2.2 Tuberculosis & Leprosy Control

Tuberculosis & Leprosy Control

Tuberculosis (TB) and Leprosy (Hansen's disease) are chronic mycobacterial infections overseen in Kenya by the National Tuberculosis, Leprosy and Lung Disease Program (NTLD-P). Kenya remains on the World Health Organization's high-burden list for TB, TB/HIV co-infection, and Multi-Drug Resistant TB (MDR-TB). For the Clinical Officers Council examinations, clinicians must demonstrate comprehensive mastery of rapid molecular diagnostics, standardized fixed-dose combination therapy, prevention protocols, drug toxicities, and the clinical management of leprosy reactions.

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1. Epidemiology & Pathogenesis of Tuberculosis

• Etiological Agent: Mycobacterium tuberculosis (MTB), an obligate aerobe, acid-fast, slow-growing bacillus with a lipid-rich, waxy cell wall containing mycolic acids. The mycolic acid barrier confers resistance to desiccation, host phagolysosomal lysis, and common antibiotics.
• Transmission: Spread via aerosolized droplet nuclei (1 to 5 μm in diameter) generated when a person with untreated pulmonary or laryngeal TB coughs, sneezes, shouts, or sings. Droplet nuclei remain suspended in air currents for hours.
• Pathophysiology: Inhaled bacilli reach the pulmonary alveoli and are engulfed by alveolar macrophages. If the initial innate macrophage response fails, bacilli replicate intracellularly, forming the primary Ghon focus (subpleural, mid-to-lower lung zone). Draining bacilli infect regional hilar lymph nodes; the combination of the Ghon focus and enlarged regional lymphadenopathy constitutes the Ghon (Ranke) complex.
  • Latent TB Infection (LTBI): In 90% of immunocompetent individuals, cell-mediated immunity (CD4+ T helper cells and interferon-gamma) encapsulates bacilli within caseating epithelioid granulomas, arresting active replication.
  • Active TB Disease: Occurs when cell-mediated containment fails, either as immediate primary progressive TB (common in children and advanced HIV) or late secondary reactivation TB (apical cavitary lesions occurring decades later during periods of immunosuppression).

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2. Diagnostic Modalities & Algorithmic Approach

Presumptive pulmonary TB is defined as any person presenting with persistent cough lasting $\ge$2 weeks (or any duration in PLHIV, children, or contacts of known TB patients), accompanied by constitutional features: fever, drenching night sweats, unexplained weight loss, and hemoptysis.

Interpreting GeneXpert MTB/RIF Results in Clinical Practice

• MTB Detected, Rifampicin Resistance NOT Detected: Initiate standard 6-month first-line drug-susceptible anti-TB therapy (2RHZE / 4RH).
• MTB Detected, Rifampicin Resistance DETECTED: Presumptive Multi-Drug Resistant TB (MDR-TB). Immediately isolate the patient, notify the County TB Coordinator, submit an additional sputum sample for Line Probe Assay (LPA) and phenotypic culture/DST, and initiate the standardized second-line all-oral bedaquiline-containing MDR-TB regimen.
• MTB NOT Detected: Active tuberculosis is not ruled out (particularly in paucibacillary extrapulmonary disease or pediatric gastric aspirates). Re-evaluate the clinical picture, review chest radiography, and consider a non-quinolone broad-spectrum antibiotic trial (e.g., amoxicillin-clavulanate) while withholding fluoroquinolones (which mask TB response).

Classic Radiographic Patterns on Chest X-Ray

• Post-Primary / Reactivation TB: Infiltrates, consolidations, and thick-walled cavitary lesions located predominantly in the apical and posterior segments of the upper lobes and superior segments of the lower lobes. Fibrotic retraction, volume loss, and tracheal deviation may occur.
• Primary TB: Mid- or lower-lung zone parenchymal consolidation accompanied by prominent ipsilateral hilar or mediastinal lymphadenopathy; pleural effusions are frequent in young adults.
• Miliary TB: Diffuse, uniform, bilateral 1 to 2 mm micronodular densities distributed symmetrically throughout both lung fields, resembling scattered "millet seeds", representing hematogenous dissemination.

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3. Drug-Susceptible Tuberculosis Treatment Regimens

Kenya National Guidelines utilize standardized Fixed-Dose Combinations (FDCs) administered daily under Direct Observation of Treatment (DOT). Therapy is divided into an intensive phase to rapidly kill actively replicating bacilli and clear symptoms, followed by a continuation phase to eliminate dormant persisters and prevent relapse.

Standard Adult Regimen: 2RHZE / 4RH (Total 6 Months)

• Intensive Phase (2 Months): Daily Rifampicin (R) + Isoniazid (H) + Pyrazinamide (Z) + Ethambutol (E) as a 4-drug FDC tablet (RHZE: 150/75/400/275 mg).
• Continuation Phase (4 Months): Daily Rifampicin (R) + Isoniazid (H) as a 2-drug FDC tablet (RH: 150/75 mg or 300/150 mg).

Important Exception: Severe extrapulmonary tuberculosis involving the central nervous system (TB Meningitis) or musculoskeletal system (Spinal / Bone TB / Pott's Disease) requires an extended 10-month continuation phase, yielding a 12-month total regimen: 2RHZE / 10RH. For TB meningitis, adjunctive systemic corticosteroid therapy (oral Prednisolone 2 mg/kg/day or IV Dexamethasone 0.4 mg/kg/day tapered over 6 to 8 weeks) is mandatory to reduce intracranial inflammation and mortality.

Monitoring Response to First-Line TB Therapy

• Follow-up sputum smear microscopy is conducted at the end of Month 2, Month 5, and Month 6.
• If the sputum smear is positive at the end of Month 2: Verify treatment adherence, recheck for rifampicin resistance on GeneXpert, and transition the patient to the continuation phase if drug-susceptible.
• A positive sputum smear at Month 5 or Month 6 defines Treatment Failure. The patient must undergo urgent drug resistance testing and be registered for second-line therapy.

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4. Tuberculosis Preventive Therapy (TPT)

Tuberculosis Preventive Therapy aims to sterilize latent infection, preventing progression to active clinical disease. Before initiating TPT, active TB must be ruled out using the 4-symptom screen (absence of current cough, fever, night sweats, and weight loss).

Target Populations for TPT in Kenya

1. All People Living with HIV (PLHIV) aged $\ge$12 months without active TB, regardless of CD4 count or ART status.
2. Household Contacts Under 5 Years of Age exposed to an index patient with bacteriologically confirmed pulmonary TB, once active disease is excluded.
3. Clinical risk groups: Patients initiating biologic therapy, organ transplant recipients, and silicosis patients.

Standard TPT Regimens

• 3HP Regimen (Preferred):
  • Weekly high-dose Rifapentine plus Isoniazid for 3 months (12 total weekly doses).
  • Dosage for adults $\ge$50 kg: Rifapentine 900 mg + Isoniazid 900 mg + Pyridoxine 50 mg taken once every 7 days for 12 weeks.
  • Preferred over 6H due to higher completion rates (>85% vs. ~50%) and significantly lower risk of drug-induced hepatotoxicity.
• 6H Regimen (Alternative):
  • Daily Isoniazid monotherapy for 6 months (180 daily doses).
  • Adults: Isoniazid 300 mg daily + Pyridoxine 25 to 50 mg daily.
  • Children: Isoniazid 10 mg/kg/day + Pyridoxine.

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5. Leprosy (Hansen's Disease) Control

Leprosy is a chronic granulomatous infection caused by Mycobacterium leprae, an acid-fast, obligate intracellular bacillus with a unique predilection for Schwann cells of peripheral nerves and skin macrophages. Transmission occurs primarily through prolonged, close contact with untreated multibacillary patients via respiratory droplet inhalation.

Cardinal Clinical Signs of Leprosy

The diagnosis requires at least one of the following three cardinal signs:

1. Hypopigmented or reddish skin macule/patch with definite, demonstrable loss of sensation (light touch, pinprick pain, temperature).
2. Enlarged, thickened, or tender peripheral nerve trunk (e.g., ulnar, common peroneal, greater auricular, posterior tibial) accompanied by sensory loss or motor weakness in its anatomical distribution.
3. Demonstration of acid-fast bacilli on skin slit smear examination.

WHO Operational Classification

• Paucibacillary (PB) Leprosy: 1 to 5 skin lesions; involvement of only one peripheral nerve trunk; negative skin slit smears at all sites.
• Multibacillary (MB) Leprosy: More than 5 skin lesions; involvement of more than one nerve trunk (regardless of lesion count); or any positive skin slit smear (Bacteriological Index $\ge$1+).

Multi-Drug Therapy (MDT) Regimens (WHO Standard)

MDT is provided free of charge through blister packs containing monthly supervised and daily self-administered components. Multi-agent therapy prevents the emergence of dapsone and rifampicin resistance.

MULTIBACILLARY (MB) LEPROSY REGIMEN — 12 MONTHS (To complete within 18 months):
  • Rifampicin: 600 mg once monthly, supervised at the health facility
  • Clofazimine: 300 mg once monthly supervised, PLUS 50 mg daily self-administered
  • Dapsone: 100 mg daily, self-administered

PAUCIBACILLARY (PB) LEPROSY REGIMEN — 6 MONTHS (To complete within 9 months):
  • Rifampicin: 600 mg once monthly, supervised at the health facility
  • Dapsone: 100 mg daily, self-administered
  • (Current WHO guidelines recommend adding Clofazimine [300 mg monthly / 50 mg daily] to PB as a 3-drug MDT regimen to eliminate relapse risk).

Key Drug Adverse Effects

• Clofazimine: Reversible reddish-brown to black skin discoloration and ichthyosis (dry scaling skin). Patients must be counseled that skin color normalizes months after treatment cessation.
• Dapsone: Dose-dependent hemolytic anemia (severe in glucose-6-phosphate dehydrogenase [G6PD] deficiency); methemoglobinemia; and Dapsone Hypersensitivity Syndrome (exfoliative dermatitis, fever, hepatitis, lymphadenopathy).

Leprosy Reactions & Clinical Management

Leprosy reactions are acute immune-mediated inflammatory episodes that occur before, during, or years after completion of MDT. They represent the primary cause of permanent nerve injury and disability.

1. Type 1 (Reversal) Reaction:
   • Mechanism: Delayed-type (Type IV) cell-mediated hypersensitivity occurring in borderline leprosy patients as cell-mediated immunity fluctuates.
   • Clinical Features: Pre-existing skin lesions become acutely inflamed, erythematous, edematous, and warm; acute, painful, tender neuritis with rapid onset of motor weakness (claw hand, foot drop, wrist drop, lagophthalmos).
   • Management: Initiate systemic corticosteroids: Oral Prednisolone starting at 40 mg daily, tapered slowly over 12 to 20 weeks. Do NOT discontinue MDT.
2. Type 2 Reaction (Erythema Nodosum Leprosum - ENL):
   • Mechanism: Immune complex-mediated (Type III) systemic vasculitis occurring exclusively in patients with multibacillary leprosy.
   • Clinical Features: Sudden eruption of widespread crops of painful, tender, erythematous subcutaneous nodules accompanied by high spiking fever, polyarthritis, dactylitis, lymphadenitis, orchitis, iridocyclitis, and glomerulonephritis.
   • Management: Mild ENL is managed with NSAIDs. Severe ENL requires oral Prednisolone or high-dose Clofazimine (up to 300 mg daily for up to 12 weeks). Thalidomide is highly effective for refractory male ENL under strict teratogenicity safeguards. Continue MDT throughout.