Tuberculosis management in special situations involves consideration of factors like renal failure, liver disorders, HIV infection, pregnancy, and central nervous system involvement. For renal failure, H, R, and Z are generally safe to use, while S and E doses may need reduction. Z should be avoided for liver disorders. HIV fuels TB progression and anti-retroviral therapy should be deferred until completion of TB treatment. All first-line TB drugs are usually safe during pregnancy except streptomycin, and treatment is important for safety of both mother and child. CNS TB requires drugs with good brain penetration like H and Z for longer durations.

1. MANAGEMENT OFMANAGEMENT OF
TUBERCULOSISTUBERCULOSIS
ININ
SPECIAL SITUATIONSSPECIAL SITUATIONS
Dr. Aswini Kumar MohapatraDr. Aswini Kumar Mohapatra
Professor & headProfessor & head

2. 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 tuberculosis5. CNS tuberculosis
Hospitalization is essential for patients withHospitalization is essential for patients with
Haemoptysis & Pneumothorax.Haemoptysis & Pneumothorax.

3. TB IN RENAL FAILURETB IN RENAL FAILURE
Principles of chemotherapyPrinciples of chemotherapy::
1) Principles of antituberculosis treatment during1) Principles of antituberculosis treatment during
dialysis and following renal transplantationdialysis and following renal transplantation
remains similar to that in other patients withremains similar to that in other patients with
tuberculosis.tuberculosis.
2) Choice of safe and effective antituberculosis2) Choice of safe and effective antituberculosis
treatment for these patients depends upon thetreatment for these patients depends upon the
pharmacology of drugs in the setting of renalpharmacology of drugs in the setting of renal
failure and during maintenance haemodialysisfailure and during maintenance haemodialysis
and their interaction with immunosuppressiveand their interaction with immunosuppressive
drugs used in patients with renal transplantation.drugs used in patients with renal transplantation.

4. 3)3) H,R,Z are all safe for useH,R,Z are all safe for use
4) In severe renal failure pyridoxine should4) In severe renal failure pyridoxine should
be added to Hbe added to H
5) S and E are given in reduced doses5) S and E are given in reduced doses

5. 6) Nearly 80% of the doses of streptomycin and6) 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 glomerularAmino glycosides are excreted by glomerular
filtration and not by active secretion.filtration and not by active secretion.
 It is preferable to give streptomycin twice orIt is preferable to give streptomycin twice or
thrice weekly without decreasing the usual dosethrice weekly without decreasing the usual dose
– load on kidney is minimized.– load on kidney is minimized.
 Recommended dose of ethambutol – 5-10Recommended dose of ethambutol – 5-10
mg/kg/day.mg/kg/day.

6. 7)7) TB with renal failure – along with H, R, ZTB with renal failure – along with H, R, Z
→→ fourth drug streptomycin is preferablefourth drug streptomycin is preferable
in comparison to Ethambutol as it canin 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

7. 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 periodH,R plus S or E may be used for a total period
of 6 months.of 6 months.
2 SHRE / 6 HR or 9 RE2 SHRE / 6 HR or 9 RE
or 2 SHE / 10 HEor 2 SHE / 10 HE

8. Acute hepatitis :Acute hepatitis :
SE for 3 months is the safest optionSE for 3 months is the safest option
followed by 6 HR if hepatitis is resolved orfollowed by 6 HR if hepatitis is resolved or
if not 12 SE.if not 12 SE.

9. TB WITH HIV INFECTIONTB WITH HIV INFECTION
 HIV fuels the TB epidemic by promotingHIV fuels the TB epidemic by promoting
progression of recent and latent M. tuberculosisprogression 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 lymphocyteslymphocytes
decline in number and function. The immunedecline in number and function. The immune
system is less able to prevent the growth andsystem is less able to prevent the growth and
local spread of M. tuberculosis.local spread of M. tuberculosis.

10.  Disseminated and extra pulmonaryDisseminated 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

11. a.a. Adult pulmonary TBAdult pulmonary TB::
In HIV infected patients, pulmonary TB is still theIn HIV infected patients, pulmonary TB is still the
commonest form of TB.commonest form of TB.
Presentations:Presentations:
Features of pulmonary TBFeatures of pulmonary TB
Stage 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 smear2. Sputum smear
resultresult
OftenOften
PositivePositive
OftenOften
NegativeNegative
3. Chest x-ray3. Chest x-ray
appearanceappearance
Often cavitatesOften cavitates
(may be normal)(may be normal)
Often infiltratesOften infiltrates
with no cavitieswith no cavities
(may be normal)(may be normal)

12. 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 meningeallymphadenopathy, 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 aHighly active antiretroviral therapy (HAART) is not a
cure for HIV infection but is associated with dramaticcure for HIV infection but is associated with dramatic
reductions in morbidity and mortality in HIV infectedreductions in morbidity and mortality in HIV infected
patients.patients.

13. HAARTHAART
a) Reverse transcriptase inhibitors (RTI)a) Reverse transcriptase inhibitors (RTI)
NRTsNRTs NNRTIsNNRTIs
(Nucleoside)(Nucleoside) (non-nucleoside)(non-nucleoside)
ZidovudineZidovudine NevirapineNevirapine
DidanosineDidanosine EfavirenzEfavirenz
StavudineStavudine
LamivudineLamivudine

14. b) Protease inhibitors-b) Protease inhibitors-
indinavirindinavir
saquinavirsaquinavir
ritonavirritonavir
Principles of chemotherapyPrinciples of chemotherapy (TB with(TB with
HIV)HIV)
1)1) Defer antiretroviral therapy until TB treatment isDefer antiretroviral therapy until TB treatment is
completed.completed.
2) Defer antiretroviral therapy until the end of the2) Defer antiretroviral therapy until the end of the
initial phase of treatment and use ethambutolinitial phase of treatment and use ethambutol
and isoniazid in the continuation phase.and isoniazid in the continuation phase.

15. 3) Treat TB with a rifampicin containing3) Treat TB with a rifampicin containing
regimen and use efavirenz + 2regimen and use efavirenz + 2
NRTIs.NRTIs.
4) Treat TB with rifampicin containing4) Treat TB with rifampicin containing
regimen and use 2 NRTIs and thenregimen and use 2 NRTIs and then
change to a maximally suppressivechange to a maximally suppressive
HAART regimen on completion of TBHAART regimen on completion of TB
treatment.treatment.

16. Drug interactions (ATT/HAART)Drug interactions (ATT/HAART)::
 Rifampicin stimulates the activity ofRifampicin stimulates the activity of
cytochrome P450 enzyme system thatcytochrome P450 enzyme system that
metabolizes Pis and NNRTIs –reductionmetabolizes Pis and NNRTIs –reduction
in blood levels of Pis, NNRTIs.in blood levels of Pis, NNRTIs.
 Pis and NNRTIs – enhance or inhibitPis and NNRTIs – enhance or inhibit
same enzyme system -altered bloodsame enzyme system -altered blood
levels of rifampicin.levels of rifampicin.

17. TB IN PREGNANCY & LACTATIONTB IN PREGNANCY & LACTATION
 Pregnant woman with tuberculosis should bePregnant woman with tuberculosis should be
treated without delay when diagnosed.treated without delay when diagnosed.
 Untreated tuberculosis represents a far greaterUntreated tuberculosis represents a far greater
hazard to a pregnant woman and her fetus thanhazard to a pregnant woman and her fetus than
does the treatment for the disease.does the treatment for the disease.

18.  All first line antituberculosis drugsAll first line antituberculosis drugs
cross placenta. None of these drugscross placenta. None of these drugs
cause teratogenic effect to the fetuscause teratogenic effect to the fetus
with the exception of streptomycin.with the exception of streptomycin.
 Streptomycin causes ototoxicity andStreptomycin causes ototoxicity and
contraindicated in pregnant womencontraindicated in pregnant women..
Streptomycin induced ototoxicity has beenStreptomycin induced ototoxicity has been
reported irrespective of period ofreported irrespective of period of
gestation.gestation.

19. Safety of second line ATT:Safety of second line ATT:
 Limited data available regardingLimited data available regarding
teratogenicity of 2teratogenicity of 2ndnd
line ATT duringline ATT during
pregnancy.pregnancy.
 Kanamycin and Capreomycin avoidedKanamycin and Capreomycin avoided
because of Ototoxicity.because of Ototoxicity.
 Teratogenic effect has been attributed to theTeratogenic effect has been attributed to the
use of ethionamide.use of ethionamide.

20. Treatment during lactationTreatment during lactation::
Tuberculosis treatment in lactating mothersTuberculosis treatment in lactating mothers
is safe as the amount of drug ingested byis safe as the amount of drug ingested by
the nursing infant is minimal. So breastthe nursing infant is minimal. So breast
feeding is encouraged in lactating mothersfeeding is encouraged in lactating mothers
receiving ATT.receiving ATT.

21. Special situationsSpecial situations::
If the mother at the time of delivery isIf the mother at the time of delivery is
smear positive, the newborn should besmear positive, the newborn should be
separated from the mother at least for aseparated from the mother at least for a
period of 2 weeks.period of 2 weeks.
Breast feeding is best avoided during thisBreast feeding is best avoided during this
two weeks and expressed milk should betwo weeks and expressed milk should be
given to the child.given to the child.

22. BCG should be given as scheduled andBCG should be given as scheduled and
INH prophylaxis should be given for 6INH prophylaxis should be given for 6
months followed by Mantaux test at themonths followed by Mantaux test at the
end of 6 months.end of 6 months.
In the event of absence of scar, BCGIn the event of absence of scar, BCG
vaccination should be repeated.vaccination should be repeated.

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

24. 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.

25. • 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

26. TUBERCULIN SKIN TESTTUBERCULIN SKIN TEST
TUBERCULIN-TUBERCULIN-
Purified protein derivative derived from tuberclePurified 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 tohypersensitivity to
tuberculintuberculin→→ local reaction within 24-48 hrs.local reaction within 24-48 hrs. →→
skin indurationsskin indurations
This reaction indicates hypersensitivityThis reaction indicates hypersensitivity

27. A positive tuberculin test does notA positive tuberculin test does not
measure immunity. By itself it does notmeasure immunity. By itself it does not
indicate the presence or extent ofindicate the presence or extent of
tuberculosis disease-only it indicatestuberculosis disease-only it indicates
infectioninfection
indurationsindurations
Positive tuberculin testPositive tuberculin test > 10 mm> 10 mm
Negative tuberculin test < 10 mmNegative tuberculin test < 10 mm

28. 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

29. Value of positive tuberculin testValue of positive tuberculin test--
Reaction of tuberculin positive after BCGReaction of tuberculin positive after BCG
vaccination-vaccination-
A child-A child- NOT BCGNOT BCG - test positive- test positive →→ skinskin
indurations 10 mmindurations 10 mm
A child-A child- BCGBCG- test positive- test positive →→ skin indurations 15skin indurations 15
mm or moremm or more
A positive tuberculin test is only one piece ofA positive tuberculin test is only one piece of
evidence in favour of diagnosis ofevidence in favour of diagnosis of
tuberculosistuberculosis

30. THANK YOUTHANK YOU