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JEEVANU TIMES INDIAN ASSOCIATION OF MEDICAL MICROBIOLOGISTS - DELHI CHAPTER www.iammdelhi.com Volume 1, January 2018 EDITORS Poonam Loomba, Sonal Saxena, Jaswinder K. Oberoi, Renu Gupta, Manisha Jain

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Page 1: JEEVANU TIMES - iammdelhi.org€¦ · JEEVANU TIMES INDIAN ASSOCIATION OF MEDICAL MICROBIOLOGISTS - DELHI CHAPTER Volume 1, January 2018 EDITORS Poonam Loomba, Sonal Saxena, Jaswinder

JEEV

ANU

TIM

ESINDIAN ASSOCIATION OF MEDICAL MICROBIOLOGISTS - DELHI CHAPTER

www.iammdelhi.com

Volume 1, January 2018

EDITORSPoonam Loomba, Sonal Saxena, Jaswinder K. Oberoi, Renu Gupta, Manisha Jain

Page 2: JEEVANU TIMES - iammdelhi.org€¦ · JEEVANU TIMES INDIAN ASSOCIATION OF MEDICAL MICROBIOLOGISTS - DELHI CHAPTER Volume 1, January 2018 EDITORS Poonam Loomba, Sonal Saxena, Jaswinder
Page 3: JEEVANU TIMES - iammdelhi.org€¦ · JEEVANU TIMES INDIAN ASSOCIATION OF MEDICAL MICROBIOLOGISTS - DELHI CHAPTER Volume 1, January 2018 EDITORS Poonam Loomba, Sonal Saxena, Jaswinder

EDITORIAL TEAM

D Poo a Sood Loo a

P ofesso

G B Pa t Hospital

Ne Delhi

D So al Sa e a

Di e to P ofesso

Lad Ha di ge Medi al College

Ne Delhi

D Jas i de K O e oi

Se io Co sulta t

Si Ga ga Ra Hospital

Ne Delhi

D Re u Gupta

Assista t P ofesso

I stitute of Beha io al Health a d Allied S ie es

Ne Delhi

D Ma isha Jai

Assista t P ofesso

VMMC & Safda ja g Hospital

Ne Delhi

JEEVANU TIMES

Official publication of Indian Association of Medical Microbiologists-Delhi Chapter

Page 4: JEEVANU TIMES - iammdelhi.org€¦ · JEEVANU TIMES INDIAN ASSOCIATION OF MEDICAL MICROBIOLOGISTS - DELHI CHAPTER Volume 1, January 2018 EDITORS Poonam Loomba, Sonal Saxena, Jaswinder

F o the Edito s Desk

G eeti gs a d el o e to the edesig ed a d e-i agi ed Jee a u Ti es. Afte a hiatus of th ee ea s, the de isio as ade to e i e a d e italise this jou al i o de to p o ide eade s ith

the latest i fo atio , details a d statisti i the field of Mi o iolog .

This de isio as suppo ted the o u it s eed of ha i g the u e t e ie s a d a ti les t e di g i the ou t as ell as o ld ide. This jou al also p o ides the ediu to a ess o igi-

al li i al ases a d sti ulati g e ie s a d featu es.

We hope that it ill also o t i ute i the fulfill e t of a othe aspi atio i.e. to ake it a i -de ed jou al. The p o ess has ee sta ted . A g eat a ou t of ha d o k a d i u e a le hou s

ill ha e to e put i to o st u t a I de Jou al. We look fo a d to ou o t i utio fo this p o idi g o igi al a ti les, e ie a ti les a d li i al ase epo ts.

With this pu li atio , eade s ill ha e oppo tu it to s uti ize a d u de sta d all the Mi o iol-og updates. A d ea h su se ue t editio ill o l i g fo th o te po a a d e ita le k o ledge.

We a e ho ou ed to e i gi g a k this ote o th pu li atio a d hope this ul i ates i e-i g as alua le as it has al a s ee .

With Best Wishes, D Poo a Sood Loo a

Edito

Jee a u Ti es

Page 5: JEEVANU TIMES - iammdelhi.org€¦ · JEEVANU TIMES INDIAN ASSOCIATION OF MEDICAL MICROBIOLOGISTS - DELHI CHAPTER Volume 1, January 2018 EDITORS Poonam Loomba, Sonal Saxena, Jaswinder

Table of Contents

Re ie a ti le

Blasto stis ho i is: A olo ise o a pathoge ? Pg. -

Ka ita Gupta, Sa oj Dash, Vija a La i Nag

All I dia I stitute of Medi al S ie es, Jodhpu

The e ol i g fa e of diag osti s i tu e ulosis: e e t ad a es Pg. - a d e ie of lite atu e

D . Gi eesha Ra al, D . Cha a jeet Ahlu alia

VMMC & Safda ja g Hospital, Ne Delhi

Re ised Natio al Tu e ulosis Co t ol P og a e: Past, P ese t a d Pg. – the Futu e ahead

Mukesh Ku a , Su u hi Mish a A ita Khokha VMMC a d Safda ju g Hospital, Ne Delhi

Sepsis Bio a ke s

Gopi Ta ila asa , Pg. -

VMMC a d Safda ju g Hospital, Ne Delhi

Cli i al ase epo t

Disse i ated No a diosis i e al t a spla t e ipie t: A Case Repo t Pg. -

Lata Sheo a , Jas i de Kau O e oi, Nee aj Goel, Ree a Ra i d a ,

Sa gha it a Dutta, K.J P asad, Cha d Wattal Si Ga ga Ra Hospital, Ne Delhi

Mi o iolog Updates f o a ou d the o ld Pg. -

Mi o iolog oss o d Pg.

JEEVANU TIMES

Official publication of Indian Association of Medical Microbiologists-Delhi Chapter

Page 6: JEEVANU TIMES - iammdelhi.org€¦ · JEEVANU TIMES INDIAN ASSOCIATION OF MEDICAL MICROBIOLOGISTS - DELHI CHAPTER Volume 1, January 2018 EDITORS Poonam Loomba, Sonal Saxena, Jaswinder

Blasto ystis ho i is: A olo iser or a pathoge ?

Autho s: Ka ita Gupta*, Sa oj Dash, Vija a La i Nag

Depa t e t: Depa t e t of Mi o iolog

I stitute: All I dia I stitute of Medi al S ie es, Jodhpu

Re ie arti le

I trodu tio

Blasto stis is a e t e el u i uitous pa asite a d the ost f e ue tl isolated pa asite i epide iologi al su -

e s. It is o ld ide dist i uted a d fou d i all age g oups - . It is the ost o o pa asite fou d i hu-

a gast o-i testi al t a t. The i ide e of B.ho i is i diffe e t egio s is epo ted to e et ee - % - , p e ale e a ies idel f o ou t to ou t a d

ithi a ious o u ities of the sa e ou t . Highe p e ale e of the pa asite is see i de elopi g ou -t ies e ause of poo h gie e, e posu e to a i als, a d o su ptio of o ta i ated food o ate . Patho-

ge i it of Blasto stis has ee e te si el de ated i the past. Despite the u esol ed o t o e s o e its pathoge i it , Blasto stis sp. e ai s o e of the ost o o i testi al pa asites i hu a s. It a gi e ise

to a a iet of sig s a d s pto s , .The ost o -o i testi al s pto s des i ed a e dia hoea a d

a do i al pai , alo g ith so e o spe ifi s pto s su h as ausea, a o e ia, loati g a do e a d flatule e ha e also ee epo ted. Dia hoea a

e ild o self li ited hile so e autho s ha e also e-po ted a ute gast oe te itis . Blasto stis i fe tio does ot see to e i asi e, despite t o ase epo ts des i i g its e o e i deepe tissues. I oth of these ases, the e e e e ide e of p edisposi g fa to s

leadi g to dis uptio of the gut a ie that p o a l led to o-i fe tio ith Blasto stis , . I ita le o el s d o e IBS as fou d to e st o gl asso iated ith Blasto stis i fe tio . IBS ould esult i a i eased sus epti ilit of Blasto stis, o a te de fo lo ge a iage , . Lo -g ade i fla atio due to o go-

i g i u e a ti atio ould pla a ole i IBS . Blasto-stis ho i is has i easi gl ee i pli ated fo dia -

heal ill ess i i u o o p o ised i di iduals . Al-le gi uta eous lesio s, pa ti ula l u ti a ia, ha e ee asso iated ith this o ga is these the esolutio of de atologi sig s a d s pto s e e epo ted afte

t eat e t a d e adi atio of the pa asite f o the stool, .

It has ee suggested that uta eous a ifestatio s i the setti g of Blasto stis a iage a e p o a l i u e

ediated, the a oe oid fo adhe es effi ie tl to the i testi al epitheliu , affe ti g gut i u e ho eostasis a d ausi g a i fla ato espo se agai st the pa a-site that led to u ti a ia although the e ha is is u -lea , , . The p ese e of Blasto stis sp. i s pto-ati patie ts a also i di ate that this pa asite ould

e i ol ed ith othe fa to s i this disease pathoph s-iolog . It is possi le that the alte atio of the i testi-

al e i o e t, p o oked pathoge s a te ia , ge eti o e i o e tal fa to s p o otes its de elop-

e t. Fu the o e, studies sho i g the o o ita t e adi atio of Blasto stis sp. ith the disappea a e of s pto s i patie ts ith IBS a e eeded to la if the ole of this pa asite.It has ee epo ted that hile B.

ho i is is ei g dete ted i - % of a ute gast oe -te itis ases ith di e t i os opi i estigatio , dete -tio ates a ea h upto %

Pathoge i pote tial Blasto stis has ee e o e ed ithout sig ifi a t diffe e es et ee as pto ati a d s pto ati g oups. S pto s do ot o elate ith the load of pa -asite. So it is assu ed that it a e a olo ise e ause if pathoge i , o e s pto ati i di iduals ould ha -

o the pa asite o pa ed to as pto ati o es. Blas-to stis p oteases a e i ule e fa to s a d o t i ute to pa asite su i al i i o deg adi g eut alizi g u o-sal a ti odies. The i i o ole of IgA i u osal defe se agai st Blasto stis is u k o , although a se ologi al stud sho ed sig ifi a tl highe se eto IgA le els i s pto ati i di iduals ith Blasto stis i fe tio s tha i as pto ati a ie s a d health i di iduals. C stei e p oteases f o li e Blasto stis pa asites edi-ate IL- se etio f o olo i epithelial ells i a NF-

_B-depe de t a e

*Co espo di g autho : d ka itagupta @g ail. o

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Fig : Pathoge esis of Blasto stis sp

Blasto stis- ediated i testi al epithelial auses a i -flu of i fla ato ells i to the i testi al u osa leadi g to assi e tissue da age a d gast oi testi al distu a es. It as epo ted that the i asio of the i testi al epitheliu pathoge s is ot e essa fo the i du tio of i fla atio Pa asite se eto o -po e ts, su h as stei e p oteases, a e e t a a iet of det i e tal effe ts o host ells, esulti g i to-pathi effe ts, a ie o p o ise, a d the p odu tio of p oi fla ato toki es Fig. .

B.ho i is ep odu es i a fissio o spo ulatio . Both thi & thi k alled sts ha e ee fou d i it s life

le. Thi alled sts a e o side ed autoi fe tious, leadi g to ultipli atio of the o ga is i i testi al t a t he eas thi k alled sts a e p o a l espo si-

le fo t a s issio fe al-o al oute. This e plai s the easo , h the pe e tage of patie ts i fe ted ith B.

ho i is is ofte u h highe tha those i fe ted ith othe i testi al p otozoa? , Fig Mo pholog o -

o l e ists i th ee ajo fo s a uola , g a ula , a d a e oid . Classi fo that is usuall see i hu a s fae es a ies t e e de ousl i size f o to

µ , a d is ha a te ised a la ge e t al od a e li ked to a oh d ate a d lipid sto age .

La oratory diag osis of Blasto ystis i fe tio

Routi e stool e a i atio s a e e effe ti e i e o e -

i g a d ide tif i g B.ho i is, although pe a e t stai ed T i h o e s ea is the p o edu e of hoi e si e the e a i atio of et p epa atio s a ot easil e eal the i oo ga is s. Fig & The o ga is

should e ua titiated o the epo t fo , i.e., as a e, fe , ode ate, o a . It has ee epo ted that

hile B. ho i is is ei g dete ted i - % of a ute gas-t oe te itis ases ith di e t i os opi i estigatio , dete tio ates a ea h to % ith T i h o e stai .

Cultu e: Jo es ediu is the ediu of hoi e fo it s ulti atio f o patie t s sa ple , , .These ultu es e ai ia le fo up to eeks. A e i ultu es of Blas-

to stis isolates a e i po ta t fo ole ula ide tifi a-tio . A e izatio a e do e the additio of a ti i-oti s. It helps i eli i atio of o ta i ati g a te ia a d

easts , , . It is ot outi el pe fo ed as the p o ess is usuall u e so e a d a take eeks to o ths, a d the su essful eli i atio of i o ial o ta i a ts is ot gua a teed.

Se olog : I di e t fluo es e t a ti od IFA testi g a d e z e-li ked i u oso e t assa ELISA a e do e to dete t i u oglo uli G IgG a d IgA , . Tit es usuall a ges f o : to : , , high tite s a e asso iated ith s pto ati i fe tio s , . Although fo atio of a ti od a take ea s o o e ith h o i i fe tio s, de o st atio of se u a ti od

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Fig : Life le of Blasto stis sp.

p o ide i u ologi al e ide e fo the pathoge i ole fo this p otozoa . At p ese t, the e is li ited k o ledge a out the host i u e espo se to Blasto-

stis spp. a d a tige i di e sit of the pa asite is high. The efo e it is ot p a ti al to i lude se olog i the ou-ti e la o ato diag osis of Blasto stis, a d it should e pe fo ed o l fo epide iologi al a d se ologi al stud-ies.

Mole ula : Su t pe-spe ifi STS diag osti p i e s also efe ed to as STS p i e s f o a do a plifi atio of

pol o phi DNA a al sis a e a aila le . PCR-RFLP a al sis of the Blasto stis ss RNA ge e is o o l e -plo ed fo p e ale e studies , . La k of sta da diza-tio of the o ditio s, p i e s hoi e, utatio s at e-st i tio sites, a d the diffi ult i i te p eti g RFLP p o-files i i ed i fe tio s a e the ajo li itatio of this te h i ue. No a da s a high-th oughput p ose ue i g te h i ue fo the apid se ue i g of the Blasto stis ss RNA ge e has ee dete ted . Va ious diag osti

ethods fo the ide tifi atio of Blasto stis isolates

su h as the FECT, pe a e t t i h o e stai i g of fe es fi ed i sodiu a etate-a eti a id-fo ali , i it o ul-tu e, a d PCR app oa hes e e o pa ed a d the PCR app oa h as sho to e supe io to the othe ap-p oa hes. Dete tio of Blasto stis-spe ifi DNA i stool sa ples as fou d as se siti e as the ultu e ethod.

The FECT is ot good due to its lo se siti it . T i h o e stai i g of di e t fe al s ea s is se siti e a d it p o ides ape a e t e o d of the spe i e . The fi di g of stai -i g should e supple e ted ith i fo atio o hethe fi e o o e pa asites a e isi le pe oil i e sio field a d ua tifi atio of pa asite a u da e should e do e usi g te s su h as a e o e to t o pa asites i e e high-po e fields , fe to ode ate o e pa asite i e e o e to fi e high-po e fields , o a u da t fi e o o e pa asites pe high-po e field . I it o ultu e is a useful ethod fo diag osis i ase of lo pa asite le el

. Di e t et ou ts stai ed ith iodi e do ot see to add additio al alue to the diag osti p o ess, si e t i-h o e-stai ed pe a e t s ea s ha e ee sho to

Fig : C st of Blasto stis ho i is i et ou t Fig : C st of Blasto stis ho i is i T i h o e stai i g.

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alo g ith stool ultu e i Jo es ediu is the est ap-p oa h fo diag osi g Blasto stis i fe tio i te s of spe ifi it a d se siti it . Fo s ee i g a d epide iologi-al studies, PCR a plifi atio of Blasto stis DNA f o

f esh stools o stool ultu es is a o e ie t alte ati e to i os op

Treat e t Ma issues a e still u esol ed a d u h de ated e-ga di g this pa asite su h as the li i al ele a e, patho-ge i it a d the eed fo t eat e t[ ]. I , a stud des i ed lasto stosis as a i fe tio that is diffi ult to get id of although t eat e t has ee a aila le a d used fo se e al de ades. Re e t data also suggest that Blasto-

stis auses s pto s f e ue tl . The efo e, the ap should e li ited to patie ts ith pe siste t s pto s su se ue t to a o plete o k up fo alte ati e etiolo-gies[ ]. Fu the , studies epo ti g the apeuti i p o e-

e t o o ita t ith pa asite lea a e i s pto ati patie ts su sta tiates the pathoge i ole of the o ga is a d he e, the eed fo t eat e t. To date a u e of a ti i o ial age ts ha e ee used to t eat Blasto stis i fe tio . This i ludes et o idazole, itazo a ide, t i e-thop i -sulfa etho azole TMP-SMX , pa a o i , io-do ui ol, keto o azole, se idazole, e eti e, ti idazole, a d the p o ioti Sa ha o es oula dii. Patie ts i fe t-ed ith Blasto stis f e ue tl p ese t ith gast oi testi-

al o plai ts a d a e t eated ith the i te tio to e adi-ate the pa asite.

Met o idazole appea s to e the ost effe ti e d ug fo Blasto stis he othe ap despite so e e ide e fo t eat e t failu e. I su h i u sta es, TMP-SMX a d

itazo a ide a e o side ed as se o d hoi e d ugs. T eat e t should e i stituted if the dia hea is pe siste t a d o othe ausati e pathoge is ide tified i fe al spe -i e s. Futu e studies should i estigate the asso iatio

et ee ge ot pes a d a iatio s i d ug sus epti ilit . The e ha is s of a tio a d the ode of esista e to ea h of the d ug has to e e aluated fu the [ ].

Basi guideli es fo la o ato diag osis of Blasto stis i fe tio the CDC

Multiple stool sa ples at least should e tested efo e a egati e esult is epo ted. To a i ize e o e of st-like fo s, stool sa ples i fo ali , o othe fi ati es, should e o -

e t ated p io to i os opi e a i atio e.g., i at × g he usi g the fo ali eth l-a etate o e t atio p o edu e .

Choi e of diag osti te h i ues depe ds o a aila le e uip e t a d eage ts, e pe ie e, a d o -side atio s of ti e a d ost.

Co lusio : Blasto stis sp. as i luded i the Wate Sa itatio a d Health p og a es of the Wo ld Health O ga izatio [WHO, ]. The te B. ho i is is o lo ge appli a le to all hu a isolates, si e e o k o that hu a s a e i fe ted u e ous ge ot pes, a of hi h

a e zoo oti . He e, la o ato ies should epo t the p es-e e of the pa asite f o patie t sa ples as ei g Blas-to stis sp. i stead of B. ho i is a d, i additio , i lude details o hethe fi e o o e pa asites a e o se ed pe oil i e sio _ , field. The i te a tio of Blas-to stis sp. ith gut i o iota eeds to e studied e-ause of the i easi g i te est i i o iota distu -

a es i the ge esis of a ious gast oi testi al d sfu -tio s. a d si e Blasto stis is a o i asi e pa asite, se eted p odu ts f o the pa asite ight i itiate the i fla ato p o ess a ti ati g ell su fa e e ep-to s. As pathoge i E. histol ti a ells p odu e the e t a-ellula elease of - to , -fold o e stei e p ote-

ases tha the o i asi e E. dispa . It ould e o th-hile to stud the elati e p otease le els a o g the

a ious Blasto stis su t pes a d to i estigate if the e is a si ila o elatio et ee p otease a ti it a d i ule e. Ge o e a al sis of the spe ies a d appli a-

tio of ode te h i ues, su h as i osatellites, i-oa a s a d diffe e tial displa oupled ith p ote-

o o i s a d ioi fo ati s a al sis a e o e likel to elu idate the diffe e es i pathoge i it , i ule e a d espo se to t eat e t[ ]. The de elop e t of e the -

apeuti optio s to ou te a ti i o ial esista e e-ui es the use of high th ough put s ee i g tools[ , ].

Refere es:

. Jeli ek, T., G. Pe e l, T. Lo¨s he , F. o So e u g, a d H. D. Nothdu ft. . The ole of Blasto stis ho i is as a possi le i testi al pathoge i t a elle s. J. I fe t. : –

. . Ta , K. S. . Blasto stis i hu a s a d a i als: e

i sights usi g ode ethodologies. Vet. Pa asitol. : – .

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. Taa as i, P., M. Mu gthi , R. Ra gsi , B. To gupp aka , W. A eekul, a d S. Leela oo a. . T a s issio of i testi al lasto stosis elated to the ualit of d i ki g

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zoa a d the i po ta e of thei dete tio a d diag osis. I t J Pa asitol ; : – .

. Ta KSW, Si gh M, Yap EH Re e t ad a es i Blasto stis ho i is esea h: hot spot i te a i og ita. I t J Pa asitol : –

. Valse hi R, Leghissa P, G e o V. Cuta eous lesio s i Blasto stis ho i is i fe tio . A ta De Ve e eol ;

: – .

. Ve a, R. a d Delfa ia , K. Blasto stis ho i is asso iated a ute u ti a ia. A J Med S i : _ .

. Poi ie , P., Wa z iak, I., Vi a es, C., Del a , F. A d El Alaoui, H. Ne i sights i to Blasto stis spp.: a po-te tial li k ith i ita le o el s d o e. PLoS Pathog : e .

. Hua g, D. B., a d A. C. White. . A updated e ie o C ptospo idiu a d Gia dia. Gast oe te ol. Cli . N. A .

: – . . O tega, Y. R., a d R. D. Ada . . Gia dia: o e ie a d

update. Cli . I fe t. Dis. : – . . Ka a, S., E. S. Ceti , B. C. A idoga , S. A ika , a d M.

De i i. . Pathoge i it of Blasto stis ho i is, a li i-al ee aluatio . Tu ki e Pa azitol. De g. : – .

. Sajid, M., a d J. H. M Ke o . . C stei e p oteases of pa asiti o ga is s. Mol. Bio he . Pa asitol. : – .

. Mah oud, M. S., a d W. A. Saleh. . Se eto a d hu o al a ti od espo ses to Blasto stis ho i is i s pto ati a d as pto ati hu a i fe tio s. J. Eg pt. So . Pa asitol. : – .

. Be kes, J., V. K. Vis a atha , S. D. Sa ko i , a d G. He ht. . I testi al epithelial espo ses to e te i pathoge s:

effe ts o the tight ju tio a ie , io t a spo t, a d i -fla atio . Gut : – .

. Be kes, J., V. K. Vis a atha , S. D. Sa ko i , a d G. He ht. . I testi al epithelial espo ses to e te i pathoge s:

effe ts o the tight ju tio a ie , io t a spo t, a d i -fla atio . Gut : – .

. Ta , K. S. . Blasto stis spp. I N. A. Kha ed. , E e g-i g p otozoa pathoge s. Ta lo a d F a is, O fo d, U it-ed Ki gdo .

. Ste zel, D. J., a d P. F. Bo eha . . Blasto stis ho i is e isited. Cli . Mi o iol. Re . : – .

. L e Sho e Ga ia , Diag osti Medi al Pa asitolog , th editio p -

. Boe k, W. C., a d J. D ohla . . The ulti atio of E ta-oe a histol ti a.A . J. H g. : – .

. Jo es, W. R. . The e pe i e tal i fe tio of ats ith E ta oe a histol ti a. A . T op. Med. Pa asitol. : .

. Ste s old, R., A. B illo ska-Da o ska, H. V. Nielse , a d M. C. A e d up. . Dete tio of Blasto stis ho i is i u p ese ed stool spe i e s usi g pol e ase hai ea tio . J. Pa asitol. : – .

. Ta , K. S., G. C. Ng, E. Quek, J. Ho e, N. P. Ra a ha d a , E. H. Yap, a d M. Si gh. . Blasto stis ho i is: a si pli-fied, high-effi ie ethod fo lo al g o th o solid aga . E p. Pa asitol. : – .

. Ng, G. C., a d K. S. Ta . . Colo g o th as a step to-a ds a e izatio of Blasto stis isolates. Pa asitol. Res. : – .

. La uza, M. D., J. A. Ca ajal, J. Villa , a d R. Bo a´s. . Des iptio of a i p o ed ethod fo Blasto stis ho i is ultu e a d a e izatio .Pa asitol. Res. : – .

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. Zie dt, C. H., a d B. Nag . . A ti od espo se to Blas-to stis ho i is i fe tio s. A . I te . Med. : – .

. Zie dt, C. H., W. S. Zie dt, a d B. Nag . . E z e-li ked i u oso e t assa fo dete tio of se u a ti od to Blasto stis ho i is i s pto ati i fe tio s. J. Pa asitol.

: – . . Ka eda Y., N. Ho iki, X Che g. . Se ologi espo se to

Blasto stis ho i is i fe tio i as pto ati i di iduals. Tokai j. E p. Cli . Med. : -

. Yoshika a, H., N. A e, a d Z. Wu. . PCR- ased ide tifi-atio of zoo oti isolates of Blasto stis f o a als a d i ds. Mi o iolog : – .

. Wo g, K. H., G. C. Ng, R. T. Li , H. Yoshika a, M. B. Ta lo , a d K. S. Ta . . P edo i a e of su t pe a o g Blas-to stis isolates f o a ajo hospital i Si gapo e. Pa asi-tol. Res. : – .

. Ste s old, C. R., M. C. A e d up, C. Jespe sgaa d, K. Møl ak, a d H. V. Nielse . . Dete ti g Blasto stis usi g pa asi-tologi a d DNA- ased ethods: a o pa ati e stud . Di-ag . Mi o iol. I fe t. Dis. : – .

. Ste s old, R., A. B illo ska-Da o ska, H. V. Nielse , a d M. C. A e d up. . Dete tio of Blasto stis ho i is i u -p ese ed stool spe i e s usi g pol e ase hai ea -tio . J. Pa asitol. : – .

. O¨ z aki , O., S. Gu¨ ese , S. E gu¨ e , Y. A. Yil az, R. Topal-og˘lu, a d G. Has ¸elik. . Cha a te isti s of Blasto stis ho i is i fe tio i a Tu kish u i e sit hospital. Tu ki e Pa azitol. De g. : – .

. O¨ z u t, M., O. Ku t, K. Møl ak, H. V. Nielse , T. Haz eda-oglu, a d C. R. Ste s old. . Mole ula epide iolog of

Blasto stis i fe tio s i Tu ke . Pa asitol. I t. : – .

. Lede , K., M. E. Hella d, M. I. Si lai , C. K. Fai le , a d R. Wolfe. . No o elatio et ee li i al s p-to s a d Blasto stis ho i is i i u o o pete t i di iduals. J. Gast oe te ol. Hepatol. : – .

. Su esh, K., a d H. S ith. . Co pa iso of ethods fo dete ti g Blasto stis ho i is. Eu . J. Cli . Mi o iol. I fe t. Dis. : – .

. Va Helle o d JJ, Molhoek N, Koele ij R, Wis a s PJ, a Ge de e PJ. Is pa o o i the d ug of hoi e fo

e adi atio of Blasto stis i adults? J I fe t Che oth-e . O t; PMID: . [Pu Med]

. Di le i i EC, E e M, Doga N, Re ha ioglu S, Ya gi ZA, Va de plas Y. Cli i al effi a of Sa ha o es ou-la dii o et o idazole i s pto ati hild e ith Blasto stis ho i is i fe tio . Pa asitol Res.

; : – . [Pu Med] . Ta KS. Ne i sights o lassifi atio , ide tifi atio ,

a d li i al ele a e of Blasto stis spp. Cli Mi o iol Re . ; : – . [PMC f ee a ti le] [Pu Med]

. Reed, S. L., W. E. Kee e, a d J. H. M Ke o . . Thiol p otei ase e p essio a d pathoge i it of E ta oe a histol ti a. J. Cli . Mi o iol. : – .

. Vassalos CM, Spa akos G, Vassalou E, Papadopoulou C, Vakalis N. Diffe e es i li i al sig ifi a e a d o -phologi featu es of Blasto stis sp su t pe . A J Cli Pathol. ; : – . [Pu Med]

. Mi za H, Teo JD, Up oft J, Ta KS. A apid, high-

th oughput ia ilit assa fo Blasto stis spp. Re eals et o idazole esista e a d e te si e su t pe-

depe de t a iatio s i d ug sus epti ilities. A ti i-o Age ts Che othe . ; : – .

. U a Seka a d M Sha thi. Cu e t ie s o the li i al ele a e of Blasto stis spp. Cu I fe t Dis Rep.

; : 8–

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The e ol i g fa e of diag osti s i tu er ulosis: re e t ad a es a d re ie of literature

Autho s: D . Gi eesha Ra al, D . Cha a jeet Ahlu alia*

Depa t e t: Depa t e t of Patholog

I stitutio : VMMC & Safda ja g Hospital, Ne Delhi

Re ie arti le

I t odu tio

Tu e ulosis TB is o e of the ost deadl , u a le i fe -tious diseases. Ithas e o e a glo al health o e ,

hose o ple it has ee o the ise due to pe siste e i agi g populatio s, HIV, a d the e e ge e of d ug-

esista t st ai s. TB is the i th leadi g ause of death o ld ide a d the leadi g ause f o a si gle i fe tious age t. A o di g to WHO statisti s, a esti ated . illio people fell ill ith TB, out of hi h % e e i fi e ou t ies: I dia, I do esia, Chi a, the Philippi es a d Pakista . The e e e a esti ated . illio TB deaths a o g HIV- egati e people a d a additio al deaths a o g HIV-positi e people. The e e e e ases ith esista e to ifa pi i RRTB , of hi h had ultid ug- esista t TB MDR-TB . Al ost half % of

these ases e e i I dia, Chi a a d the Russia Fede a-tio . Glo all , the TB o talit ate is falli g at a out % pe ea . TB i ide e is falli g at a out % pe ea a d

% of TB ases die f o the disease; , these figu es eed to i p o e to – % pe ea a d %, e-spe ti el , to ea h the fi st ilesto es of the E d TB St ateg .

Rapid a d ea l TB diag osis a e halle gi g a d diffi-ult. Fo diag osi g pul o a TB, hest X- a is useful ut ot spe ifi . Also, TB a p ese t ith at pi al s p-

to s a d adiologi featu es, i disti guisha le f o p eu o ia. The t aditio al ethod fo diag osi g late t TB i fe tio , tu e uli ski test, has a ious d a a ks i ludi g lo spe ifi it , a d lo se siti it i i u o-o p o ised patie ts.

La o ato ies ha e a u ial ole i TB diag osis, thus st e gthe i g apa it a d pe fo a e of la o ato ies is fo e ost fo its o t ol. Wo ld ide, a la s a e o ti -ui g to use the sa e te h i ues as e e used half a e -tu ago, i.e. Ziehl Neelse stai ed s ea i os op a d ultu e. The se siti it of s ea i os op is su opti al

- % .Cultu e i p o es dete tio ate of TB -

%, dete ti g e e ases ith lo o a te ial load. It is also e ui ed fo d ug esista e testi g a d spe ies dete tio . Routi el , ultu e a take - eeks o lo ge .A ti i o ial sus epti l testi g ofte takes

o ths, is diffi ult to pe fo , a sho dis o da e ith so e d ugs e.g. etha utol , a d AST fo se o d-

li e d ugs is still poo l sta da dized a d ot idel a ail-a le.

P o pt diag osis of a ti e pul o a TB is of p i e i -po ta e fo o t olli g TB, oth fo t eati g the patie t a d fo pu li health i te e tio sai ed at edu i g fu -the sp ead i the o u it . Thus, a u ge t eed pe -sistsfo e e te h i ues that ill e a le apid TB dete -tio , as ell as AST to ide tif esista t st ai s.

Re e tl , se e al o ole ula a d ole ula ethods ha e ee de eloped to add ess these issues. This e ie a ti le dis usses the e e t ad a es allo i g ette a d apid diag osis of TB. The ad a tages a d p a ti al li ita-

tio s of e te h i ues ha e ee des i ed, ased o a e te si e lite atu e e ie .

FLUORESCENCE-BASED METHODS

Fluo es e t Light E itti g Diode LED Mi os op : Fluo es e e i os op fo TB dete tio usi g fluo o-h o e stai s e.g. au a i e hashigh se siti it a d take

little ti e. Ho e e , its li itatio s i lude e ui e e t of fluo es e t i os ope, da k oo , a d e pe si e light sou e Thus, the ad a tages of fluo es e t i os op a e etai ed, hile eli i ati g its d a a ks. A o di g to

the e o e datio WHO, o e tio al fluo es e e i os op should e epla ed LED i os op a d

LED i os op should e phased i as a alte ati e fo o e tio al light i os op .

CULTURE-BASED METHODS

Li uid ultu e edia: As o pa ed to o e tio al solid ultu e edia, the se siti it of li uid edia is o e

*Co espo di g autho : ha a jeet.ahlu alia@ ediff ail. o

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up to % i ease i positi it a d dete tio ti e is less - da s e sus - eeks . But its d a a k is the o ta i atio ate, hi h is highe fo li uid edi-

u .WHO e o e ds use of solid edia alo g ith li uid edia i p i a isolatio of o a te ia. Ho e-

ased li uid oth ultu e a e used o tai i g Middle-ook H oth supple e ted ith % OADC olei

a id, al u i , de t ose, a d atalase a d, fo p e e tio of o ta i atio , PANTA pol i , a phote i i B,

alidi i a id, t i ethop i , a d azlo illi .

Mi o olo dete tio o solid edia:

This ethod ide tifies the ha a te isti st i gs a d ta -gles of M. tu e ulosis o plates ha i g a thi la e of Middle ook H aga ediu Dif o usi g light i-

os op . Dete tio this lo - ost ethod takes less tha a eek, ut its effi ie is lo .

Mi os opi O se atio D ug Sus epti ilit MODS As-sa :

This is a oth i otite ethod fo dete tio of M. tu-e ulosis a d its esista e to iso iazid a d ifa pi . I

this ethod, i otite plates o tai i g Middle ook H oth, g o th supple e ts, a d a ti i o ial age ts

a e used. A ti-TB d ugs a e added to so e ells. These ells a e the i o ulated ith li i al spe i e s, sealed,

a d e a i ed pe iodi all . Positi e ultu es sho g o th ith o di g.D ug esista e is dete ted i hi itio of

g o th i ells o tai i g d ugs. This te h i ue is i e -pe si e a d si ple, ith a se siti it a i g f o . % to . %.,,,, Its d a a ks i lude e ui e e t of te h-

i al e pe tise, spe ialised e uip e t ste eos opi i-os ope , eage ts, a d supplies, a d testi g at Biosafet

Le el .

BACTEC TB: BACTEC TB Be to Di ki so , Spa ks, MD, USA has lo g ee ega ded the est ethod fo apid dete tio of sus epti ilit of M. tu e ulosis to a ti-tu e ula d ugs ifa pi i , iso iazid, etha utol, p azi a ide a d st epto i .It is a adio et i te h i ue, i hi h

eta olis of C la eled su st ate C la eled pal iti a id i H ediu o a te ia leads to p odu -tio of CO , hi h is easu ed as g o th i de . The ti e take this ethod is half as e ui ed o e -tio al ultu e ethods.A o di g to a p e ious stud ,thiste h i uea hie ed % of the positi e esults

ithi a eek a d % ithi t o eeks., Thus, i ou -

t ies e de i fo tu e ulosis, this ost effe ti e ethod e a les ea l diag osis.

ESP lood ultu e s ste : The ESP s ste Dif o La o ato ies, Det oit, Mi h. de-te ts o su ptio a d p odu tio of gas ot o l CO

i o es. The lood ultu e ottles a e o ito ed e e- - i utes fo ha ges i o ge o su ptio a d

gas p odu tio , hi h a e asso iated ith i o ial g o th. ESP Cultu e S ste II: ESP Cultu e S ste II Dif o La o ato ies, Det oit, Mi h. is a full auto ated o ti uous o ito i g ultu e s ste used fo g o th a d dete tio of i oo ga is s i ludi g M tu e ulosis . M o a te ial g o th is i te -

p eted assessi g gas o su ptio , hi h auses p es-su e ha ges. A stud epo ted ea ti e fo e o e of all o a -te ia i ludi g M tu e ulosis a d M o a te iu a iu o ple a gi g f o . to . da s.

MB/Ba T:

MB/Ba T O ga o Tek ika, Tu hout, Belgiu uses a olo i et i se so a d efle ted light to o ito CO o e t atio o ti uousl i ultu e ediu .

A o di g to a stud , ea ti e to dete t M tu e ulosis f o sputu , e e ospi al fluid CSF a d u i e spe i-

e s as . ± . da s fo MB/Ba T, . ± . fo BACTEC a d . ± . da s fo egg- ased ultu e e-dia. Thus, MB/Ba T is a a epta le alte ati e to BAC-TEC ,although it hasfe disad a tages, i.e. slightl lo ge ti e fo g o th dete tio a d i eased o ta i-

atio .

Nit ate edu tase assa NRA : This assa is ased o edu tio of it ate to it ite M. tu e ulosis, hi h is dete ted G iess eage t added to Lö e stei -Je se LJ ediu ith i o po ated potas-siu it ate KNO ,gi i g ise to a olou ed ea tio . The patie t's sa ple is i o ulated o edia ith a d ithout a ti ioti s fo testi g esista e.

Colo i et i Assa s : This ethod is ased o the p i iple of o e sio of

ello d e [ - , -di eth lthiazol- - l - , diphe l te-t azoliu o ide o MTT] to a pu ple olou M. tu-

e ulosis, that a e dete ted isuall o spe t opho-to ete . This ethod has a highl o o da t ith

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up to % i ease i positi it a d dete tio ti e is less - da s e sus - eeks . But its d a a k is the o ta i atio ate, hi h is highe fo li uid edi-

u .WHO e o e ds use of solid edia alo g ith li uid edia i p i a isolatio of o a te ia. Ho e-

ased li uid oth ultu e a e used o tai i g Middle-ook H oth supple e ted ith % OADC olei

a id, al u i , de t ose, a d atalase a d, fo p e e tio of o ta i atio , PANTA pol i , a phote i i B,

alidi i a id, t i ethop i , a d azlo illi .

Mi o olo dete tio o solid edia:

This ethod ide tifies the ha a te isti st i gs a d ta -gles of M. tu e ulosis o plates ha i g a thi la e of Middle ook H aga ediu Dif o usi g light i-

os op . Dete tio this lo - ost ethod takes less tha a eek, ut its effi ie is lo .

Mi os opi O se atio D ug Sus epti ilit MODS As-sa :

This is a oth i otite ethod fo dete tio of M. tu-e ulosis a d its esista e to iso iazid a d ifa pi . I

this ethod, i otite plates o tai i g Middle ook H oth, g o th supple e ts, a d a ti i o ial age ts

a e used. A ti-TB d ugs a e added to so e ells. These ells a e the i o ulated ith li i al spe i e s, sealed,

a d e a i ed pe iodi all . Positi e ultu es sho g o th ith o di g.D ug esista e is dete ted i hi itio of

g o th i ells o tai i g d ugs. This te h i ue is i e -pe si e a d si ple, ith a se siti it a i g f o . % to . %.,,,, Its d a a ks i lude e ui e e t of te h-

i al e pe tise, spe ialised e uip e t ste eos opi i-os ope , eage ts, a d supplies, a d testi g at Biosafet

Le el .

BACTEC TB: BACTEC TB Be to Di ki so , Spa ks, MD, USA has lo g ee ega ded the est ethod fo apid dete tio of sus epti ilit of M. tu e ulosis to a ti-tu e ula d ugs ifa pi i , iso iazid, etha utol, p azi a ide a d st epto i .It is a adio et i te h i ue, i hi h

eta olis of C la eled su st ate C la eled pal iti a id i H ediu o a te ia leads to p odu -tio of CO , hi h is easu ed as g o th i de . The ti e take this ethod is half as e ui ed o e -tio al ultu e ethods.A o di g to a p e ious stud ,thiste h i uea hie ed % of the positi e esults

ithi a eek a d % ithi t o eeks., Thus, i ou -

t ies e de i fo tu e ulosis, this ost effe ti e ethod e a les ea l diag osis.

ESP lood ultu e s ste : The ESP s ste Dif o La o ato ies, Det oit, Mi h. de-te ts o su ptio a d p odu tio of gas ot o l CO

i o es. The lood ultu e ottles a e o ito ed e e- - i utes fo ha ges i o ge o su ptio a d

gas p odu tio , hi h a e asso iated ith i o ial g o th. ESP Cultu e S ste II: ESP Cultu e S ste II Dif o La o ato ies, Det oit, Mi h. is a full auto ated o ti uous o ito i g ultu e s ste used fo g o th a d dete tio of i oo ga is s i ludi g M tu e ulosis . M o a te ial g o th is i te -

p eted assessi g gas o su ptio , hi h auses p es-su e ha ges. A stud epo ted ea ti e fo e o e of all o a -te ia i ludi g M tu e ulosis a d M o a te iu a iu o ple a gi g f o . to . da s.

MB/Ba T:

MB/Ba T O ga o Tek ika, Tu hout, Belgiu uses a olo i et i se so a d efle ted light to o ito CO o e t atio o ti uousl i ultu e ediu .

A o di g to a stud , ea ti e to dete t M tu e ulosis f o sputu , e e ospi al fluid CSF a d u i e spe i-

e s as . ± . da s fo MB/Ba T, . ± . fo BACTEC a d . ± . da s fo egg- ased ultu e e-dia. Thus, MB/Ba T is a a epta le alte ati e to BAC-TEC ,although it hasfe disad a tages, i.e. slightl lo ge ti e fo g o th dete tio a d i eased o ta i-

atio .

Nit ate edu tase assa NRA : This assa is ased o edu tio of it ate to it ite M. tu e ulosis, hi h is dete ted G iess eage t added to Lö e stei -Je se LJ ediu ith i o po ated potas-siu it ate KNO ,gi i g ise to a olou ed ea tio . The patie t's sa ple is i o ulated o edia ith a d ithout a ti ioti s fo testi g esista e.

Colo i et i Assa s : This ethod is ased o the p i iple of o e sio of

ello d e [ - , -di eth lthiazol- - l - , diphe l te-t azoliu o ide o MTT] to a pu ple olou M. tu-

e ulosis, that a e dete ted isuall o spe t opho-to ete . This ethod has a highl o o da t ith

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ith o e tio al AST.,

MDR-XDR TB Colo Test: This utilizes Thi -La e Aga TLA te h olog ith oth ultu e a d di e t AST ethod o a si gle aga plate. Its asis is the olou ha ges i uad a ts of the plate, ith uad a t fo dete ti g g o th a d the othe uad a ts fo AST uad a t ea h fo iso iazid, ifa -

pi , a d ip oflo a i . This assa is highl se siti e a d spe ifi fo dete ti g d ug esista e a d its o ta i a-tio ate is u h lo e .,,,

INTERFERON IFN -GAMMA-RELEASE ASSAYS IGRAS These a e i it o lood tests of ell- ediated i u it , that easu e T ell elease of IFN-γafte patie t's lood sa ple is sti ulated TB-spe ifi a tige s ESAT- a d CFP- . IGRAs a ot diffe e tiate et ee late t a d a ti e TB a d should ot e used fo diag osis of a ti e TB.Re e tl , a stud epo ted that IGRAs a e o e se si-ti e tha tu e uli ski test TST fo the diag osis of M tu e ulosis i fe tio i HIV-i fe ted patie ts., A o d-i g to Ra os et al, dual se ue tial testi g ith oth TST a d IGRAs is a opti al app oa h fo s ee i g of late t tu e ulosis i fe tio i HIV-i fe ted patie ts.

Qua tiFERON-TB Gold:

I this test, lood sa ple is olle ted, sti ulati g a ti-ge s a e added, follo ed i u atio at °C fo - hou s, ha esti g of plas a a d additio of o jugate solutio . The sa ples a e agai i u ated at oo te -pe atu e fo t o hou s, the plates a e ashed at least si ti es a d su st ate is added. The sa ples a e i u-

ated fo i utes, stop solutio is added, a so a e is ead at a d esults a e al ulated. Usi g this

ethod, esults a e o tai ed i hou s.

Qua tiFERON-TB Gold I -Tu e: Qua tiFERON-TB Gold ould e used o l he lood testi g ould egi ithi a fe hou s afte olle tio . This li itatio as o e o e Qua tiFERON-TB Gold I -Tu e Cellestis Li ited, Ca egie, Vi to ia, Aust alia ,

hi h uses a i tu e of peptides ESAT- , CFP- a d TB . .

T-SPOT.TB:

T-SPOT.TB O fo d I u ote Li ited, A i gdo , U it-ed Ki gdo , i u ates pe iphe al lood o o u-

lea ells ith peptide i tu es ESAT- , CFP- a d uses e z e-li ked i u ospot assa ELISpot to de-te t i eases i u e of ells se eti g IFN-γ.25

Mo oki e-a plified IFN- γ elease assa s MIGRAs : These assa s a e ased o the p i iple that IFN elease su se ue tl leads to elease of IFN- espo si e he o-ki es MIG a d IP- , hi h a e easu ed fo dete -tio of o a te ial i fe tio a d a tige -spe ifi T-

ell espo ses.

ANTIGEN-ANTIBODY REACTION BASED TESTS

These tests pla a ole i dete tio of late t tu e ulosis i fe tio .

A tige dete tio : The e eto -se eto p otei ES- as o e of the fi st a tige s dete ted to e useful i diag osi g TB i -fe tio . A stud o pa ed sa d i h ELISA test fo ES- , ES- , a d EST- ith o ospe ifi a ti-ES- a ti od dete tio i s ea -positi e TB ases, epo ti g - % se siti it fo the th ee a tige s a d - % fo the

o ospe ifi test. A tige s hi h a e dete ted he p ese t at o -e t atio of - g/ L a e o a te ial so i ates,

tu e uli pu ified p otei de i ati e PPD a d a tige s , A , P a d LAM. These a e dete ted usi g sa d-i h o i hi itio ELISA, late aggluti atio o e e se

passi e he aggluti atio RPHA tests. The se siti it of these tests is lo - % , ut spe ifi it is - %.

Dete tio of lipoa a i o a a : Lipoa a i o a a LAM is a ell all lipopol sa ha-ide a tige of M tu e ulosis. A stud de o st ates

u i a LAM to e elated to host i u e fa to s a d its stead de li e afte t o eeks of a ti-tu e ula the a-p . LAM-ELISA a e used fo diag osis of HIV-

asso iated TB i u i e sa ple f o patie t ha i g lo CD ell ou ts. A othe app oa h is use of dipsti k to dete t LAM i u i e a d pul o a spe i e s % se siti it a d % spe ifi it . ,

Multi-a tige a d a ti od assa s SEVA TB ELISA : I a stud usi g SEVA TB ELISA ith a o ktail of ES- a d EST- o tai i g ES- a d ES- a tige s a d thei IgG a ti odies fo e aluati g se a o pleu al fluid spe i e s of patie ts ith suspe ted TB pleu itis, the test as see to de o st ate % se siti it a d %

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spe ifi it . This test has a added ad a tage, i that it a dis i i ate et ee late t i fe tio a d a ti e

TB.

MOLECULAR METHODS

TB peptide u lei a id PNA FISH: PNA ole ules a e pseudopeptides ith DNA- i di g apa it i hi h suga phosphate a k o e of DNA has ee epla ed pol a ide a k o e.FISH usi g these

p o es disti guishes et ee TB dete tio se siti it - % a d o -TB o a te ia dete tio se siti it - % i o a te ial ultu es. Both t pes of p o es

de o st ated diag osti spe ifi ities a d p edi ti e al-ues of %.

Nu lei a id a plifi atio NAA : Nucleic acid tests are used mostly for confirmation of smear-positive TB or for primary diagnosis, in combina-tion with other methods. Their advantages include rapid availability of results,and high specificity (98-100%)31, and sensitivity (>95% in acid-fast bacilli positive sputum; 60-70% in smear-negative, culture-positive sample).,Use of these methods is still limited to developed countries, due to high price and complexity, but their availability in developing countries is gradually increasing.

PCR: PCR a plifies DNA se ue es i it o, to e a le its apid isualizatio a d ide tifi atio . The ost o o ta get

used fo PCR is i se tio se ue e IS , hi h is spe-ifi fo M tu e ulosis a d offe s ultiple ta gets fo

a plifi atio , as it is p ese t up to ti es i the ge-o e.

T a s iptio ediated a plifi atio TMA - AMPLIFIED MTD M o a te iu tu e ulosis Di e t Test: AMPLIFIED MTD Test Ge -P o e, Hologi dete ts M -o a te iu tu e ulosis i oso al i o u lei a id RNA di e tl a d apidl . TMA p odu es o e illio

opies of RNA a pli o hi h a e the dete ted h -idizatio p ote tio assa s HPA . It has % se siti it

a d % spe ifi it fo M tu e ulosis o s ea -

positi e spe i e s. False- egati e o false-positi e esults a e due to o ta i atio o s all u e of a illi. A othe disad a tage is that esults a e e o ded

as positi e fo ia le as ell as dead a illi. ,

Ligase hai ea tio LCR :

It is ased o ligatio of t o adja e t s theti oligo u-leotide p i e s hi h u i uel h idize to o e of the

st a ds of ta get DNA. A se o d pai of oligo u leotides is desig ed to h idize to the o ple e ta DNA, i the sa e egio . Whe the u leotides a e p ese t, the DNA pol e ase a d ligase eate a gap et ee adja e t p i e s, hi h ill the e filled ith app op i-ate u leotides leadi g to ligatio of the p i e s.

Loop-Mediated Isothe al A plifi atio : The Loop-Mediated Isothe al A plifi atio assa Eike Che i al Co pa utilizes a o el fo of u le-

i a id a plifi atio ha i g suffi ie t effi ie so that ade uate DNA is ge e ated to ake dete tio isual i spe tio of fluo es e e possi le. The ethod has

ee epo ted to ha e high se siti it fo s ea -positi e ases ut lo se siti it o s ea - egati e ases.

Oligo u leotide Mi oa a : Oligo u leotide i oa a e a les si ulta eous dete -tio of ultiple ge eti se ue es, hi h a e used to dete t eithe o se ed se ue es fo dete tio of i-

oo ga is s o utated se ue es that i pa t d ug esista e to a isolate. O e of these assa s, the TB-

Bio hip E gelha dt I stitute of Mole ula Biolog , has ee assessed fo dete tio of esista e to ifa pi i

M. tu e ulosis. I a stud o pa i g oligo u leotide i oa a ith o e tio al AST, the fo e sho ed % se siti it fo dete ti g esista e to ifa pi .

T ue at MTB

A heape , i dige ousl de eloped ole ula diag osti test fo d ug-se siti e a d ifa pi i - esista t TB is e -te i g the fi al leg of pe fo a e alidatio a d ope a-tio al feasi ilit testi g the I dia Cou il of Medi al Resea h ICMR . Based o the esults of a p eli i a test a ied out o patie t sa ples i , the se siti it a ilit of a test to o e tl ide tif those

ith the disease of T ue at MTB as fou d to e o e % a d the spe ifi it a ilit of the test to o e tl

ide tif those ithout the disease as %.

The atte -ope ated, ha d-held a hi e takes a out i utes fo DNA e t a tio a d a othe i utes

fo diag osi g TB. It takes a additio al o e hou fo testi g ifa pi i esista e. Co pa ed ith a o e l of sa ple eeded he Ge eXpe t, a ole ula test

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test de eloped i the U.S., is used, o l a out . l is e ui ed fo a test ith T ue at MTB.

While Ge eXpe t is a losed a tilage s ste , T ue at MTB is a ope s ste — the DNA is fi st e t a ted a d the testi g is a ied out usi g a po tio of that DNA.

The Eas NAT Diag osti Kit fo M o a te iu tu e u-losis Co ple Usta Biote h ologies, Chi a , is a iso-the al a plifi atio kit ith a - i a plifi atio ea tio step at °C a d - i isual dete tio usi g

a late al flo de i e. Whe used to test thi ed a d o e t ated sputu , the epo ted se siti it o pa ed ith ultu e o Lo e stei –Je se e e . % % CI . – . % a d . % % CI . – . % , espe ti e-

l , a d the se siti it i s ea - egati e ases as . % % CI . – . % .

DRUG SENSITIVITY TESTING DST TECHNIQUES

Xpe t MTB/RIF: The Xpe t MTB/RIF assa Cepheid is a self-e losed, apid PCR de i e that dete ts TB a d its esista e to ifa pi i di e tl f o sputu ithi hou s of olle -

tio . Its a t idges a e p e-loaded ith eage ts e ui ed fo sa ple p o essi g, DNA e t a tio , a plifi atio , a d lase dete tio of a plified po B ge e ta get. Bei g self-e losed, it e ui es less sophisti ated i f ast u -tu e i te s of la fa ilities, use t ai i g, a d suppl hai a age e t. The assa as epo ted to ha e

% se siti it fo dete ti g s ea -positi e ases ut o l . % se siti it fo dete ti g s ea - egati e ul-tu e-positi e ases, a d a spe ifi it of . %.Additio of a se o d MTB/RIF test i s ea - egati e ultu e-positi e ases i eased se siti it . %; additio of a thi d

MTB/RIF test i eased se siti it a additio al . %. This assa has high se siti it fo dete tio of ifa pi esista e, o e tl ide tif i g . % of the ifa pi - esista t ases a d . % of the ifa pi sus-epti le ases. I a ilit to dete t iso iazid esista e is

a disad a tage of this ethod.

Li e p o e assa LPA : Ite a les apid dete tio of ge e a ke s asso iated

ith ifa pi i esista e alo e o i o i atio ith iso iazid. po B egio utatio s a e see i % ifa -pi i - esista t ases. Resista e to iso iazid is a ou t-ed fo ai l utatio s i katG, follo ed uta-tio s at I hA a ti e site a d i p o ote egio of ahp

C.,

The fi st LPA as INNO-LiPA Rif TB I oge eti s NV . The ethodolog i ludes DNA e t a tio f o o-

a te ial isolates o li i al spe i e s, a plifi atio of esista e-dete i i g egio of ge e PCR, h idiza-

tio of la elled PCR p odu ts ith oligo u leotide p o es i o ilized o a st ip, a d olo i et i de elop-

e t hi h e a les isualisatio of li es he e e p o es a e lo ated. LPA ha e high se siti it ≥ % a d spe ifi it ≥ % fo dete tio of esista e to ifa pi -i , alo e o i o i atio ith iso iazid ≥ % se siti -it ,≥ % spe ifi it , i M. tu e ulosis isolates a d i s ea -positi e sputu spe i e s. Ne e theless, LPA a ot epla e o e tio al ultu e ith DST, a d ul-

tu e fo s ea - egati e spe i e s ith DST si e se -o d-li e a ti-TB d ugs a e still eeded.

GENOTYPING METHODS

Spoligot pi g: It utilizes PCR a plifi atio of a highl pol o phi di-e t epeat lo us i ge o e of M. tu e ulosis fo dete -

tio a d t pi g. P io a te ial ultu e is e ui ed, hose esults a e a aila le ithi hou s, ith % se siti i-

t a d % spe ifi it .

DNA fi ge p i ti g: This utilizes IS u i ue to M tu e ulosis - ased est i tio f ag e t le gth pol o phis , a d is useful

i ph loge eti studies of TB. RFLP DNA fi ge p i ti g is gold sta da d fo st ai t pi g i o a te iolog .,,

Its disad a tages i lude e ui e e t ofa la ge ell ass a d diffi ult i o pa iso si e esults a e i the

fo of a d patte s, hi h a e ha d to o e t i to digital fo ats.

M o a te ial i te spe sed epetiti e u it t pi g:

This te h i ue akes use of a ia le u e s of ta -de epeat at lo i i ge o e of M tu e ulosis.

Ne t-Ge e atio Se ue i g fo Ide tif i g P a-zi a ide Resista e i M o a te iu tu e ulosis: Ne t-ge e atio se ue i g NGS of the p A ge e of MTB a p o ide a ethod to ette u de sta d PZA esista e a d, o se ue tl , a aid ith i p o i g

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patie t a e as ell. A spe ifi ad a tage of NGS is the depth of o e age ie, deep se ue i g that a e o tai ed. Phe ot pi d ug se siti it testi g a ot dete t esista t MTB su pop-ulatio s ithi a spe i e , he these e ist. Deep se-

ue i g allo s fo the dete tio of hete o esista e i populatio s of o ga is that ha o oth esista t a d sus epti le su populatio s. I the ase of PZA, fo e a -ple, a isolate ith a lo o e t atio of esista t o -ga is s to the d ug a i itiall e epo ted as se siti e

phe ot pi ethods, ut du i g the ou se of the a-p , the PZA- esista t su populatio a p opo tio all gai do i a e.

OTHER METHODS

FAST Pla ue TB: FAST Pla ue TB BIOTEC La o ato ies Ltd, FIND – Fou -datio fo I o ati e Ne Diag osti s utilizes o a -te io-phages fo dete tio of M tu e ulosis di e tl f o sputu sa ples. A spe ifi o a te iophage i fe ts ells of M tu e ulosis o ple p ese t i the spe i e . Follo i g this, the sa ple is t eated ith a i u idal age t to dest o phages hi h a e ot i fe ti g

host ells. The the e ai de i t a ellula phages u -de go epli atio ith su se ue t elease f o host ells. These eleased phages a e allo ed to i fe t a la

of o -pathoge i o ga is s i a aga plate i u a-tio , he e the u de go fu the epli atio a d l se the

o -pathoge i o ga is s, eati g zo es of lea i g pla ues o the su fa e of the aga , thus i di ati g a

positi e sa ple. This test has . - . % se siti it a d . - . % spe -ifi it . , This test is apid esults a aila le ithi hou s of sa ple p epa atio , safe ultu e of M tu e -ulosis is ot e ui ed , a d has lo ate of false positi i-

t dete ts o l li e a illi . Thus, it ight tu out to e e efi ial i high u de ou t ies. Ho e e , it has e tai d a a ks i ludi g lo se siti it i s ea -

egati e ultu e-positi e ases, e ui e e t of te h i al e pe tise, a d assess e t o sputu sa ples o l , as of o .

FAST Pla ue-Respo se: This is a e te sio of FAST Pla ue TB, hi h e a les apid dete tio of ifa pi i esista e usi g o-a te iophages. S ea -positi e sputu spe i e a e

i u ated ith a d ithout ifa pi i o e ight at °C.

M tu e ulosis st ai s hi h a e ifa pi i - esista t su i e the d ug a d eate pla ues, as opposed to sus-epti le st ai s hi h a e u a le to do so.

Ade osi e dea i ase ADA : ADA has ee suggested as a effe ti e su ogate a k-e fo TB i pleu al, pe ito eal a d pe i a dial fluids. A stud de o st ated % se siti it , . % spe ifi it , a d utoff alue of U/L fo ADA i the afo e e -tio ed fluids.

CONCLUSION:

Va ious p o isi g diag osti tests fo TB a e u e tl u de de elop e t a d so e u de use i se e al ou -t ies, diffe i g a o di g to the feasi ilit of i ple e ta-tio i thei health a e s ste . So e ajo issues i diag osis of TB still e ui e e tifi atio . These i lude-e ui e e t fo i easi g the se siti it of TB dete tio

i ases ha i g e t apul o a o pau i a illa TB, i u o o p o ised ases a d hild e . The ideal TB diag osti test should e si ple, lo - ost, se siti e, spe ifi , poi t of- a e, i e pe si e eal-ti e test. Re-e tl , a ious poi t-of- a e tests fo TB a e u de e al-

uatio , hi h i lude ad a ed se ologi assa s, ha d-

held ole ula de i es, eath- ased assa s to dete t olatile o ga i o pou ds, i o hip te h ologies a d

p oteo i s- ased a d eta olo i s- ased te h i ues. These a d se e al othe e tests ill i ease the se -siti it , spe ifi it a d ease of diag osi g TB, ut pe -haps a e a aila le at dist i t o e t al efe al la o -ato ies o l . Ho e e , it is a ti ipated that the ill ha e a sig ifi a t i pa t o o t ol of TB. Also, i o de to eet the p essi g pu li health eeds a d TB o t ol ta gets, s ift i ple e tatio of p o e e ethods is

u ial. A o p ehe si e u de sta di g of these te h-ologies has lead to sig ifi a t i p o e e t i dete -

tio of o a te ia, ut o e li i al t ials a e a -a ted fo o pa iso a d ost- e efit a al ses of ea h

test.

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: – . . Ma ti A, Paas h F, Vo G oll A, et al. Thi -la e aga fo

dete tio of esista e to ifa pi i , oflo a i a d ka a-i i M o a te iu tu e ulosis isolates. I t J Tu e

Lu g Dis ; : – . . Ro ledo J, Mejia GI, Pa iagua L, Ma ti A, Guz a ´ A.

Rapiddete tio of ifa pi i a d iso iazid esista e i M o a te iu tu e ulosis the di e t thi -la e aga

ethod [sho t o u i atio ]. I t J Tu e Lu g Dis ; : – .

. S ha e g T, Rei he t B, S hu ¨li T, Lode H, Mau h H. Rap-id d ug sus epti ilit testi g of M o a te iu tu e ulo-sis usi g o e tio al solid edia. Eu Resp J ;

: – . . Mazu ek GH, Je e J, Ve o A, LoBue P, Gold e g S, Cas-

t o K, IGRA E pe t Co ittee., Ce te s fo Disease Co -t ol a d P e e tio CDC .Updated guideli es fo usi g I te fe o Ga a Release Assa s to dete t M o a te-iu tu e ulosis i fe tio - U ited States, . MMWR

Re o Rep. ; RR- : - . . A a ă V, Tiliş a C, Io DA, Mihăiles u R, Mu tea u D,

St ei u-Ce el A, et al. Se u adipoki es a d HIV i al epli atio i patie ts u de goi g a ti et o i al the ap .

Ge s. ; : - . . Gua aldi G. E ol i g app oa hes a d esou es fo li i al

p a ti e i the a age e t of HIV i fe tio i the HAART

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e a. Ge s. ; : - .

. Ra os JM, Ro leda o C, Masiá M, Belda S, Padilla S, Rod íguez JC, et al. Co t i utio of i te fe o ga a e-lease assa s testi g to the diag osis of late t tu e ulosis i fe tio i HIV-i fe ted patie ts: a o pa iso of Qua ti-FERON-TB Gold I Tu e, T-SPOT.TB a d tu e uli ski test. BMC I fe t Dis. ; : .

. Wa g X, Jia g J, Cao Z, Ya g B, Zha g J, Che g X. Diag osti pe fo a e of ultiple toki e a d he oki e assa fo tu e ulosis. Tu e ulosis Edi . ; : - .

. Kasp o i z VO, Hallida JS, Mit hell J, Kle e a P. MIGRAs: a e the the e IGRAs? De elop e t of o o-ki e-a plified IFN-γ elease assa s. Bio a k Med.

; : - . . Ha i ath BC, Ku a S, Ro SS, Hi udka S, Upadh e V,

She de N. A o ktail of affi it -pu ified a ti odies ea ti e ith diag osti all useful o a te ial a tige s ES- , ES-

, a d EST- fo dete ti g the p ese e of M o a te iu tu e ulosis. Diag Mi o iol I fe t Dis. ; : - .

. Wood R, Ra o K, Bekke LG, Middelkoop K, Vogt M, K eis i th BN, et al. Lipoa a i o a a i u i e du i g tu e ulosis t eat e t: asso iatio ith host a d pathoge fa to s a d o a te iu ia. BMC I fe t Dis. ; : .

. La SD. Poi t-of- a e dete tio of lipoa a i o a a LAM i u i e fo diag osis of HIV-asso iated tu e ulosis:

a state of the a t e ie . BMC I fe t Dis. ; : . . Ala i-Nai i R, Meta at M, Alija i E, Mozaffa H. Patho-TB

test fo the apid diag osis of pul o a tu e ulosis. J Res Med S i. ; : - .

. Wa khade G, Maju da A, Ka le PD, De S, Ha i ath BC. Multi-a tige a d a ti od assa s SEVA TB ELISA fo the diag osis of tu e ulous pleu al effusio . I dia J Tu e .

; : - . . Shi a a a CT, Kato h VM, Sha a VD, Patil MA, Kato h

K, Bha ad aj VP, et al. Dete i atio of o a te ial ph loge o the asis of i u ologi al elated ess of supe o ide dis utases. I t J S st Ba te iol. ; : -

. . Naka u a RM, Ei k L, Vel o te MA, Ka aji i K, A g CF,

Delasllagas CE, et al. Dete tio of a ti e tu e ulosis a MPB- t a sde al pat h: a field stud . S a d J I fe t Dis.

; : - . . Ste de H, Lu d K, Pete se KH, Ras usse OF,

Ho g a ee P, Miö e H, et al. Fluo es e e I situ h -idizatio assa usi g peptide u lei a id p o es fo

diffe e tiatio et ee tu e ulous a d o tu e ulous o a te iu spe ies i s ea s of o a te iu ul-

tu es. J Cli Mi o iol. ; : - . . Cata za o A, Pe S, Cla idge JE, Du a S, Good ight-

White S, LoBue PA, et al. The ole of li i al suspi io i e aluati g a e diag osti test fo a ti e tu e ulosis: esults of a ulti e te p ospe ti e t ial. JAMA.

; : - . . Cla idge JE d, Sha a RM, Shi i k TM, Plika tis BB.

La ge-s ale use of pol e ase hai ea tio fo dete tio of M o a te iu tu e ulosis i a outi e o a te iol-og la o ato . J Cli Mi o iol. ; : - .

. A e C, Hi a o K, Wada M, Kazu i Y, Takahashi M, Fu-kasa a Y, et al. Dete tio of M o a te iu tu e ulosis i li i al spe i e s pol e ase hai ea tio a d Ge -P o e A plified M o a te iu Tu e ulosis Di e t Test. J Cli Mi o iol. ; : - .

. Wied a M, Wilso WJ, Czajka J, Luo J, Ba a F, Batt CA. Ligase hai ea tio LCR --o e ie a d appli atio s. PCR Methods Appl. ; :S - .

. Boeh e CC, Na eta P, He ost oza G, et al. Ope atio al feasi ilit of usi g loop- ediated isothe al a plifi atio fo diag osis of pul o a tu e ulosis i i os op e te s of de elopi g ou t ies. J Cli Mi o iol

; : –

. Caoili JC, Ma o o a A, Sikes D, Hi k a L, Plika tis BB, Shi i k TM. E aluatio of the TB-Bio hip oligo u leotide

i oa a s ste fo apid dete tio of ifa pi e-sista e i M o a te iu tu e ulosis. J Cli Mi o iol

; : – .

. Hel D, Jo es M, Sto E, et al. Rapid dete tio of M o-a te iu tu e ulosis a d ifa pi esista e use of

a o -de a d, ea patie t te h olog . J Cli Mi o iol ; : – .

. Boeh e CC, Na eta P, Hille a D, et al. Rapid ole ula dete tio of tu e ulosis a d ifa pi esista e. N E gl J Med ; : – .

. Zha g Y, Ye WW. Me ha is s of d ug esista e i M -o a te iu tu e ulosis. I t J Tu e Lu g Dis.

; : - .

. Ra as a S, Musse JM. Mole ula ge eti asis of a ti i o ial age t esista e i M o a te iu tu e u-losis: update. Tu e Lu g Dis. ; : - .

. Wo ld Health O ga izatio . Mole ula li e p o e assa s fo apid s ee i g of patie ts at isk of ultid ug-

esista t tu e ulosis MDR-TB : poli state e t. Ge e-a: Wo ld Health O ga izatio ; [O li e] A aila le

f o : http:// . ho.i t/t /la o ato /lpa_poli .pdf[A essed De . ]

. Go i A, Ba de a A, Ma hetti G, Degli Esposti A, Catozzi L, Na di GP, et al. Spoligot pi g a d M o a te iu tu e -ulosis. E e g I fe t Dis. ; : - .

51. Bifa i P, Ku epi a N, Mathe a B, Wa g XM, K eis i th B. Ge ot pi g of M o a te iu tu e ulosis li i al isolates

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usi g IS - ased est i tio f ag e t le gth pol o phis a al sis. Methods Mol Biol. ; : – .

. Suppl P, Maza s E, Lesjea S, et al. Va ia le hu a i i-satellite egio s i M tu e ulosis ge o e. Mol Mi o ial.

; : – . . Ca e MD, Eise a h KD, Te pleto G, Salfi ge M, Mazu ek

G, Bates JH, et al. Sta ilit of DNA fi ge p i t patte p o-du ed ith IS i st ai s of M o a te iu tu e ulo-sis. J Cli Mi o iol. ; : – .

. Og ai i-E o o E. Cu e t t e ds i the la o ato diag-osis of tu e ulosis. Be i Jou al of Postg aduate Medi-i e. ; suppl.: – .

. Bio edi al C Cos os Bio edi al's Ra ge of P odu ts a d Reage ts fo Ba te iolog . FastPla ueTB a d FastPla ue-

Respo se Diag osti Assa s. A aila le at: http://. os os io edi al. o / a ti/kitsa dse s/

fastpla uet .sht l [A esed De . ]. . Mathu P, Ti a i K, T ikha S, Ti a i D. Diag osti alue of

ade osi e dea i ase ADA a ti it i tu e ula se ositis.

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I t odu tio

Tu e ulosis also k o as Ksha a Rogo Tapediki Hi di, Phthisi G eek is ost o o l aused M o a te-iu Tu e ulosis. It is a disease of i fe tious etiolog as

p o ed afte the dis o e of tu e ulosis a illi Ro -e t Ko h o hose a e its also k o as Ko h s a illi,

ut it is also elated to po e t as its i ide e de li ed i Eu opea so iet a d U ited states ith the ad e t of

ette sa itatio a d h gie i p a ti es. I ode ti es also, tu e ulosis e ai s a ajo glo al health p o le as a out o e-thi d of glo al populatio is affe ted it a d a out - % ill de elop the disease i thei lifeti e. I dia has the highest u de of disease

ith % of the glo al u e of ases, highest u e of MDR-TB Multi D ug Resista e-Tu e ulosis ases a d se o d highest u e of HIV+TB ases. The disease also is a ajo so ial, health a d e o o i p o le of the ou t . TB a ou ts fo . illio deaths a uall .

The i ide e of TB has edu ed f o pe lakh pe ea i to pe lakh pe ea i a d the o talit due to TB has edu ed f o pe lakh pe ea

i to pe lakh pe ea i Figu e .

HIV epide i is a ajo o t i uto i o se i g the situ-atio of TB i the ou t as sus epti ilit of i fe tio is i eased a o g i fe ted patie ts a d the p og essio of

TB is u h takes u h i te si e ou se a o g su h pa-tie ts.

TB also o t i utes to i e se so ial a d e o o i u -de o e the ou t . Be ause of it - % of a ual household i o e is lost. A a e age of ea s of i -o e is lost if a i di idual die of TB. TB kills o e o -

e tha a othe i fe tious disease a d o e tha all auses of ate al o talit o i ed. A d also, o -

e a e stig atized e ause of TB a d a of the a e eje ted thei fa ilies e ause of TB. Ma hild e

a e also ad e sel affe ted it as a the e o e o pha s e ause of TB a d e e ea i I dia alo e lakhs of the lea e s hool o a ou t of thei

Re ie arti le

Re ised Natio al Tu er ulosis Co trol Progra e: Past, Prese t a d the Future ahead

Autho s: Mukesh Ku a , Su u hi Mish a A ita Khokha * Depa t e t: Depa t e t of Co u it Medi i e I stitutio : VMMC a d Safda ju g Hospital

Tu e ulosis o Ksha a Rogis ost o o l aused M o a te iu Tu e ulosis e ai s a ajo health p o le i ode ti es also. I dia has the highest u de of disease ith highest u e of MDR-TB ases. Tu e ulosis o t ol i I dia sta ted ith esta lish e t of sa ato ia follo ed do i ilia t eat e t st ateg . Follo i g the Na-

tio al Sa ple Su e of I dia Cou il of Medi al Resea h, Natio al Tu e ulosis P og a e as de eloped a d i ple e ted i

hi h as late e ie ed to pa e a fo Re ised Natio al Tu e ulosis P og a e i , ased o DOTS st ateg . The p o-g a e o e ed hole ou t i Ma h . It has le els of ad i ist ati e st u tu e a aged Ce t al TB Di isio of MoHFW. Co side i g E d-TB St ateg of , atio ide et o k of sputu i os op la s, assisted CBNAAT e te s a d DST e te s ha e also ee esta lished u de RNTCP. I te itte t egi e has ee ha ged to dail d ug egi e at sites i the ou t . I ol e e t of p i ate se to has ee e phasized a d o side ed ith ase otifi atio th ough e po tals like Niksha a d pa t e i g p i ate la s fo ualit testi g a d diag osis. Co epts like DOTS a e also ei g i ple e ted fo ette ICT ased ad-he e e the patie ts. Despite all a hie e e ts, la k of a a e ess a o g people ega di g diag osti fa ilities a aila le, sputu sa ple olle tio f o atego ies like pediat i TB, E t a-pul o a TB ases et poses a g eat halle ge. La ge size of patie ts ei g ate ed p i ate

se to ithout a poli fo patie t a age e t i p i ate se to adds up to these halle ges.

Case per 100000 per year

Figu e :I ide e of Tu e ulosis o e the ea s

*Co espo di g autho : a itakh @ ahoo. o

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Tu e ulosis o t ol i I dia: The o e e t fo o t ol of TB i I dia sta ted i p e-

i depe de e e a ith esta lish e t of sa ato ia hi h o ks to a ds st e gthe i g a pe so s esista e to-a ds disease. Late ith the ad e t of a ti-TB d ugs like

St epto i , Pa a-a i osali li A id PAS , Thioa eta-zo e, Iso iazid hi h e olutio ized the o t ol i a a -

e that effe ti e o i atio a d dosage of d ugs e e ei g o side ed.

Just afte the ou t got i depe de t the fo us as shifted to a ds tu e ulosis o t ol a of BCG a -i atio iti g it to e e o o i al a d o e feasi le ethod at that ti e. The f o - I dia Cou il of

Medi al Resea h ICMR had Natio al Sa ple Su e i zo es of the ou t to get the i p essio of TB o idi-t i the ou t .

Natio al Tu e ulosis P og a e as de eloped keepi g i i d the a aila le esou es fo diag osis a d t eat-

e t a d a ious epide iologi al, so iologi al a d ad-i ist ati e aspe ts i the ou t . The p og a e

lau hed i i phased a e th oughout the ou -t , fo used o e o diag osis of the disease ith the help of X- a a d had e lo t eat e t o pletio a o g the diag osed ases. It as i e iste e till ,

he isi g HIV epide i a d sp ead of ulti-d ug e-sista e th eate i g to o se the situatio lead to e al-uatio of p og a e e eli g its a age ial eak esses, i ade uate fu di g, o e - elia e o e X- a fo diag o-sis, f e ue t i te uptio s i d ug supplies. Follo i g this Go e e t of I dia alo g ith assista e f o Wo ld Ba k i ple e ted Re ised Natio al Tu e ulosis P og a e RNTCP si e adopti g DOTS Di e tl O se ed T eat e t Sho t ou se st ateg . DOTS has o po e ts:

Politi al a d ad i ist ati e o it e t. Good ualit diag osis, p i a il sputu

s ea i os op . U i te upted suppl of good ualit d ugs. Di e tl o se ed t eat e t DOT . S ste ati o ito i g a d e aluatio .

The goal of RNTCP is to de ease o idit a d o talit due to TB a d to ut t a s issio of i fe tio u til TB eases to e a ajo pu li health p o le . This goal is to e a hie ed th ough follo i g o je ti es:

To a hie e a d ai tai u e ate of at least

% a o g e l dete ted i fe tious ases. To a hie e a d ai tai dete tio of at least

% of su h ases i the populatio . RNTCP sta ted i O to e o pilot asis i sites i diffe e t states i.e. Delhi, Guja at, Ke ala, Maha asht a a d West Be gal o e ed . illio a d o e ed a -othe illio o e apid s ale up as do e, till . RNTCP o p ises of le els i.e. Natio al, State, Dist i t, su -Dist i t a d Pe iphe al Health I stitutio s.Fu tio s of de elopi g te h i al poli ies, d ug p o u e e ts, p e-pa i g t ai i g odules, p og a es a d fi a ial o -ito i g, ualit assu a e, ad o a , ope atio al e-sea h p io ities a d fu d o ilizatio is do e Ce t al TB di isio i Mi ist of Health a d Fa il Welfa e MoHFW .

The atio ide la o ato et o k o sists of desig at-ed sputu i os op e te DMC , hi h a e supe -ised i te ediate efe e e la IRLs at state le el, atio al efe e e la NRL a d e t al TB di isio at atio al le el . The e a e si NRL i I dia hi h a e o k-

i g alo g ith IRLs to o ito a d supe ise IRLs a ti i-ties a d fo a i g out t ai i g fo staff. The ost pe-iphe al la o ato u de RNTCP et o k is the DMC hi h o e s a populatio of a ou d , i

t i al a d hill a eas

Tu e ulosis Coalitio fo Te h i al Assista e TBTCA de eloped I te atio al Sta da ds fo TB Ca e ISTC

hi h a e adopted RNTCP as Sta da ds fo TB Ca e i I dia STCI . The e a e sta da ds fo Diag osis, T eat-

e t, Pu li Health Respo si ilit a d So ial i lusio adopted i .

RNTCP had e te ed a a itious Natio al St ategi Pla NSP - as pa t of ou t s thFi e- ea Pla ith the e U i e sal A ess fo ualit diag osis a d

t eat e t fo all TB patie ts i the o u it ith a ta get of ea hi g the u ea hed. It had a isio of TB-

f ee I dia-th ough a hie i g U i e sal A ess p o i-sio of ualit diag osis a d t eat e t fo all TB patie ts i the o u it a d a Goal to de ease the o idit a d o talit ea l diag osis a d ea l t eat e t of all TB ases the e utti g the hai t a s issio . The a ti ities pla ed i luded Alig e t of asi RNTCP su-dist i t a age e t u its ith NRHM lo ks, Hu a esou e a age e t, i p o ed la o ato diag osis

a d D ug-sus epti ilit testi g.

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P og a e I ple e tatio Co e age, A hie e e ts a d P ese t Situatio

RNTCP has a hie ed atio ide o e age i Ma h . O e a lakh patie t a e ei g put o t eat e t e e

o th. Si e the egi i g of the p og a e o e . illio people ha e ee i itiated o t eat e t a d

ea l a illio additio al li es ha e ee sa ed. The u e ate as o siste tl a o e % a d the last fe ea s has e eeded the glo al e h a k of %. O e the ea s the ase dete tio ate i eased g adual-l a d as % i .

The e has ee a effe ti e a d a ou ta le deli e s ste ith deli e of diag osti a d t eat e t se i es

ade a aila le th ough a et o k of a out la o a-to ies a d o e lakh DOTS e te s.Sta da dized odu-la t ai i g is p o ided to all le els of health staff ith the help of t ai i g odules de eloped at CTD, MoHFW i -o po ati g e e i itiati es.D ug deli e i patie t ise o es e su ed full ou se of d ugs fo i di idual pa-

tie ts.Fo o ito i g the pe fo a e of the p o-g a e, i o ati e tools, he klists, e o ds a d i di a-to s a e ide tified.Va ious health a e p o ide s i ludi g pu li a d p i ate a e e plo ed u de Pu li P i ate Mi DOTS PPM DOTS , edi al olleges, a NGOs, a d o po ate houses a e i ol ed p oa ti el i the p o-

g a e. E te al Qualit Assess e t has ee i ple e ted fo all sputu i os op la s i the ou t .A joi t RNTCP-

NACP Natio al AIDS Co t ol P og a e a tio pla has ee de eloped a d is ei g i ple e ted i states ith pla of ou t ide e pa sio .

Co p ehe si e fi a ial guideli es ha e ee de eloped a d disse i ated. Fu ds a e eleased f o e te to state so ieties fo o a d dis u se e t to the dist i t so ieties. This is do e i a o da e to the de e t alized fi a ial a age e t s ste u de RNTCP.A e t al le el esea h o ittee a d edi al ollege task fo e

e ha is esta lished to p o ote a d guide ope atio al esea h.I pa t assess e t studies to easu e the

t e ds i i ide e p e ale e, o talit a d d ug e-sista e a e ei g u de take to e o d the p og ess of I dia to a ds Mille iu De elop e t Goals a d ulti-

ate goal of TB eli i atio . RNTCP had e pa ded faste tha a othe TB o t ol p og a e i the histo of DOTS, as a k o ledged joi t WHO-RNTCP e ie i Septe e . The p o-g a e as fou d to highl e o o i al osti g less tha Rs pe apita pe ea .

Re e tl , a e s ste of Mo ito i g of p og a e th ough Co posite I di ato has ee i t odu ed to e a le o ito i g of i put, p o ess a d out o e i di a-to s. The e has ee e isio of Supe isio a d Mo i-to i g st ateg to add ess ha gi g eeds. Cases a aged p a titio e s outside pu li heath s ste a e to e otified usi g po tals like Niksha . It is a ase ased, e ased TB su eilla e s ste – NIKSHAY de eloped to fa ilitate otifi atio s.

Wo ld Health Asse l i de ided to e d glo al TB epide i E d TB St ateg ,a p og a e ith ta get of a o ld f ee of death a d suffe i g due to TB. Co sid-e i g this i i d RNTCP has esta lished a atio ide la o ato et o k fo a i g out sputu i os op

ith e te al ualit assess e t a d apid ole ula test CBNAAT, a Ca tilage Based Nu lei A id A plifi a-tio Test i sele ted ke populatio .The i o iolog depa t e t of edi al olleges a e also i ol ed fo p o idi g diag osti se i es. The e a e RNTCP e tified C & DST Cultu e a d D ug Se siti it Testi g

la s i ou t hi h i ludes pu li se to la s also . To i p o e thei teg atio ith ge e al health s ste Tu e ulosis U its TUs e e alig ed a d epo ti g as

o Ma h . The ualit assu a e a ti ities a e also a ied o egula asis.

Si e egi i g uptill , o e tha o es patie ts e e i itiated o t eat e t a d o e tha lakhs ad-

ditio al li es ha e ee sa ed. I Ma h , RNTCP e ised its te h i al a d ope atio al guideli es ak-

i g so e ajo additio s hi h a e dail egi e fo t eat e t of TB a d use of eda uilli e fo t eat e t of d ug esista e TB ith d ug sus epti ilit testi g guided t eat e t.

Dail dose egi e has ee sta ted i stead of i te -itte t egi e hi h used toad i iste ed ea lie so

that it ill help i i easi g o plia e as ell as de-easi g elapse ate a d d ug esista e.

Ta le . Dail dose egi e fo a age e t of Tu e u-losis

T pe of TB Case T eat e t egi e i IP

T eat-e t

egi-e i

CP

Ne HRZE HRE

P e iousl T eated HRZES + HRZE

HRE

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Fi ed dose o i atio ill e used a d fo hild e hild f ie dl fo ulatio as dispe si le ta let ill e dist i ut-ed. The dail egi e ill e gi e to TB/ HIV o-i fe ted patie ts a oss the ou t . This egi e has ee olled out i phased a e , fi st ei g i itiated i states o l o e i g o e populatio of the ou t .

MDR TB ases ill e t eated as efo e hi h o sisted of si to i e o ths of ka a i , le oflo a i , etha u-tol, p azi a ide, ethio a ide a d lose i e i i itia-tio pe iod a d eightee o ths of o ti uatio phase of le oflo a i , etha utol, ethio a ide, lose i e. All d ugs a e gi e dail u de supe isio . Ne e d ug e-da uilli e has ee i t odu ed i fi e states fo MDR TB patie ts ith esista e to flou o ui olo es a d / o se -o d li e i je ta le, i ed patte of esista e. Till De-e e , o e tha d ug esista t TB patie ts

ha e ee i itiated o eda uilli e o tai i g t eat-e t .Re ised guideli es fo P og a ati a age-e t of D ug Resista t Tu e ulosis e e also i t o-

du ed ith i lusio of diag osti a d t eat e t guide-li es fo XDR-TB patie ts.

DOTS a ICT ased patie t e t i adhe e e suppo t s ste as lau hed i i high- u de ART e te s fo TB-HIV o-i fe ted patie ts alo g ith use of dail fi ed-dose o i atio FDC edi atio s. I , RNTCP e pa ded this to HIV-TB patie ts at all ART A ti-

Ret o i al The ap Ce te s i I dia. This a e used to see the patie t adhe e e, se di g usto ized SMS e-

i de s to ale t issed doses a d t igge additio al ou seli g. Se io Dist i t / State / Cou t le el p og a

staff a also get a tio a le epo ts fo all patie ts.

A f a e o k fo olla o atio ai i g to edu e o idit a d o talit doi g i-di e tio al s ee i g fo dia e-tes a d TB has ee de eloped joi tl RNTCP a d Na-tio al P og a fo P e e tio a d Co t ol of a e , dia-

etes, CVD & st oke NPCDCS . Futu e halle ges ahead:

Despite of all the st ategies a d e e i itiati e fo a -age e t of a ious ases of TB, a halle ges still e ai i f o t of us. The e has ee la k of a a e ess

i the o u it o TB diag osti fa ilities i the p o-g a e. A d also, e diag osti algo ith ill e ui e additio al esou es fo CXR, a d ole ula tests.

E su i g a ti e ase fi di g i at isk g oups is still a g eat halle ge ith epeati g this a ti it pe iodi all . Populatio g oups like ig ato populatio , slu d ell-e s, i ha ita ts of jails, old age ho es et e ui e spe-ial atte tio i diag osis a d ase a age e t .

A igge issue lies ith e gagi g ith p i ate se to a d ope i g RNTCP diag osti fa ilities i the p i ate se to

hi h ate s to a la ge se tio of the patie ts. S ale of p i ate se to e gage e t is eag e elati e to the size a d o t i utio to TB a e, the se to . A se e of a poli fo p i ate se to e gage e t. Fu ds ea a ked fo p i ate se to a e used fo othe a ti ities at the state/dist i t le el. E ha ed hu a esou es suppo t to states ot utilized full a d u ifo l . Use of i ap-p op iate tools, u e tai ualit sta da ds a d out of po ket e pe ditu e o ti ues.

The e has ee little o o i fo atio o t eat e t p a ti es, adhe e e a d t eat e t out o es f o the p i ate se to , a ou ti g to ost of the TB patie ts i the ou t . The high ate of e u e e f o li ited studies is a othe ause of o e .

It e e eas to olle t of app op iate spe i e s f o hild e a d EPTB E t a-pul o a TB ases. So ette odalities a e eeded to e de ised fo this also. The

apa it fo spe i e olle tio hild e a d EPTB at dist i t le el is also defi ie t.

P o u e e t of e uip e t s ith o igi al a ufa tu e s

Weight category Number of tablets Inj Streptomycin (gm)

Intensive phase (HRZE) 75/150/400/275

Continuation phase

(HRE) 75/150/275

25-39 kg 2 2 0.5

40-54 kg 3 3 0.5

55-69 kg 4 4 0.75

≥70 kg 5 5 1.0

Ta le . Fi ed dose o i atio fo adult patie ts

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f o outside the ou t ha i g o o est i ted post sales se i es i the ou t th eate s u hi de ed la ope atio s. The u e t app oa h to t eat e t o ito i g is health s ste e t i i stead of ei g patie t e t i , p io itizi g p og a e o fo t i stead of patie t eeds. Although t eat e t su ess ates a o g e ases a e satisfa to at the atio al le el, a dist i ts epo t lo e tha e pe ted su ess ates. A essi ilit to d ug egi e s o tai i g i je tio s i the u al a eas is u e tl a o -e o i g to the guideli es li iti g the use of i je tio s

t ai ed health p o ide . Dela i i itiatio of t eat-e t of DRTB D ug Resista t TB o i g to o -

a aila ilit of p et eat e t e aluatio se i es at the dist i t a d su dist i t le el .

Co lusio : Tu e ulosis o t ol i I dia has gai ed o e tu u -de the aegis of RNTCP ith adoptio of WHO DOTS st ateg hi h has p o e to e effe ti e t eat e t o-dalit fo a ious TB ases. A lot has ee a hie ed i past fe ea s o side i g the i pa t DOTS a d RNTCP has o e the epide iolog of the disease ut still a lot is

eeded to e do e to keep the su essful o k ei g do e i the ou t to a hie e the ta get of tu e ulosis eli i atio . Mai tai i g ualit se i es ith i p o i g

ualit a o g poo pe fo i g dist i ts spe iall fo us-i g upo la ge states e ai s a ajo a ea to e looked i to. Mig ato a d u de p i ileged populatio is eed-ed to e se ed a d ad e t of HIV-TB a d MDR/XDR-TB ases a e eeded to e take a e to a hie e the ulti-ate goal.

Refe e es: . TB I dia : RNTCP A ual Status Repo t. A aila le

f o :https://t i dia.go .i /W iteReadData/TB% I dia%.pdf Last a essed o De e e , .

. TB I dia . RNTCP Status Repo t. Di e to ate of Health a d Fa il Welfa e, Ce t al TB Di isio , Go e e t of I dia, .

. I dia Cou il of Medi al Resea h; Tu e ulosis i I dia: A Natio al sa ple su e - . ICMR te h i al epo t se ies Ne Delhi, ICMR .

. Tu e ulosis p og a e e ie -I dia. Wo ld Health O -ga izatio , Ge e a. ; Natio al Tu e ulosis I stitute, Su a ies of NTI studies, ; .

. WHO. T eat e t of tu e ulosis. Guideli es fo Natio al P og a es. Ge e a: WHO; WHO/CDS/TB ; .

. P og a e I ple e tatio Pla : RNTCP Phase II. Di e -to ate of Health a d Fa il Welfa e, Ce t al TB Di isio , Ni a Bha a , Ne Delhi. .

. Re ised Natio al Tu e ulosis P og a : Natio al St ategi Pa fo Tu e ulosis Co t ol - . A aila le f o : https:// .t fa ts.o g/ p- o te t/uploads/ / /NSP- - .pdf Last a essed o De e e , .

. Tu e ulosis Coalitio fo Te h i al Assista e. I te atio -al Sta da ds fo Tu e ulosis Ca e ISTC , se o d edi-tio . . A aila le f o : http:// .ist e .o g Last a essed o De e e , .

. Sta da ds fo TB Ca e i I dia. WHO Cou t offi e fo I dia. . A aila le f o https://t i dia.go .i /

sho file.php?lid= Last a essed o De e e , .

. E pe t o ittee eeti g to esti ate TB u de i I dia. Ma h . U pu lished data, Di e to ate of Health a d Fa il Welfa e, Ce t al TB Di isio , Go e e t of I dia,

. . Go t. of I dia , Re ised Natio al TB Co t ol P o-

g a e Te h i al a d Ope atio al Guideli es fo Tu e -ulosis Co t ol i I dia, , Mi ist of Health a d Fa i-

l Welfa e, Ne Delhi. . Joi t Tu e ulosis P og a e Re ie , I dia, Septe e

. Wo ld Health O ga izatio , Regio al Offi e fo South-East Asia, Ne Delhi. SEA-TB- , Fe .

. RNTCP: Niksha Logi . A aila le o : https://iksha .go .i /Use /Logi .asp Last a essed o De e -e , .

. Natio al f a e o k fo joi t TB-Dia etes a ti ities, Ma h . Di e to ate Ge e al of Health Se i es, Mi ist of

Health a d Fa il Welfa e, Go t of I dia. A aila le o : https://t i dia.go .i /W iteReadData/Natio al%

f a e o k% fo % joi t% TB% dia etes% %Aug% .pdf Last a essed o De e e , .

. Re ised Natio al Tu e ulosis P og a : Natio al St ategi Pa fo Tu e ulosis Eli i atio . A aila le f o : https://t i dia.go .i /W iteReadData/NSP% D aft%

. . % .pdf Last a essed o De e e , .

Food poisoning can be b cereus

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Sepsis Bio arkers

Autho s: Gopi Ta ila asa

Depa t e t: Depa t e t of Mi o iolog

I stitute: VMMC & Safda ja g Hospital, Ne Delhi

Re ie arti le

I t odu tio :

Sepsis is a ajo o e e ause of high le els of a ti-ioti o su ptio a d of the i easi g p e ale e of

a ti i o ial esista e. Ba te ae ia is ide tified i a s all pe e tage of patie ts ith sig s a d s pto s of sepsis . I de eloped ou t ies, it is fou d to e % of o talit o u s i sepsis patie ts. With the a aila il-it of i o iologi al diag osti s, a te e ia is o l ide tified i a s all p opo tio of patie ts ho p ese t

ith sepsis a d loodst ea i fe tio s . Bio a ke s a e idel used i li i al p a ti e a d the a e useful fo dete ti g a d o ito i g the i fe tious p o ess a d also helps i guidi g a ti a te ial the ap . Bi-o a ke s ha e g eat pote tial to i p o e the diag osis a d t eat e t of sepsis.

Se e al io a ke s a e al ead a aila le fo li i al use i sepsis; ho e e , thei effe ti e ess i a i sta es is li ited the la k of spe ifi it a d se siti it . Ma io a ke s a e used i sepsis, ut o e has suffi ie t spe ifi it o se siti it to e outi el e -plo ed i li i al p a ti e. PCT a d CRP ha e ee ost

idel used, ut e e these ha e li ited a ilities to dis-ti guish sepsis f o othe i fla ato o ditio s o to p edi t out o e. I ie of the o ple it of the sepsis espo se, it is u likel that a si gle ideal io a ke ill

e e e fou d .

Wh diag osi g a sepsis is e diffi ult?

Sepsis is a state aused i o ial i asio f o a lo al i fe tious sou e i to the loodst ea hi h leads to sig s of s ste i ill ess i e ote o ga s, this as the fi st s ie tifi defi itio of sepsis p oposed D .

S hott ulle i . The septi espo se is a e -t e el o ple hai of e e ts i ol i g i fla ato a d a ti-i fla ato p o esses,hu o al a d ellula ea tio s a d i ulato a o alities , .Sepsis a e asso iated ith i al o fu gal i fe tio s, ut the i -

fla ato espo se is ge e all less a ked i these ases, a d the ajo it of patie ts ith sepsis ill ha e a a te ial i fe tious sou e . The e is o spe ifi t eat-e t fo patie ts ith sepsis, a d a age e t the e-

fo e elies o i fe tio o t ol— ith sou e e o al a d effe ti e a ti ioti s—a d o ga fu tio suppo t .

The th ee p oi fla ato toki es p odu e a s ste i i fla ato espo se s d o e SIRS hi h is ha a -te isti of ea l sepsis. A o pe sato a ti-

i fla ato espo se s d o e CARS has ee de-s i ed Bo e that ofte follo s the h pe i fla -

ato phase, espe iall i patie ts ho de elop hat is alled se e e sepsis. I se e e sepsis, e ide e of ide-

sp ead o ga d sfu tio is also p ese t, i ludi g ulti-o ga d sfu tio lu g, li e , a d/o kid e i ju . The so- alled septi sho k, i hi h patie ts suffe a dio as-ula ollapse u espo si e to fluid esus itatio a d asop esso the ap , is ofte the te i al e e t of se-e e sepsis . Ho e e , o gold sta da d e ists fo

p oof of i fe tio .

Gi e these diffi ulties ith diag osis, it is ot su p isi g that sepsis a so eti es e u de - o o e diag osed, pe haps espe iall health a e staff ho less f e ue t-l e ou te su h patie ts. Gi e these o ple ities a d the diffe e t ti es at hi h i di idual io a ke le els a e ele ated, I do ot elie e that a si gle a ke ill e e e of use alo e to diag ose sepsis i the hete oge-

Sepsis is a se ious i fe tio a d still a o o ause of o idit a d o talit i de elopi g atio s su h as I dia. Ma agi g sepsis is diffi ult, due to a ied easo s, o e of the ost o o ei g diag osi g a d assessi g the se e it . Bio a ke s pla a i -po ta t ole i a agi g sepsis. The a help i a a s, assessi g p ese e o a se e of sepsis, diag osti a ke , p og os-ti a ke , guidi g a ti ioti the ap , assessi g t eat e t espo se, assessi g the a te ial pathoge , p edi ti g sepsis o pli atio a d o ga d sfu tio . The ha e thei o sho t o i gs too. I this a ti le, e ill dis uss a out the ost o o io a ke s of sepsis a d thei ad a tages a d disad a tages

E ail: gopi @ ahoo.i

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Figu e . Sepsis a e di ided i to t o phases. Follo i g i fe tio , a h pe -i fla ato phase is ha a te ized SIRS. This a esol e o the patie t a p og ess to hat is alled se e e sepsis. Du i g this phase, the e is e ide e of CARS ith i u osupp essio a d ultiple o ga d sfu tio . This a also esol e, espe iall ith app op iate suppo t, ut it ofte leads to death

of o i atio s o pa els of io a ke s, pote tiall o i ed ith li i alsig s.The e ill al a s e a g a

a ea et ee defi iti e sepsis a d defi iti e a se e of sepsis. I po ta tl , a a ke o a o i atio of a k-e s ill e e epla e a a eful li i alassess e t a d

ust e o side ed as a o ple e ta tool to diag o-sis .

Bio a ke s I , NIH defi ed a io a ke as a ha a te isti that a e o je ti el easu ed a d e aluated as a i di a-

to of o al iologi al p o esses, pathologi al p o ess-es o pha a ologi al espo ses to a the apeuti i te -e tio .Mo e tha io a ke s ha e ee p o-

posed a d assessed li i all , i ludi g a ious to-ki es, ell su fa e a ke s, e epto s, o ple e t fa -to s, oagulatio fa to s, a ute phase ea ta ts, a d

a othe s , , , ut o e has % spe ifi it fo sepsis .

Bio a ke lassifi atio : Based o the pathoph siologi-al o igi , io a ke s a e toki e/ he oki e i-

o a ke s, ell a ke io a ke s, e epto io a ke s, oagulatio io a ke s, io a ke s elated to as ula

e dothelial da age, io a ke s elated to asodilatio io a ke s of o ga d sfu tio , a d a ute phase p o-

tei io a ke s.I fu tio al lassifi atio , io a ke s a e diag osti io a ke s, o ito i g io a ke s,

su ogate io a ke s a d st atifi atio o stagi g i-o a ke s.

P o al ito i

P o al ito i is a a i o a id p e u so of al ito i ith la gel u k o iologi al fu tio , a d its o e -

t atio is sta le up to th ee hou s afte lood is d a . P o al ito i offe s fa o a le ki eti s fo a io a ke : is-i g p io to t o hou s , elia l dete ta le et ee a d hou s, peaki g at hou s, a d ai tai i g a plateau th ough a d hou s . At ph siologi ho eostasis, PCT is dete ta le i e lo le els i the se u i health i di iduals a d a i ease -fold du i g a ti e i fe tio . Additio all , the e ha e ee studies sho i g that a te e ia is highl u likel he PCT le els a e e-lo the th eshold . g/ L .P o al ito i PCT has

ee p oposed as a o e spe ifi a d ette p og osti a ke tha CRP,although its alue has also ee hal-

le ged .The su i i g sepsis guideli es i luded p o al-ito i as a io a ke fo sepsis diag osti ite ia . The

test is o e e pe si e ut o e a u ate tha CRP testi g as sho a eta-a al sis .Ho e e , it is aised i o -i fe tious o ditio s as ell as i a te ial sepsis. No -al se u alues a e elo . g/ L, a d a alue of

. g/ L suggests a sig ifi a tl i eased isk of sepsis, he eas alues of . - . g/ L suggest a i te ediate

likelihood of sepsis .I a e e t eta-a al sis, the se si-ti it a d spe ifi it of p o al ito i to dis i i ate sepsis f o o -i fe tious auses e e % % o fide e i te al . to . a d % . to . , espe ti el

.This i di ates a odest diag osti pe fo a e.

CRP C Rea ti e P otei

CRP, used fo a ea s as a a ke of i fla atio , a e useful i o ito i g the patie t s ou se th ough a h o i ill ess, ut it la ks spe ifi it to diag ose sepsis. It

is a a ute phase plas a p otei s thesised hepato-tes, so its plas a o e t atio ises i espo se to i -

fe tio o s ste i i fla atio . I health ou g adult olu tee lood do o s, the edia o e t atio of CRP is elo . g/L a d a i ease , -fold i e-spo se to a a ute-phase sti ulus , . CRP hepati s -thesis sta ts apidl afte a sti ulus ith ise oted a out hou s ith peak a ou d hou s a d a plas a half-life of app o i atel hou s.CRP has ee used su ess-full du i g i itial sepsis diag osis, ut its spe ifi it is fu -the edu ed late i the ou se due to pe siste tl ele at-ed le els . CRP has ee fou d to e sig ifi a tl ele at-ed i sepsis due to g a egati e i fe tio s o pa ed ith g a positi e i fe tio s suggesti g a diffe e ti u o-

odulato espo se . Sugitha i i et al. fou d

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that CRP le els e e sig ifi a tl ele ated i eo ates ith sepsis o pa ed ith those ithout .

While Sugitha i i s stud did ot epo t se siti it of CRP i dete ti g sepsis, a stud o pa i g CRP le els i septi pediat i patie ts i I dia ith health pediat-i o t ols fou d that CRP had a se siti it of %,

spe ifi it %, PPV %, a d NPV % .

T igge i g e epto e p essed o eloid ells-

T igge i g e epto e p essed o eloid ells- TREM-

is a i u oglo uli hose sig ali g i du es the p odu tio of toki es, he oki es a d ea ti e o -ge spe ies, all of hi h o t i ute to the i fla ato espo se. Fu the o e, TREM- sig ali g leads to

deg a ulatio of eut ophils a d i eased phago to-sis. A solu le fo of TREM- sTREM- a e eas-u ed i od fluids a d has pote tial as a sepsis diag os-ti io a ke .Ele ated sTREM- , sa pled a d easu ed f o the lo atio of i fe tio , is highl p edi ti e of a -te ial i fe tio .sTREM- ha e i luded assa s f o

od fluids ot li ited to lood sa pli g e e ospi al fluid [CSF], pleu al fluid, u i e , hi h a de ease its utilit as a diag osti io a ke gi e a pote tial dela i o tai i g su h site-spe ifi sa ples. A e e t eta-

a al sis fou d that the se siti it of sTREM- fo the diag osis of a te iali fe tio as % a d that the spe ifi it as % .

IL-

IL- is a hete odi e i toki e p odu ed a tige -

p ese ti g ells upo e posu e to i o ial p odu ts a d i fla ato sti uli , . IL- egulates T- ell fu tio a d has oth p o- a d a ti-i fla ato effe ts

, . Studies ha e de o st ated that a IL- se u o e t atio > g/ l had > % spe ifi it a d posi-

ti e p edi ti e alue fo ide tif i g iti all ill hild e ith la o ato - o fi ed a te ial i fe tio . Fu the -o e, IL- outpe fo ed p o al ito i PCT i a o-

ho t, a d a de isio t ee o i i g IL- a d PCT pe -fo ed ette tha eithe io a ke alo e . C iti all ill hild e ith sepsis ha e a g eate apa it to p odu e

IL- tha thei adult ou te pa ts . these studies sug-gest that IL- a tu out to e a o e useful sepsis diag osti io a ke i the pediat i populatio a d illust ate the i po ta e of testi g io a ke pe fo -

a e i ultiple patie t populatio s .

Solu le u oki ase-t pe plas i oge a ti ato e epto suPAR

suPAR is p ese t o a ell t pes i ludi g o o tes a d a ophages a d is i ol ed i the ig atio of i -fla ato ells f o the loodst ea i to tissues.suPAR has ee de o st ated i ultiple e e t studies to ha e p og osti utilit a d is a p o isi g io a ke i this ate-go .High se u suPAR o e t atio s o elated ith

o talit i patie ts ith a ti e tu e ulosis .That ele-ated suPAR ight e i di ati e of disease se e it .Highe

CSF suPAR le els o elated ith o talit . Sig ifi a tl highe ad issio suPAR le els i o -su i o s o pa ed

ith su i o s, p o idi g fu the suppo t fo the p og osti utilit of suPAR .

Neut ophil CD

E p essed o eut ophils a d o o tes, CD is the high-

affi it i u oglo uli F γ e epto I a d ediates phag-o tosis of a te ia. CD has pote tial oth as a diag os-ti a d p og osti sepsis io a ke . CD e p essio is elati el spe ifi fo a te ial i fe tio . CD e p essio as sig ifi a tl i eased he o pa ed ith health

o t ols a d that highe le els o elated ith o se i g se e it of sepsis as dete i ed li i ia s upo e oll-

e t a d ia A ute Ph siolog a d Ch o i Health E alua-tio APACHE-II s o i g. Fu the o e, -da o talit

as sig ifi a tl asso iated ith i eased CD e p es-sio .

P esepsi

CD is a gl op otei e p essed o o o tes a d a -ophages, se i g as a e epto fo lipopol sa ha ides a d

the e pla i g a ole i the i ate i u e s ste a ti-ati g a p oi fla ato sig ali g as ade upo o ta t ith pathoge s . P esepsi has pote tial oth as a di-

ag osti a d p og osti sepsis io a ke . thatp esepsi le els e e sig ifi a tl lo e i o -i fe ted patie ts, a d although i eased le els of p esepsi t e ded ith i -

eased sepsis se e it , the diffe e e et ee g oups as ot sig ifi a t. The fu the o luded that p esepsi le -

els e e highest i i fe ted patie ts at the ea liest ti e poi t easu ed, aki g it a ideal a didate as a diag os-ti io a ke . p esepsi easu ed at p ese tatio i pa-tie ts ith se e e sepsis o septi sho k as highe i o -

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su i o s he o pa ed ith su i o s .p esepsi le els e ai ed sig ifi a tl highe o

da s a d i o -su i o s he o pa ed ith su i-o s. o l p esepsi did ot de ease o e ti e i the

u fa o a le p og osis g oup, agai i di ati g its utilit as a p og osti io a ke .

Ne io a ke s/ o i atio of io a ke s:

A stud of patie ts ith a te ial i fe tio s e e e aluated ith io a ke s i ludi g sTREM- ,

CRP, a d PCT a d fou d that a o i atio of the a k-e s sho ed i p o ed diag osti a ilit o pa ed ith a si gle ake . Co lusio

I o de to ad a e the field of io a ke esea h i I -dia, ell-desig ed studies a e e essa to e aluate th eshold alues fo the diag osis a d de-es alatio of a -ti ioti s i I dia patie ts ith sepsis. Additio all , o e stud of spe ifi su g oups, i ludi g pediat i e sus adult patie ts, a i g se e it of sepsis, edi al e sus su gi al patie ts, a d othe populatio s ith spe ifi s d o es is

eeded i ge e al, a d i I dia, i spe ifi . Fu the stud of i estigatio al io a ke s that a hold p o ise fo e alu-ati g sepsis eithe as a i di idual test o i o ju tio

ith othe tests to i p o e se siti it a d spe ifi it eeds to e i estigated fo thei pote tial use i I dia.Data a out io a ke s a d PCT i sepsis a e g aduall i eas-i g a d ill help p o ide i fo ed e t steps fo esea h i I dia

Bi liog aph . He i uez-Ca a ho C, Losa J. Bio a ke s fo sepsis. Bio-

ed Res I t. ; . . Nelso GE, Ma e V, Gupta A. Bio a ke s fo sepsis: A

e ie ith spe ial atte tio to I dia. Bio ed Res I t. Hi da i Pu lishi g Co po atio ; ; .

. Pie akos C, Vi e t J-L. Sepsis io a ke s: a e ie . C it Ca e [I te et]. ; :R . A aila le f o : http://

fo u . io ed e t al. o /a ti les/ . /

. Rei ha t K, Baue M, Riede a NC, Ha tog CS. Ne ap-p oa hes to sepsis: Mole ula diag osti s a d io a ke s. Cli Mi o iol Re . ; : – .

. Hot hkiss RS, Ka l IE. The pathoph siolog a d t eat e t of sepsis. N E gl J Med [I te et]. Ja ; : –

. A aila le f o : http:// . i. l . ih.go /pu ed/

. Gullo A, Bia o N, Be lot G. Ma age e t of se e e sepsis a d septi sho k: halle ges a d e o e datio s. C it Ca e Cli [I te et]. Jul; : – , i . A aila le f o : http:// . i. l . ih.go /pu ed/

. Vi e t JL. The Cli i al Challe ge of Sepsis Ide tifi atio a d Mo ito i g. PLoS Med. ; : – .

. Delli ge RP, Le MM, Rhodes A, A a e D, Ge la h H, Opal SM, et al. Su i i g sepsis a paig : i te atio al guideli es fo a age e t of se e e sepsis a d septi sho k: . C it Ca e Med [I te et]. Fe ; :– . A aila le f o : http:// . i. l . ih.go /pu ed/

. Balk R. Roge C. Bo e, MD a d the e ol i g pa adig s of sepsis. Co t i Mi o iol [I te et]. ; : – . A aila-

le f o : http:// . i. l . ih.go /pu ed/

. Fai JD. C iti al Re ie s i Cli i al La o ato S ie es Bio a ke s of sepsis Bio a ke s of sepsis*. C it Re Cli

La S i C it Re Cli La S i. ; : – . . Bio a ke s Defi itio s Wo ki g G oup. Bio a ke s a d

su ogate e dpoi ts: p efe ed defi itio s a d o eptual f a e o k. Cli Pha a ol The [I te et]. Ma ;

: – . A aila le f o : http:// . i. l . ih.go /pu ed/

. Cho SY, Choi JH. Bio a ke s of Sepsis. I fe t Che othe . ; : – .

. Vi e t J-L, Beu ie M. Diag osti a d p og osti a ke s i sepsis. E pe t Re A ti I fe t The [I te et]. Ma ; : – . A aila le f o : http://

. i. l . ih.go /pu ed/

. M Lea AS, Ta g B, Hua g SJ. I estigati g sepsis ith io a ke s. B j [I te et]. ; ja :h –h .

A aila le f o : http:// . j. o / gi/doi/ . /j.h

. B u kho st FM, Hei z U, Fo ki ZF. Ki eti s of p o al i-to i i iat oge i sepsis. I te si e Ca e Med. Aug; : – .

. Da do a P, Ni D, Wilso MF, Aljada A, Lo e J, Assi ot M, et al. P o al ito i i ease afte e doto i i je tio i

o al su je ts. J Cli E do i ol Meta . De ;: – .

. S ide RH, N le ES, Be ke KL. P o al ito i a d its o -po e t peptides i s ste i i fla atio : i u o he i-al ha a te izatio . J I estig Med. De ; : –

.

18. Riedel S, Mele dez JH, A AT, Rose au JE, Ze il a JM. P o al ito i as a a ke fo the dete tio of a te e-

ia a d sepsis i the e e ge depa t e t. A J Cli Pathol. Fe ; : – .

19. Naka u a A, Wada H, Ikeji i M, Hatada T, Saku ai H, Matsushi a Y, et al. Effi a of p o al ito i i the ea l diag osis of a te ial i fe tio s i a iti al a e u it.

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Cli i al ase report

I t odu tio :

No a diosis is a oppo tu isti i fe tio lo alized o dis-se i ated , pa ti ula l i a patie t ith u de l i g i -

u e supp essio , a d is aused se e al spe ies of ge-us No a dia. No a dia e ui es a da s to g o i ultu e leadi g to dela i dete tio a d t eat e t. Dis-

se i atio to o e tha o e o ga s ste s, espe iall i patie ts ith supp essed i u it a d othe o o idi-ties, fu the o t i utes to its poo p og osis. We p ese t a fatal ase of disse i ated o a diosis i e al t a spla t e ipie t ho p ese ted ith uta eous a ifestatio s ut late as fou d to ha e pul o a a d CNS i ol e-e t.

Case:

A ea old ale f o Ha i pu , Utta P adesh, a e al allog aft e ipie t o t iple i u osupp essio ta oli us, ophe olate ofetil, p ed isolo e , p e-

se ted ith odula s elli gs o e the poste io aspe t o ight leg, ight hest a d left a do i al all fo da s.

He also had fe e , d ough a d diffi ult i alki g fo da s. P io to the ad issio patie t had de eloped si ila t pe of odula s elli g o e the poste io aspe t of the left alf fo hi h i isio a d d ai age as do e da s

a k i so e othe hospital. O e a i atio , Patie t as o s ious a d ale t, had pal-lo a d pedal ede a ith o othe s ste i a o alit . The e as a o heali g ul e o e left alf a d fi , o-

ile, te de odula s elli g o e poste io aspe t of left thigh s elli g, ight hest all a d left side of a do e Fig . A dis ha gi g si us as p ese t o e the left alf. A

p o isio al diag osis of p o ositis ith sepsis as ade a d the patie t as e pi i all sta ted o i/ efope a-

zo e+sul a tu g t i e dail alo g ith i/ li da i g hou l .

Fig. : odula s elli g o e ight hest all

O i estigatio , TLC as , /dL, gl os lated Hae oglo i . a d p o al ito i < . g/ l. As the patie t o ti ued to e fe ile i spite of a ti ioti s, e pi i al a tifu gals, i.e. i j. a pho-te i i B g a d i j. flu tosi e e e added a d a pus s a f o dis ha gi g si uses as se t fo i o iologi al i estigatio s hi h as i o -lusi e.

I the ea hile, lood ultu e take o the da of ad issio sig aled positi e afte da s of i u-

atio a d a g a stai of positi e lood ultu e oth e ealed g a positi e a hi g fila e -

tous a te ia Figu e a . A ki ou stai ed s ea sho ed the p ese e of a id fast a hi g fila-

e tous a te ia Figu e . A p o isio al diag-osis of o a diosis as ade a d the sa e as

i fo ed to the t eati g u it. O i o iologist ad i e, patie t as sta ted o i j. Cot i o azole a d

Disse i ated No a diosis i e al t a spla t e ipie t: A Case Repo t

Lata Sheo a , Jas i de Kau O e oi, Nee aj Goel, Ree a Ra i d a , Sa gha it a Dutta, K.J P asad, Cha d Wattal

Depa t e t Of Cli i al Mi o iolog A d I u olog , Si Ga ga Ra Hospital, Ne Delhi

Disse i ated No a diosis is a a e, life th eate i g disease i i u o o p o ised patie ts. We he e des i e a fatal ase of dis-se i ated o a diosis i a e al t a spla t patie t o t iple i u osupp essa ts ho p ese ted ith fe e , ultiple uta eous lesio s a d diffi ult i alki g. N. fa i i a as isolated i itiall f o lood & ski lesio s. Late the patie t de eloped CNS a d pul o a o pli atio s, a d the sa e o ga is as e o e ed f o o heoal eola la age. N. fa i i a is a a e ut i eas-i gl e og ized ause of disse i ated o a diosis i i u o o p o ised patie ts, is diffi ult to t eat a d has a high o talit . Rapid spe ies ide tifi atio te h i ues like MALDITOF a help i i stitutio of ea l app op iate a ti ioti the ap .

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i j. e ope e a d i u osupp essa ts e e odified. Blood suga as a aged ith i suli .

Fig. a G a stai ed s ea of positi e lood ultu e oth sho i g g a positi e, a hi g a te ia

Fig. Ki ou stai ed s ea of positi e lood ultu e oth sho i g a id fast, a hi g a te ia

I the ea hile su ultu e of lood ultu e oth o uffe ed ha oal east e t a t aga BYCE afte hou s

of i u atio of g e halk hite adhe e t olo ies e e see Fig. hi h as ide tified as No a dia fa i i a MALDI-TOF/MS, i.e Vitek MS ioMe ieu , F a e . Sa e o ga is as isolated f o iops spe i e s f o uta-

eous s elli gs. A defi iti e diag osis of disse i ated No a diosis as ade, a ti ioti t eat e t o ti ued a d the patie t e a e afe ile.

Fig. Chalk hite olo ies o BYCE aga

O da the patie t o plai ed of de eased isio & de eloped alte ed se so iu , MRI ai sho ed e ide e of dis ete ell defi ed s all odula to i g like lesio

see i the left e e ella pa e h a, ight deep tha-la i egio a d i the high ight poste io f o tal su -o ti al egio , suggesti e of e e ella o a diosis. O

da patie t de eloped ough ith lood ti ged spu-tu , hest X- a e ealed B/L o ho oge ous opa i-ties, o e p o i e t i left lo e zo e ith te ti g of left he i-diaph ag a d lo ulated effusio alo g the left hest all Fig. . B o hoal eola la age fluid se t fo a al sis also sho ed p ese e of o a dia. Patie t de eloped espi ato dist ess & h pote sio . I spite of asop esso s a d e tilato suppo t, patie t su -u ed to his disease.

Fig. Chest X a sho i g B/L opa ities ith lo ulated effusio o left side

Dis ussio : No a dia spe ies, a ed afte Ed o d No a d, ho des i ed it fo the fi st ti e i i a attle ith

o i e fa , a e ae o i g a -positi e, pa tiall a id-

fast a hi g fila e tous a te ia elo gi g to ae o-i o a difo a ti o etes. , The a e p ese t

u i uitousl as e i o e tal saph oph tes fou d o ld ide, o o l i t opi al a d su t opi al e-

gio s like Me i o, Ce t al &South A e i a, Af i a a d I dia.4 No a dia sp. a affe t oth i u o o pete t

% a d i u o o p o ised % hosts. Cell e-diated i u it t pi all pla s g eatest ole i o t ol-li g a d lea i g o adial i fe tio , the efo e i u o-o p o ised patie ts o lo g te ste oids, o ga

t a spla tatio . - . % o e all , he atologi alig-a , AIDS o othe o ditio s su h as al oholis a d

dia etes a e at highest isk. , Most o o oute of t a s issio a e i halatio - % a d di e t i o ula-tio of the ski o th ough i o t au a - % .

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Disease spe t u of No a diosis g eatl a a gi g f o lo alized uta eous disease to disse i ated, ulti-o ga i asio s, depe di g o a o i atio of oute of a uisitio of i fe tio , i ule e of the spe ifi o-a dial st ai , a d i u e status of the affe ted host.

No a dia spe ies ha e pote tial to etastasize hae a-toge ousl to dista t od o ga s ste s.

Disse i ated o a diosis is defi ed as isolatio of o-a dia fou d f o o e tha o e od site a d ostl

i ol es i u osupp essed patie ts. CNS is the ost o o o ga i ol ed, e ause of thei spe ial t o-

pis fo the eu al tissue, ith o talit epo ted as high as % a d % i i u o o p o ised a d i -

u o o pete t patie ts, espe ti el . Othe o o o ga s ste s hi h a e i ol ed i disse i ated

o a diosis a e lu gs, e e, kid e , ski , su uta eous tissue a d o e. Disse i ated o a diosis te d to e-ha e as p oge i a te ial i fe tio s a d the esult is t pi all a suppu ati e a s ess at the e oli e d poi t. The a s ess te ds to p og ess o e la ge i to the su -ou di g tissue fila e tous e te sio a d self li ita-

tio of disease is a e.

Out of ide tified spe ies ause hu a i fe tio a d sho spe ies tissue t opis . No a dia aste oides o ple a ou ts fo - % of o a diosis a d ostl auses o - uta eous i asi e s ste i a d CNS i fe -

tio s. No a dia asilie sisis is the d ost o o spe ies, a ou ti g fo - % of o a diosis, ostl uta eous a d l pho uta eous. No a dia fa i i a a d

othe spe ies likeNo a dia pseudo asilie sis, N. t a s-ale sis a d N. otitidis a a iu a e less o o auses

of o a diosis.

Diag osis of o a diosis is diffi ult as li i al sig s a d s pto s a e o spe ifi ith adiologi al i agi g fi di gs ei g o pathog o i i i ki g othe e tities su h as tu e ulosis o alig a ies. The efo e, i o i-ologi al e a i atio a d high deg ee of li i al suspi-io i a i u o op o ised setti g pla a ital ole i

diag osi g o a diosis. No a dia spe ies a e o -se ed positi e i os opi dete tio of g a posi-ti e a d eakl a id fast a hi g fila e tous a te ia a d a e o fi ed ultu e follo ed ide tifi a-tio . Spe iatio of No a dia is diffi ult as o e tio al

ethods take eeks to o plete a d a e ostl i -o lusi e, ole ula te h i ues su h as ge e se ue -

i g, RFLP a e e pe si e, u e so e a d a e diffi ult to i ple e t i outi e la o ato . MALDI TOF Mat i -

Assisted Lase Deso ptio Io izatio – Ti e of Flight Mass Spe t o et fo Ide tifi atio has a ad a tage of apidit h fo ide tifi atio ith high a u a

% . I the p ese t ase also ide tifi atio as do e MALDI TOF/MS.

N. fa i i a o igi all des i ed as a o i e pathoge , is ei g i easi gl e og ized a d epo ted as a age t

of disse i ated o a diosis, pa ti ula l i i u o o -p o ised patie ts. Blood ultu es a e a el positi e i N. fa i i a i fe tio s ith e fe ases ei g epo t-ed i the lite atu e. O e ase had disse i ated i fe tio

ith e e al a s ess a d as u ed ith o al a ti ioti the ap a d, a othe had o a dial e do a ditis of a ao ti al e p osthesis a d did ell ith a o i atio of i ipe e a d a ika i follo ed o al TMP-SMX. A othe stud sho ed that out of isolates i a g oup of i u o o p o ised patie ts, fou isolates e e o tai ed f o post- o te lood ultu e, of hi h o l o e as N. fa i i a. N. fa i i a a te ae ia has a p o-pe sit fo ausi g disse i ated disease o o l i -ol i g lu gs, ai a d su uta eous tissue. - The

p ese t ase also, the patie t had disse i ated o a di-osis ith uta eous, CNS a d espi ato i ol e e t.

Ma age e t of disse i ated o a diosis i ludes su gi-al a age e t aspi ate, d ai age, e isio alo g ith

a ti ioti s guided i - it o sus epti ilit testi g. Spe i-atio of No a dia spe ies a e helpful as esista e patte s a diffe a o gst spe ies a d et ee st ai s

ithi a spe ies. T pi all , t eat e t is i itiated i t a e-ousl ith high doses of t i ethop i /

sulpha etho azole fo - eeks follo ed o al the a-p . I ase of alle g o esista e alte ati e d ugs like

i o li e, a ika i , i ipe e , eft ia o e a d fluo-o ui olo es a e gi e . Li ezolid ha e ee sho

to ha e ade uate li i al effi a ith little do u e ted esista e.

A disti guishi g featu e of No a dia fa i i a is its te -de to e esista t to u e ous a ti ioti s a d has a high o talit asso iated ith i ade uate t eat e t. Se e al studies o e the ea s suggest that this spe ies of No a dia has i ate esista e to d ge e atio ephalospo i s, e th o i , to a i , ge ta i i ,

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ka a i , a d eta-la ta a ti ioti s. I it o data sug-gests that t o e e a ti ioti s, i ipe e a d li ezolid, ha e a ti it agai st N. fa i i a. The o ga is , ho e e , appea s to ha e a ia le esista e patte s to d ugs i the a ape e lass. T eat e t su ess has ee e-po ted ith the ui olo e a ti ioti o iflo a i , though sulfo a ides e ai the ai sta of the ap agai st N. fa i i a i fe tio .

Co lusio : No a diosis a e a diffi ult i fe tio to ide tif a d t eat. diag osed late i the disease ou se.

While uta eous disease is ofte oted ea l , i asi e disease i i u o o p o ised i di iduals is ofte De-la ed diag osis a lead to a poo out o e. I additio , N. fa i i a p ese ts the u i ue t eat e t halle ge of

ei g esista t to a of the o o d ugs used to t eat othe No a dia spe ies. No a dial i fe tio should

e o side ed ea l i the diffe e tial diag osis of all i u osupp essed patie ts ith fe e a d uta eous, pul o a o CNS lesio s.

Refe e es: . Bea a BL, Bea a L. No a dia spe ies: host-pa asite ela-

tio ships. Cli Mi o iol Re . ; : – . . So ell TC, Mit hell DH, I edell JR. No a dia spe ies. U: Ma -

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, st . – . . B o , J. M., a d M. M. M Neil. . No a dia, Rhodo o -

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. Valdezate S, Ga ido N, Ca as o G, Medi a-Pas ual MJ, Villaló P, Na a o AM, Saéz-Nieto JA. Epide iolog a d sus epti ilit to a ti i o ial age ts of the ai No a dia spe ies i Spai . Jou al of A ti i o ial Che othe ap .

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. Woj o EDT, Hu te CA. Ne di e tio s i the asi a d t a slatio al iolog of i te leuki - . T e ds I u ol.

Fe ; : – . . Bos a M, Wa d PA. Modulatio of i fla atio

i te leuki - . J Leuko Biol. De ; : – . . Pfla z S, Ti a s JC, Cheu g J, Rosales R, Ka zle H, Gil e t

J, et al. IL- , a hete odi e i toki e o posed of EBI a d p p otei , i du es p olife atio of ai e CD + T ells. I u it . Ju ; : – .

. Villa i o A V, La ki J, Sa is CJM, Cato AJ, Lu as S, Wo g T, et al. Positi e a d egati e egulatio of the IL- e-epto du i g l phoid ell a ti atio . J I u ol.

Ju ; : – . . Sa d uist M, Wo g HR. Bio a ke s of sepsis a d thei

pote tial alue i diag osis, p og osis a d t eat e t. E pe t Re Cli I u ol [I te et]. ; : – . A aila le f o : http:// .ta dfo li e. o /doi/full/ . / X. .

. Euge -Olse J, Gustafso P, Side ius N, Fis he TK, Pa e J, Aa P, et al. The se u le el of solu le u oki ase e-epto is ele ated i tu e ulosis patie ts a d p edi ts o talit du i g t eat e t: a o u it stud f o Gui -

ea-Bissau. I t J Tu e Lu g Dis. Aug; : – . . Ulla M, Pizzolato E, Lu hia i M, Loia o o M, Soa do F,

Fo o D, et al. Diag osti a d p og osti alue of p esepsi i the a age e t of sepsis i the e e ge depa t e t: a ulti e te p ospe ti e stud . C it Ca e.

Jul ; :R . . Masso S, Cai o i P, Spa uth E, Tho ae R, Pa igada M,

Sa gio gi G, et al. P esepsi solu le CD su t pe a d p o al ito i le els fo o talit p edi tio i sepsis: data f o the Al u i Italia Out o e Sepsis t ial. C it Ca e.

Ja ; :R . . Kofoed K, A de se O, K o o g G, T ede M, Pete se J,

Euge -Olse J, et al. Use of plas a C- ea ti e p otei , p o al ito i , eut ophils, a ophage ig atio i hi ito-

fa to , solu le u oki ase-t pe plas i oge a ti ato e epto , a d solu le t igge i g e epto e p essed o

eloid ells- i o i atio to diag ose i fe tio s. C it Ca e. ; :R .

. Luzza i A, Polati E, Do izzi R, Ru gats he A, Pa a R, Me li i A. Co pa iso of p o al ito i a d C- ea ti e p otei as

a ke s of sepsis. C it Ca e Med. Ju ; : – . . Ta g BMP, Esli k GD, C aig JC, M Lea AS. A u a of p o-

al ito i fo sepsis diag osis i iti all ill patie ts: s ste -ati e ie a d eta-a al sis. La et I fe t Dis. Ma ;

: – . . Si o L, Gau i F, A e DK, Sai t-Louis P, La oi J. Se u

p o al ito i a d C- ea ti e p otei le els as a ke s of a te ial i fe tio : a s ste ati e ie a d eta-a al sis.

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. Wa ke C, P k o A, B u kho st FM, S hlatt a P. P o al i-to i as a diag osti a ke fo sepsis: a s ste ati e ie a d eta-a al sis. La et I fe t Dis [I te et]. Ma ;

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. Shi e B, de Bee FC, Pep s MB. Solid phase adioi u oas-sa s fo hu a C- ea ti e p otei . Cli Chi A ta. ;

: – . . Ga a C, Kush e I. A ute-phase p otei s a d othe s ste i

espo ses to i fla atio . N E gl J Med. Fe ;: – .

. Sak Y, Bu gett U, Na ul FE, Rei ha t K, B u kho st F. Lipo-pol sa ha ide i di g p otei i a su gi al i te si e a e u it: a a ke of sepsis? C it Ca e Med. Jul; :– .

. A e R, Oda S, Sadahi o T, Naka u a M, Hi a a a Y, Tateishi Y, et al. G a - egati e a te e ia i du es g eate ag i-tude of i fla ato espo se tha G a -positi e a te e-

ia. C it Ca e. ; :R . . Sugitha i i V, P e a A, Be la Tha ga E. I fla ato e-

diato s of s ste i i fla atio i eo atal sepsis. I fla Res. De ; : – .

. Nelso GE, Ma e V, Gupta A. Bio a ke s fo sepsis: A e ie ith spe ial atte tio to I dia. Bio ed Res I t. ; .

. Ji o g J, Tia ha H, Wei C, Huahao S. Diag osti alue of the solu le t igge i g e epto e p essed o eloid ells- i

a te ial i fe tio : a eta-a al sis. I te si e Ca e Med. Ap ; : – .

Salmonella and shigella were in love..

Their parents didn't agree for marriage..

So they decided to run away to and get married..

But they could not do so.. why?

Coz shigella is non motile

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Microbiology Updates from around the world….

Mi ro iology Update :

Zika i us e posu e dete ted i patie ts p e-se ti g ith e eu oi fla ato o di-tio s

Zika i us, a fla i i us sp ead the Aedes os uito that i fe ted to . illio people i B azil as ell as othe Lati A e i a ou t ies f o to . Case se ies ha e suggested a li k et ee Zika i us i fe tio a d eu ologi o pli atio s i ludi g GBS, e i goe ephalitis a d t a s e se

elitis.

A p ospe ti e oho t stud f o B azil fou d ole u-la o se ologi e ide e of e e t Zika Vi us i fe -tio i ost patie ts ad itted ith e pa ai fe -tious/ eu oi fla ato o ditio s i ludi g Guil-lai -Ba é s d o e GBS , e i goe ephalitis, o t a s e se elitis.

Rates of ad issio fo eu oi fla ato o ditio s e e highe i B azil du i g the stud pe iod tha fo

a si ila ti e pe iod p io to the B azil ZIKV out-eak.

Refe e e: Fe ei a da Sil a et al. Neu ologi Co pli atio s Asso i-ated ith the Zika Vi us i B azilia Adults. JAMA Neu ol.

; : - .

Mi ro iology Update :

O al Kle siella Ca I du e I testi al I fla a-tio

It has ee suggested that i testi al olo izatio a te ia f o the o al a it a e e te si el i -ol ed i gut i fla ato diseases. Ho e e , it e-ai s u lea hi h su set of o al o ga is s a

olo ize the i testi e a d a i du e i fla ato i u e espo ses.

Re e tl , it has ee sho that st ai s of Kle siella f o the sali a i o iota olo ize i the i testi e a d a i du e h o i i fla atio .

Colo izatio of the i testi e these o ga is s a ti-ates de d iti ells a d epithelial ells ia Toll-like e epto s to p odu e i te leuki , hi h the e-uits a d a ti ates TH ells a d thus esults i i -

fla atio .

Refe e e: Ata ashi K et al. E topi olo izatio of o al a te ia i the i testi e d i es TH ell i du tio a d i fla atio . S ie e. : , .

Mi ro iology Update :

Ca didate d ug to p e e t HIV i fe tio i o e safe a d ell-tole ated i phase t ial

HIV p e e tio is a i po ta t a ea of pu li health, as o e illio e HIV i fe tio s o u a uall o ld-ide. O e ethod of HIV p e e tio is p e-e posu e p oph la is.

Ma a i o p e-e posu e p oph la is egi e s e e o se ed to e safe a d ell tole ated i patie ts.

No e HIV i fe tio s o u ed du i g the ou se of the - eek stud . Refe e e: Ro M. Guli k et al. Safet a d Tole a ilit of Ma a i o -Co tai i g Regi e s to P e e t HIV I fe tio i Wo e : A Phase Ra do ized T ial. A I te Med. ; : - .

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Microbiology Updates from around the world….

Mi ro iology Update :

Plas a Epstei –Ba i us DNA useful fo a-sopha geal a i o a s ee i g

A al sis of i ulati g plas a DNA i a e patie ts has ee t pi all used to guide t eat e t optio s a d assess p ese e of disease. Ideall , plas a DNA a al sis ould also e used to s ee fo i itial a -e p ese e a d pi k-up ea l stage ases.

As pto ati stud pa ti ipa ts ith pe siste tl ele ated se u Epstei -Ba i us EBV le els e e diag osed ith asopha geal a i o a at ates highe tha e pe ted ithout s ee i g.

Patie ts s ee ed plas a EBV le els e e diag-osed ith ea lie stage, a d the efo e o e t eata-le, asopha geal a i o as tha patie ts p e-

se ti g ith asopha geal a i o a ho e e e e s ee ed.

Refe e e: A i de et al.Plas a Epstei –Ba Vi us DNA fo S ee i gN E gl J Med ; : - August ,

DOI: . /NEJMe

Mi ro iology Update :

Ne t-ge e atio etage o i s se ue i g a sleuth out ha d-to-fi d i uses i the

lood

Ne t-ge e atio etage o i se ue i g NGMS is a te h i ue that i ol es the se ue i g of all the DNA o RNA i a tissue, follo i g i te p etatio of esults ith o el ioi fo ati s tools. As this te h-i ue is elati el e , a uestio s e ai u a -

s e ed as to the apa it NGMS has fo dete tio of pathoge s a d its se siti it

Ne t-ge e atio etage o i s dete ted Hu a Hepegi i us- HhpgV- i a oho t of patie ts ho i je t d ugs ut li i al sig ifi a e of dete ti g HHpgB- i fe tio is u e tl u lea .

O e all, NGMS a e e efi ial fo dete ti g ha d-

to-fi d i uses i lood sa ples i the futu e. Refe e e: Ka dathil et al. P ese e of Hu a Hepegi i us- i a Coho t of People Who I je t D ugs. A I te Med.

; : - .

Mi ro iology Update :

Di e t-a ti g a ti i al the ap fo hepatitis C i us asso iated ith hepatitis B i us ea ti atio i o-i fe ted patie ts

Ch o i hepatitis C i us HCV i fe tio is the top ause of i hosis, li e a e , a d li e t a spla t. Di e t a ti g a ti i al DAA t eat e t fo HCV gi es patie ts a high ha e of ea hi g a sustai ed i ologi espo se SVR ,

hi h is i di ati e of su essful HCV i fe tio t eat e t. SVR is the a se e of HCV RNA dete tio i the lood fo eeks o o e afte o pletio of t eat e t. Co-i fe tio ith HBV is o o i a eas he e HCV a d HBV

i fe tio s a e e de i . HBV-Rea ti atio is a sudde i ease i HBV epli atio i patie ts ho ha e esol ed o i a ti e HBV i fe tio .

Patie ts ho ha e ee i fe ted ith hepatitis B i us HBV a d a e ei g t eated ithDAAs fo HCV i fe tio should e o ito ed du i g thei t eat e t ou se fo possi le de elop e t of HBV ea ti atio .

HBV ea ti atio is a a agea le ad e se e e t, a d DAAs o ti ue to e a safe a d e effe ti e t eat e t fo i fe tio ith HCV.

Refe e e:

Be soff-Mat ha et al. Hepatitis B Vi us Rea ti atio Asso iated With Di e t-A ti g A ti i al The ap fo Ch o i Hepati-tis C Vi us: A Re ie of Cases Repo ted to the U.S. Food a d D ug Ad i ist atio Ad e se E e t Repo ti g S ste . A I te Med. ; : - .

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Clues

A oss

. I e to of Hot ai o e

. JC Pol o a i us auses

. Rapid ethod fo TB diag osis

. Cell all defi ie t fo

. Ce i al a e ell li e

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. Mediu fo Ca p lo a te

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. Adoles e t a i atio i di ated fo

. Risus Sa do i us is see i

. L ti a ea o a te ial ultu e phage

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Answers on website

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