Tb : Recent recommendation Dr.Ketan Shah
Tbc : Clinician If you think It is easy to diagnose : u r not good clinician It is difficult to diagnose :U r not alone doctor to think this 6/22/2015 Ketan Shah IAP surat 2
6/22/2015 5yrs/Female- Vibhuti FTT Poor appetite Wt < 25 th percentile O/E ; no lymph-adenopathy No organo-megaly Repeatedly parents insist for FTT Pediatrician has not kept Growth chart Frustrated Pediatrician asked for MT Ketan Shah IAP surat 3
Look at the lab request 6/22/2015 Ketan Shah IAP surat 4
MT : most trusted test????? Report 10 mm of indurations and 15 mm of erythema MT strength 10Tu/0.1 ml 6/22/2015 Ketan Shah IAP surat 5
Fallacies in case History of Wt loss Many reasons Actual 5% of last 3 months Fussy eater Other reasons No growth chart TST /MT fallacies 6/22/2015 Ketan Shah IAP surat 6
TST/MT 5 TU PPD-S= 2 TU PPD RT 23 with Tween 80 Available at Gayatri chemicals,surat 6/22/2015 Ketan Shah IAP surat 7
TST (MT)FAQs TST >20 mm Suggest Just infection not sever disease Ulceration = severe disease? What if comes after 7 days? read BCG test more useful? No Repeat TST after completion of ATT? No Reactivation or re-infection what happens to TST? No correlation 6/22/2015 Ketan Shah IAP surat 8
TST MT : most un--trusted and asked test. Mantoux test suggest infection with MTB not disease, Isolated positive test does not merit treatment 6/22/2015 Ketan Shah IAP surat 9
There is H/o Contact with TB in family MT done 10mm report (2TU/0.1 mm )????? Do you start ATT Investigate /define and start /prophylaxis 6/22/2015 Ketan Shah IAP surat 10
Contact tracing Due importance Go for microbiological diagnosis Insist for the same Investigate for disease and if no disease found start prophylaxis INH 10 mg/kg/day 6 months 6/22/2015 Ketan Shah IAP surat 11
Six months old child coming with lymph node in axilla. Has received BCG at birth FNAC shows mycobacteria positive in microscopy. AKT????????? ( rule out disseminated BCG Tb ) NO 6/22/2015 Ketan Shah IAP surat 12
Nistha 12 yrs/f H/o chronic cough Productive cough f/h/o open case of Koch s 6/22/2015 Ketan Shah IAP surat 13
X-ray chest 6/22/2015 Ketan Shah IAP surat 14
Will you ask for sputum? If yes ; how?, What? How many days? What is recent recommendation? Gastric aspirate ; good option try 6/22/2015 Ketan Shah IAP surat 15
Bronchoscopy and BAL If available should be tried 6/22/2015 Ketan Shah IAP surat 16
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What you will ask in sputum? Miscroscopy Direct microscopy by staining Fluorescent microscopy more preferred CBNAAT (genexpert/rif) Culture :liquid culture :MGIT Solid culture :LJ media 6/22/2015 Ketan Shah IAP surat 19
Parents want urgent reports Asked for Ab detection (serology ) Ag detection Interferon gamma release tests (IGRA) 6/22/2015 Ketan Shah IAP surat 20
Interferon gamma assay IGRA Elispot-Tb Quantiferon Tb gold Just indicates child has latent Tb infection Does not indicate disease Limitations Not routinely recommended 6/22/2015 Ketan Shah IAP surat 21
Summary of available diagnostic tests for Tb Smear Sputum /gastric aspirate Culture MGIT LJ CBNAAT Radiology TST Be ware of false results Indicates infection but not disease 6/22/2015 Ketan Shah IAP surat 22
8yrs /M H/o acute onset of fever Chest pain O/E : suggestive of pneumonia and mild effusion 6/22/2015 Ketan Shah IAP surat 23
1 st x-ray 6/22/2015 Ketan Shah IAP surat 24
Effusion increased 6/22/2015 Ketan Shah IAP surat 25
Repeat x-ray 6/22/2015 Ketan Shah IAP surat 26
Does TST helps? Does CBC, ESR helps? Plural fluid study Exudative :p : >3 gm %,not pus Straw color Lymphocytic count 50-to-few thousands ADA No role CB-NAAT /ZN staining Plural biopsy Search for Tb at other site Gastric aspirate /sputum if available 6/22/2015 Ketan Shah IAP surat 27
Lymph node Tb >2 cm Trial of AB (not linezolid, quinolones ) No response go for FNAC FNAC Smear Histo-pathology MGIT CBNAAT 6/22/2015 Ketan Shah IAP surat 28
Search for evidance at other site TST +ve but biopsy negative do not start ATT USG gland : central hypo-echogenicity Necrotic gland 6/22/2015 Ketan Shah IAP surat 29
Ab Tb Necrotic gland Other constitutional s/s Think of Tb r/o IBD (Crohn s etc ) Send any available material for CB-NAAT 6/22/2015 Ketan Shah IAP surat 30
Treatment Intensive phase Continuation phase Purpose 6/22/2015 Ketan Shah IAP surat 31
Ethambutol safe Good drug for neuro Tb than SM 6/22/2015 Ketan Shah IAP surat 32
In HIV + ve cases intermittent regime not useful Daily Observed therapy ( DOT daily ) is recommended HIV ve : Intermittent /daily recommended 6/22/2015 Ketan Shah IAP surat 33
India is in high INH resistance country Huge Impact on treatment 6/22/2015 Ketan Shah IAP surat 34
IAP-RNTCP 2015 Cat of treatment Type of Pt Regimens New (old cat 1) Retreatment (old Cat 2 ) New Bacterilogically confirmed Tb Clinically diagnosed Tb Extra pulmonary Bact confirmed retreatment Microbiologically +failure Microbiologically +ve defaulter Other 2HRZE + 4HRE 2HRZE + 1HRZE +5HRE Others : Sputum-ve /extra pulmonary recurrence 6/22/2015 Ketan Shah IAP surat 35
Note changes in doses 3/week Daily R 15 ( 12-17) 10-12 (Max 600) H 15 (12-17) 10 ( max 300 ) Z 35 (30-40) 20-25 (max 1500 ) E 30 (25-30) 30-35 (max 2000 ) S 15 15 (max 1 gm ) 6/22/2015 Ketan Shah IAP surat 36
FDC Recommended Ratio 1:1.5:3 ( 10:15 ;30 ) Not 1:2 H :50, R : 75,Z : 150 ideal Non of the formulation has this combination 6/22/2015 Ketan Shah IAP surat 37
Role of steroid /adjuvant drugs In CNS Tb for 4 weeks than taper In pericardial effusion Tb : yes In plural effusion : if bilateral /massive yes /not must Pyridoxine ; in pregnancy and sever malnutrition Not routinely 6/22/2015 Ketan Shah IAP surat 38
Thank you BUT STILL MORE TO LEARN 6/22/2015 Ketan Shah IAP surat 39
History Vicky M/9 yrs Dec. 2005 admitted for PUO All reports negative,x-ray normal? Enteric fever Responded to ceftriaxone 6/22/2015 Ketan Shah IAP surat 40
HISTORY After 20 days fever reappeared Toxic child admitted After 4 days drowsy X-ray shows Miliary Tb CT brain shows localised Tuberculoma 6/22/2015 Ketan Shah IAP surat 41
1st X-ray Jan 2006 Miliary- snow-storm pattern 6/22/2015 Ketan Shah IAP surat 42
Treatment AKT Steroid Anticonvulsant Better for 2 months Steroid tapered after 2 months 6/22/2015 Ketan Shah IAP surat 43
Convulsion S/S of RICT Repeat CT shows increased lesions Bilateral 6/22/2015 Ketan Shah IAP surat 44
1st CT scan Left parietal Granuloma 6/22/2015 Ketan Shah IAP surat 45
New lesions in CT Right side,, After 3 months of AKT, X-ray normal ( march 2006) 6/22/2015 Ketan Shah IAP surat 46
New lesions in CT 6/22/2015 Ketan Shah IAP surat 47
What happened? Why so? 6/22/2015 Ketan Shah IAP surat 48
Therapeutic paradox Immune phenomena Resistant bacteria? How to differentiate What is the approach? 6/22/2015 Ketan Shah IAP surat 49
Trial of AKT Is IT a good clinical judgment??? 6/22/2015 Ketan Shah IAP surat 50
Abdominal pain 12 yrs /F R A P (recurrent abdominal pain ) Good growth No other findings USG shows Mesenteric LN 1-2 cm in size MT : 0 mm, CBC: Normal, ESR:25 mm AKT started????????/comment.. 6/22/2015 Ketan Shah IAP surat 51
Rekha, 8 years girl, Resident of Delhi H/o: Swelling in neck for 5 months Occasional vomiting and low grade fever, no cough, distress No history of definite contact with Tb patient Physical Examination Weight 14 kg, Height 110 Cms HR 100/ min, RR 28 /min Bilateral cervical nodes, multiple, matted 3-4 Cms in size Discharging sinus over sternum Rest WNL 6/22/2015 Ketan Shah IAP surat 52
Investigations Mantoux test positive: 25 mm CXR: Superior mediastinum wide, no lung parenchymal lesions Hb; 10, TLC 10200, P 55, L42, E 3, ESR 23 mm PS: Normal no atypical cells, Platelets adequate Family survey for Tb WNL FNAC from node suggest: Granuloma, Necrosis, AFB positive 6/22/2015 Ketan Shah IAP surat 53
Q 1: What should be the treatment for this patient? 6/22/2015 Ketan Shah IAP surat 54
Treatment received Child was started on 2 HRZE 4 HR No improvement in size of the node and discharging sinus No weight gain Developed daily low grade pyrexia and poor appetite after 2 months of treatment 6/22/2015 Ketan Shah IAP surat 55
Q: How this patient should be managed now? 6/22/2015 Ketan Shah IAP surat 56
Course of illness Screened for other infections including UTI, and intensive phase extended for another one month. ( RNTCP ) No significant improvement in symptoms after extended one month of intensive phase AFB positive from the discharging sinus. 6/22/2015 Ketan Shah IAP surat 57
Gene expert study shows resistance pattern 6/22/2015 Ketan Shah IAP surat 58
Q: What should be the management now? 6/22/2015 Ketan Shah IAP surat 59
Course of illness Culture for AFB taken Child was started on cat 2 regimen: 2 SHRZE, 1 HRZE, 5 HRE No weight gain, continue to have low grade fever, no decrease in size of nodes Culture available after 2 months and M Tb resistant to HR 6/22/2015 Ketan Shah IAP surat 60
Q: How to manage this patient now? 6/22/2015 Ketan Shah IAP surat 61
Course of illness Admitted in hospital, Started on Ethionamide, Kanamycin, ofloxacin and pyrazinamide Monitored for side effects in hospital by doing LFTs twice a week and discharged after two weeks 6/22/2015 Ketan Shah IAP surat 62
Follow up In TB clinic: Fever and discharge from sinus responded in 2 weeks, appetite improved. No AFB from sinus discharge at 2, 3 months At 6 months: Lymphnodes < 1 Cm, sinus healed completely, kanamycin stopped, rest of medications continued At 18 months of treatment: weighs 20 Kg, no systemic manifestations: ATT stopped At 24 months asymptomatic 6/22/2015 Ketan Shah IAP surat 63
Step 1 Begin with any First line agents to Which the isolate is Susceptible Use any available First-line drugs PLUS One of these Fluoroquinolones PLUS One of these Injectable agents Add a Fluoroquinolone And an injectable Drug based on susceptibilities Pyrazinamide Ethambutol Ofloxacin Levofloxacin Moxifloxacin Amikacin Capreomycin Streptomycin Kanamycin 64 6/22/2015 Ketan Shah IAP surat 64 BS
Step 1 Begin with any First line agents to Which the isolate is Susceptible Use any available First-line drugs PLUS One of these Fluoroquinolones PLUS One of these Injectable agents Add a Fluoroquinolone And an injectable Drug based on susceptibilities Pyrazinamide Ethambutol Levofloxacin Moxifloxacin Amikacin Capreomycin Streptomycin Kanamycin Step 2 Add 2 nd line drugs until you have 4-6 drugs to which isolate is susceptible (which have not been used previously) Pick one or more of these Oral second line drugs Cycloserine Ethionamide PAS 65 6/22/2015 Ketan Shah IAP surat 65
Step 1 Begin with any First line agents to Which the isolate is Susceptible Use any available First-line drugs PLUS One of these Fluoroquinolones PLUS One of these Injectable agents Add a Fluoroquinolone And an injectable Drug based on susceptibilities Pyrazinamide Ethambutol Levofloxacin Moxifloxacin Amikacin Capreomycin Streptomycin Kanamycin Step 2 Add 2 nd line drugs until you have 4-6 drugs to which isolate is susceptible (which have not been used previously) Step 3 Pick one or more of these Oral second line drugs Cycloserine Ethionamide PAS Consider use of these 66 If there are not 4-6 drugs available consider 3 rd line in consult with MDRTB experts Third line drugs Imipenem Linezolid Macrolides Amoxicillin/Clavulanate 6/22/2015 Ketan Shah IAP surat 66 BS
What is status of chemoprophylaxis for contacts of MDR TB? 6/22/2015 Ketan Shah IAP surat 67
Causes of Drug resistance Essentially drug resistance is a man made phenomenon Providers/Programmes: Inadequate regimens Drugs: Inadequate supply Poor quality Patients: Inadequate drug intake 6/22/2015 Ketan Shah IAP surat 68
What is X DR TB? Extensive drug-resistant TB (XDR-TB) is defined as a multidrug-resistant TB strain which is also resistant to Quinolones and one of the injectable XDR-TB is related to the poor management of MDR-TB cases (which in turn is the consequence of sub optimally managed susceptible TB). Countries with high incidence of MDR-TB are at high risk for emergence of XDR-TB. 6/22/2015 Ketan Shah IAP surat 69
Resistant tuberculosis: Drugs used and their doses Drugs Dose per kg per day Ethionamide 15-20 (PO) Cycloserine 15-20 (PO) Ciprofoxacin 10-20 (PO) Ofloxacin 10 (PO) Kanmycin 15 (IM) Amikacin 15 (IM) 6/22/2015 Ketan Shah IAP surat 70
Management of MDR TB Resistance to Drugs in intensive phase Minimum duration in months Drugs in continuation phase Duration in months H and R Aminoglycosides Ethionamide 3-6 3 Ethionamide Ofloxacin 18-21 18-21 PZA 3 Ethambutol 18-21 Ofloxacin Ethambutol 3 3 Cycloserine/ PAS 18-21 Cycloserine/ PAS 3 HSR and E Aminoglycosides Ethionamide 3-6 3 Ethionamide Ofloxacin 18-21 18-21 PZA Ofloxacin 3 3 Cycloserine/ PAS 18-21 Cycloserine/ PAS 3 6/22/2015 Ketan Shah IAP surat 71
Suraj, 3 years boy, resident of UP Known HIV positive for past 5 months on Three ART (lamivudine, nevirapine and stavudine) P/c: fever, cough, breathing difficulty: 15 days Treated with oral antibiotics (Augmentin) No improvement Mother died of HIV illness 2 months ago and had severe emaciation Father is HIV positive but asymptomatic 6/22/2015 Ketan Shah IAP surat 72
X-ray /CT and BAL proved tuberculosis of lungs 6/22/2015 Ketan Shah IAP surat 73
Q1: How to manage this patient? Shall we give ATT alone or ATT and ART? If both than what modifications in ART? 6/22/2015 Ketan Shah IAP surat 74
Considerations for the choice of first-line ARV regimens in children receiving rifampicin containing TB treatment The co-management of TB and HIV, and the treatment of HIV infection, is complicated by drug interactions, particularly rifampicin and the NNRTI and PI These drugs have similar routes of metabolism and coadministration results in subtherapeutic antiretroviral drug levels 6/22/2015 Ketan Shah IAP surat 75
HIV TB co-infection In HIV-infected children with TB disease, the initiation of TB treatment is the priority. Optimal timing for the initiation of ART during TB treatment is not known Decision on when to start ART after starting TB treatment is balance of following child s age pill burden potential drug interactions overlapping toxicities and possible immune reconstitution syndrome versus the risk of further progression of immune suppression with its associated increase in mortality and morbidity. 6/22/2015 Ketan Shah IAP surat 76
Clues to Tbc Red elevated nodular lesion on shin border??? Erythema nodosa 6/22/2015 Ketan Shah IAP surat 77
Red eye with phlycten.phlyctencular conjunctivitis 6/22/2015 Ketan Shah IAP surat 78
Sorry to confuse u. 6/22/2015 Ketan Shah IAP surat 79