Tuberculosis: Pathogenesis, Diagnosis (Mantoux, Diaskintest, CT), and Treatment Regimens

1. Epidemiology

• Globally, ~10 million new cases and 1.5 million deaths occur annually.
• Russia is among the 30 countries with a high burden of TB and MDR-TB.
• Risk groups: HIV-infected individuals, migrants, prisoners, people with diabetes, smokers, and close contacts.

2. Pathogen and pathogenesis

Mycobacterium tuberculosis is a slow-growing acid-fast bacillus. Transmission occurs via airborne droplets < 5 µm. The infectious dose is 1–3 bacilli.

Upon reaching the alveoli, macrophages engulf the pathogen, but M. tuberculosis is able to inhibit phagosome-lysosome fusion. A granuloma is formed (typically featuring Langhans giant cells) with central caseous necrosis. 90% of infected individuals develop a latent form, while 10% develop active TB during their lifetime. In HIV infection, the risk of reactivation is 7–10% per year.

3. TB classification

• Latent tuberculosis infection (LTBI) — infection without clinical symptoms or imaging changes.
• Active tuberculosis:
  • Primary complex (Ghon focus + lymphangitis + lymphadenitis).
  • Disseminated (miliary) tuberculosis.
  • Infiltrative tuberculosis — the most common form in adults.
  • Caseous pneumonia.
  • Tuberculoma.
  • Cavernous, fibro-cavernous tuberculosis.
  • Cirrhotic tuberculosis.
  • Pleurisy, tuberculosis of the bronchi, larynx.
  • Extrapulmonary tuberculosis (bones, kidneys, intestines, meninges, pericardium, lymph nodes).

4. Clinical presentation

• Fever (usually low-grade, > 2–3 weeks).
• Cough > 3 weeks, productive.
• Hemoptysis (in destructive forms).
• Night sweats, weight loss, fatigue.
• Chest pain in pleurisy.
• Extrapulmonary TB — symptoms depend on localization.

5. Diagnosis of latent infection

6. Diagnosis of active TB

• Sputum smear microscopy (Ziehl-Neelsen stain): low sensitivity (~50%), but fast and inexpensive.
• Culture on liquid (BACTEC MGIT) and solid media (Lowenstein-Jensen) — gold standard; result 2–8 weeks, DST.
• GeneXpert MTB/RIF — PCR + rifampicin resistance detection in 2 h, WHO-recommended screening.
• LPA (line probe assay) — detection of isoniazid and fluoroquinolone resistance.
• X-ray and CT — infiltrates, cavities, dissemination, lymphadenopathy.
• Bronchoscopy with BAL — in the absence of sputum.
• Biopsy — in extrapulmonary forms; histology + culture + PCR.

7. Treatment of LTBI

• Isoniazid 5 mg/kg for 6–9 months (standard).
• Rifampicin for 4 months — alternative with lower hepatotoxicity.
• Short regimen 3HP: isoniazid + rifapentine once weekly for 12 doses.
• Indications: TB contacts, HIV, TNF inhibitors, transplant candidate.

8. Treatment of drug-susceptible TB

Standard DOTS regimen:

• Intensive phase 2 months: HRZE — isoniazid (H) + rifampicin (R) + pyrazinamide (Z) + ethambutol (E).
• Continuation phase 4 months: HR.
• Total duration — 6 months; 9 months for extrapulmonary forms, HIV, meningitis.
• The drug is taken daily under direct observation (DOT).

Side effects

• Isoniazid — hepatitis, peripheral neuropathy (prevention — pyridoxine 25 mg/day).
• Rifampicin — hepatitis, CYP induction (decreases concentration of OCs, warfarin, protease inhibitors), red discoloration of biological fluids.
• Pyrazinamide — hepatitis, hyperuricemia, arthralgia.
• Ethambutol — retrobulbar neuritis (monitoring visual acuity and color vision).

9. MDR- and XDR-TB

• MDR-TB — resistance to isoniazid and rifampicin.
• Pre-XDR-TB — MDR + resistance to fluoroquinolones OR to one of the second-line injectable drugs.
• XDR-TB — MDR + fluoroquinolone + second-line drugs (injectables or bedaquiline/linezolid per 2021 definition).
• BPaLM regimen (6–9 months): bedaquiline + pretomanid + linezolid + moxifloxacin — WHO-recommended regimen for MDR-TB and pre-XDR-TB.
• Previously — 18–24 months of injectable drugs (capreomycin, amikacin); today — transition to all-oral regimens.

10. TB and HIV

• Screening for 4 symptoms in all HIV+ individuals: cough, fever, night sweats, weight loss.
• Disseminated and extrapulmonary forms are more common.
• ART is initiated within the first 2 weeks of TB therapy if CD4 < 50 cells/mcL and within 8 weeks if CD4 ≥ 50.
• Rifampicin is replaced by rifabutin when using PIs; efavirenz is compatible with rifampicin.
• IRIS (immune reconstitution inflammatory syndrome) — a complication of rapid ART initiation.

11. Prevention

• BCG — to newborns in the maternity hospital; revaccination at age 7 (with a negative Mantoux test).
• Screening — annual fluorography; in children — Mantoux/Diaskintest.
• Isolation of bacillary patients until cessation of bacterial excretion.
• Infection control — masks, ventilation, UV irradiation in hospitals.

12. FAQ

Why is Diaskintest better than Mantoux?
Contains only recombinant ESAT-6/CFP-10 proteins absent in BCG and most non-tuberculous mycobacteria — fewer false-positive reactions.

Why is it forbidden to shorten the course of therapy?
M. tuberculosis divides very slowly; a short course leaves "persisters" — risk of relapse and development of resistance.

What to do in case of refusal of treatment?
A patient in an epidemiologically hazardous condition is hospitalized compulsorily by a court decision. This is the only disease in Russia with such a regulation (Federal Law No. 77).

Can BCG be administered in HIV?
In children with unknown HIV status — yes; with confirmed HIV — no (disseminated BCG disease).

When is the patient removed from the dispensary register?
Upon cure: after 1–3 years of follow-up depending on the form; in the presence of residual changes or risk groups — group III registration is maintained.

See also: HIV · Pneumonia · COPD · Antibiotics · Infectious Diseases Catalog