What is the difference in treatment approach between relapse and recurrent tuberculosis (TB)?

Difference Between Relapse and Recurrent Tuberculosis

Relapse is recurrent TB caused by the same M. tuberculosis strain due to incomplete sterilization during initial treatment, while recurrent TB is the broader term that includes both relapse (same strain) and reinfection (new strain), with critical treatment implications based on prior therapy adherence and drug resistance risk. 1

Key Definitions

Relapse (True Relapse):

• Recurrent TB caused by the same M. tuberculosis strain identified at baseline 1
• Results from failure of chemotherapy to sterilize host tissues, enabling endogenous recrudescence of the original infection 1
• Represents incomplete eradication of the initial infection 1

Recurrent TB (Broader Term):

• Any circumstance where a patient whose sputum became and remained culture-negative during treatment becomes culture-positive again OR experiences clinical/radiographic deterioration consistent with active TB after completion of therapy 1
• Includes both relapse (same strain) and reinfection (new strain) 1

Reinfection:

• Recurrent TB caused by a different M. tuberculosis strain than the original infection 1
• More common in high-incidence settings or where infection control is poor 1
• In urban areas with high TB burden, reinfection can account for up to 42% of recurrent cases 2

Clinical Timing and Risk Factors

Temporal Pattern:

• Most relapses occur within the first 6-12 months after completion of therapy 1

High-Risk Patients for Relapse:

• Extensive disease at baseline 1
• Sputum cultures remaining positive after completion of the intensive phase (2 months) of treatment 1
• Note: Culture-positive status at 2 months has low sensitivity for predicting relapse 1

Critical Treatment Approach Differences

For Patients Previously Treated with DOT Using Rifamycin-Containing Regimens:

The majority of relapses occur with susceptible organisms 1, 3

Treatment Algorithm:

• Restart the standard intensive phase regimen (daily INH, RIF, PZA, and EMB) until susceptibility results are available 1, 3
• All drugs administered via DOT 3
• This approach is appropriate because drug resistance is uncommon in this scenario 1

For Patients Who Did NOT Receive DOT or Had Irregular Treatment:

The risk of acquired drug resistance is substantial 1

Treatment Algorithm:

• Obtain immediate microbiological confirmation with sputum cultures and drug susceptibility testing for first- and second-line drugs 3
• Perform rapid molecular tests (e.g., Xpert MTB/RIF) to detect rifampicin and isoniazid resistance 3
• Consider an expanded empiric regimen consisting of the standard intensive phase regimen (INH, RIF, PZA, EMB) PLUS a later-generation fluoroquinolone 1
• Consult with experts in drug-resistant TB treatment 1

Additional High-Risk Scenarios for Drug Resistance:

The risk of acquired drug resistance is substantial in patients who relapse after: 1

• Self-administered therapy (SAT)
• Highly intermittent regimens in HIV-infected patients
• Non-rifamycin-containing regimens (including only INH and EMB in continuation phase)
• Second course of first-line regimen reinforced by streptomycin
• Initial drug susceptibility testing was not performed and patient fails/relapses with rifamycin-containing regimen using DOT (suggests organisms were resistant from the outset)

Diagnostic Workup for Recurrent TB

Essential Steps:

• Vigorous efforts to establish microbiologic confirmation of relapse 1
• Obtain cultures for drug susceptibility testing to enable testing for drug resistance 1
• Use rapid molecular and phenotypic diagnostics whenever feasible 1, 3

Critical Caveat with Molecular Testing:

• Exercise caution when interpreting PCR/molecular test results at suspected recurrence 1, 3
• False-positive detection of M. tuberculosis DNA and rifampicin resistance have been reported 1, 3
• PCR cannot distinguish between viable and dead organisms 3

Special Considerations

In High-Incidence Settings:

• Consider exogenous reinfection with a new strain rather than true relapse 1, 3
• If a source case with resistant TB is identified, base the empirical regimen on the source case's resistance profile 3

Expanded Regimen Indications:

• Compromised immunity 3
• Limited respiratory reserve 3
• Central nervous system involvement 3
• Persistent bacilloscopy 3
• Circumstances where an inadequate regimen would have severe consequences 3

Common Pitfalls

• Never modify treatment without first obtaining samples for culture and susceptibility testing, as this eliminates the opportunity to identify the resistance pattern 3
• Do not assume all recurrent TB is relapse—in high-burden settings, up to 42% may be reinfection with a different strain 2
• Do not rely solely on molecular tests for treatment decisions; culture confirmation remains essential 3
• Adjust the regimen immediately according to the resistance pattern once sensitivity results are available 3