What are the symptoms and treatment options for tuberculosis?

Symptoms of Tuberculosis

Primary Respiratory Symptoms

The most common symptom of pulmonary tuberculosis is persistent cough with or without sputum production lasting more than 2–3 weeks. 1

• Cough may be accompanied by sputum production, though this is not always present 1
• Haemoptysis (coughing up blood) occurs but is less common 1
• These respiratory symptoms overlap significantly with other conditions including acute respiratory infections and COPD exacerbations, requiring careful evaluation 1

Constitutional Symptoms

• Fever is a frequent accompanying symptom 1
• Night sweats occur commonly 1
• Weight loss is characteristic and should raise suspicion 1
• Anorexia may be present 1

Extrapulmonary Manifestations

• Organ-specific signs and symptoms depend on the site of involvement 1
• Lymphadenopathy can occur, particularly in HIV-infected patients experiencing immune reconstitution 1

Important Clinical Considerations

Immunosuppressed individuals may have tuberculosis without specific signs or symptoms of disease. 1 This represents a critical diagnostic pitfall—absence of classic symptoms does not exclude TB in high-risk populations.

In children, tuberculosis typically presents as primary disease with intrathoracic adenopathy and mid- to lower lung zone infiltrates, often without cavitation 1. Adolescents more frequently develop adult-type disease with upper lobe infiltration and cavitation 1.

Risk Factors to Elicit in History

• Previous TB diagnosis or treatment 1
• History of TB contact, particularly within the family 1
• Conditions causing immunosuppression 1
• TB in a child is a "sentinel event" indicating recent transmission from a source case 1

---

Treatment of Tuberculosis

Standard Drug-Susceptible TB Treatment

The recommended regimen consists of 2 months of isoniazid, rifampin, pyrazinamide, and ethambutol (initial phase), followed by 4 months of isoniazid and rifampin (continuation phase). 1, 2, 3

Initial Phase (2 months)

• Rifampin 10 mg/kg daily 4
• Isoniazid 5 mg/kg daily 4
• Pyrazinamide 35 mg/kg daily 4
• Ethambutol 15 mg/kg daily 4

The four-drug initial regimen is necessary because of the risk of isoniazid resistance, unless community INH resistance rates are documented to be less than 4% 3.

Continuation Phase (4 months)

• Rifampin 10 mg/kg daily 4
• Isoniazid 5 mg/kg daily 4

Treatment Monitoring

Obtain sputum for acid-fast bacilli smear and culture at baseline, then monthly until two consecutive specimens are negative. 4 After 3 months of appropriate therapy, 90–95% of patients should have negative cultures 1. Patients with positive cultures after 4 months should be considered treatment failures 1.

Baseline liver function tests are mandatory, with weekly monitoring for the first 2 weeks if hepatotoxicity risk factors are present. 4 Drug-induced hepatitis is the most frequent serious adverse reaction, caused by isoniazid, rifampin, or pyrazinamide 1.

Special Populations

HIV-Infected Patients

• Patients with CD4 counts <100/μL must receive daily or three-times-weekly treatment, never once-weekly continuation phase therapy. 1 Once-weekly rifamycin-based regimens in HIV-infected patients have unacceptably high relapse rates with acquired rifamycin resistance 1.
• Rifampin interactions with antiretroviral agents require expert consultation 1
• Paradoxical reactions (temporary worsening despite effective treatment) may occur with immune reconstitution; severe reactions may require prednisone 1–2 mg/kg daily 1

Children

• The same regimens used for adults are appropriate for children 1
• Ethambutol is generally avoided in young children due to inability to monitor visual acuity, unless drug resistance is suspected 1
• Children with adult-type disease (cavitation, upper lobe infiltrates) require the full four-drug initial phase 1
• Treatment success rate exceeds 95% with adverse effect rates below 2% 1

Cavitary Disease

Cavitary disease requires the full 6-month treatment regimen without modification. 4 Treatment should be extended beyond 6 months if the patient remains sputum or culture positive, if resistant organisms are present, or if HIV-positive 3.

Directly Observed Therapy (DOT)

Directly observed therapy should be implemented to ensure treatment adherence, as compliance is the major determinant of treatment outcome. 4 DOT is especially critical for HIV-infected patients and children 1.

Treatment Failure and Relapse

Never add a single drug to a failing regimen—this leads to acquired resistance. 1 Instead, add at least two, preferably three, new drugs to which susceptibility can be inferred 1.

For treatment failure (positive cultures after 4 months), empirical retreatment should include:

• A fluoroquinolone (levofloxacin, moxifloxacin, or gatifloxacin) 1
• An injectable agent (streptomycin if not previously used, amikacin, kanamycin, or capreomycin) 1
• An additional oral agent (PAS, cycloserine, or ethionamide) 1

Drug-Resistant TB

Multidrug-resistant TB (resistant to at least isoniazid and rifampin) requires expert consultation immediately. 1 Treatment should only include drugs to which the isolate has documented or high likelihood of susceptibility 1. Regimens are individualized and typically last at least 2 years 5.

Common Pitfalls

• Do not discontinue treatment prematurely if mild adverse effects occur—these can often be managed symptomatically with antiemetics or dose timing adjustments 1
• Repeat drug susceptibility testing if cultures remain positive after 3 months or if bacteriological reversion occurs 1
• In the EU setting, TB is not the leading cause of persistent cough, and cough is not necessarily the most common TB symptom 1—maintain high clinical suspicion based on risk factors, not symptoms alone