MANAGEMENT OF MANAGEMENT OF TUBERCULOSISTUBERCULOSIS

IN IN SPECIAL SITUATIONSSPECIAL SITUATIONS

Dr. Aswini Kumar MohapatraDr. Aswini Kumar MohapatraProfessor & headProfessor & head

SPECIAL SITUATIONSSPECIAL SITUATIONS

1.1. TB in Renal failureTB in Renal failure

2.2. TB in Liver disordersTB in Liver disorders

3.3. TB with HIV infectionTB with HIV infection

4.4. TB in Pregnancy and LactationTB in Pregnancy and Lactation

5. CNS tuberculosis 5. CNS tuberculosis

Hospitalization is essential for patients with Hospitalization is essential for patients with

Haemoptysis & Pneumothorax.Haemoptysis & Pneumothorax.

TB IN RENAL FAILURETB IN RENAL FAILURE

Principles of chemotherapyPrinciples of chemotherapy::

1) Principles of antituberculosis treatment during 1) Principles of antituberculosis treatment during dialysis and following renal transplantation dialysis and following renal transplantation remains similar to that in other patients with remains similar to that in other patients with tuberculosis.tuberculosis.

2) Choice of safe and effective antituberculosis 2) Choice of safe and effective antituberculosis treatment for these patients depends upon the treatment for these patients depends upon the pharmacology of drugs in the setting of renal pharmacology of drugs in the setting of renal failure and during maintenance haemodialysis failure and during maintenance haemodialysis and their interaction with immunosuppressive and their interaction with immunosuppressive drugs used in patients with renal transplantation.drugs used in patients with renal transplantation.

3) 3) H,R,Z are all safe for useH,R,Z are all safe for use

4) In severe renal failure pyridoxine should 4) In severe renal failure pyridoxine should be added to Hbe added to H

5) S and E are given in reduced doses 5) S and E are given in reduced doses

6) Nearly 80% of the doses of streptomycin and 6) Nearly 80% of the doses of streptomycin and ethambutol excreted unchanged in the urine.ethambutol excreted unchanged in the urine.

Amino glycosides are excreted by glomerular Amino glycosides are excreted by glomerular filtration and not by active secretion.filtration and not by active secretion.

It is preferable to give streptomycin twice or It is preferable to give streptomycin twice or thrice weekly without decreasing the usual dose thrice weekly without decreasing the usual dose – load on kidney is minimized. – load on kidney is minimized.

Recommended dose of ethambutol – 5-10 Recommended dose of ethambutol – 5-10 mg/kg/day. mg/kg/day.

7) 7) TB with renal failure – along with H, R, Z TB with renal failure – along with H, R, Z fourth drug streptomycin is preferable fourth drug streptomycin is preferable in comparison to Ethambutol as it can in comparison to Ethambutol as it can result in blindness. result in blindness.

8) 8) Safest RegimenSafest Regimen – 2 HRZ / 4 HR – 2 HRZ / 4 HR

TB IN LIVER DISORDERSTB IN LIVER DISORDERS

H, R, Z are all hepatotoxic drugs.H, R, Z are all hepatotoxic drugs.

Z should be avoided.Z should be avoided.

H,R plus S or E may be used for a total period H,R plus S or E may be used for a total period

of 6 months.of 6 months.

2 SHRE / 6 HR or 9 RE 2 SHRE / 6 HR or 9 RE

or 2 SHE / 10 HEor 2 SHE / 10 HE

Acute hepatitis :Acute hepatitis :

SE for 3 months is the safest option SE for 3 months is the safest option

followed by 6 HR if hepatitis is resolved or followed by 6 HR if hepatitis is resolved or

if not 12 SE.if not 12 SE.

TB WITH HIV INFECTIONTB WITH HIV INFECTION

HIV fuels the TB epidemic by promoting HIV fuels the TB epidemic by promoting progression of recent and latent M. tuberculosis progression of recent and latent M. tuberculosis infection to active TB disease.infection to active TB disease.

HIV also increases the rate of recurrent TB.HIV also increases the rate of recurrent TB.

As HIV infection progresses, CDAs HIV infection progresses, CD44 lymphocytes lymphocytes decline in number and function. The immune decline in number and function. The immune system is less able to prevent the growth and system is less able to prevent the growth and local spread of M. tuberculosis. local spread of M. tuberculosis.

Disseminated and extra pulmonary Disseminated and extra pulmonary disease is more common.disease is more common.

Two formsTwo forms : :

a)a) Adult pulmonary TBAdult pulmonary TB

b)b) Adult extra pulmonary TBAdult extra pulmonary TB

a. a. Adult pulmonary TBAdult pulmonary TB::

In HIV infected patients, pulmonary TB is still the In HIV infected patients, pulmonary TB is still the commonest form of TB. commonest form of TB.

Presentations:Presentations:

Features of pulmonary TBFeatures of pulmonary TBStage of HIV infectionStage of HIV infection

EarlyEarly LateLate

1. Clinical picture1. Clinical picture Often resemblesOften resembles

Post-primary TBPost-primary TB

Often resemblesOften resembles

Primary TBPrimary TB

2. Sputum smear 2. Sputum smear

resultresult

OftenOften

PositivePositive

OftenOften

Negative Negative

3. Chest x-ray 3. Chest x-ray

appearanceappearance

Often cavitatesOften cavitates

(may be normal)(may be normal)

Often infiltrates Often infiltrates with no cavities with no cavities (may be normal)(may be normal)

b. b. Adult Extra pulmonary TBAdult Extra pulmonary TB::

Comment forms of adult EPTB are pleural effusion, Comment forms of adult EPTB are pleural effusion,

lymphadenopathy, pericardial and meningeal lymphadenopathy, pericardial and meningeal

disease, haematogenous (disseminated / miliary)disease, haematogenous (disseminated / miliary)

TB treatment and antiretroviral therapyTB treatment and antiretroviral therapy

Highly active antiretroviral therapy (HAART) is not a Highly active antiretroviral therapy (HAART) is not a

cure for HIV infection but is associated with dramatic cure for HIV infection but is associated with dramatic

reductions in morbidity and mortality in HIV infected reductions in morbidity and mortality in HIV infected

patients. patients.

HAARTHAART

a) Reverse transcriptase inhibitors (RTI)a) Reverse transcriptase inhibitors (RTI)

NRTsNRTs NNRTIs NNRTIs(Nucleoside)(Nucleoside) (non-nucleoside)(non-nucleoside)

ZidovudineZidovudine Nevirapine NevirapineDidanosineDidanosine Efavirenz EfavirenzStavudineStavudineLamivudineLamivudine

b) Protease inhibitors-b) Protease inhibitors-indinavirindinavirsaquinavirsaquinavirritonavirritonavir

Principles of chemotherapyPrinciples of chemotherapy (TB with (TB with HIV)HIV)

1)1) Defer antiretroviral therapy until TB treatment is Defer antiretroviral therapy until TB treatment is completed.completed.

2) Defer antiretroviral therapy until the end of the 2) Defer antiretroviral therapy until the end of the initial phase of treatment and use ethambutol initial phase of treatment and use ethambutol and isoniazid in the continuation phase.and isoniazid in the continuation phase.

3) Treat TB with a rifampicin containing 3) Treat TB with a rifampicin containing regimen and use efavirenz + 2 regimen and use efavirenz + 2 NRTIs.NRTIs.

4) Treat TB with rifampicin containing 4) Treat TB with rifampicin containing regimen and use 2 NRTIs and then regimen and use 2 NRTIs and then change to a maximally suppressive change to a maximally suppressive HAART regimen on completion of TB HAART regimen on completion of TB treatment.treatment.

Drug interactions (ATT/HAART)Drug interactions (ATT/HAART)::

Rifampicin stimulates the activity of Rifampicin stimulates the activity of cytochrome P450 enzyme system that cytochrome P450 enzyme system that metabolizes Pis and NNRTIs –reduction metabolizes Pis and NNRTIs –reduction in blood levels of Pis, NNRTIs.in blood levels of Pis, NNRTIs.

Pis and NNRTIs – enhance or inhibit Pis and NNRTIs – enhance or inhibit same enzyme system -altered blood same enzyme system -altered blood levels of rifampicin. levels of rifampicin.

TB IN PREGNANCY & LACTATIONTB IN PREGNANCY & LACTATION

Pregnant woman with tuberculosis should be Pregnant woman with tuberculosis should be treated without delay when diagnosed.treated without delay when diagnosed.

Untreated tuberculosis represents a far greater Untreated tuberculosis represents a far greater hazard to a pregnant woman and her fetus than hazard to a pregnant woman and her fetus than does the treatment for the disease. does the treatment for the disease.

All first line antituberculosis drugs All first line antituberculosis drugs cross placenta. None of these drugs cross placenta. None of these drugs cause teratogenic effect to the fetus cause teratogenic effect to the fetus with the exception of streptomycin.with the exception of streptomycin.

Streptomycin causes ototoxicity and Streptomycin causes ototoxicity and contraindicated in pregnant womencontraindicated in pregnant women. . Streptomycin induced ototoxicity has been Streptomycin induced ototoxicity has been reported irrespective of period of reported irrespective of period of gestation.gestation.

Safety of second line ATT:Safety of second line ATT:

Limited data available regarding Limited data available regarding

teratogenicity of 2teratogenicity of 2ndnd line ATT during line ATT during

pregnancy.pregnancy.

Kanamycin and Capreomycin avoided Kanamycin and Capreomycin avoided

because of Ototoxicity.because of Ototoxicity.

Teratogenic effect has been attributed to the Teratogenic effect has been attributed to the

use of ethionamide. use of ethionamide.

Treatment during lactationTreatment during lactation::

Tuberculosis treatment in lactating mothers Tuberculosis treatment in lactating mothers is safe as the amount of drug ingested by is safe as the amount of drug ingested by the nursing infant is minimal. So breast the nursing infant is minimal. So breast feeding is encouraged in lactating mothers feeding is encouraged in lactating mothers receiving ATT.receiving ATT.

Special situationsSpecial situations::

If the mother at the time of delivery is If the mother at the time of delivery is smear positive, the newborn should be smear positive, the newborn should be separated from the mother at least for a separated from the mother at least for a period of 2 weeks.period of 2 weeks.

Breast feeding is best avoided during this Breast feeding is best avoided during this

two weeks and expressed milk should be two weeks and expressed milk should be given to the child. given to the child.

BCG should be given as scheduled and BCG should be given as scheduled and INH prophylaxis should be given for 6 INH prophylaxis should be given for 6 months followed by Mantaux test at the months followed by Mantaux test at the end of 6 months. end of 6 months.

In the event of absence of scar, BCG In the event of absence of scar, BCG vaccination should be repeated. vaccination should be repeated.

When there is doubt about the presence When there is doubt about the presence of active tuberculosis, the child should be of active tuberculosis, the child should be treated. treated.

CNS TUBERCULOSIS

• Treatment is difficult and challenging.

• Depends on identification of drugs that reliably penetrate CSF and brain parenchyma.

• INH- small, non protein bound molecule and penetrates blood brain barrier whether or not the meninges are inflamed.

• Z- good penetration like – INH.

• Drug of choice for CNS tuberculosis – H & Z

• Duration of treatment –

TB- meningitis –

Stage I, II – 9-12 months

Stage – III – 12-18 months

Tuberculoma – 18-24 months

TUBERCULIN SKIN TESTTUBERCULIN SKIN TEST

TUBERCULIN-TUBERCULIN-

Purified protein derivative derived from tubercle Purified protein derivative derived from tubercle bacillibacilli

Also called- Purified Protein Derivative (PPD)Also called- Purified Protein Derivative (PPD)

Injected to an infected personInjected to an infected person→ → hypersensitivity to hypersensitivity to tuberculintuberculin→→ local reaction within 24-48 hrs. local reaction within 24-48 hrs. →→ skin indurationsskin indurations

This reaction indicates hypersensitivityThis reaction indicates hypersensitivity

A positive tuberculin test does not A positive tuberculin test does not measure immunity. By itself it does not measure immunity. By itself it does not indicate the presence or extent of indicate the presence or extent of tuberculosis disease-only it indicates tuberculosis disease-only it indicates infectioninfection

indurationsindurations

Positive tuberculin test Positive tuberculin test > 10 mm> 10 mm

Negative tuberculin test < 10 mmNegative tuberculin test < 10 mm

Conditions suppressing skin testConditions suppressing skin test--

HIVHIV

malnutritionmalnutrition

severe bacterial infectionssevere bacterial infections

viral infections-measles, chicken poxviral infections-measles, chicken pox

cancercancer

immunosuppressive drugsimmunosuppressive drugs

Value of positive tuberculin testValue of positive tuberculin test-- Reaction of tuberculin positive after BCG Reaction of tuberculin positive after BCG

vaccination-vaccination-

A child- A child- NOT BCGNOT BCG - test positive - test positive →→ skin skin indurations 10 mmindurations 10 mm

A child- A child- BCGBCG- test positive - test positive →→ skin indurations 15 skin indurations 15 mm or moremm or more

A positive tuberculin test is only one piece of A positive tuberculin test is only one piece of evidence in favour of diagnosis of evidence in favour of diagnosis of tuberculosistuberculosis

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