HIV & TUBERCULOSIS ( The Double Menace)

( World AIDS Day ) December 1

By

Dr.K.BujjibabuDr.K.Bujjibabu.M.D.

OVERVIEW

Emergence of HIV epidemic posed major challenge to TB control efforts.

Co-infection of HIV & TB worldwide- 5-6 Million ( 90% in developing countries )

TB-50%life time risk of developing active disease in HIV patients.

New TB infection & Risk of disease REACTIVATION- common in HIV infected people.

Epidemiology

TB infection-1/3 of world’s population(~ 9 million new cases of TB & ~3 million deaths each year.)

Co-infection- 5 - 6 million(90% reside in developing countries.)

Incidence of TB in HIV infected- >100 times that of general population.

Study/Author Place(Period) Percentage of TB patients

who are HIV+ve1) Purohit SD, et al157 - Ajmer - 0.7%

(1993-95) 

2) Mohanty KC, et al158 - Mumbai - 6.7% (1989-94)

 

3) Paranjpe S, et al159 - Pune - 15% (1991-96)

 

4) Tripathy SP, et al160 - Pune - 12.1% (1995)

  

5) Solomon S, et al 161 - Chennai - 1.7% (1991-93)

 

6) Samuel NM, et al162 - Chennai - 17% (1996)

 

7) WHO/IUATLD Project163 Delhi - 1% (1995)

8) Sharma SK, et al164 - Delhi - 0.4% (1994-99)

 9) Vasudevaiah V, 165 - Pondicherry - 4.1%

(1994-96) 

HIV in WOMEN

Important entity for several reasons

Raising in no., steadily

Female CSW–constant source & Major reservoir of infection.

transmitting to their children- increasing the infant&child mortality rate.

Women as a group less access to medical care&potent ART agents.

PathogenesisHIV on TB

TB.Disease-Progression of recent infection/ Reactivation of LATENT infection/ Exogenous reinfection.

CD4+ T lymphocytes producing IFN- - A central role in Immune defenses against MTB.

HIV-causes selective depletion of CD4+

Defects in Macrophage & Monocyte function

PathogenesisTB on HIV

MTB-elicits the production of pro inflammatory cytokines(TNF) which up regulates the Intracellular HIV replication.HIV viremia increases.Further reduction of CD4+ counts.

Progression of HIV disease.

Clinical Features Pulmonary KochsActive TB develops early in the course of HIV infection.60-80% PTB & 30-40% Extra Pulmonary.Clinical features vary with CD4+ count.High CD4+(>300) - Typical PTB manifestations.Low CD4+ - Disseminated disease;Atypical presentations;lower lung infiltrations (high incidence of Mycobacteremia->25%) PTB occurring in late stage of HIV disease- CXR may be normal in 40% cases.Advanced HIV- PTB may occur with TB elsewhere in the body.

Constitutes 70% of HIV-related TB cases when the CD4+ count < 300. TB lymphedinitis (peripheral,mediastinal,abdominal)-most commonFeatures similar in both HIV infected & Immunocompetent but in TWO exceptions– 1) TB lymphadenitis(severe immuno-suppression)-may be acute resembling Acute pyogenic lymphadenitis. 2)Abdominal TB-Visceral lesions & intra abdominal lymphadenopathy with necrosis.

Clinical Features Extra Pulmonary Kochs

Bone marrow is also a common site – Granulomas in 60% advanced HIV cases.CNS : TUBERCULOMA is one among the various CNS manifestations leading to Seizures in HIV patients- ~ 13.04%TB meningitis may resemble bacterial meningitis-CSF may be normal.Pericardial Effusions constitute ~ 11%

Clinical Features Extra Pulmonary Kochs

TBM Incidence 5-7% of patients infected with HIV Acute to subacute illness Duration of symptoms may vary from 5 days –

9months Presenting features

fever, can be absent Headache ,photophobia in 15-20% Drowsiness and meningism in 20% of cases

Less common features Cranial nerve palsies, Visual symptoms Focal neurological deficit B/L papilledema, raised ICT

Matted cervical TB lymphedinitis

Tuberculous Lymphedinitis

Beaded AFB- FNAC CLN

MOTT in HIV

Infections with atleast 12 different types have been reported.(CD 4 + < 50).

Most common is with MAI complex.Prior infection with MTB decreases the risk of MAC infection.Can cause Endo bronchial lesions, abdominal pain, diarrhoea & lymphadenopathy. by blood cultures/ tissue culture.Rx Clarithromycin + Ethambutol

Investigations & DiagnosisSputum microscopy ( ZN Staining).

Sputum for AFB+ ve in 40-67% of PTB.

Cultures+ ve in 74-95% .

Sputum+ decreases with low CD4 counts.

5% of HIV+ve PTB patients have sputum+ve despite normal CXR.

Cultures are essential to increase the yield.

Blood cultures for MTB+ve in 15% of HIV-TB cases.

Acid-Fast bacilli in Sputum

Chest RadiographCXR features varies with CD4 levels.

CD4> 300 /cu mm:- The pattern is similar as reactivation TB involving upper lobes with cavitation/infiltrates

CD4<300/cu mm:- The patern is difuse or lower lobe Bilateral reticulo nodular infiltrates or milliary pattern.

Pleural effusions

Bilateral hilar/mediastinal adenopathy.

Pericardial effusions

LEFT UPPER LOBE TB

Before treatment

AFTER TREATMENT

CLINICAL /CXR/SPUTUM DIFFERENCES IN PTB IN EARLY & ADVANCED HIV

FEATURES STAGE OF HIV

EARLY ADVANCED

CLINICAL PRESENTATION

Often resembles post- primary TB

Often resemblesPrimary TB

SPUTUM SMEAR Often Positive Often Negative

CHEST X-RAY Cavities upper lobe

Often infiltrates,lower lobesNo Cavities

MANTOUX

More than 5 mm considered as positive

7-10% of Mx +ve HIV patients develop active TB each year

1% of Mx positive HIV - ve patients develop active disease

Mx is considered as routine test for screening all HIV+ve patients to start chemo prophylaxis.

Used as an adjunt to diagnose Childhood TB.

Limited value for diagnosing adult TB infection.

Other InvestigationsBronchoscopy :

BAL / Trans Bronchial Biopsy : Yield - 30 - 40 %

Rapid Diagnostic tests :

NAA: Nucleic acid amplification tests: 2 tests have

been approved by FDA-

1) Amplified MTB Direct( MTD)

2) Amplicor MTB test

AFB POSITIVE + POSITIVE NAA = ACTIVE MTB

AFB POSITIVE + NEGATIVE NAA = MOTT

Investigations- Extra Pulm. TBLymph node biopsy

CT/US guided aspirations

CT/US guided Biopsy of LIVER, Spleen, Abdominal LN

Bone marrow aspiration/biopsy

Synovial fluid analysis

Skin biopsy

(Treatment Regimens for Tuberculosis-WHO)

Recommended RegimenTx Category

1

Intensive Phase Continuation Phase

2 EHRZ

2 SHRZE + 1 EHRZ11

4 HR

5 HRE

5 HRE111 2 HRZ

SituationPTB& CD4<50/mmor extra pulm TB

PTB & CD4 50-200or total lymp.count<1200

PTB & CD4 >200 or total lymph count >1200

RecommendationsATT plus one of the following:• AZT / LAM / EFZ• AZT / LAM / ABC• AZT / LAM / SQV/ r

HAART after TWO months of ATT:• AZT / LAM / EFZ• AZT / LAM / ABC• AZT / LAM / SQV/r

ATT plus CD4 Monitoring; start

HAART if indicated.

ART for individuals with TB

NVP can be used only if no option, as RIF reduces its efficacy

Screening and PreventionAll HIVs should be screened yearly for TB with tuberculin skin test.

Induration of 5 mm or more is considered as positive.

All patients with positive tuberculin test should undergo clinical and radiological evaluation to exclude active TB.

Indications for prophylaxis for TB in HIV.

1.Induration of 5 mm or more at 48 hours on tuberculin skin test.

2. History of close contact with persons who have active TB.

3. Finding of anergy in patients with prolonged exposure M.tuberculosis (eg.in homeless shelter,Jail)

Recommendations(as by CDC`s advisory committee for the Elimination of TB)

1. INH 300mg OD for 6-9 months.2.INH twice weekly for 9 months(minimum 76 doses).3. RIF+PZA daily for 2 months (Minimum 60 doses) in patients receiving NNRTI`s or Pis4 RIF 600 mg OD for 6-12 months5. Completion of therapy is based on the total number of doses received, not on duration of therapy alone.Prophylaxis in patients with MDR TB

PZA+fluroquinolone daily for 12 months PZA+ETB daily for 12 months.

Ccontd