Tuberculosis (TB)

Definition

The Pathogen

• Non-motile, non-spore-forming, facultative anaerobe
• Rod-shaped, ~2-4 μm in length
• Doubles every 18-24 hours (extremely slow growth; culture may take weeks)
• "Waxy" cell envelope rich in mycolic acids - responsible for acid-fast staining (resists decolorization with strong acids after carbol fuchsin staining)
• The complex lipid-rich envelope creates a formidable barrier to antibiotic entry and is central to pathogenesis

Epidemiology

• TB is a major global health problem, particularly in sub-Saharan Africa, Southeast Asia, and Eastern Europe
• ~10 million new cases and ~1.5 million deaths per year globally (WHO)
• Risk factors for infection: close-contact exposure to active TB, congregate settings (prisons, shelters), healthcare work, travel to endemic regions
• Risk factors for progression from latent to active TB: HIV infection (strongest), TNF inhibitors, corticosteroids, diabetes mellitus, malnutrition, end-stage renal disease, silicosis, tobacco use, alcohol use, age extremes

Pathogenesis

1. Inhalation: Droplet nuclei (1-5 μm) containing M. tuberculosis reach the alveoli
2. Initial infection: Alveolar macrophages phagocytose the bacilli, but M. tuberculosis resists killing by inhibiting phagosome-lysosome fusion
3. T-cell immune response: CD4+ T cells activate macrophages via IFN-γ and TNF to form granulomas - organized collections of macrophages, epithelioid cells, Langerhans giant cells, and lymphocytes that wall off the bacteria
4. Latent TB infection (LTBI): In ~90% of immunocompetent individuals, immune control is established. Bacteria remain dormant within granulomas. The tuberculin skin test (TST) or IGRA becomes positive
5. Primary progressive TB: In ~5-10% of newly infected persons (especially the immunocompromised), infection progresses directly to active disease
6. Reactivation TB: Occurs in ~5-10% of latently infected persons over their lifetime when immunity wanes (e.g., HIV, immunosuppression, aging)

Clinical Manifestations

Pulmonary TB (most common, ~85%)

• Upper lobe predilection due to high oxygen tension
• Cavitation indicates high bacterial burden and is highly infectious
• Miliary TB: Hematogenous dissemination produces 1-2 mm nodules throughout both lungs

Extrapulmonary TB

Diagnosis

Tuberculin Skin Test (TST / Mantoux)

• Intradermal injection of purified protein derivative (PPD); read at 48-72 hours
• Positive if induration ≥5 mm (HIV+, immunosuppressed, close contacts), ≥10 mm (high-risk groups), ≥15 mm (low-risk general population)
• Cannot distinguish latent from active TB

Interferon-Gamma Release Assays (IGRAs)

• Blood-based tests (QuantiFERON-TB Gold, T-SPOT.TB)
• More specific than TST (not affected by BCG vaccination); preferred in BCG-vaccinated individuals
• A 2025 WHO guideline update consolidated recommendations on new IGRA classes

Sputum Examination

• Smear microscopy (AFB smear): Fast but low sensitivity (~50-60%)
• Culture: Gold standard; Lowenstein-Jensen or BACTEC liquid media; takes 2-8 weeks; allows drug susceptibility testing (DST)
• Nucleic acid amplification (GeneXpert MTB/RIF, Xpert Ultra): Rapid (~2 hours), high sensitivity, simultaneously detects rifampin resistance - WHO-recommended first-line test

Next-Generation Sequencing (NGS)

• Targeted NGS now validated for detecting drug-resistant TB; a 2024 Lancet meta-analysis confirmed high accuracy [PMID: 38795712]

Imaging

• CXR: Upper lobe infiltrates, cavitation, miliary pattern, adenopathy
• CT: More sensitive for early disease, mediastinal nodes, miliary spread

Treatment

Latent TB Infection (LTBI)

• 9H: Isoniazid (INH) daily x 9 months (classic regimen)
• 3HP: Isoniazid + rifapentine weekly x 12 weeks (preferred for adherence)
• 4R: Rifampin daily x 4 months

Drug-Susceptible Active TB - Standard Regimen

Key Drug Details

• Pyridoxine (vitamin B6) should be co-administered with isoniazid in at-risk patients to prevent neuropathy

Drug-Resistant TB (DR-TB)

• MDR-TB: Resistant to at least isoniazid + rifampin
• XDR-TB: MDR-TB + resistance to fluoroquinolones and at least one injectable agent
• Treatment requires newer agents: Bedaquiline (BDQ), Linezolid (LZD), Pretomanid - the BPaL regimen (6 months) has shown strong results for XDR-TB
• A 2025 WHO consolidated guideline update covers new DR-TB regimens

TB-HIV Co-infection

• HIV is the most powerful risk factor for TB progression and death
• TB is the leading cause of death in HIV-positive individuals globally
• Antiretroviral therapy (ART) should be started within 2-8 weeks of TB treatment initiation (except TB meningitis - defer ART 4-8 weeks due to immune reconstitution inflammatory syndrome/IRIS risk)
• Rifampin significantly reduces levels of many antiretrovirals (CYP induction); rifabutin is often substituted

Prevention

• BCG vaccine: Bacille Calmette-Guérin - derived from attenuated M. bovis. Given at birth in endemic countries. Highly protective against miliary and meningeal TB in children; modest protection against pulmonary TB in adults
• Infection control: Airborne precautions (negative-pressure rooms, N95 respirators), prompt diagnosis and treatment of infectious cases
• Screening and treatment of LTBI: Key strategy in low-incidence countries

Special Populations

• Children: More likely to develop extrapulmonary and disseminated disease; diagnosis more challenging (paucibacillary)
• Pregnancy: TB treatment should not be delayed; avoid streptomycin (ototoxic to fetus); pyrazinamide safety in pregnancy is debated
• Renal impairment: Pyrazinamide and ethambutol require dose adjustment; isoniazid and rifampin are hepatically cleared and generally safe
• TB Meningitis: A 2026 Lancet clinical practice guideline provides updated management recommendations [PMID: 40840485]

Tuberculosis (TB) - Roman Urdu Mein

Tarif (Definition)

Jarsuma (The Pathogen)

• Akar mein chhati (rod-shaped), ~2-4 μm lamba
• Har 18-24 ghante mein ek baar taqseem hota hai - bohat slow growth
• Culture karne mein hafton lag sakte hain
• "Momy" (waxy) cell envelope jis mein mycolic acids hote hain - yahi wajah hai ke acid-fast stain mein rang pakad leta hai
• Ye moti diwar antibiotics ko andar aane se rokti hai
• Acid-fast bacillus (AFB) kehte hain kyunke strong acid se rang nahi ukharta

Wabai Kasrat (Epidemiology)

• Duniya mein har saal ~1 crore naye cases aur ~15 lakh mautein
• Zyada tar: Sub-Saharan Africa, South-East Asia, Eastern Europe
• Infection ka khatra zyada in logon mein:
  • TB patient ke qareeb rehne wale
  • Jail, shelter, hospital mein rehne wale
  • Healthcare workers
  • Mahez maqamat (endemic areas) ka safar
• Latent se Active TB hone ka khatra:
  • HIV infection (sabse taqatwar factor)
  • TNF inhibitors (jaise Biologics)
  • Corticosteroids
  • Diabetes mellitus
  • Kudhorosazi (malnutrition)
  • Renal failure, silicosis, sigret, sharab

Bimari Kaise Lagti Hai (Pathogenesis)

1. Saanson ke zariye andar aana: Chhoti droplet nuclei (1-5 μm) phuphdon ke alveoli tak pahunchti hain
2. Pehla hamla: Macrophages bacteria ko nigal lete hain, lekin TB ka jarsuma un macrophages ke andar bhi bachne ki salahiyat rakhta hai - phagosome-lysosome fusion rok deta hai
3. Immune response: CD4+ T cells activate hoti hain, IFN-γ aur TNF release hota hai, aur granuloma banta hai - ek deewar jo bacteria ko band kar deti hai
4. Latent TB (LTBI): ~90% mein immune system qaboo pa leta hai - bacteria so jate hain. TST ya IGRA test positive ho jata hai
5. Active TB: ~5-10% mein ya toh seedha bimari ho jati hai (primary progressive) ya baad mein immunity kamzor hone par reactivation hoti hai

Alamaat (Clinical Manifestations)

Phuphde ki TB (Pulmonary TB) - Sabse Aam (~85%)

• Upper lobe mein zyada hoti hai kyunki wahan oxygen zyada hoti hai
• Cavity matlab zyada bacteria - bohat infectious
• Miliary TB: Khoon ke zariye poore jism mein phelti hai, chhote chhote dhabbe (1-2 mm) dono phuphdon mein

Baahar ke andar ki TB (Extrapulmonary TB)

• Bukhaar, sar dard, gardan akad jaana
• Aankhon ki nerves mutasir, hosh mein kami
• Alamaat 5-30 din mein aati hain
• HIV waalon mein zyada common
• CT scan par ring-enhancing lesions (tuberculoma) nazar aate hain

• Gardan ki giltiyaan (posterior cervical nodes) - dard nahi hota
• Dheere dheere peet kar naasoor ban jaata hai
• Bacchon mein zyada
• Pakistan/endemic areas mein ye TB se hoti hai, US mein aksar non-tuberculous mycobacteria se

• Peshaab mein pus ya khoon (sterile pyuria/hematuria)
• Aurtein: Haiz mein khallal, bachcha paida karne mein mushkil
• Mard: Khusyon mein ganth, epididymitis
• CT par: Gurde mein daag, nali mein tangiyaan (strictures)

• Dheere dheere pani jama hota hai - tamponade ka khatra
• Bukhaar, raat ko pasina, saans ki takleef, paon mein sojan
• Baad mein Constrictive Pericarditis ho sakti hai

• Haddi gal ke khamda ho jaati hai (kyphosis / "gibbus deformity")
• Reeh ki haddi dab sakti hai - paralysis ka khatra

• Aant ke nihayat aakhri hisse (terminal ileum) aur ileocecal valve pe hoti hai
• Crohn's disease se milti julti hai
• Dast, roadstay (obstruction), nasooren (fistulae)

Tashkhees (Diagnosis)

Tuberculin Skin Test (TST / Mantoux)

• Jild ke neeche PPD ka injection - 48-72 ghante baad padha jaata hai
• Positive agar sujan (induration):
  • ≥5 mm: HIV+ ya immunocompromised mein
  • ≥10 mm: High-risk groups mein
  • ≥15 mm: Aam logon mein
• Latent aur active TB mein farq nahi kar sakta
• BCG vaccine lagey hoin to false positive aa sakta hai

IGRA Test (Blood Test)

• QuantiFERON-TB Gold ya T-SPOT.TB
• Khoon ka test - BCG se mutasir nahi hota
• BCG lagay hue logon mein TST se behtar

Balgham ka Muayena

• AFB Smear: Jaldi hota hai, lekin ~50-60% sensitivity
• Culture: Gold standard - 2-8 hafton mein nataija, drug resistance bhi pata chalta hai
• GeneXpert MTB/RIF (Xpert Ultra): Sirf 2 ghante mein nataija + rifampin resistance bhi detect karta hai - WHO ka pehla recommended test

Next-Generation Sequencing (NGS)

• Drug-resistant TB pakarne mein bohat accurate
• 2024 ki Lancet meta-analysis ne iski saheeh accuracy confirm ki [PMID: 38795712]

Imaging (Tasweerain)

• CXR: Upper lobe infiltrates, cavities, miliary pattern, nodes
• CT Scan: Zyada sensitive - chhoti abnormalities bhi nazar aati hain

Ilaaj (Treatment)

Latent TB Infection (LTBI) - Active hone se rokne ka ilaaj

Active Drug-Susceptible TB - Standard Regimen

Dawaaon ki Tafseel

• Pyridoxine (Vitamin B6) Isoniazid ke saath dena chahiye - neuropathy se bachata hai

Drug-Resistant TB (DR-TB)

• MDR-TB: Isoniazid + Rifampin dono se resistance
• XDR-TB: MDR-TB + fluoroquinolones aur injectable agents se bhi resistance
• Naye ilaaj:
  • Bedaquiline (BDQ) + Pretomanid + Linezolid (LZD) = BPaL regimen - sirf 6 mahine, XDR-TB mein kaafi kamyaab
• WHO ne 2025 mein naye DR-TB guidelines jari kiye hain

TB aur HIV

• HIV sabse taqatwar risk factor hai TB ke active hone ka
• TB, HIV+ logon ki maut ki sabse badi wajah hai duniya mein
• ART (antiretroviral therapy) TB treatment shuru hone ke 2-8 hafte mein shuru karein
  • Exception: TB Meningitis mein ART 4-8 hafte delay karein - IRIS ka khatra
• Rifampin bohat si ARV dawaaen weak kar deta hai (CYP induction) - aksar Rifabutin use karein

Bachao (Prevention)

• BCG Vaccine: Bacille Calmette-Guérin - M. bovis se bana hua. Bacchon ko paida hote hi lagaai jaati hai. Miliary aur meningeal TB se bohat achha bachao karta hai
• Infection Control: Negative-pressure kamre, N95 mask, jaldi tashkhees aur ilaaj
• LTBI ki screening aur ilaaj: Kam-incidence mulkon mein bimari khatam karne ki key strategy

Khaas Haalaat (Special Populations)