Tuberculosis (TB) is a contagious (spreadable) bacterial infection caused by Mycobacterium tuberculosis (also called the "tubercle bacillus"). It mainly attacks the lungs (pulmonary TB) but can also affect other parts of the body like the brain, spine, kidneys, and bones (extrapulmonary TB).

• Airborne Transmission: TB spreads when an infected person coughs, sneezes, or talks, releasing droplet nuclei into the air.
• Latent vs. Active: Not everyone who gets infected becomes sick. Some people have latent TB (sleeping TB) where the bacteria are walled off by the immune system (granulomas) but are not causing symptoms. Active TB means the person is sick, symptomatic, and can spread the disease to others.
• TB is one of the top 10 causes of death worldwide and remains a major public health problem in Uganda.

Uganda is classified as a high-burden TB country. This means:

• Many people in Uganda get TB every year.
• TB and HIV often occur together (co-infection), as HIV depletes the CD4 T-cells needed to keep TB dormant.
• The government, through the National Tuberculosis and Leprosy Program (NTLP), manages TB care.
• Community health workers, nurses, and village health teams (VHTs) play a critical role in finding TB cases and supporting treatment.

• Nurses are often the first point of contact for patients.
• Nurses give Directly Observed Therapy (DOT) – physically watching patients take their medicine to ensure compliance.
• Nurses educate families and communities about TB prevention and infection control.
• Nurses monitor for severe adverse side effects and ensure patients complete the long treatment course.

TB treatment always uses multiple drugs together, never just one drug. This is because:

• Different mechanisms: Different drugs attack the bacteria in different ways – some kill quickly (bactericidal), some kill slowly (bacteriostatic).
• Prevents drug resistance: Mycobacteria mutate rapidly. If you use only one drug, the bacteria will naturally mutate and survive it.
• Improves cure rates: Using 4 drugs in the intensive beginning phase gives the best chance of killing all the rapidly dividing bacteria and penetrating the thick granulomas.

Anti-TB drugs are divided into groups based on how effective they are and when they are used.

These are the most effective, best-tolerated drugs used for drug-susceptible TB (TB that responds to standard treatment).

Used when first-line drugs fail or when the bacteria are resistant. These drugs are: Less effective, more toxic (more side effects), more expensive, and often given for longer periods (up to 18-24 months).

• Group A (Fluoroquinolones) – Most effective second-line drugs: Levofloxacin, Moxifloxacin.
• Group B (Injectable agents) – Given by injection: Amikacin, Kanamycin, Capreomycin.
• Group C (Other core second-line agents) – Cycloserine, Ethionamide / Prothionamide, Para-aminosalicylic acid (PAS).
• Group D (Add-on agents)
  • D1: Pyrazinamide, Ethambutol, High-dose Isoniazid.
  • D2: Bedaquiline, Linezolid, Delamanid, Clofazimine.
  • D3: Amoxicillin-clavulanate, Imipenem, Meropenem, Clarithromycin.

These are recently developed drugs for drug-resistant TB:

• Bedaquiline (Bdq): First new anti-TB drug in 50 years!
• Pretomanid (Pa): Used in combination with bedaquiline and linezolid (BPaL regimen).
• Delamanid (Dlm): Another new oral drug.

Isoniazid is the most important first-line anti-TB drug. It is highly effective at killing rapidly growing TB bacteria.

• Mechanism of Action: Prevents the bacteria from making mycolic acid – a special fatty acid that forms the unique, waxy outer wall of TB bacteria. Without mycolic acid, the bacteria cannot build their protective coat and they die. (Think of it like removing the bricks from a house – the house collapses!)
• Pharmacokinetics:
  • Absorption: Well absorbed from the stomach when taken on an empty stomach.
  • Distribution: Goes everywhere in the body, including the brain (crosses the blood-brain barrier).
  • Metabolism: Broken down in the liver by enzymes (via acetylation).
  • Excretion: Removed from the body mainly through the kidneys in urine.
• Dosing in Uganda: Adults = 10 mg/kg (max 300 mg/day). Children = 10 mg/kg (range 7-15 mg/kg).
• Side Effects (Adverse Effects):
  • Peripheral Neuropathy: Numbness, tingling, or burning sensation in hands and feet. Why: Isoniazid uses up and promotes the excretion of vitamin B6 (pyridoxine). Prevention: Give pyridoxine 25-50 mg daily.
  • Hepatotoxicity (Liver Damage): Jaundice, dark urine, abdominal pain, nausea. Nursing action: Monitor LFTs. Stop drug if jaundice appears.
  • Other: Nausea, vomiting, rash, fever, joint pains.
• Contraindications: Active liver disease, known allergy, severe liver damage.
• Drug Interactions: Phenytoin (increases phenytoin levels ➔ toxicity), Warfarin (effect reduced by Rifampicin), Carbamazepine (levels increased).
• Nursing Implications: Always give pyridoxine. Take on an empty stomach (1 hr before or 2 hrs after food). Monitor for signs of liver damage. Educate patient to report numbness/tingling immediately.

Rifampicin is a broad-spectrum antibiotic that kills both actively growing and "sleeping" TB bacteria. It is one of the most powerful anti-TB drugs.

• Mechanism of Action: Blocks DNA-dependent RNA polymerase – the enzyme the bacteria need to transcribe DNA into mRNA to make proteins. Without RNA polymerase, the bacteria cannot communicate or reproduce (like cutting the phone line).
• Pharmacokinetics:
  • Absorption: Well absorbed, but food reduces absorption.
  • Distribution: Reaches all tissues (brain, bones, lungs).
  • Metabolism & Excretion: Broken down in liver, removed mainly through bile (into stool) and some in urine.
• Dosing in Uganda: Adults = 10 mg/kg (max 600 mg/day). Children = 15 mg/kg.
• Side Effects:
  • Hepatotoxicity: Liver damage (especially when combined with INH and PZA).
  • Orange/Red Discoloration: Urine, sweat, tears, and saliva turn orange-red. Harmless, but patients MUST be warned to avoid panic. Contact lenses may be permanently stained.
  • Flu-like Syndrome: Fever, chills, muscle aches (usually with intermittent dosing).
  • GI Upset & Thrombocytopenia: Low platelet count (rare but serious).
• Drug Interactions (VERY IMPORTANT!): Rifampicin is a strong CYP450 enzyme inducer – it speeds up the breakdown of many other drugs.
  • Oral contraceptives: Reduced effectiveness ➔ unplanned pregnancy (Use condoms/IUD).
  • Warfarin: Reduced anticoagulant effect (Monitor INR).
  • Nevirapine/Dolutegravir (HIV drugs): Reduced HIV treatment levels.

Pyrazinamide is a unique drug that kills TB bacteria in acidic environments – like inside human macrophages where TB bacteria hide.

• Mechanism of Action: Converted inside the bacteria into pyrazinoic acid. This disrupts the bacteria's ability to make energy and build cell walls. It is a special key that opens a locked door inside cells to kill dormant bacteria.
• Dosing in Uganda: Adults = 30-40 mg/kg (max 2500 mg/day). Children = 35 mg/kg.
• Side Effects:
  • Hyperuricemia (High Uric Acid): Causes gout-like joint pains. Why: PZA prevents the kidneys from removing uric acid. Manage with paracetamol/ibuprofen.
  • Hepatotoxicity: High risk when combined with INH and RIF.
  • Photosensitivity & Rash: Skin sensitive to sunlight.

Ethambutol is a bacteriostatic drug – it stops bacteria from growing rather than killing them directly. Used to prevent resistance.

• Mechanism of Action: Blocks arabinosyl transferase, stopping arabinogalactan synthesis (needed to build the bacterial cell wall). Like stopping the delivery of building materials.
• Dosing in Uganda: Adults = 15 mg/kg. Children = 20 mg/kg.
• Side Effects:
  • Optic Neuritis (Eye Nerve Damage): The most serious side effect! Symptoms: Blurred vision, reduced color vision (especially red-green), visual field defects. Action: Stop drug immediately. Reversible if caught early.
• Contraindications: Pre-existing optic neuritis. Children under 5 years (because it is too difficult for a toddler to communicate that they are losing their color vision!).

• Mechanism of Action: An injectable aminoglycoside. Binds to the 30S bacterial ribosome (protein-making factory) and prevents protein synthesis.
• Side Effects: Ototoxicity (Inner ear damage causing permanent hearing loss, ringing/tinnitus, vertigo) and Nephrotoxicity (Kidney damage).
• Contraindications: Pregnancy (can cause congenital deafness in the baby).

• Levofloxacin and Moxifloxacin: Most effective second-line drugs.
• Mechanism: Inhibit DNA gyrase (prevents bacteria from copying their DNA).
• Side Effects: Tendon damage/rupture (rare), QT prolongation (heart rhythm problems), photosensitivity. Monitor ECGs.

• Amikacin, Kanamycin, Capreomycin: Can cause severe Ototoxicity and Nephrotoxicity. Monitor electrolytes (low K+ and Mg2+).
• Cycloserine: Causes severe psychiatric problems (depression, psychosis, seizures). Give pyridoxine.
• Ethionamide / Prothionamide: Causes severe metallic taste, severe nausea, and hypothyroidism.
• Para-aminosalicylic Acid (PAS): Inhibits folate synthesis. Severe GI upset.

• Bedaquiline: Inhibits ATP synthase (cuts off the bacteria's energy supply). Watch for QT prolongation.
• Pretomanid: Used in the BPaL regimen. Inhibits cell wall synthesis.
• Linezolid: Inhibits protein synthesis. Watch for bone marrow suppression (low blood counts) and lactic acidosis.

For Adults and Adolescents (>15 years): 2RHZE / 4RH

• Initial Phase (2 months): Rifampicin + Isoniazid + Pyrazinamide + Ethambutol
• Continuation Phase (4 months): Rifampicin + Isoniazid
• Total Duration: 6 months (Given as Fixed-Dose Combination tablets based on weight bands: 33-39kg = 1 tab, 40-54kg = 2 tabs, 55-70kg = 3 tabs, >70kg = 4 tabs).

For Children:

• All forms (except meningitis/bone): 2RHZE / 4RH
• TB Meningitis / Bone TB (Osteoarticular): 2RHZE / 10RH (Requires a full 12 months because these tissues are very hard for drugs to penetrate).
• Note: Weigh the child at EVERY visit and adjust doses!

The WHO and Uganda are introducing a shorter 4-month regimen for eligible adults/adolescents:

• Intensive Phase (2 mos): Isoniazid + Rifapentine + Pyrazinamide + Moxifloxacin
• Continuation Phase (2 mos): Isoniazid + Rifapentine + Moxifloxacin
• Eligibility: >12 years, >40 kg, drug-susceptible, HIV+ with CD4 >100 on compatible ART (efavirenz/dolutegravir).
• NOT Eligible: Pregnant/breastfeeding, <12 years, severe extrapulmonary TB.

Children aged 3 months to 16 years with Non-Severe TB (e.g., uncomplicated peripheral lymph node TB) can be treated for just 4 months. Do NOT use for severe TB (miliary, meningitis, cavitary).

• MDR-TB (Resistant to Rifampicin and Isoniazid): Requires individualized steps using Groups A, B, C, D for 18-24 months.
• New 6-Month All-Oral Regimens:
  • BPaLM: Bedaquiline, Pretomanid, Linezolid, Moxifloxacin (for fluoroquinolone-susceptible MDR-TB).
  • BPaL: Bedaquiline, Pretomanid, Linezolid (for fluoroquinolone-resistant MDR-TB).

• Mono-Resistance: Resistance to ONE first-line drug only (e.g., INH mono-resistance).
• Poly-Resistance: Resistance to more than one first-line drug (but NOT both RIF and INH).
• Multidrug-Resistant TB (MDR-TB): Resistance to BOTH Rifampicin and Isoniazid. Highly dangerous.
• Extensively Drug-Resistant TB (XDR-TB): MDR-TB PLUS resistance to any fluoroquinolone AND at least one injectable second-line drug. Extremely high death rate.
• Rifampicin-Resistant TB (RR-TB): Treated exactly the same as MDR-TB.

Causes: Incomplete treatment, poor adherence, wrong prescribing, substandard drugs, or catching a mutated strain from someone else.

• Signs to Watch For: Jaundice (yellow eyes/skin), dark urine, pale stools, severe nausea/vomiting, abdominal pain (especially Right Upper Quadrant).
• What to Do: Stop ALL hepatotoxic drugs immediately (INH, RIF, PZA). Keep ethambutol/streptomycin if needed to cover the patient. Monitor Liver Function Tests (LFTs) until they return to normal. Reintroduce drugs one by one starting with the least hepatotoxic.

• Signs: Severe rash with blisters, peeling skin, sores in mouth/eyes/genitals, severe fever.
• What to Do: This is a medical emergency. Stop ALL anti-TB drugs immediately. Admit to hospital for fluids/pain relief. Do NOT reintroduce drugs without specialist help.

TB and HIV are a deadly duo. When treating both, timing and drug choices are critical:

• Preferred ART in Uganda: TDF + 3TC (or FTC) + DTG (Dolutegravir). Alternative: TDF + 3TC + EFV (Efavirenz).
• Important Timing Notes:
  • Rifampicin reduces Dolutegravir (DTG) levels. You MUST separate timing or double the DTG dose to ensure the HIV is controlled.
  • Rifampicin severely reduces Lopinavir/Ritonavir.
  • Efavirenz is the most compatible with Rifampicin.

DOT means a healthcare worker, VHT, or trained family member watches the patient physically swallow every dose. This is the gold standard because it ensures correct dosing, prevents resistance, and allows daily monitoring of side effects.

• About Infection Control: "Cover your mouth when coughing. Sleep in a separate room for the first 2 weeks. Open windows for fresh air."
• About Treatment: "Do NOT stop taking medicine even if you feel better after a month. Missing doses creates super-bacteria."
• About Side Effects: "Orange urine is normal (Rifampicin). Report yellow eyes, severe nausea, or numbness immediately."

• Children Under 5: Screen for symptoms. If NO symptoms, they must receive Isoniazid Preventive Therapy (IPT) for 6 months (10 mg/kg + pyridoxine daily).
• PLHIV (People Living with HIV): Screen at every visit (Cough, Fever, Weight loss, Night sweats). If no symptoms, give TPT (Tuberculosis Preventive Treatment).
• Uganda TPT Regimens: 6H (Isoniazid for 6 mos), 3HP (Rifapentine+INH for 3 mos), 1HP (for 1 month).
• Note: For PLHIV starting dolutegravir-based ART, delay TPT for 3 months to avoid drug interactions.

• Orange urine? ➔ Rifampicin (It's NOT blood!)
• Requires pyridoxine? ➔ Isoniazid.
• Eye problems? ➔ Ethambutol.
• NOT for children under 5? ➔ Streptomycin (hearing) AND Ethambutol (can't test vision).
• Enzyme inducer? ➔ Rifampicin.

• Patient: Diagnosed with pulmonary TB. On oral contraceptives (Lo-femenal). Has a 3-year-old child.
• Nursing Actions: Start 2RHZE/4RH. Change contraception immediately (Rifampicin destroys estrogen pill efficacy; recommend IUD or condoms). Screen the 3-year-old child; if asymptomatic, start the child on 6 months of IPT (Isoniazid + Pyridoxine). Warn her about orange urine.

• Patient: CD4 150. On TDF/3TC/NVP (nevirapine-based ART).
• Nursing Actions: Start 2RHZE/4RH. The Nevirapine MUST be switched because Rifampicin will cause it to fail. Switch to an Efavirenz or Dolutegravir-based regimen. Give Pyridoxine (HIV is a risk for neuropathy). Monitor for Immune Reconstitution Inflammatory Syndrome (IRIS).

• Patient: 24-year-old pregnant woman (second trimester).
• Nursing Actions: Do NOT delay treatment. Start standard 2RHZE/4RH. Avoid Streptomycin completely (causes fetal deafness). Give pyridoxine (essential in pregnancy). TB drugs are safe for breastfeeding, but the baby should get BCG and pyridoxine if nursing.

• New drug-susceptible TB (adults): 2RHZE/4RH (6 months)
• New drug-susceptible TB (children, non-severe): 2HRZE/2HR (4 months)
• TB meningitis / Bone TB: 2RHZE/10RH (12 months)
• MDR-TB (new shorter oral): BPaLM or BPaL (6 months)

• Ministry of Health Uganda (MoH). National Tuberculosis and Leprosy Programme (NTLP) Manual for Management and Control of Tuberculosis.
• World Health Organization (WHO). WHO consolidated guidelines on tuberculosis: Module 4: Treatment - Drug-susceptible tuberculosis treatment.
• World Health Organization (WHO). WHO consolidated guidelines on tuberculosis: Module 4: Treatment - Drug-resistant tuberculosis treatment.
• Uganda Clinical Guidelines (UCG). National Guidelines on Management of Common Conditions.