bu ya\u015f aral\u0131\u011f\u0131nda olmayan hastalar\u0131n\nkurtulmas\u0131 daha d\u00fc\u015f\u00fck bir ihtimaldir. D\u00fcnyada yap\u0131lan bir\u00e7ok \u00e7al\u0131\u015fma bu\nhastal\u0131\u011f\u0131n Hindistan\u2019da evrildi\u011fini ortaya \u00e7\u0131karm\u0131\u015ft\u0131r. Widal testleri,\nhastadan al\u0131nan kan\u0131n antikor \u00fcretip \u00fcretmedi\u011fine bak\u0131ld\u0131\u011f\u0131 testlerdir ve en\n\u00e7ok Asya ve Afrika \u00fclkelerinde uygulanmaktad\u0131r. ELISA metoduyla spesifik\nIgA\u2019lara bak\u0131larak te\u015fhis konmas\u0131 yeni ve daha g\u00fcvenilir bir y\u00f6ntemdir. <\/p>\n\n\n\n

\"\"
(Tifo kavram haznesi. G\u00f6rsel Kayna\u011f\u0131: Depositphotos. <\/a>https:\/\/tr.depositphotos.com\/stock-photos\/tifo.html?offset=120&filter=all<\/a>) <\/figcaption><\/figure>\n\n\n\n

Tifo insan v\u00fccudunda\nhematolojik de\u011ferler \u00fczerinde \u00f6nemli de\u011fi\u015fimlere neden olur. S. Typhi <\/em>bakterisi kemik ili\u011finde toksin\nsalg\u0131lar. Hematopoezde aksama olur ve dalak, lenf nodlar\u0131 ve bademcikler bundan\nolumsuz etkilenir. Sonu\u00e7ta beyaz kan h\u00fccreleri azal\u0131r ve hematokrit de\u011feri\nd\u00fc\u015fer. \u00c7o\u011fu hastada ilk evrelerde hemoglobin de\u011feri ayn\u0131d\u0131r ancak s\u00fcre\u00e7\nilerledik\u00e7e azal\u0131r. Yap\u0131lan bir \u00e7al\u0131\u015fmada hastalar\u0131n %42.9\u2019unun anemi oldu\u011fu\nsaptanm\u0131\u015ft\u0131r. Ba\u015fka bir \u00e7al\u0131\u015fmada da bu de\u011fer %34\u2019t\u00fcr. Fakat \u015fiddetli anemi\ng\u00f6r\u00fclmesi i\u00e7in ba\u011f\u0131rsak kanamas\u0131, hemoliz ya da s\u0131tma olmas\u0131 gerekir. Bunlar da\nnadir g\u00f6r\u00fclen durumlard\u0131r. <\/p>\n\n\n\n

Kad\u0131n Tifo hastalar\u0131nda\ntrombosit miktar\u0131 erkeklere g\u00f6re daha fazlad\u0131r. Bu, kad\u0131nlar\u0131n menstruasyonda\nkan kaybetmesi ve bununla ili\u015fkili mekanizmalarla ilgili olabilir. Trombositler\nbakteriyle kar\u015f\u0131la\u015f\u0131nca aktive olur ve damar i\u00e7inde p\u0131ht\u0131 olu\u015fturur. Sonu\u00e7ta\ntrombosit miktar\u0131n\u0131n azalmas\u0131 anlam\u0131na gelen trombositopeni olu\u015fur. Pek \u00e7ok\nara\u015ft\u0131rmaya g\u00f6re Tifo kad\u0131nlarda daha \u00e7ok g\u00f6r\u00fcl\u00fcr. Erkeklerin daha az\nyakalanmas\u0131n\u0131n sebebi mesleki ve sosyal \u00e7evrede edindikleri ba\u011f\u0131\u015f\u0131kl\u0131k\nolabilir. <\/p>\n\n\n\n

S. Typhi<\/em>\u2019nin\nH58 ya da di\u011fer ad\u0131yla 4.3.1 haplotipi \u00e7o\u011fu ilaca kar\u015f\u0131 diren\u00e7 sa\u011flar. Bakterinin\nd\u00fcnyan\u0131n farkl\u0131 b\u00f6lgelerine yay\u0131l\u0131p ortama uyum sa\u011flamas\u0131n\u0131n nedeninin bu\noldu\u011fu d\u00fc\u015f\u00fcn\u00fcl\u00fcyor. Ayr\u0131ca bu \u00e7oklu direncinden \u00f6t\u00fcr\u00fc antibiyotik tedavilerine\ndaha yava\u015f tepki g\u00f6sterir. \u00d6zellikle antibiyotiklerin re\u00e7etesiz al\u0131nd\u0131\u011f\u0131 bir\n\u00fclkede daha \u00e7ok antibiyotik kullan\u0131lmas\u0131na sebep olur. Bu durum bakterinin\ndirencini daha da artt\u0131r\u0131r. Bununla birlikte baz\u0131 \u00fclkelerde S. Typhi<\/em>\u2019ninVi kaps\u00fcl antijeni \u00fczerine a\u015f\u0131lar geli\u015ftirilmi\u015ftir. <\/p>\n\n\n\n

Genetik Ara\u015ft\u0131rmalar<\/p>\n\n\n\n

Yap\u0131lan bir ara\u015ft\u0131rmada S. Typhi<\/em> ve S. Typhimurium <\/em>bakterilerinin genetiklerinin do\u011fal formlar\u0131yla ayn\u0131\nolup olmad\u0131\u011f\u0131na bak\u0131lm\u0131\u015f ve do\u011fal formlar\u0131 aras\u0131nda b\u00fcy\u00fck gen benzerli\u011fi\nbulunmas\u0131na ra\u011fmen \u015fimdiki gen benzerliklerinin sadece %6 oldu\u011fu tespit\nedilmi\u015ftir. DNA\u2019da Endonukleaz aktivitesi incelendi\u011finde de XbaI ve AvrII\nenzimlerinin k\u00f6keninin iki bakteride de farkl\u0131 oldu\u011fu g\u00f6r\u00fclm\u00fc\u015ft\u00fcr. Bu iki\nbakterinin di\u011fer bir fark\u0131 da S. Typhi<\/em>\u2019nin\nsadece insan\u0131 ve S. Typhimurium<\/em>\u2019un insan\nharicinde pek \u00e7ok t\u00fcr\u00fc enfekte edebilmesidir. \u00c7al\u0131\u015fmada S. Typhi<\/em>\u2019ye k\u0131yasla \u00e7o\u011fu Salmonella\n<\/em>serotipinin S. Typhimurium<\/em>\u2019a\ngenetik olarak daha \u00e7ok benzedi\u011fi bulunmu\u015ftur. Dolay\u0131s\u0131yla bu veriler \u00e7o\u011fu Salmonella <\/em>bakterisinin insana\nbula\u015fmad\u0131\u011f\u0131n\u0131 g\u00f6sterir. Tifo bakterisinin ba\u015fka t\u00fcrlere bula\u015fmas\u0131 i\u00e7in bir Tip\nIII Salg\u0131 Sistemi (T3SS) efekt\u00f6r proteini olan gtgE<\/em>\u2019ye ihtiyac\u0131 vard\u0131r ve bunu \u00fcretebilmesi i\u00e7in de gtgE <\/em>geni gereklidir. S. Typhi<\/em>\u2019nin evrimle\u015fmeden \u00f6nce bu gene\nsahip oldu\u011fu ancak insan h\u00fccrelerini enfekte etmek i\u00e7in de\u011fi\u015firken geni\nkaybetti\u011fi d\u00fc\u015f\u00fcn\u00fcl\u00fcyor. <\/p>\n\n\n\n

Tifo\u2019ya neden olan bakteri genellikle S. Typhi <\/em>olarak g\u00f6sterilse de S. Paratyphi <\/em>de Tifo\u2019ya yol a\u00e7maktad\u0131r. \u0130kisinin de salg\u0131lad\u0131\u011f\u0131 toksin A2B5\u2019tir. Toksinin be\u015f alt birimi bulunur ve bunlar\u0131n ikisi A alt birimidir. Di\u011ferleri pltB<\/em>, ADP Ribozil Transferaz pltA<\/em> ve DNaz CdtB\u2019dir. Konak h\u00fccrenin zehri atabilmesi ancak otokrin ve parakrin yoluyla olur. Toksinin bakteriden ekstrasel\u00fcler matrikse salg\u0131lanmas\u0131 PltB<\/em> B alt birimi ile olur ve konak h\u00fccreye etki edebilmesi i\u00e7in glikan i\u00e7eren spesifik resept\u00f6rlere ba\u011flanmal\u0131d\u0131r. N-asetiln\u00f6raminik asit (Neu5Ac) de bir\u00e7ok memelide bulunan N-glikoliln\u00f6raminik asitten (Neu5Gc) farkl\u0131 olarak insanda bulunur. Bu da toksin i\u00e7in gerekli resept\u00f6rd\u00fcr. <\/p>\n\n\n\n

\"\"
(Tifo bakterisi. G\u00f6rsel Kayna\u011f\u0131: decade3d – anatomy online\/Shutterstock<\/a>, ID: 208188289)<\/figcaption><\/figure>\n\n\n\n

PltB<\/em>\u2019si GFP geni ile de\u011fi\u015ftirilmi\u015f mutant bakteriler h\u00fccreye girer ve FACS y\u00f6ntemiyle GFP\u2019nin \u00e7ok ve az salg\u0131land\u0131\u011f\u0131 bakteriler ayr\u0131\u015ft\u0131r\u0131l\u0131r. INSeq sekanslama ile transpozon insersiyon b\u00f6lgelerinin yay\u0131l\u0131m ve bollu\u011fu belirlenir. SCV\u2019de phoP<\/em> bakteriyi aktive eder. Bakteri kofulun d\u0131\u015f\u0131ndaysa H-NS onu inaktive eder.<\/p>\n\n\n\n

Toksinin pltB <\/em>alt birimi \u00e7\u0131kart\u0131l\u0131p yerine GFP\n(Ye\u015fil Floresans Protein) konuldu\u011funda bakteriler, insan Henle-407 epitel\nh\u00fccrelerinin yer ald\u0131\u011f\u0131 k\u00fclt\u00fcrde ye\u015file boyanmam\u0131\u015ft\u0131r. Bu, toksinin bu alt\nbirimi olmazsa etkisi olmad\u0131\u011f\u0131n\u0131 g\u00f6sterir. FACS (Floresans-Aktif H\u00fccre\nS\u0131n\u0131fland\u0131rmas\u0131) ile GFP ile boyanm\u0131\u015f ve boyanmam\u0131\u015f bakteriler iki havuza\nayr\u0131\u015ft\u0131r\u0131l\u0131r. INSeq (\u0130nsersiyon Sekanslama) ile de transpozon insersiyon\nb\u00f6lgelerinin yay\u0131l\u0131m ve bollu\u011fu belirlenir. Bu y\u00f6ntemle toksin y\u00fcz\u00fcnden GFP\nsalg\u0131lanmam\u0131\u015fsa bu bakterilerin de tespit edilmesi sa\u011flan\u0131r. Bir\ntranskripsiyonel d\u00fczenleyici protein olan phoP<\/em>\nbakteriyi Salmonella <\/em>kofulu (SCV)\ni\u00e7inde aktive ederek toksinin salg\u0131lanmas\u0131n\u0131 sa\u011flarken bir histon benzeri\nprotein olan H-NS, bakteri SCV d\u0131\u015f\u0131ndayken toksinin salg\u0131lanmas\u0131n\u0131 engeller. phoP<\/em>, H-NS\u2019e ba\u011flanarak aktivitesini\nazalt\u0131r ve bakterinin toksin salg\u0131lamas\u0131n\u0131 sa\u011flar. H-NS \u00fcretilmiyorsa\naktivasyon i\u00e7in phoP<\/em>\u2019a gerek yoktur. <\/p>\n\n\n\n

A2B5 toksininin\nsalg\u0131lanmas\u0131n\u0131 d\u00fczenleyen gen proteinleri aras\u0131nda transkripsiyonel d\u00fczenleyici\nproteinler (phoP, phoQ, slyA<\/em>), ABC\ntransporter bile\u015fenleri (yrbD, yrbE, yrbF<\/em>),\nfonksiyonu bilinmeyen bir flavodoksin (yqcA<\/em>),\nsifA<\/em>, magnezyum transporteri (mgtA<\/em>) ve p\u00fcrin biyosentezi i\u00e7in gerekli purL<\/em>,\npurF<\/em>, purC<\/em>, purM <\/em>ve purH<\/em> bulunur.\nBulgulara g\u00f6re ya\u011f asidi sentezi i\u00e7in gerekli olan biyotin \u00fcretilmedi\u011finde S. Typhi <\/em>toksin salg\u0131lamamaktad\u0131r. \u0130nsersiyon\nmutasyonlar\u0131 ne kadar \u00e7ok gene yap\u0131l\u0131rsa bakteriler o kadar toksin salg\u0131lama,\nreplikasyon ve hayatta kalma becerilerini kaybederler.<\/p>\n\n\n\n

Sens\u00f6r Kinaz phoQ<\/em> bakterinin bulundu\u011fu \u00e7evre\nko\u015fullar\u0131n\u0131 alg\u0131lar. \u00d6rne\u011fin magnezyumun az oldu\u011fu bir ortamda bakteri toksin\nsalg\u0131lar. Ancak mgtA <\/em>transporteri\u2019nin\nSalmonella<\/em>\u2019n\u0131n phoP<\/em> \u00fcretebilmesi i\u00e7in bu ortamdan yeterli magnezyumu bakteriye almas\u0131\ngerekir. <\/p>\n\n\n\n

SIP-2 T3SS efekt\u00f6r\u00fc olan SifA <\/em>genine insersiyon yap\u0131ld\u0131\u011f\u0131nda\nbakteri daha az toksin \u00fcretir. G\u00f6zlemlere g\u00f6re bu gen ne kadar de\u011fi\u015fime u\u011frarsa\nbakteri, i\u00e7inde bulundu\u011fu kofuldan konak h\u00fccre sitoplazmas\u0131na o kadar \u00e7ok\nka\u00e7maktad\u0131r. Bu da phoP<\/em>\u2019un H-NS\ngenine ba\u011flanmas\u0131n\u0131 engelledi\u011fi ve dolay\u0131s\u0131yla H-NS \u00fcretimini artt\u0131rd\u0131\u011f\u0131 i\u00e7in\ntoksin \u00fcretimi azal\u0131r. <\/p>\n\n\n\n

S. Typhi <\/em>konak\nh\u00fccreden etkilenmemek i\u00e7in \u00e7e\u015fitli ba\u011f\u0131\u015f\u0131kl\u0131k mekanizmalar\u0131ndan kendini korur.\nBunlardan biri TLR4 arac\u0131l\u0131 sinyal kaskad\u0131d\u0131r. S. Typhi <\/em>kendi membran\u0131n\u0131 yenileyerek direncini artt\u0131r\u0131r ve TLR4\u2019\u00fcn\nonu alg\u0131lamas\u0131n\u0131 engeller. Ayr\u0131ca TLR5 bakteride flagelline ba\u011flanarak konak\nh\u00fccrenin do\u011fal ba\u011f\u0131\u015f\u0131kl\u0131\u011f\u0131n\u0131 harekete ge\u00e7irir. TLR5 geninde polimorfizm olmas\u0131\nbakteriye kar\u015f\u0131 duyarl\u0131l\u0131\u011f\u0131 artt\u0131r\u0131r gibi dursa da Tifo ile TLR5 polimorfizmi\naras\u0131nda bir ili\u015fki bulunmam\u0131\u015ft\u0131r. Ayn\u0131 \u015fekilde di\u011fer TLR genlerinin de bu\nhastal\u0131\u011fa net bir etkisi g\u00f6r\u00fclmemi\u015ftir. Yine de bu genler Tifo i\u00e7in g\u00f6z ard\u0131\nedilmemelidir.<\/p>\n\n\n\n

\u0130spanya\u2019da yap\u0131lan bir\n\u00e7al\u0131\u015fmada Tifo\u2019nun Hemofagositik Lenfohistiyositoz (HLH: \u0130mm\u00fcn h\u00fccrelerinin\nnormalin \u00fcst\u00fcnde salg\u0131lanmas\u0131) ile paralel oldu\u011fu g\u00f6r\u00fclm\u00fc\u015ft\u00fcr. Genetik nedenle\nortaya \u00e7\u0131kan birincil HLH genelde bebek ve k\u00fc\u00e7\u00fck \u00e7ocuklarda olurken, enfeksiyon\nve vir\u00fcs gibi bir\u00e7ok etkenin tetiklemesi sonucu a\u00e7\u0131\u011fa \u00e7\u0131kan ikincil HLH genelde\nolgun \u00e7ocuklar ve yeti\u015fkinlerde g\u00f6r\u00fcl\u00fcr. Tifo\u2019ya yakalanm\u0131\u015f bireylerde ikincil\nHLH ortaya \u00e7\u0131kabilir. Tifo\u2019nun son a\u015famas\u0131 olan \u00fc\u00e7\u00fcnc\u00fc a\u015famada kal\u0131c\u0131 ate\u015f,\nkaraci\u011fer tutulumu, anemi veya l\u00f6kopeni g\u00f6r\u00fclebilir. Bu semptomlar HLH hastas\u0131\nbireylerde de g\u00f6r\u00fcl\u00fcr. Belirtilen iki hastal\u0131\u011f\u0131n bu kadar uyu\u015fmas\u0131n\u0131n sebebi S. Enterica<\/em>\u2019n\u0131n replikasyon i\u00e7in\nmakrofajlar\u0131 kullanmas\u0131 olarak g\u00f6r\u00fcl\u00fcyor. Enfekte makrofajlar karaci\u011fer, dalak,\nlenf nodlar\u0131 ve kemik ili\u011fine gelir. Burada makrofaj aktivasyonunu sa\u011flayan\nsitokin kaskadlar\u0131 ba\u015flar. Sonu\u00e7ta makrofajlar\u0131n o b\u00f6lgedeki sa\u011fl\u0131kl\u0131 h\u00fccreleri\n\u00f6ld\u00fcrmesi anlam\u0131na gelen hemofagositoz olur. Kemik ili\u011fi analizleri, kan ve d\u0131\u015fk\u0131\nanalizlerinden daha g\u00fcvenilir oldu\u011fu i\u00e7in doktorlar hastan\u0131n HLH olup\nolmad\u0131\u011f\u0131n\u0131 anlamak i\u00e7in kemik ili\u011fine bakar. Fakat Tifo i\u00e7in kan analizleri\ndaha uygundur. Bu y\u00fczden HLH\u2019nin temel nedenini bulmak i\u00e7in daha geni\u015f\nanalizler yap\u0131labilir. <\/p>\n\n\n\n

Tayvan\u2019da bir \u00e7al\u0131\u015fmada S. Typhi<\/em>\u2019nin Siprofloksasin\u2019e kar\u015f\u0131 daha diren\u00e7li oldu\u011fu ve Beta laktamlar, Kloramfenikol ve Trimetoprim-s\u00fclfametoksazol\u2019e kar\u015f\u0131 daha duyarl\u0131 oldu\u011fu g\u00f6r\u00fclm\u00fc\u015ft\u00fcr. Bu b\u00f6lgedeki tifonun k\u00f6keni de bu hastal\u0131\u011f\u0131n endemik oldu\u011fu \u00fclkelerden gelen insanlard\u0131. <\/p>\n\n\n\n

\"\"
(Tifo testi. G\u00f6rsel Kayna\u011f\u0131: Novikov Aleksey\/Shutterstock<\/a>, ID: 1688120329)<\/figcaption><\/figure>\n\n\n\n

A\u015f\u0131 \u00c7al\u0131\u015fmalar\u0131<\/p>\n\n\n\n

Tifo i\u00e7in y\u0131llard\u0131r a\u015f\u0131 yap\u0131lmaktad\u0131r. 1990\u2019l\u0131 y\u0131llarda parenteral tam h\u00fccre a\u015f\u0131lar\u0131 ne kadar iyi bir koruma sa\u011flasa da ate\u015f, ba\u015f a\u011fr\u0131s\u0131 ve lokal inflamasyona neden olmu\u015ftur. Fakat zay\u0131flat\u0131lm\u0131\u015f S. Typhi<\/em>\u2019ler canl\u0131 oral a\u015f\u0131 olarak verildi\u011finde farelerde \u00f6nemli koruma sa\u011flam\u0131\u015ft\u0131r. Bu a\u015f\u0131lar Salmonella<\/em>\u2019ya kar\u015f\u0131ba\u011f\u0131\u015f\u0131kl\u0131k tepkisini artt\u0131rm\u0131\u015ft\u0131r. Bu \u00f6zellik ke\u015ffedilince bir\u00e7ok \u00fclke S. Typhi <\/em>Ty2\u2019nin bir galE <\/em>mutant\u0131 olan Ty21a\u2019y\u0131 a\u015f\u0131 olarak kullanmaya ba\u015flam\u0131\u015ft\u0131r. Ty21a olu\u015fturulurken S. Typhi <\/em>Ty2\u2019ye mutajenez yap\u0131lm\u0131\u015ft\u0131r. AroA, aroC <\/em>ve aroD <\/em>genleri de a\u015f\u0131 \u00fcretmek i\u00e7in odak noktas\u0131yd\u0131 \u00e7\u00fcnk\u00fc \u00fcretilen a\u015f\u0131lar fare ve s\u0131\u011f\u0131rlar \u00fczerinde etkiliydi. Dolay\u0131s\u0131yla iki aro <\/em>geninden yoksun olan S. Typhi<\/em>\u2019ler a\u015f\u0131 i\u00e7in aday say\u0131labilir.<\/p>\n\n\n\n

S. Typhi<\/em>\u2019nin\ncanl\u0131 a\u015f\u0131lar i\u00e7in kullan\u0131lan ba\u015fka genleri de bulunur. Bunlar aras\u0131nda\nd\u00fczenleyici protein kodlayan ompR <\/em>ve\nstres yan\u0131t\u0131nda g\u00f6rev alan htrA <\/em>vard\u0131r.\nBu genler mutasyona u\u011frad\u0131\u011f\u0131nda bakteri zay\u0131flar. <\/p>\n\n\n\n

Bu geli\u015fmelerden sonra Bill\nve Melinda Gates Vakf\u0131\u2019n\u0131n fonuyla 2010-2014 y\u0131llar\u0131 aras\u0131nda Afrika Tifo\nG\u00f6zetim Program\u0131 (TSAP) kurulmu\u015ftur. Programda yap\u0131lan g\u00f6zlemlerde Afrika\u2019n\u0131n\n\u00e7o\u011fu b\u00f6lgesinde S. Typhi <\/em>ve Dublin, Enteritidis, Typhimurium <\/em>gibi\ndi\u011fer Salmonella <\/em>serotiplerinin kanda\nen \u00e7ok bulunan bakteriler oldu\u011fu g\u00f6r\u00fclm\u00fc\u015ft\u00fcr. \u00d6yle ki Streptococcus Pneumoniae <\/em>ve Eschericia\nColi\u2019<\/em>yige\u00e7mi\u015ftir. TSAP\u2019nin bu \u00e7al\u0131\u015fmalar\u0131\ndaha \u00e7ok sermaye al\u0131nmas\u0131n\u0131 sa\u011flad\u0131 ve b\u00f6ylece Afrika\u2019n\u0131n bir\u00e7ok b\u00f6lgesinden\nyeni bilgiler al\u0131nd\u0131. Bu da TSAP\u2019yi a\u015f\u0131 geli\u015ftirmeye itti. <\/p>\n\n\n\n

Bilgi Kaynak\u00e7as\u0131<\/p>\n\n\n\n

  1. ScienceDirect. A. Ndako, James. T. Dojumo, Victor. A. Akinwumi, Jeremiah. O. Fajobi, Victor. O. Owolabi, Akinyomade. Olatinsu, Oludolapo. \u201cChanges in some haematological parameters in typhoid fever patients attending Landmark University Medical Center, Omuaran-Nigeria\u201d Heliyon. <\/em>(6):5. May\u0131s 2020. <\/li>
  2. ScienceDirect. Dougan, Gordon. \u201cTyphoid in Africa and Vaccine Deployment\u201d The Lancet Global Health. <\/em>(5):3, e236-e237. Mart 2017. <\/li>
  3. ScienceDirect. Tang, Le. Wang, Chun-Xiao. Zhu, Song-Ling. Li, Yang. Deng, Xia. Johnston, Randal N.. Liu, Gui-Rong. Liu,  Shu-Lin. \u201cGenetic boundaries to delineate the typhoid agent and other Salmonella serotypes into distinct natural lineages\u201d Genomics. <\/em>(102):4, 331-337. Ekim 2013. <\/li>
  4. ScienceDirect. C. Fowler, Casey. E. Galan, Jorge. \u201cDecoding a Salmonella Typhi Regulatory Network that Controls Typhoid Toxin Expression within Human Cells\u201d Cell Host & Microbe. <\/em>(23):1, 65-76.e6. Ocak 2018. <\/li>
  5. ScienceDirect. Sivaji, Ilakkia. Duraisamy, Senbagam. Balakrishnan, Senthilkumar. \u201cAnalysis of TLR polymorphisms in typhoid patients and asymptomatic typhoid carriers among the schoolchildren\u201d Egyptian Journal of Medical Human Genetics. <\/em>(17):4, 353-357. Ekim 2016. <\/li>
  6. ScienceDirect. Chien, Shao-Chien. Iap, Tsong-Him. Chiu, Yin-Rong. Shie, Shian-Sen. Chen, Chih-Jung. \u201cMicrobiological features of indigenous typhoid cases in Taiwan and relatedness to imported cases, 2001\u20132014: A cross-sectional analysis\u201d Travel Medicine and Infectious Disease. <\/em>(27), 92-98. Ocak-\u015eubat 2019. <\/li>
  7. ScienceDirect. Chatfield, S. N.. Fairweather, N.. Charles, I.. Pickard, D.. Levine, M.. Hone, D.. Posada, M.. Strugnell, R. A.. Dougan, G.. \u201cConstruction of a genetically defined Salmonella typhi Ty2 aroA, aroC mutant for the engineering of a candidate oral typhoid-tetanus vaccine\u201d Vaccine. <\/em>(10):1, 53-60. 1992. <\/li>
  8. ScienceDirect. S\u00e1nchez-Morenoa, Paula. Olbrich, Peter. Falc\u00f3n-Neyra, Lola. Manuel Lucena, Jose. Aznar, Javier. Neth, Olaf. \u201cTyphoid fever causing haemophagocytic lymphohistiocytosis in a non-endemic country \u2013 first case report and review of the current literature – Fiebre tifoidea como causa de linfohistiocitosis hemofagoc\u00edtica en un pa\u00eds no end\u00e9mico: primer caso reportado y revisi\u00f3n de la literatura\u201d Enfermedades Infecciosas Y Microbiologia Clinica. <\/em>(37):2, 112-116. \u015eubat 2019. <\/li>
  9. SlidePlayer. Buyurgan, Vedat. https:\/\/slideplayer.biz.tr\/slide\/2426686\/<\/a> <\/li><\/ol>\n\n\n\n

    G\u00f6rsel Kaynak\u00e7as\u0131<\/p>\n\n\n\n

    1. Festa\/Shutterstock<\/a><\/li>
    2. decade3d – anatomy online\/Shutterstock<\/a>, ID: 208188289<\/li>
    3. Depositphotos. https:\/\/tr.depositphotos.com\/stock-photos\/tifo.html?offset=120&filter=all<\/a> <\/li>
    4. Novikov Aleksey\/Shutterstock<\/a>, ID: 1688120329<\/li><\/ol>\n","protected":false},"excerpt":{"rendered":"

      Giri\u015f Tifo, Salmonella Typhi bakterisinin yol a\u00e7t\u0131\u011f\u0131 enterik bir enfeksiyondur. Kontamine olmu\u015f yiyecek ve i\u00e7eceklerin t\u00fcketilmesiyle bula\u015f\u0131r. Sadece insanlara bula\u015f\u0131r<\/p>\n","protected":false},"author":267,"featured_media":7007,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[1,25],"tags":[357,988,844,157,985,984,866,493,187,74,894,893,998,274,865,149,115,810,990,107,986,621,991,174,55,999,297,996,265,993,995,987,159],"acf":[],"views":652,"_links":{"self":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts\/7001"}],"collection":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/users\/267"}],"replies":[{"embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/comments?post=7001"}],"version-history":[{"count":4,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts\/7001\/revisions"}],"predecessor-version":[{"id":9298,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts\/7001\/revisions\/9298"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/media\/7007"}],"wp:attachment":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/media?parent=7001"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/categories?post=7001"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/tags?post=7001"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}