This document discusses the close interlink between tuberculosis (TB) and HIV, noting that TB is a leading cause of HIV-related morbidity and mortality. It explains that HIV increases the risk of developing active TB for those with latent TB infections, and that people living with HIV have a 10-50% increased lifetime risk of developing TB compared to HIV-negative individuals. The document also describes how TB and HIV interact and influence each other, exacerbating the diseases. It provides details on diagnosing and treating co-infections of TB and HIV.
Cytoskeleton and Cell Inclusions - Dr Muhammad Ali Rabbani - Medicose Academics
Tuberculosis & hiv coexistence
1. Tuberculosis & HIV Coexistence
Dr. Kanwal Deep Singh Lyall
M. D. Microbiology
2. TB/HIV
• TB and HIV are closely interlinked.
• TB is leading cause of HIV-related morbidity & mortality.
• HIV is most important factor fuelling TB epidemic
• HIV is most powerful factor known to ↑ risk of TB.
• TB can occur at any point in the course of progression of HIV
infection
• A person infected with HIV has a 10 times ↑ risk of
developing TB.
3. • HIV ↑ susceptibility to infection with M. Tb
• HIV ↑ risk of progression of M. Tb infection to Tb disease.
• ↑ rate of progression of recent or latent M. Tb infection to
disease.
HIV status Lifetime risk of developing TB
negative 5–10%
positive 50%
4. Facts
• TB - leading cause of death among people living with HIV in
Africa & a major cause of death elsewhere.
• ≈ 1.4 million HIV positive TB patients globally in 2008
• 500,000 people died of HIV-associated TB in 2008.
• At least 1/3 of the 33.2 million people living with HIV
worldwide are infected with TB,
• Are 20-30 times more likely to develop TB than those without
HIV
• 1 in 4 people with HIV die due to TB.
• People living with HIV are facing emerging threats of drug-
resistant TB
5. Co-pathogenicity of TB & HIV Disease
• M. Tb enter lungs- taken up by alveolar macrophages- present
Ags to Ag-specific CD4+ T cells
• T cells release cytokines that activate macrophages & enhance
their ability to contain M.tb infection.
• Activated macrophages also release pro-inflammatory cytokines,
such as TNF & IL-1
• Mycobacteria & their products also enhance viral replication
• They induce nuclear factor kappa-B, the cellular factor that binds
to promoter regions of HIV
6. • In Tb major effecter cell in cell mediated immunity are CD4+
T-cells
• In HIV the target cells are the same CD4+T-cells
• So without protection the Tb infection disseminates
7. • Immune activation from TB enhances both systemic and local
HIV replication.
• The plasma HIV RNA level rises substantially before Tb is
diagnosed
• TB treatment alone leads to reductions in the viral load in
these dually infected patients.
• TB & HIV also interact in lungs, site of 1º infection with
M. Tb
• In HIV-infected patients with Tb, researchers found that viral
load was higher in BAL from affected versus unaffected lung
8. Consequences of coexistence
• Over diagnosis of sputum smear-negative PTB
• Under diagnosis of sputum smear-positive PTB
• Inadequate supervision of anti-TB chemotherapy
• Low cure rates
• High morbidity during treatment
• High mortality rates during treatment
• High default rates because of adverse drug reactions
• High rates of TB recurrence
• ↑ transmission of drug-resistant strains among HIV-infected
9. HIV /TB in children
• Several HIV-related diseases, including TB, may present in a
similar way
• The interpretation of tuberculin skin testing is less reliable
• In early HIV infection-immunity good, signs of TB are similar
to those without HIV
• In late HIV infection -immunity declines-dissemination of TB
• Tubercular meningitis, miliary TB, widespread tuberculous
LAP
10. Clinical Features Suggestive Of HIV Co-infection In TB Patients
Past history •Sexually transmitted infection history
•Herpes zoster (shingles)
•Recent or recurrent pneumonia
•Severe bacterial infections (sinusitis, bacteraemia, pyomyositis)
•Recent treated TB
Symptoms •Weight loss (> 10 kg or > 20% of original weight)
•Diarrhoea (> 1 month)
•Retrosternal pain on swallowing(suggests oesophageal candidiasis)
•Burning sensation of feet(peripheral sensory neuropathy)
Signs •Scar of herpes zoster
•Pruritic (itchy) papular skin rash
•Kaposi sarcoma
•Symmetrical generalized lymphadenopathy
•Oral candidiasis
•Angular cheilitis
•Oral hairy leukoplakia
•Necrotizing gingivitis
•Giant aphthous ulceration
•Persistent painful genital ulceration
11. Radiological findings
• The classical pattern is more common in HIV-negative patients, & atypical
pattern in HIV-positive patients.
CLASSICAL PATTERN ATYPICAL PATTERN
upper lobe infiltrates , bilateral infiltrates interstitial infiltrates (especially lower zones)
Cavitation intrathoracic lymphadenopathy
pulmonary fibrosis and shrinkage no cavitation, no abnormalities
Early HIV Late HIV
12. • PTB is commonest form of TB
• The commonest forms extrapulmonary TB are:
• Pleural effusion, lymphadenopathy, pericardial disease, miliary
disease, meningitis, disseminated TB (with mycobacteraemia)
Features of PTB Stage of HIV infection
Early late
Clinical picture Often resembles
post-primary PTB
Often resembles primary PTB
Sputum smear
result
Often positive Often negative
CXR appearance Often cavities Often infiltrates
with no cavities
13. Tuberculin skin (Mantoux) test
• Tuberculin skin reactivity - dependant on cytokine mediated
cellular immunity
• An induration of ≥5 mm , in response to 1 TU of PPD
tuberculin = a positive response, in HIV-infected individuals
• In TB high prevalence countries like India, tuberculin skin
testing has no value in TB diagnosis, as a positive test
indicates prior infection only & false negativity
14. Treatment of TB & HIV co-infection
• Till date no cure is available for HIV/AIDS
• Anti retroviral drugs used to treat HIV/AIDS effectively slow
down action of virus & prolong life of patients
• Treatment for TB is same for HIV infected as for non-HIV
infected TB patients.
• Same criteria determine treatment category for TB patients
irrespective of HIV status.
15. • Current guidelines recommend that irrespective of HIV status,
TB requires a minimum of 6 months of treatment with 4 drugs
(including rifampin) in intensive phase & 2 drugs in
continuation phase
• Treatment consists of INH, RIF, EMB & PYZ x 2 months
• f/b INH and RIF for 4 months, given either daily or
intermittently.
16.
17. Anti-TB drug resistance
• MDR-TB is marginally higher (3-4%) in HIV positive patients
with newly diagnosed TB
• Rifampicin mono- resistance is more common in HIV infected
patients may be due to malabsorption of anti-TB drugs
• Outcome of MDR-TB in HIV is poor
• Strains of M. tuberculosis labelled as (XDR) TB have emerged
and spread rapidly through HIV-infected populations leading
to high mortality
HRZE x 3 times a week x 2 mnths
HR x 3 times a week x 4-5 mnths
Immune reconstitution inflammatory syndrome (IRIS) is defined as transient worsening or appearance of new symptoms,
signs or radiographic manifestations after initiation of HAART. Tuberculosis is the most frequent pathogen associated
with IRIS, of which, lymph node enlargement is the commonest manifestation.