Chinmoy tb presentation
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Treatment Guidelines of Childhood Tuberculosis and
RNTCP
Presenter: Dr. Chinmoy Lath
1st June’12
Aims of Therapy in Tuberculosis
The main objectives of anti-TB treatment are to:• Cure the patient of TB (by rapidly eliminating most of the
bacilli).• Prevent death from active TB or its late effects.• Prevent relapse of TB (by eliminating the dormant bacilli).• Prevent the development of drug resistance (by using
combination of drugs).• Decrease TB transmission to others.
Evolution in Treatment of TBClassical (long course) chemotherapy regimen :
• 18 months duration daily regimens• Used INH with one or two bacteriostatic drugs• High failure and relapse rate• Poor compliance
Short course chemotherapy regimen
• Combination of 3-4 drugs used in intensive phase (2 mths)• Drugs give either daily / intermittently• Minimum duration of treatment – 6 months• Drugs – preferably given together and as single dose
Advantages• Faster, powerful bactericidal and sterilizing action• Patient exposed to toxic drugs for shorter duration• Less expensive• Reduction in emergence of drug resistant bacilli• Good tolerance and adherence
Results of six month treatment regimen for TB
Author, country & year
Diagnostic Criteria
No. of children
Regimen Results
Al Dossary et al, USA, 2002
Clinical and radiological
175 2 weeks daily HRZ f/b 6 wks HRZ2 / 4RH2
81% t/t completion 1 relapse
Te Water Naude et al, S. Africa, 2000
Clinical & radiological
89117
2 RHZ2/4RH26RHZ
t/t outcome & adherence equivalent 1 relapse
Varudkar, India, 1985
Clinical & radiological
1004045
2 HRE/4HE2 HZE/4HE6 HRE3
0 failures,0 relapses
Kumar et al, India, 1990
Clinical & bacteriological
3739
2 HRZ / 4HR29 HR
2 deaths not related to TB 0 relapse
Ramachandran et al, India, 1998
Clinical & bacteriological
6869
2 HRZ3 / 4RH23 (2%) died, 0 failures, 3 relapses
TRC studies on extrapulmonary TBStudies Rx regimen Duration
(mon)No. of pts
Follow-up period (months)
Overall favourable response
%
TB spine 6 HR7 + modified HongKong Surgery
6 78 120 90
6HR76 78 120 94
TBM 2 HRS7/ 4HE7S2 / 6HE7
12 69 24 33
2R2 HZS7/ 10HE7 12 70 24 36
Pott’s paraplegia
2SHER7 / 7HR2 9 11 60 73
Abd TB 2HRZ7/4HR76 85 60 94
Brain tubeculoma
3HRZ7 / 6HR2 9 47 24 89
• Tuberculosis Research Centre (TRC) studies have clearly established efficacy of short course treatment.
• Intermittent regimens proven as effective as daily regimen
• Overall favourable response varied from 87-99% except in TBM (33%) and Pott’s spine (73%)
• In TBM, outcome is related to stage of disease at the start of treatment and duration of symptoms prior to admission
• Similarly in Pott’s spine recovery influenced by factors like initially motor power, presence or absence of bed sores and duration of kyphosis
• Therefore early diagnosis and treatment is recommended for these two conditions
Management of pediatric TB under RNTCP –
Diagnosis
Suspected cases of pulmonary TB include• Fever and/or cough > 2 wks• Weight loss or failure to thrive• H/o contact with suspected / diagnosed case of active TB in
last 2 yrs• Suspect TBM in child with neurological symptoms,
irritability, refusal to feed, headache, vomiting, altered sensorium
Bacteriological testing• Sputum examination whenever possible• Gastric lavage if sputum not available (yield is 20%)• Multiple samples to be takenTuberculin Test• Mantoux test using 1 TU PPD RT 23 Tween 80• +ve test >10 mm induration at 48-72 hrsRadiology• CXR – suggestive findings mediastinal / hilar lymphadenitis
with / without parenchymal lesions, pleural effusion, miliary and fibro-caseous pictures
• Persistent pneumonia >4 wks inspite of antibiotic therapy
PCR• Low sensitivity for gastric aspirates• Routine use not recommended• May be useful in neuro TB• Sensitivity ranges from 4-80% & specificity 80-100%Serology• Low sensitivity, specificity and positive predictive value
RNTCP diagnostic algorithm for pediatric pulmonary TB
Standard Case Definitions
New case• Pt. who never had treatment for TB / or taken ATT <4 wksRelapse• Pt. declared cured of TB in past after one full course of
ATT, and has become sputum smear +veTreatment failure• A pt. who while on treatment remained or become again
smear positive 5 months or more after starting therapy• A pt. initially smear negative become sputum +ve after 2nd
month of therapy
Treatment after interruption
• Patient who interrupts t/t for 2 months or more, and return with smear +ve
Chronic case
• Patient who remained or become smear +ve after completing fully supervised re-treatment regimen
Smear positive pulmonary TB
• One or more initial sputum smear +ve for AFB
Smear negative pulmonary TB
• At least 2 sputum specimen –ve for AFB• Radiological abnormality consistent with active pulm TB• No response to a coarse of broad spectrum antibiotics• Decision by clinician to treat with full course of ATT
Treatment OutcomesCure• Initially sputum smear-positive patient who
• has completed treatment and• had negative sputum smears on two occasions, one of
which was at the end of the treatment.Treatment completed• Pt. who has completed t/t without proof of cure.Treatment failure• Pt. who remaining or becomes again smear +ve at 5
month / later during t/tTransfer out• Pt. transferred to other reporting unit
Treatment RegimenTreatment category
Type of patients TB treatment regimens
Intensive phase
Continuation phase
Category I New sputum smear-positive PTB Seriously ill sputum smear-negative PTB Seriously ill extrapulmonary tuberculosis
(EPTB)
2H3R3Z3E3 4H3R3
Category II Sputum smear-positive relapse, Sputum smear-positive treatment failure, Sputum smear-positive treatment after
default
2S3H3R3Z3E3/ 1H3R3Z3E3
5H3R3E3
Category III Sputum smear-negative and EPTB not serious ill
2H3R3Z3 4H3R3
New RNTCP Classification
Category I &
III
Category II
• Seriously ill sputum smear negative pulm. TB: all forms of PTB other than primary complex
• Seriously ill EPTB: TBM, disseminated miliary TB, TB pericarditis, TB peritonitis and intestinal TB, B/L or extensive pleurisy, spinal TB with or without neurological complications, genitourinary tract TB, bone & joint TB
• Not seriously ill EPTB: lymph node TB and U/L pleural effusion
• In pts with TBM on category I treatment, 4 drug use during intensive phase should be HRZS instead of HRZE. Continuation phase to be given for 7 months. Total duration of treatment 9 months
• Steroids to be used initially in hospitalized cases of TBM and TB pericarditis for 6-8 weeks.
Suggested pediatric dosages for intermittent therapy
Drug Dosage (mg/kg)
Weight range in kg
6-10 11-17 18-25 26-30
Isoniazid 10 75 150 225 300
Rifampicin 10 75 150 225 300
Pyrazinamide 30-35 250 500 750 1250
Ethambutol 30 200 400 600 1000
Streptomycin 15
• During intensive phase, patient swallows drug under supervision of Health worker 3 times a week
• In continuation phase, pt is issued medicine for 1 wk in multiblister combipack of which 1st dose swallowed in presence of health worker
Chemoprophylaxis• Asymptomatic children <6 yrs exposed to infectious TB
should be given 6 month of INH (5 mg/kg daily)Monitoring & evaluation• Sputum examined after 2 month of intensive phase in
Category I, after 3 months in Category II, if +ve IP given for 1 more month.
Lacunae in RNTCP
• Children can’t appreciate symptoms / bring out sputums difficulty in diagnosis
• CXR – intra and interreader variations, not available at primary health centres
• Tubeculin test, gastric lavage and FNAC – limited to hospitals, not available in primary health centres
• Problem in direct observation of t/t – non-availability of child due to clash with school timing, non-availability of parents due to work
• Social stigma, especially for female pts
Consensus Statement
Recommendations of IAP, 2010
Diagnostic algorithm for tubercular lymphadenitis
Recommended doses of antitubercular drugs
• All drugs to be given empty stomach single dose• Vit B6 – not needed in children taking INH• Daily treatment regimen is advised• Fixed dose combination of INH and rifampicin acceptable• Use pyrazinamide separately
Prednisolone
Indications• Tubercular meningitis.• Tubercular pericarditis.• Mediastinal compression syndrome due to Tuberculosis.• Endobronchial tuberculosis.• Pleurisy with severe dystress.• Milliary disease with alveolocapillary block.• Dose:2-4 mg/kg/day for 2-4 wks then tapper over 2 weeks.
Microbiological Basis of TreatmentTypes of bacterial population• Group I – metabolically active continuously growing bacilli
in neutral pH present extracellularly, killed by INH f/b rifampicin and streptomycin
• Group II – intermittent multiplying organisms (semidormant) in hypoxic environment of cacious material killed by rifampicin
• Group III – intracellular bacilli in acidic pH killed by pyrazinamide
• Group IV – drug resistant mutants, acted upon by rifampicin and INH
Pharmacological principles• Drugs are divided in three categories
1. Early bactericidal activity – ability to kill bacilli in first few days of t/t, max. in INH f/b Etham. and Rifampicin2. Sterilizing activity – ability to eradicate persisters - intracellular bacilli, seen with Rifampicin & Pyz3. Prevention of drug resistance to companion drug, seen
in INH and Rifampicin
CLASSIFICATION OF
ANTITUBERCULAR DRUGS
Tuberculocidal Tuberculostatic
Isoniazid, Rifampicin Streptomycin, AmikacinPyrazinamideCapreomycin, Quinolones, Rifamycin
Ethambutol (except in inflamed meninges)Thiacetazone, EthionamidePara-aminosalicyclic acidCycloserine
TRADITIONAL CLASSIFICATIONFIRST LINE DRUGS:
INH (H)
RIFAMPICIN (R) PYRAZINAMIDE (Z)ETHAMBUTOL (E)STREPTOMYCIN (S)
SECOND LINE DRUGS:
AMIKACIN, KANAMYCIN
FLUOROQUINOLONESPAS, CYCLOSERINE
RECENT WHO CLASSIFICATION
GROUP 1 (FIRST LINE ORAL AGENTS)– INH
GROUP 2 (INJECTABLE AGENTS)– KANAMYCIN
GROUP 3 (FLUOROQUINOLONES)– LEVOFLOXACIN
GROUP 4 (ORAL BACTERIOSTATIC AGENTS)– ETHIONAMIDE
GROUP 5 (AGENTS WITH UNCLEAR EFFICACY)– LINAZOLID, AMX-CLV
ANTI-TB DRUGS USED IN RNTCP
FIRST LINE DRUGS:INH (H)RIFAMPICIN (R) PYRAZINAMIDE (Z)ETHAMBUTOL (E)STREPTOMYCIN (S)
SECOND LINE DRUGS: AMIKACIN, KANAMYCIN,FLUOROQUINOLONES,CAPREOMYCIN, ETHIONAMIDEPAS, CYCLOSERINE, etc…
Adverse effects of ATT drugs
Drug Adverse effects
Isoniazid Hepatotoxicity, peripheral neuritis, hypersensitive reactions may precipitate epilepsy, drug induced lupus, psychotic changes
Rifampicin Hepatotoxicity, gastrointestinal, autoimmune reactions (more with intermittent administration), which include flu syndrome, thrombocytopenias, purpura, respiratory shock syndrome, acute hemolytic anemia, ARF)
Pyrazinamide Hepatotoxicity, arthralgia, hyperuricemia, gastrointestinal, allergic reactions
Ethambutol Optic neuritis, colour blindness, gastrointestinal, allergic reactions, hyperuricemia
Streptomycin Vestibular dysfunction, deafness, nephrotoxicity, neuromuscular blockade, peripheral neuritis
Adverse effects of ATT drugs (contd…)
Drug Adverse effects
Thioacetazone Exfoliative dermatitis, Steven Johnson syndromeQuinolones GI symptoms, CNS, phototoxicity, tendinopathy &
tendinitis, nephrotoxicity, skin rashEthionamide GI symptoms, psychiatric (hallucination & depression),
hepatitis, hypothyroidism, GynaecomastiaCycloserine CNS (convulsions), psychiatric (depression, suicidal
tendency)PAS GI symptoms, hepatic dysfunction, hypokalemia,
hypothyroidism
Second-line anti-TB drugs for t/t of MDR-TB in children
Drug Mode of action Recommended daily doseRange (mg/kg bw) Max
(mg)Ethionamide or prothionamide
Bacteriostatic 15-20 1000
Fluoroquinolones
Ofloxacin Bactericidal 15-20 800 Levofloxacin Bactericidal 7.5-10 - Moxifloxacin Bactericidal 7.5-10 - Gatifloxacin Bactericidal 7.5-10 - Ciprofloxacin Bactericidal 20-30 1500Aminoglycosides
Kanamycin Bactericidal 15-30 1000 Amikacin Bactericidal 15-22.5 1000 Capreomycin Bactericidal 15-30 1000Cycloserine terizidone Bacteriostatic 10-20 1000
Contraindications for anti TB drugs
Isoniazid
• Known hypersensitivity to isoniazid• Active hepatic disease
Rifampicin
• Hypersensitivity to rifampicin• Hepatic dysfunction
Pyrazinamide
• Known hypersensitivity to pyrazinamide
• Severe hepatic impairment• Gout
Streptomycin
• Hypersensitivity• Auditory nerve impairment• Myasthenia gravis• Pregnancy
Ethambutol
• Hypersensitivity• Preexisting optic neuritis• Pts with creatinine clearance
of <50 ml/min
Important side effects with clinical implications
Hepatotoxicity
• Hepatotoxicity drugs include INH, rifampicin, PYZ
• Chances if higher doses / combination are used
• Children with severe disease like TBM, miliary TB are at greater risk
• Children with preexisting liver dysfunction and malnutrition more predisposed
• Routine lab monitoring needed in high risk cases
Hepatotoxicity (clinically evident jaundice / ALT >5 times normal)
Stop IHN, Rifamp & Pyz, start Etham & Strepto
Repeat AST, ALT If they stay as normal / or show a declining trend
Rifamp 10. mg/kg/day + add INH 2.5 mg/kg/d (repeat LFT)
PZA (30 mg/kg/d)+ INH (5 mg/kg/d)
(7 days)
Ocular toxicity• Seen in 5%, if doses of Ethambutol b/w 25-50 mg/kg/d.• Rare in dose of 15 mg/kg/day.• Result in reversible optic neuritis, blurred vision, scotoma,
colour blindness.• Literature review suggests it is safe in children at a dose of
15-25 mg/kg/day.Peripheral neuritis• Clinically manifest peripheral neuritis is rare in children.• Manifest and pins and needle sensation in hands and feet.• More common in malnourished children, HIV +ve,
breastfeeding infants.• Supplemental pyridoxine 5-10 mg/kg/day is recommended
in the predisposed population.
Role of Surgery in TBPulmonary TB
Indications
• Major airway obstruction due to– Extraluminal LN compression – nodal curettage– Intraluminal granulation tissue - bronchoscopy
• Post-TB pulmonary destruction – lung resection• Late pleural fibrosis – decortication• Release of post-tubercular constrictive pericarditis• Drainage of active TB lung abscess
Neuro TB
Indications• Failure of medical management• TB with hydrocephalus and uncontrolled raised ICT• Cerebral abscess• Tuberculoma – for diagnosis of difficulty cases / features of
SOL• Tubercular spinal arachnoiditis compressing cord
Early VP shunts for mild to mod. Hydrocephalus, morbidity & mortality, no effect on stage III pts prognosis
Abdominal TB
Indications• Diagnostic in case of peritoneal abd. TB• Exploratory laparotomy in acute abdomen• Management of complications like stricture, adhesion,
fistula, bleedingPeritoneal
Wet / Ascitic Dry / Sclerosing
Laparoscopy and biopsy Open biopsy
Intestinal
Ulcers MassStricture Perforation
Local resection
Local resection (ileoceocotomy)
Minimal narrowing
Local resection /
enterostomy (rarely)
Significant narrowing
Multiple or very long stricture
ATT Stricturoplasty Local resection
Genitourinary TB
For complications like• Ureteral stricture, abscesses and non-functioning kidneysRadical procedures• Nephrectomy• Partial nephrectomy• EpididymectomyReconstructive procedures• Strictures
– For PUJ obstruction: Pyeloplasy, percutaneous nephrostomy– Ureteric strictures: Double J stenting, resection anastomosis– Vesicoureteric junction obstruction: ureteric reimplantation
Potts spine
Indications for surgery• Paraplegia despite conservative treatment• Sudden acute paraplegia• Paraplegia accompanied by uncontrolled spasticity• Paraplegia in flexion• Flaccid paraplegia• Surgical procedure – anterolateral decompression
MDR-TB
An MDR TB SUSPECT Whose SPUTUM Is CULTURE POSITIVE for M.Tb that are invitro resistant to Isoniazide AND rifampicin with or without resistant to other drugs from an RNTCP accredited laboratory.
Treatment of Multi-Drug Resistant TB• Prevalence of primary MDR in India – <3%
• Prevalence of MDR TB among treated cases – 12-17%(Paramsivan et al, IJMR 2004; 277-86)
Initial drug resistance
• INH – 20-30%, Streptomycin <10%, Rifampicin – 2-3%
Acquired drug resistance
• INH – 50-60%, Rifampicin – 20-30%, Streptomycin – 15-30%(Amdekar YK. Indian Pediatr 1998; 35: 715-18)
Drug-resistant TB should be suspected if any of the features are present
• Features in the source case suggestive of drug-restating TB– Contact with a known case of drug-resistant TB– Remains sputum smear-negative after 3 months of t/t– H/o previously treated TB– H/o treatment interruption
• Features of child suspected of having drug-resistant TB– Contact with a known case of drug-resistant TB– Not responding to the anti-TB treatment regimen– Recurrence of TB after adherence to treatment
Types of resistance
Natural resistance
• Species specific resistance to drug without strain being ever exposed to it
Primary resistance
• Pt infected with drug-resistant population without having received prior treatment
Secondary (acquired) drug resistance
• Pt harbous organisms which were previously drug susceptible but resistance developed during course of t/t
Alternative method of grouping ATT drugsGrouping Drugs (abbreviation)
Group 1: First line oral Anti TB agents
Isoniazid (H); Rifampicin (R); Ethambutol (E); Pyrazinamide (Z)
Group 2: Injectable Anti TB agents
Streptomycin (S); Kanamycin (Km); Amikacin (Am); Capreomycin (Cm); Viomycin (Vi)
Group 3: Fluoroquinolones Ciprofloxacin (Cfx); Ofloxacin (Ofx); Levofloxacin (Lfx); Moxifloxacin (Mfx); Gatifloxacin (Gfx)
Group 4: Oral bacteriostatic second-line anti TB agents
Ethionamide (Eto); Protionamide (Pto); Cycloserine (Cs); Terizidone (Trd); p-aminosalicylic acid (PAS); Thioacetazone (Th)
Group 5 – Anti TB agents with unclear efficacy (not recommended by WHO for routine use in MDR-TB pts)
Clofazimine (Cfz); Amoxicillin / Clavulanate (Amx / Clv); Clarithromycin (Clr); Linezolid (Lzd)
Principles of Treatment• Never add one drug to a failing regimen.• Treat child according to the drug susceptibility pattern and
using t/t history of source case strain if isolate from child is not available
• Use at least 4 drugs with certain effectivity• Use daily treatment, directly observed• Use bactericidal drugs as far as possible• Use all oral 1st line drug to which isolate is sensitive• An injectable agent is used for minimum of 6 months after
culture conversion
Principles of Treatment contd..
• Oral quinolone used for entire duration of therapy • t/t to be given for at least 18 months after cultures are –ve• Drug dosing to be determined by body weight• Counsel caregiver regarding adverse events & compliance• Follow-up is essential – clinical, radiological and
bacteriological• Monitor LFT, KFT, hearing periodically
Concept of DOTS plusIndividualized treatment regimen • Regimen designed as per resistance pattern of strain
infecting pt.• Heavily dependent on drug sensitivity testing• Unlikely to fail• Less applicable in resource poor countriesStandardized regimen• Based on common resistance pattern identified in a given
population• Low cost, simpler implementation, less dependent on
laboratories
Management of MDR TB under RNTCP• RNTCP will be using a Standardized Treatment regimen
RNTCP CATEGORY IV REGIMEN: 6 (9) Km Lvx Eto Cs Z E / 18 Lvx Eto Cs E
• Minimum recommendation is that intensive phase to be given for 6 months
• After 6 months – continuation phase started if 4th month culture are negative
• If 4th month culture is still awaited after 6 months of t/t, IP is extended
• After maximum of 9 months CP started for 18 months
MDR patient referred to state level DOTS plus site with DTS result
DOTS plus site decides on whom to start Rx
Pt admitted at DOTS plus site for 1 monthDischarged with 1 wk drug supply
Given treatment at a facility near to home
Indications for Surgery in MDR-TB• As adjuvant may improve results of chemotherapy in
selected cases• Ideally operate early in therapy, b/w 6-9 month• After surgery continue therapy for 18 months• If disease is resectable, surgery considered in following
– Absence of response despite 6-9 mon of t/t– High risk of failure or relapse due to high degree of resistance– Morbid complications e.g. haemoptysis, bronchiectasis,
bronchopleural fistula– Recurrence of positive smear or culture during t/t– Relapse after completion of anti-TB treatment
MDR TB in special situations
MDR-TB in pts with renal failure
• Drugs requiring dose or interval adjustment in renal failure are – ethambutol, quinolones, aminoglycosides, cycloserine, PAS, ethionamide
• Monitor blood urea, nitrogen and creatinine frequently
• In mild renal failure – dose of aminoglycoside reduced
• In severe renal failure – aminoglycosides are discontinued
Drug Method of modi-
fication
GFR (ml/min)
>50 10-50 <10
Kanamycin D, I 7.5-15 mg/kg/24 hr 4-7.5 mg/kg/24 hr 3 mg/kg/48 hr
Ethambutol I 20 mg/kg/24 hr 20 mg/kg/24-36 hr 20 mg/kg/48 hr
Pyrazinamide D 30 mg/kg/24 hr 30 mg/kg/24 hr 15-30 mg/kg/24 hr
Ofloxacin D 100% 50-75% 50%
Ethionamide D 100% 100% 50%
Cycloserine D 100% 50-100% 50%
PAS D 100% 50-75% 50D = dose adjustment; I = interval adjustment; *%age of recommended dose to be given
MDR-TB in pts with pre-existing liver disease• In category IV regimen, PYZ, PAS and ethionamide are
hepatotoxic• Most of the 2nd line drugs can be safely used in mild
impairment as they are less hepatotoxic than 1st line drugs• PYZ should be avoided in such patientsMDR-TB in pts with seizure disorders• If seizures are not under control, initiation of anti-seizure
drugs will be needed prior to start of MDR-TB therapy• Cycloserine, ethionamide, quinolone have been associated
with seizures, use carefully• Pyridoxine should be given with cycloserine to prevent
seizures
• Avoid cycloserine in pts with uncontrolled seizures• Anti-epileptic drugs may have interaction with cycloserine
and quinolones, monitoring of serum levels may be needed
MDR-TB in pts with psychosis
• High baseline incidence of depression and anxiety in pts with MDR-TB due to chronicity and socioeconomic factors
• Quinolones, ethionamide – associated with psychosis• Pyridoxine prophylaxis recommended• Cycloserine causes severe psychosis but not abs. C/I• If pt. on cycloserine develop psychosis, stop cycloserine
and start anti-psychotics• Resume cycloserine once pt is stabilized
XDR TB(extensively drug resistance TB)
• XDR TB is resistance to at least INH and rifampicin (i.e. MDR TB) + resistance to any fluoroquinolones and any one of the second line anti-TB injectable drugs (Am, Cm, Km)
• Worldwide noted in 41 countries till date• Isolated reports indicate existence of XDR TB in India, but it
is not possible to estimate its magnitude from present data• Effective treatment of MDR pts through DOTS plus can
prevent XDR TB generation• Extremely difficult to treat with poor outcomes
SUMMARY(RNTCP)
DIAGNOSIS OF PTB
• DURATION OF COUGH
3 WEEKS 2 WEEKS
–NUMBER OF SPUTUM SMEARS TO BE COLLECTED
3 SMEARS 2 SMEARS
–NUMBER OF + SMEARS REQUIRED FOR DX OF PTB+
2 SMEARS 1 SMEAR
• CATEGORY III HAS BEEN PHASED OUT
• NEW (DOTS)
• PREVIOUSLY TREATED (DOTS)
• CATEGORY IV FOR MDRTB
• CATEGORY V FOR XDRTB
SUMMARY(RNTCP)
TREATMENT OF PTB
Treatment of Congenital TBAs per IAP
• Continue breastfeeding
• BCG given at birth
• If CXR normal – 6 HR
• If CXR abnormal – 2 HRZ/7HR
• Congenital TB – 2 HRZ/7 HR
As per WHO – active pulm TB diagnosed after delivery
<2 months after >2 months afterTreat mother, breastfeed, INH x 6 m (5 mg/kg/d), BCG after stopping INH
Treat mother, breastfeed, INH x 6 m (5 mg/kg/d), if BCG not given at birth give after stopping INH
>2 month <2 month beforeSmear-ve just before delivery Smear +ve just before
deliveryTreat mother, breastfeed, INH x 6 m (5 mg/kg/d), BCG after stopping INH
Treat mother, breastfeed, no preventive CT, BCG at birth
Treat mother, breastfeed, INH x 6 m (5 mg/kg/d), BCG after stopping INH
As per WHO – active pulm TB diagnosed before delivery
As per RNTCPTreat mother
Continue breast feeding
Mother
Sputum +ve Sputum -ve
Chemotherapy to infant x 3 months
BCG given
No chemotherapyMTx at 3 months
+ve -ve
BCG givenBCG not given continue CT x 6 mths
As per National Neonatology Forum (NNF)If child has clinical features of perinatal TBStart ATT• 2 HRZ + 7 HR• May add streptomycin for first 2 months• HIV co-infection – 2 HRZS + 7 to 10 HR• Extra pulmonary TB – 2 HRZS + 7 to 10 HR• MDR TB – 12 to 18 HRZS or RHZEAdd steroids (prednisolone 1-2 mg/kg/d for 4-8 wks) if• Meningitis, neuro TB, miliary TB, TB involving serous
layers, endobronchial / segmental lesions, genitourinary TB, sinus formation
Breastfed infants / neonates on INH must be supplemented with B6
If the child is clinically normal but mother high riskMother Mx negative (induration <10 mm)
Symptomatic Asymptomatic
CXR abnormal CXR normal Presumed uninfected
Investigate & treat mother
No investigationsNo t/t
Investigate & treat mother, no t/t of baby
Screen baby
Normal
Abnormal
Chemoprophylaxis (6 HR)
T/t as perinatal TB
If the child is clinically normal but mother high riskMother Mx Positive (induration >10 mm)
Abnormal Normal
CXR
No active TB Active TB
Screen mother
Continue breastfeedFollow-up
T/t mother
Screen baby
Normal
Abnormal
Chemoprophylaxis (6 HR)
T/t as perinatal TB
Symptomatic Asymptomatic
Screen mother Breastfeed, no t/t
High risk mothers
• Old case of TB and on irregular t/t• Sputum +ve• Having signs and symptoms• Miliary TB or CXR• TBM
General instructions
• Continue breastfeeding• Give BCG at birth• Separation not needed• Follow-up both mother and child
Discontinue breastfeeding + separation
• Mother so sick to need admission• MDR TB suspected• Proven default• Sputum +ve mother not put on ATT
TB and HIV• 60% of PLHA develop TB• 16-18% of children with TB have HIV• Active TB is commonest OI among HIV infected individualsDiagnosis of TB in HIV infected children
3 or more of following• Chronic symptoms s/o TB• Physical signs s/o TB• CXR s/o TB• Positive Mx >5 mm induration
Problems in treatment• Potential for drug interactions, esp. b/w rifampicin and anti-
retroviral agents• Problems of drug toxicity and adverse effects• IRIS• Pill burden, adherenceKey therapeutic principles• Treatment of TB takes precedence over t/t of HIV infection• In pts already on HAART, continue same with modification
in both HAART and ATT• If pt. not receiving HAART, timing of initiation of ART
decided on basis of immune suppression and CD4 counts and type of TB
WHO recommends ART be given to• All pts with extrapulmonary TB (stage 4)• All those with pulm TB unless CD4 count >350 cells/mm3
• ART recurrence and fatality rates in TBClassification of HIV-associated immunodeficiency in
children
Classification of HIV-associated
immunodeficiency
Age-related CD4 values
11 months (%)
12-35 months (%)
35-59 months (%)
5 years (cells/mm3)
Not significant >35 >30 >25 >500
Mild 30-35 25-30 20-25 350-499
Advanced 25-30 20-25 15-20 200-349
Severe <25 <20 <15 <200
Initiation of first-line ART in relation to anti-TB therapy
WHO pediatric clinical stage
Timing of ART following start of anti-TB t/t
Recommended ART regimen
4 (extrapulm TB other than LN TB)
Start ART soon after anti-TB t/t (b/w 2 & 8 wks following start of anti-TB t/t)
In children aged <3 yrs • preferred: triple NRTI first line
regimen – d4T or AZT + 3 TC + ABC
• Alternative: standard first-line regimen – two NRTIs + NVP
In children aged 3 yrs • Preferred: triple NRTI first-line
regimen – two d4T or AZT + 3TC + ABC
• Alternative: standard firstline-line regimen – two NRTIs + EFV
3 (pulm TB and LN TB)
With clinical management alone•Start ART soon after start of anti-TB t/t (b/w 2-8 wks following start of ATT)•Consider delaying start of ART until anti-TB t/t is completed – if excellent clinical response to ATT in first 2-8 wks and child is stable
WHO pediatric clinical stage
Timing of ART following start of anti-TB t/t
Recommended ART regimen
3 (pulm TB and LN TB)
When CD4 values are available
• Severe immunodeficiency CD4 <200 – start ART b/w 2-8 wks as soon as ATT tolerated
• Advanced immunodeficiency (CD4 200-350) – start ART 8 wks after starting ATT
• Mild or no immunodeficiency (CD4 >350) – consider delaying start of ART until ATT completed
Regimens as recommended above
• EF V is not currently recommended for <3 yrs / <10 kg and not given to postpubertal adolescent girls who are sexually active and not using contraception
ART recommendations for pts who develop TB within 6 months of starting a first-line ART regimen
1st line or 2nd line ART regimen
ART regimen at the time of TB occurs
Management options
1st line ART (AZT or D4T) + 3TC + EFV Continue with two NRTIs + EFV(AZT or D4T) + 3TC + NVP Substitute NVP with EFV, or
Substitute with triple NRTI regimen
AZT + 3TC + TDF Continue with triple NRTI regimen
2nd line ART Two NRTIs + PI Substitute or continue with LPV/r – containing regimen and adjust the dose of RTV
Immune reconstitution inflammatory syndrome• Characterised by clinical deterioration after initial
improvement• Occurs in 1/3rd of pts on ATT who have started ART• Presents within 3 months of ART initiation• Fever, worsening of pre-existing LAP + resp disease• Most cases resolve without intervention• Serious reactions may require use of steroidsART failure• If TB occurs within 6 months of initiation of ART, it should
not be considered as failure of t/t• If episode occurs after 6 months of ART, with no other
clinical / immunological evidence of disease progression, it should not be considered ART failure
• Extrapulm TB should be considered ART failure
Drug interactions and toxicity
• Thiacetazone is contraindicated in HIV pts
• HIV pts more prone to develop INH induced peripheral neuritis therefore given pyridoxine supplementation
• Both ATT and NVP – cause hepatotoxicity close monitoring needed
• Rifampicin induces cyt p450 enzymes and reduces conc of PI by 80%, NVP level by 20-58%, EFV level by 25%
• PI resistant mutants of HIV may emerge if unboosted PIs are used with rifampicin
Chemoprophylaxis (6HR)
• All HIV pts with MTx >5 mm given prophylaxis
• Also in anergic pts exposed to active TB
BCG vaccination
• WHO recommends all asymptomatic HIV infected children should receive BCG except those with symptoms of AIDS related complex / AIDS. This is especially true for high TB prevalent countries like India
• BCG should not be given to HIV-infected children in low TB prevalence countries
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