tb in special situations

7/30/2019 TB in special situations

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TUBERCULOSIS

IN SPECIAL

SITUATIONSDR VIPUL

ASSISTANT PROFESSORTB & RESPIRATORY MEDICINE


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SPECIAL SITUATIONS

PREGNANCY AND LACTATION

DIABETES MELLITUS

ELDERLY LIVER DISEASE

HIV/AIDS

CHILDREN MDR AND XDR TB


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Treatment During Pregnancy

Risk to mother and fetus is far greater fromuntreated TB than from the drugs used to treatTB

Increased risk of spontaneous abortionIncrease in perinatal mortality

Small for gestational age births

Increased maternal morbidity

Congenital TB

Increased risk of perinatal and early post-nataltransmission


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Isoniazid (INH), rifampicin and ethambutol areknown to be safe for administration during

pregnancy There is insufficient data on the teratogenic

effect of PZA

Pregnant and postpartum women are atincreased risk of INH induced hepatitis

Supplement with pyridoxine 50mg/day

Monitor for signs of hepatotoxicity duringpregnancy and immediate post-partum


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SM induced ototoxicity has been reported

irrespective of period of gestation. Therefore

SM should not be used during pregnancy.

WHO recommends standard chemotherapy

under DOTS for pregnant patients.

Duration of ATT need not be modified.


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MDR TB IN PREGNANCY

Almost all second line drugs are teratogenic.

Pregnancy is best avoided.

If required treatment should be postponed tillsecond trimester.

The decision should be based on analysis of

relative risks and benefits.


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Breastfeeding

Most of the TBmedications are secretedinto breast milk but notin significant

concentrations (usually 5 times if asymptomatic

INH, PZA and RIF can all cause hepatotoxicity

Hepatitis from INH is age related, from PZA is dose related,

and RIF is unpredictable and less common


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GRADING

Grade I: ALT 51-125 IU/L

Grade II: ALT 126-250 IU/L

Grade III: ALT 251-500 IU/L Grade IV: ALT > 500 IU/L


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TB Treatment and Hepatitis

If3x normal with symptoms or >5x normalwithout symptoms:

stop all anti-TB medications and evaluate patient

refer patient to doctor for clinical evaluation

try to rule out other causes of acute liver disease

if severely ill, may start 3 non-hepatotoxic drugs

after AST


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REINTRODUCTION OF DRUGS

When AST levels reach less than 2 times normal,reintroduction should be tried.

Restart RIF first followed by INH and PZA


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TB and HIV infection

the cursed duet


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Immunopathogenesis

Kaufmann et al, Nature Medicine 2005


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HIV TB pandemic

TB is the leading opportunistic infection in

HIV infected patients

Often the first indicator of immune deficiency (AIDSdefining Illness)

World wide 40 million HIV infected of whom15million are co infected with TB

Tuberculosis accelerates the progression of HIVinfection and HIV increases the likelihood of active TBdisease


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Immunopathogenesis of TB-HIV

HIV infection is associated to:

Decreased chemotaxis

Defective granuloma formation and maintenance

Impaired antigen processing and presentation

Loss of CD4+ T cells

Selective clonal deletion ofM. tuberculosis-specific CD4+ T

cells Loss of IFN-g+/IL-2+ CD4+T cell precedes the loss of IFN-

g+ /TNF-a+ CD4+ T cells


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Opportunistic diseases in the course

of HIV-infection

CD4+

(cells/L)

800-

600-

400-

200-

0-

0 2 4 6 8 10

50-

Seroconversion:

Acute retroviral syndrome

MACCMV

Pneumococcal pneumonia

Candida vaginitis

ITP

Years after infection

Oral Candida-infection

Kaposi sarcoma

Lymphoma

Dementia

Oral haircell-leukoplacia

CachexiaToxoplasmosis

PCP

HSV

Candida esophagitis

Cryptococcosis

TB

P l l


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Pulmonary vs extra-pulmonary

TB: HIV+ vs HIV-


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TB diagnosis in HIV+ persons

Microbiology

Radiology

TST

IGRA
http://www.chestjournal.org/cgi/content/full/121/3/774/F1


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Microbiological diagnosis

Microscopy, AAFB sputum staining: 1 day

Culture: liquid medium (2-8 weeks), solid medium (8-18weeks)

Identification: analysis of positive cultures by molecularbiology assays (2-4 weeks)

Drug- sensitive assays:

to INH and RFP: 2-4 weeksto other drugs: 6-8 weeks


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Microbiological diagnosis

Microscopy, smear AAFB sputum: sensitivity isaround 45% in HIV+ compared to 60% of HIV-patients (Hirao et al, 2007)

Probably due to the reduction of cavitationwhich results in a lower number of bacilliexpectorated

R di l i l f f HIV+


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Radiological features of HIV+

patients

cavitary TB

CD4+ 510 (23%)

TB Pleuritis

CD4+ 34 (8%)

miliary TB

CD4+ 194 (18%)

Lange et al, Pneumologie 2004


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Radiological tools

Pulmonary TB:

Chest xRay: 14% of those with culture-positive TBhave a normal chest xRay

CT-scan: mediastinal and hilarlymph nodes

HRCT (1 mm slices): interstitial lesions tree and bud appearance

Extra-pulmonary TB:

Radio-nuclide scans/MRI (bone, CNS)CT-scan


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TST


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Positive TST

M. tuberculosis

Active TB diseaseLatent TB infection

(past exposure to M.tuberculosis)

Latent TB infection(recent exposure to M.

tuberculosis)

NTMExposure to environmental

mycobacteria

BCG-vaccination

BCG-vaccination

Tuberculin skin test (TST)

TST does not distinguish

among all these different clinical situations


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Tuberculin skin testing

Tuberculin reactivity four fold less in HIV infection

Reactivity declines with increasing immunesuppression

early HIV 40-70 % advanced HIV 10-30%

Annual tuberculin testing for HIV infection to

detect latent infection

Tuberculin anergy assoc. with risk of active TB iscontroversial


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T cell-based assays

Interferon Gamma Release Assay (IGRA)

New generation of diagnostic tests for TB that

measure in vitro the interferon- release fromactivated T-cells in response to TB specific RD1antigens (ESAT6, CFP10,+/-TB7.7)

Commercially available IGRAs

QuantiFERON-TB Gold (QF-TB-2G), in Tube (QF-TB-3G) T-SPOT.TB (TSPOT)


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Treatment of TB/HIV complicated by

Optimal regimen for treatment of co-infection not defined

Optimal timing of HAART unclear

Drug-drug interactions

Large pill burden

Variable drug absorption

Risk of further AIDS-defining illnesses if HAART is deferred

during TB treatment Paradoxical reactions


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ART drug Classes

Nucleoside reverse transcriptase inhibitors(NRTI)

Non nucleoside reverse transcriptase

inhibitors (NNRTI)

Protease inhibitors (PI) Fusion inhibitors


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NRTIS

Zidovudine

Lamivudine

Stavudine

Zalcitabine

Didanosine

Abacavir

Tenofovir

Emtricitabine


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Protease Inhibitors

Indinavir

Ritonavir

Nelfinavir

Saquinavir

Amprenavir

Lopinavir

Atazanavir


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NNRTIs Nevirapine

Delavirdine

Efavirenz

FUSION INHIBITORS

Enfuviritide


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Combinations never used

AZT+ Stavudine - antagonistic

Ddi+ Stavudine

Stavudine+Zalcitabine

Zalcitabine+ Ddi additive toxicity

Atazanavit+Indinavir

Emtricitabine +lamivudine ~ resistance profile Efavirenz based regime in pregnancy


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Drug interactions

Use of Rifampicin with PI / NNRTI based

ART is contraindicated.

NRTI are not metabolized by hepatic cytochrome P450 enzyme system hence they can safely be used withRifampicin based ATT

Other first line ATT (SHEZ) no interactions with ARTand can be used safely : SHEZ x 2 months followed bySHZx7months


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Rifabutin :less potent inducer and can be used in

place of Rifampicin in ATT with PI

NNTRI based ART ( equivalent bactericidal

action, clinical cure rates )

Ritonavir retards Rifabutin metabolism(levels 35 fold) toxic reactionsuveitis,

neutropenia , arthralgia occur. combination

is contraindicated


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ART+ ATT Recommendations

CD4 count 350cells/mm3

Treat TB. Monitor CD4 counts. Defer ART.

A i i l h


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Antiretroviral therapyfor HIV infection in adults

and adolescents2010 revision

HIV/TB co infection Irrespective of CD4 cell counts, patients co

infected with HIV and TB should be started

on ART as soon as possible after starting TBtreatment


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THANK YOU

tb in special situations

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