What is the diagnosis and treatment for primary complex, specifically in the context of tuberculosis?

Diagnosis and Treatment of Primary Complex (Primary Tuberculosis)

Diagnosis

Primary complex (Ghon complex) on chest radiography is considered positive for latent tuberculosis, but when accompanied by enlarged mediastinal lymph nodes, it is usually indicative of active, primary tuberculosis. 1

Diagnostic Approach

• Tuberculin skin test (TST) or interferon-gamma release assay (IGRA) should be performed as the initial screening test, with positivity defined as ≥10 mm induration for high-risk individuals (healthcare workers, residents of congregate settings, immigrants from high-burden countries) or ≥15 mm for those without risk factors 1, 2

• Chest radiography is mandatory after any positive TST/IGRA to distinguish between latent infection and active disease, particularly in endemic regions 1, 2

• Radiographic findings requiring action:

  • Ghon complex alone = latent TB 1
  • Ghon complex + enlarged mediastinal lymph nodes = active primary TB 1
  • Scarring of unknown significance requires clinical correlation 1

• Sputum examination (microscopy, culture, and molecular testing) is indicated when chest radiograph is abnormal or when clinical symptoms (cough ≥2 weeks, fever, night sweats, weight loss) are present 1, 3

• Three consecutive negative sputum smears on different days are required before discontinuing isolation precautions 3

Common Diagnostic Pitfalls

• A negative TST does not exclude TB in immunocompromised patients; consider anergy testing (mumps and Candida antigens) with positivity defined as ≥5 mm induration, though this remains controversial 1
• Repeat TST on the opposite arm within 5 weeks if initial test validity is questioned 1

Treatment

Active Primary Tuberculosis (Ghon Complex + Enlarged Lymph Nodes)

All patients with active primary TB should receive a four-drug regimen consisting of isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB) for 2 months, followed by INH and RIF for 4 months (total 6 months). 1, 3

Initial Phase (2 months):

• INH + RIF + PZA + EMB daily 1, 3
• EMB can be discontinued once drug susceptibility confirms INH and RIF susceptibility 1
• Four drugs are necessary because of the relatively high proportion of INH-resistant organisms 1
• Alternative dosing: daily for 2 weeks, then twice weekly for 6 weeks, or three times weekly throughout (requires directly observed therapy) 1

Continuation Phase (4 months):

• INH + RIF daily or intermittently 1, 3
• If PZA cannot be used (severe liver disease, gout, pregnancy), extend total treatment to 9 months with INH + RIF + EMB for 2 months, then INH + RIF for 7 months 1

Pediatric Considerations:

• Same four-drug regimen as adults 3
• EMB is usually avoided in young children whose visual acuity cannot be monitored, unless there is increased likelihood of INH resistance or "adult-type" upper lobe disease with cavitation 1
• Dosing for children: 20-40 mg/kg daily (max 1 g) for streptomycin if used instead of EMB 4

Latent Tuberculosis (Ghon Complex Without Enlarged Lymph Nodes)

For latent TB infection, treat with 3 months of weekly rifapentine plus isoniazid, or 3-4 months of daily isoniazid plus rifampin. 2

Treatment Options:

• Preferred: 3-month weekly rifapentine + INH 2
• Alternative: 3-4 months daily INH + rifampin 2
• Traditional (less preferred): INH alone for 9 months or rifampin alone for 4 months 1

When to Treat Latent TB:

• Positive TST/IGRA with Ghon complex on chest radiograph but no enlarged lymph nodes 1
• No treatment needed if TST is negative and chest radiograph is normal 1
• If from area with >10% drug resistance background, consider two-drug therapy even for latent infection 1

Critical Treatment Principles

Directly observed therapy (DOT) should be the central element of treatment to maximize completion rates and prevent drug resistance. 1

• Never add a single drug to a failing regimen as this promotes resistance 5
• Single-drug therapy should never be used for active TB 2
• Treatment completion is defined by number of doses ingested, not just duration 1
• Maximum lifetime streptomycin dose should not exceed 120 g 4

Monitoring During Treatment

Liver function tests must be monitored every 2-4 weeks during antituberculous treatment. 1, 2, 5

• Educate patients about hepatotoxicity symptoms (nausea, vomiting, jaundice) and instruct them to stop medication and seek immediate care if these develop 2
• Pyridoxine (vitamin B6) supplementation should be given with INH to prevent peripheral neuropathy, especially in HIV-infected persons 2
• Monitor for visual disturbances with ethambutol use 5
• Clinical assessment for symptom improvement (fever resolution, weight gain, decreased cough) 5
• Radiological follow-up to evaluate treatment response 5

Special Populations

• HIV co-infected patients: Same four-drug regimen; antiretroviral therapy should be initiated within 2 weeks of starting TB treatment; may require extended treatment to 9 months 5
• Patients on immunosuppressive therapy/biologics: Treat latent TB before continuing or initiating biologic therapy 2
• Pregnant women: PZA may be withheld (extend treatment to 9 months); monitor liver function closely 1, 2
• Patients >60 years: Use reduced streptomycin dosage (500 mg twice daily instead of 1 g) due to increased toxicity risk 4
• Renal/hepatic disease: Dose adjustments required; avoid hepatotoxic drugs in severe liver disease 1

Drug-Resistant TB

If drug resistance is suspected (from area with >10% background resistance or previous treatment failure), use 5-7 drugs initially while awaiting susceptibility results. 1, 6

• Consider fluoroquinolones, injectable agents, and additional oral agents 5
• Consultation with TB expert is mandatory for drug-resistant cases 4, 7
• Treatment duration typically extends beyond 6 months 5