HIV-TB Coinfection

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HIVTB COINFECTION
Dr. S. K. Jindal www.jindalchest.com
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ISSUES

• Magnitude of problem
• Immunology of TB
• Effect of co-infection
• Clinical manifestations
• Role of molecular diagnostics
• Treatment guidelines

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Resurgence of TB
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Magnitude HIV burden
WHO region HIV inf TB Prev. Coinfection
Africa 18.7M 48 9M
SEA/W pacific 6.0M 40 2.4M
Americas 1.3M 30 0.4M
East Mediteran 0.18M 23 0.04M
Europe/USA 1.35M 11 0.15M
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Global Scenario

• 13-14 million co-infected with HIV and TB
• In 2003, estimated 9 (700 000) of all new TB
  cases (8.8m) were HIV positive
• In some regions of Africa, 75 of TB patients are
  HIV-infected
• In 2003, estimated 15 (230 000) of all TB
  deaths (1.7m) were HIV positive
• Effect of HIV on TB is most striking in Africa
  where 29 of TB is attributable to HIV
• Rising TB incidence in Africa is offsetting the
  stable or falling TB incidence in the rest of the
  world
• (Global TB incidence continues to rise by 1 per
  annum)

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Indian Scenario

• TB Situation
• Estimated 40 population infected
• 1.8 million new TB cases annually
• Incidence of TB is higher in north
• Estimated up to 5 of TB patients are HIV positive

• HIV Situation
• HIV prevalence in general population lt 1
• 50-60 HIV infected are expected to develop TB
• Prevalence of HIV higher in south
• TB is leading cause of deaths in people with HIV

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TB and AIDS
Lifetime Risk of TB
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Mechanisms of Coinfection

• Impairment of immune response
• Progressive depletion dysfunction of CD4
  lymphocytes
• Impaired macrophage function
• Invasion of inflamed bronchial walls the
  breeding sites

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Potentiation of HIV replication
Alveolar macrophages
Tubercle bacilli
Induces n FKB which binds promoter region of HIV
CD4 T cell
IFN Gamma
Increased viral replication in monocytes T
cells
Activated macrophages
IL1/ TNF a
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Augmented Effects

• HIV on TB
• Rapid progression
• Active disease (40)
• Higher morbidity
• Mortality 4 times higher (than HIV ve), 20-35
• Increased ADRs to ATT
• Increased drug resistance
• TB on HIV
• Increased viral replication, load, immune
  suppression, infections, morbidity and mortality

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How does TB occur?

• Endogenous reactivation
• HIV is most potent risk factor
• Exogenous (Re) infection
• Increased chances of TB exposure in hospitals

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Clinical Features

• Early stage (CD4 gt 200/mm3)
• Typical reactivation TB
• (Upper lobes infiltrates/cavities)
• Advanced stage (CD4 lt 200/mm3)
• Atypical disease
• Disseminated/extrapulmonary TB

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Clinical Presentation, Symptoms

• Fever, cough, chest pain, weight loss
• Chronic diarrhoea
• Generalized lymphadenopathy
• Organ specific symptoms and signs

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Atypical Manifestations (Pulmonary)

• Lower lobe/diffuse involvement
• Absence of cavity formation
• Endobronchial involvement
• Prominent hilar/mediastinal
• Pleural effusion common
• Miliary TB
• Chest wall abscess/cutaneous sinuses

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Clinical Immunopath CourseHIV-Related TB
Density of bacilli in lesions
500
PTB
Nodal, serous TB
TBM
MTB
400

300
Median CD4 count (mm 3)

200

100

0
Duration of HIV infection
DeCock et al, JAMA 1992
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Clinical features TB with HIV
Clinical feature HIV negative Early HIV Advanced HIV/AIDS
Tuberculin reactivity gt10mm 75-85 40-70 10-30
Chest X Ray 50-70 typical(UL fibronodular lesions) 50 cavities Mixed typical and atypical Increased adenopathy effusions,L Zone inv miliary infiltrates Reduced Cavitation
Sites Involved Pulmonary 80 Extra pulmonary 16 Both 4 Intermediate Pulmonary 20-30 Extrapulm 20-50 Both 30-70
Sputum smear positivity 70-80 50 30-40
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Extrapulmonary TB

• LYMPHATIC
• Commonest extra-pulmonary site
• Peripheral
• Intrathoracic
• Intra-abdominal with necrosis
• (accompanying visceral involvement)
• DISSEMINATED
• Miliary or more than one XP site
• Mycobacteremia

• SKIN
• May co-exist with pulmonary TB
• Erythematous papules, purpura,
• subcutaneous nodules, pustules
• Biopsy- little granuloma, AFB
• HEPATOSPLENIC
• Round, hypoechoic, multiple lesions lt1 cm
• TB MENINGITIS
• CSF findings may be normal
• LARYNGEAL

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Atypical manifestations

• Sputum smears negative despite extensive
  involvement
• Normal chest x rays sputum positive for AFB
  endobronchial TB or mycobacteremia
• Mycobacteria may be isolated from blood, marrow,
  urine fluids
• Lymph node aspirate/Bx- poorly formed granulomas
  , focal areas of necrosis teeming with AFB

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TB Lymphadenitis

• Size gt 4 cm
• Rapid enlargement
• Asymmetrical
• Tender/Painful no local infection
• Matted/fluctuant
• Presence of constitutional symptoms
• May be acute resemble pyogenic lymphadenitis

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Unusual Manifestations

• Massive abd. lymphadenopathy
• Hemophagocytosis syndrome
• Broncho esophageal fistula
• Multiple visceral/brain abscesses
• Cutaneous, soft tissue abscess
• Osteomyelitis
• Sepsis with septic shock

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HIV related TB in Children

• Features of HIV infection
• Wt. loss, slow growth
• Ch. Diarrhoea (gt 1 month)
• Prolonged fever
• Generalized L.N. enlargement
• Recurrent ear, throat infection
• Oropharyngeal candidiasis
• Persistent cough
• Disseminated TB
• Extrapulmonary TB

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Radiologic features in HIV-TB
Series HIV negative Early HIV CD 4gt200 Advanced HIVAIDS
Abouya et al Ivory Coast 1990-92 Cavitary 56 Noncavitary 42 Hilar LNE 2 Miliary 2 Effusions 4 53 39 8 3 8 29 58 20 9 11
Batungwanyo et al Rwanda 1988-89 Cavitary 91 Upper lobe 55 Hilar LNE 0 Miliary 9 Effusions 9 69 30 7 23 46 28 16 40 26 42
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CxR Findings in TB Patients with HIV Infection
Late HIV (severely immuno-compromised)
Early HIV
Source Various references including WHO
Clinical Guide Allen AM, Namaambo K, Allen BW,
et al. Negative sputum smear results in
HIV-positive patients with pulmonary tuberculosis
in Lusaka, Zaire. Tuberc Lung Dis
199374191-94.
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Tuberculin skin testing

• Tuberculin reactivity four fold less in HIV
  infection
• Reactivity declines with increasing immune
  suppression
• - 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
  is controversial

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Tuberculin skin testing

• The reaction declines with immunesuppression, 5mm
  induration is considered significant in HIV
  infection (CDC/ATS)
• (Some have advocated reducing to 2mm)
• Recommended to give prophylactic therapy in such
  cases to prevent disease
• Close contacts of infectious cases and
  populations with high prior probability of TB are
  also recommended to be given prophylactic therapy
  

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Role of FOB

• Valuable in early diagnosis
• Diagnosis of endobronchial TB
• TBLB yield is greater (82) than BAL (26)
• 
  Miro et al Chest, 1992
• TBNA has a role in mediastinal lymph nodal
  tuberculosis with negative sputum smears
• Harkin
  et al AmJ Resp Crit Care Med ,1998

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Molecular diagnosis RFLP

• Identify the specific strains of Myco TB by
  pattern of gene fragments
• Has shown that recent infection is responsible
  for upto 50 TB cases in both HIV negative and
  HIV infected
• Used to confirm that cluster of TB cases are
  linked by recent transmission especially during
  nosocomial outbreaks
• 
  Halvir DV, Barnes PF N Engl J Med 1999

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MANAGEMENT

• Treatment of Tuberculosis
• Managing Viral infection
• Drug interactions/Adverse reactions
• Paradoxical reactions
• MDR/ XDR-Tb
• Chemoprophylaxis
• BCG vaccination

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HIV related TB management

• RNTCP schedule
• Evaluate for other infections
• Start cotrimoxazole prophylaxis
• Nutrition
• Screening of family
• Screen for side-effects
• Consideration for anti-retroviral drugs

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HIV Tb Treatment

• Duration of treatment 6 months (2HREZ / 4HR)
• Rifampicin contra-indicated with PI/nevirapine
  containing HAART regimens
• Possible options for ART in patients with active
  TB
• Defer ART until TB treatment is completed
• Defer ART until the continuation phase' of
  treatment for TB, and use HE as continuation.
• Treat TB with RIF containing regimen and use
  Efavirenz 2 NRTIs

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Tuberculosis and ARV Therapy
Status When to Start ARV Therapy
CD4 less than 200/mm3 Start TB Therapy Start ARV as soon as TB therapy can be tolerated
CD4 between 200 and 350/mm3 Start TB therapy Start ARV therapy after 2 mo. Of TB therapy with EFV
CD4 greater than 350/mm3 Treat TB, start ARV therapy according to general indications
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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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Life cycle of HIV
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Drug interactions

• Use of Rifampicin with PI / NNRTI based ART is
  contraindicated.
• NRTI are not metabolized by hepatic cytochrome P
  450 enzyme system hence they can safely be used
  with Rifampicin based ATT
• Other first line ATT (SHEZ) no interactions with
  ART and can be used safely SHEZ x 2 months
  followed by SHZx7months

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Drug interactions

• 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 reactions uveitis, neutropenia ,
  arthralgia occur . combination is contraindicated

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Management strategies
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Initiation of Antiretroviral Therapy for Patients
with TB To Start or to Delay?
Reasons to start ART Decrease morbidity and
mortality related to HIV/AIDS Reasons to delay
ART - Overlapping side effects from ART and
anti-TB therapy - Complex drug-drug interactions
- Immune reconstitution inflammatory syndrome
(paradoxical reactions) - Difficulties with
adherence to multiple medications - Pill burden
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HIV MDR/ XDR TB

• Poor immune response leads to increased rapidly
  dividing bacilli and spontaneous mutations
• Noncompliance due to frequent ADR
• Large pill burden
• Malabsorption of ATT
• Use of Rifabutin prophylaxis for MAC

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Adverse drug reactions

• More frequently in HIV infected, 20-25
• Related to level of immune activation and immune
  suppression
• Thiacetazone induced exfoliative dermatitis, TEN,
  Steven Johnson syndrome can be fatal
  (contraindicated with HIV)
• ATT induced hepatitis four fold higher than
  seronegative patient
• Risk factors- anergy , lymphopenia, Elevated
  Neopterin levels

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Therapy outcomes

• Early clinical and microbiological response
  similar to HIV negative patients with TB
• Relapse rates higher in developing world than in
  the developed nations
• Data conflicting about higher rate of relapse in
  HIV infected than HIV ve.
• CDC guidelines, MMWR,
  Oct 1998

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Recommendations

• CDC/ATS recommendation 6 months ATT with drug
  sensitive TB prolongation to 9 months if slow
  clinical /micro response
• Factors assoc with poor outcome advanced immune
  suppression, noncompliance, delayed clinical/
  microbiological response physician should prolong
  duration of ATT

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Paradoxical reaction

• Defined as temporary worsening of clinical
  condition, appearance of new radiologic
  manifestations after initiation of Tt ,and are
  not due to Tt failure or a second process
• Due to recovery of immunological Th 1 response to
  mycobacterial antigen
• Heightened granulomatous response may clear the
  organism but itself may cause tissue damage

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Paradoxical reation Clinical findings

• Hectic fever, peripheral /mediatinal
  lymphadenopathy, miliary infiltrates, pleural
  effusion
• Worsening of original lesions pulmonary
  infiltrates, tuberculomas may be life
  threatening
• Self limited, usually lasts 10-40 days

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Mimickers of PDR

• Treatment failure
• Drug resistance
• Non compliance
• Drug fever
• Development of another OI
• Condition not related to TB or HIV

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Heart attacks

• Incidence with ATT alone 7 with ARTATT 36
• Substantial reduction in viral load and increase
  in CD4 counts found( immune reconstitution)
• Increased tuberculin reactivity noted
• Stronger immune response to Mycobact TB results
  in PR
• Kunimoto et al Int J Tuberc Lung Dis 1999

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Treatment of PDR

• Rarely requires stopping ATT / HAART
• Requires NSAID for symptomatic relief
• For life threatening states short course
  steroids may be give to suppress inflammation
  while ATT and ART are continued

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Chemoprophylaxis

• Latent infection in HIV patients (TST gt5mm) must
  be treated to prevent disease and spread in
  community.
• INH daily x 9 months
• Rifabutin PZI daily x 2 mths(On ART)
• Rifampicin PZI daily x 2 mths(No ART)
• Rifampicin daily x 9 months

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Chemoprophylaxis

• Rifampicin regime- INH resistant strain,
  intolerance, poor compliance
• In India ,INH resistance is significant the use
  of combination drugs is advised
• For HIV positive contacts of MDR TB
• PZI Flouroquinolone daily x 12 months
• PZI Ethambutol daily x months
• WHO does not recommend CP in region where
  prevalence is high

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Problems with Preventive Chemotherapy Problems with Preventive Chemotherapy
o Ensuring certainty to exclude active tuberculosis
o Efficacious but inefficient
o Rare adverse drug events
o Difficulties in ensuring adherence
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Role of BCG

• Contraindicated with persons with advanced HIV
  disease/AIDS because of risk of disseminated
  BCGiosis
• But in countries where risk of TB is high, WHO
  recommends BCG should be given as soon after
  birth.
• Disseminated BCGiosis treated with INHRifampicin

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Conclusions I

• TB-HIV coinfection is a common occurrence
• TB often precedes other AIDS defining illnesses
• Clinical presentation depends on level of immune
  function
• Symptoms are usually nonspecific
• Extrapulmonary TB is common

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Conclusions II

• Screen all cases of TB for HIV infection
• Initiate ATT with DOT
• Consider optimal antiretroviral therapy
• Understand drug interactions of Rifamycins with
  PI/NNRTI based ART
• Observe for paradoxical reactions
• Identify drug resistant tuberculosis

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Conclusion IIILikely impact of HIV on TB in
India?

• Scenario without RNTCP
• HIV would increase TB prevalence (by 1),
  incidence (by 12), and mortality rates (by 33)
  between 1990 and 2015
• Scenario with RNTCP
• Expect substantial reductions in prevalence (by
  68), incidence (by 41), and mortality (by 39)
  between 1990 and 2015
• Nationally, RNTCP should be able to reverse the
  increases in TB burden due to HIV but, to ensure
  that TB mortality is reduced by 50 or more by
  2015, HIV-infected TB patients should be provided
  with antiretroviral therapy in addition to the
  recommended treatment for TB
• Methodology Mathematical modeling using data
  from HIV sentinel surveillance, studies on TB
  prevalence and incidence, and RNTCP notification
  data
• Ref Williams et al. The impact of HIVAIDS on the
  control of tuberculosis in India. Proceedings of
  National Academy of Sciences (US) July 5, 2005
  vol. 102 no. 27 96199624

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WHO Recommendations 2002
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Pulmonary Tuberculosis in HIV-Infected Patients
in Zaire A Controlled Trial of Treatment for
Either 6 or 12 Months

• After 6 months (2HREZ/4HR)
• Treatment failure rates similar 3.8 and 2.7
  (p0.70)
• At 24 months, the HIV-seropositive patients who
  received extended treatment had a relapse rate of
  1.9 vs. 9.0 among the HIV-seropositive patients
  who received placebo for the second 6 months
  (Plt0.01)
• Relapse among the HIV-seronegative patients 5.3
  
• Extended treatment did not improve survival

Perriëns JH et al. NEJM 1995332779-785
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Revised National TB Control Programme (RNTCP)

• Following 1992 review, RNTCP designed based on
  internationally recommended DOTS strategy
• DOTS is a five-point strategy to control TB
• Political and administrative commitment
• Diagnosis primarily by sputum microscopy
• Uninterrupted supply of good quality drugs
• Directly Observed Treatment (DOT)
• Standardized recording, reporting and monitoring
• RNTCP started on a pilot scale in 1993
• Scaling up as national programme started in 1997

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RNTCP Objectives

• To achieve and maintain a case detection of at
  least 70 of new sputum positive TB patients
• To achieve and maintain a cure rate of at least
  85 in such patients

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Referral from VCTC/ ART clinic to RNTCP

• Think TB if
• Cough gt 3 weeks duration
• Unexplained fever
• Loss of weight
• Haemoptysis
• Enlarged lymph nodes
• Suspicion of TB at other sites

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RNTCP Drug Regimens Treatment Outcome
HIV PTB Patients 95
Culture Positive PTB 66
New 46
Old 20
Cure Rate
92
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Mortality
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Source TRC GHTM, Tambaram Pilot Study
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A Review of Efficacy Studies of 6-Month
Short-Course Therapy for Tuberculosis Among
Patients Infected with HIV
HIV () HIV- ()
Cure 59.4 97.1 62.3 88.0
Relapse 0.0 10.0 0.0 3.4
Treatment success 34.0 100 91.2 98.8
Treatment effectiveness 29.4 88.2 70.6 83.8
El-Sadr W et al. Clin Infect Dis   200032623-632
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TB Mortality Recurrence

• 65 died in 40 month f/u period, 40 by 2 years.
• Of 31 patients who completed a full course of
  regular anti-TB therapy and were followed up to
  24 months, 12 had a recurrence (39)
• DNA fingerprinting done on pre-treatment and
  relapse cultures using IS 6110 and DR probes.
• All 8 pairs of cultures that were fingerprinted
  had a new strain of Mycobacterium tuberculosis
  re-infection) at time of recurrence.

TRC GHTM, TAMBARAM PILOT STUDY 11th CROI, 2004
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VCTC RNTCP cross-referrals

• VCTC clients (irrespective of HIV status)
  screened for TB symptoms and referred to RNTCP
  designated microscopy centres (DMC)
• At DMC all such referrals are screened for TB and
  those diagnosed with TB disease are put on DOTS
  treatment
• RNTCP staff communicate to VCTC staff about TB
  diagnosis and treatment of all referred clients
• VCTC staff, on the basis of information received
  from RNTCP, generate monthly disaggregated data,
  based on HIV status
• Confidentiality of HIV status is not breached
• Similarly TB cases with history of high risk
  behaviour, STD, or any other OI, are referred to
  the nearest VCTC

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How are patients treated?

• Standard intermittent regimen with 3 categories
  of treatment
• Treatment under direct observation of a DOT
  provider (DP)
• Entire course of drugs packaged in a Patient Wise
  Box (PWB)
• Category decided by MO (Cat I / II / III)
• Treatment started after counseling, address
  verification, identification of DOT-Provider
  transportation of PWB to DP
• Drugs to be taken three times a week under direct
  observation of the DP
• Intensive phase (2-3 months) - all doses given
  under observation
• Continuation phase (4-5 months) - first dose of
  the week given under observation
• Doses are recorded on treatment cards
• If patient misses any dose, home visit made
  immediately to retrieve patient

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TB/HIV collaborative activities

• National, State and District level coordination
  committees established and meetings held
• Guidelines and training material developed
  jointly
• On-going training of staff on TB/HIV
• Cross-referral between VCT and DOTS services
  developed, piloted and implemented
• Involvement of NGOs and PPs
• Collaborative IEC activities
• Joint monitoring of activities

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Diagnosis of Pulmonary TB
Source Global Tuberculosis Control WHO Report
1999 (WHO/TB/99.259) and World Health
Organization. Treatment of tuberculosis.
Guidelines for national programs. (Second
Edition.) WHO/TB/97.220,1997.
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Treatment Categories
TB treatment TB Patients category

• New smear-positive pulmonary TB
• New smear-negative pulmonary TB with extensive
  parenchymal involvement
• New cases of severe forms of extra-pulmonary TB

I II III

• Sputum smear-positive relapses
• Sputum smear-positive treatment failure cases
• Sputum smear-positive cases requiring treatment
  after interruption

• New smear-negative pulmonary TB
• New less severe forms of extra-pulmonary TB

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TB in AIDS patients in Taiwan(1994-1997)
Disseminated TB Disseminated MAC
No. 22 No. 15
Clinical Features Clinical Features
Night sweats Hepatosplenomegaly
Peripheral LN Elevated SGOT,
AFB in sputum SGPT, SAP
Hilar enlargement Leukopenia
Lack of prior AIDS-defining illness Poor survival
Hsieh et al 1998
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TB and HIV in Tokyo

• Questionnaire survey of 48 institutes for TB with
  AIDS
• 11 Japanese and 6 foreign patients
• Clinical Features
• Advanced HIV infection
• Middle age, fever and cough
• Nonspecific chest infiltrates
• Low lymphocyte count
• Negative tuberculin test
• 
  Kanazama et al 1996

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Differential Diagnosis of PTB

• Pneumococcal pneumonia
• Typhoid septicemia
• Fungal pneumonia
• Pneumocystis carinii pneumonia
• Lymphocytic interstitial pneumonia
• Kaposis sarcoma
• Lymphoma

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Distribution of Tuberculosis (1990-99)
Eastern Europe 2,020,000
North America 320,000
East Asia Pacific 20,460,000
Western Europe 1,110,000
South Southeast Asia 35,140,000
North Africa Middle East 7,502,000
Sub-Saharan Africa 15,012,000
Latin America Caribbean 6,065,000
Australia New Zealand 30,000
Total cases 88 million
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Magnitude of HIV Burden
WHO region HIV infection Prevalence of TB () Coinfection
Africa 18.7 M 48 9 M
SEA / W Pacific 6.0 M 40 2.4 M
Americas 1.3 M 30 0.4 M
East Mediterranean 0.18 M 23 0.04 M
Europe / USA 1.35 M 11 0.15 M
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HIV TB - I

• IMPACT OF HIV INFECTION ON TB
• Risk of development of TB in HIV infection-
• - 6.9 cases/100 person-year (TRC Chennai, 2000)
• Increasing HIV prevalence in TB clinic attendees-
• - 3.2 in 1991 to 20.1 in 1996 (Pune)
• - 0.77 in 1991 to 3.4 in 1993 (M.C.Chennai)
  16 in 1996 (TRC, Chennai)

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HIV TB - II

• IMPACT OF TB ON HIV
• TB induces cytokines ? viral replication.
• Negative impact of TB on HIV infection course.
• Death rate of patients with TB and HIV infection
  twice that of CD4 matched controls with HIV
  infection.
• Most deaths due to HIV infection and not TB.

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TB Presentation prior to diagnosis of AIDS
Coinfection Coinfection
Total No. TB before AIDS
SF (Chaisson, 1987) 35 62
NY (Louie, 1986) 24 62
NY (Hand Wesger, 1987) 30 60
Newark (Sunderam, 1986) 29 48
LA (Modilevsky, 1989) 39 67
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Case study

• A 25 year old man presents with a PUO of 3 months
  duration.
• On examination he is febrile (102 F)
• He has large nodes in the axillary and
  cervical regions. On examination of the abdomen
  he has hepatosplenomegaly and respiratory system
  reveals crackles diffusely bilaterally.

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CMC, Vellore
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What is your differential diagnosis?

• Disseminated tuberculosis
• Lymphoma
• Histoplasmosis
• Cryptococcosis
• Cytomegalovirus
• Mycobacterium avium intracellulare

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Pulmonary Opportunistic Infections in HIV
subjects in India
1991-94 1991-94 1994-97 1994-97
No. No.
No. of HIV ve 78 112
Infections Infections Infections Infections Infections
Pulm TB 24 30.8 32 28.6
EPT 21 26.9 25 22.3
Disseminated TB 5 6.4 20 17.9
URI 16 20.5 16 14.3
Interstitial (PCP) 2 2.6 10 8.9
Non TB 24 30.8 30 26.8
Arora Kumar 1999 Arora Kumar 1999 Arora Kumar 1999 Arora Kumar 1999 Arora Kumar 1999
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Role of steroid therapy

• Indications
• TB meningitis/ cerebral involvement
• TB pericardial effusion
• TB adrenal involvement (replacement doses only)
• Schedule (for meningitis, pericarditis)
• Prednisolone 60 mg OD for 2 weeks and then taper
  over four weeks

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Extra Pulmonary TB

• Lymphadenitis Most common
• Disseminated Tb. Bacteraemia
• 
  Blood, bone marrow)
• Genitourinary
  37
• Abnormal urinalysis
• Positive urine culture
• Meningeal TB 10
• Meningitis/Hydrocephalus
• Abnormal CT and CSF
• TB abscesses Pancreas, spleen, breast, liver,
  abd. wall, psoas, mediastinal

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Atypical Features (Extrapulmonary)

• Generalized lymphadenitis
• Hepatosplenomegaly, anemia, leukopenia,
  pancytopenia
• Genitourinary TB
• GI involvement Peritoneal/intestinal
• CNS meningitis, tuberculomas
• Pericarditis/myocarditis
• Disseminated involvement

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Impact

• Increase in morbidity and mortality due to active
  tuberculosis and HIV infection
• Increases spread to contacts horizontal
  transmission in community
• Increased incidence of drug resistant organism
• Nosocomial outbreaks of MDR tuberculosis

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Strategies to prevent MDR

• Early diagnosis- previous therapy for TB
• Isolation of MDR cases
• Active treatment with second line drugs under
  direct supervision
• Culture and drug susceptibilty testing
• Proper reporting of MDR cases
• Chemoprophylaxis for contacts

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What treatment would you start?

• Anti-tuberculous therapy
• Category I DOTS
• Duration not less than 6 months
• Cotrimoxazole DS 1 tablet daily, life long

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Impact of HIV in the U.S.A.

• App. 28000 excess cases of TB between 1984-1990
• Largest increase in areas with greatest number of
  AIDS cases and highest HIV infection
• 
  CDC 1991

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Drug resistance and HIV
CDC guidelines, MMWR, Oct 1998
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HIV TB Coinfection Concerns

1. Resurgence of TB
2. Reactivation / Re-infection
3. Augmented effects
4. Clinical Manifestations
5. Diagnosis and Management - difficulties

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? Incidence ? TB transmission ? Drug resistance ?
Mortality
TB
HIV
? Viral load ? CD4 count ? Survival
Tripathi Narain TB 2001
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TB Resurgence

• TB Leading opportunistic infection in HIV
• AIDS defining illness (1st indication of immune
  deficiency)
• Coinfection About 38 (15 of 40 million,
  globally)
• Risk of TB 7-10 per year (Almost 100 life time
  risk)
• TB in HIV (100 times population incidence)

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Endogenous reactivation

• HIV is the most potent risk factor for
  reactivation of latent tuberculosis
• HIV negative rate lt1 per year
• (10
  lifetime)
• HIV positive rate 7-10 per year
• (apprx 100
  lifetime)
• Incidence of TB is 100 times in HIV than in
  general population

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Exogenous infection

• Patient with HIV infection develops infection
  with Myco Tuberculosis 40 develop active
  disease within weeks and progresses rapidly.
• Associated with increased morbidity and mortality
• despite optimal treatment
• Spread the disease rapidly among contacts and
  health care workers leading to nosocomial
  outbreaks

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Evidence exogenous infection

• HIV patients with low CD4 counts are likely to
  visit hospitals where TB transmission is likely
• Usually have pattern of L Zone infiltrates,
  adenopathy, pleural effusion suggestive of recent
  infection
• RFLP analysis has confirmed 40 of such patients
  have identical strain of MTB suggesting
  clustering of contacts

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HIV related TB-clinical features
HIV negative Early HIV Advanced HIV
Chest X-ray U. lobe- 50 Cavities- 50 Mixed Adenopathy Effusion Lower lobe Miliary
Sites Pulm-80 Extrapulm-16 Both-4 Intermediate Pulm-30 Extrapulm-30 Both-30
Sputum 70 50 30
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Molecular diagnosis-RFLP
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Bacteriophage Assay

• Utilizes specific mycobacteriophage to identify
  presence of viable t. b. in sputum
• Virucidal solution added to kill free phages
• Bacilli infected with phage amplified by adding
  nonpathogenic mycobacteria
• Colony of phages visualized as plaques on lawn of
  mycobacteria
• Drug susceptibility results possible in 48 hrs

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Initiating ART in HIV infection
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