Review
Recurrence in tuberculosis: relapse or reinfection?

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Summary

The importance of reinfection as a cause for recurrence of tuberculosis is unclear and has potential public-health implications. We systematically searched published material for studies using DNA fingerprinting to provide data on the issue. Very few studies were designed for that particular research objective and/or report on a sufficient number of observations. Differences in methods—eg, case-definitions—seriously hamper comparisons between studies. The proportion of recurrences due to reinfection ranged between 0% and 100%; however, this figure cannot be a useful indicator since the two causes of recurrence— relapse and reinfection—are essentially independent. Only one study provides an estimate of the incidence of recurrence due to reinfection, indicating its importance for HIV-infected patients in an environment with an unusually high tuberculosis incidence. We argue that apart from extreme situations like this one the problem of recurrence of tuberculosis due to reinfection has few implications for tuberculosis-control programmes.

Section snippets

Mechanisms and causes of recurrence

The risk of developing a second episode of tuberculosis after reinfection by Mycobacterium tuberculosis depends first on the risk of reinfection after a first episode (a function of what we have called here “background tuberculosis incidence”) and, second, on the risk of this reinfection breaking down into a second tuberculosis episode. A study2 has shown that HIV-infection, a major risk for an infection (or reinfection) breaking down into a first tuberculosis episode,6 was also a major risk

Methods for the systematic literature review

The methods we used in our search of published articles are given in the Search strategy and selection criteria (see page 286). For comparability reasons, we included only patients in whom the site of disease included the lungs (with or without extrapulmonary involvement) during both initial and recurrent episodes. We extracted frequency measures, data on methods used (study design, case definitions), and risk factors for relapse (treatment regimen, drug-resistance patterns). We classified data

Results

The search through electronic databases returned 391 hits. Most of them were epidemiological studies reporting on previously untreated patients or laboratory studies; eight met our inclusion criteria. Screening 188 articles reviewed for the study on the incidence of recurrence, and the bibliography of all articles meeting our inclusion criteria, allowed retrieval of five more studies. We did not exclude any study on the basis of a small sample size. The main characteristics and findings of the

Discussion

We are confident that our review did not miss any major study recorded in the databases searched, but these databases are notoriously biased towards articles published in the English language. We retrieved only few studies that attempted to quantify the contribution of reinfection to the problem of recurrence of tuberculosis. Fewer still were designed for that particular research objective and/or report on a number of observations such that the study results truly contribute to this research

Conclusions

Only one study in our review2 has reliably compared the incidence rates of recurrence due to reinfection and relapses with a methodology that allows conclusions to be drawn on the increased risk for reinfection (not relapse) among HIV-positive patients in an environment with extremely high-background-tuberculosis incidence.

As our present knowledge basically stems from one study, it would make sense to replicate it, particularly in high-tuberculosis-incidence countries, and among HIV-positive

Search strategy and selection criteria

Data for this review were identified by searches of Medline and Cab Health. Search terms (free text) were “tuberculosis” and “DNA-fingerprinting”. We also looked at articles screened for the purpose of another systematic literature review on the incidence of tuberculosis recurrence; finally we scrutinised the bibliography of the relevant articles retrieved that way. There were no language restrictions. The following inclusion criteria were used: studies published up to July 2002, reporting on

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