Who misses the second step of evaluation in tuberculosis contact screening?

To the Editors:

Assessment of people likely to have been recently infected with Mycobacterium tuberculosis is important because of the risk to these people of progressing to active tuberculosis (TB) within 1–2 yrs [1]. In Portugal, contact investigation is an integral part of the TB control programme, enabling the identification and treatment of individuals with latent TB infection (LTBI), thus preventing active TB.

National guidelines require a two-step evaluation of pulmonary TB contacts, with the first step being performed at the moment the index case is diagnosed and the second performed 10–12 weeks later if the first evaluation was negative. We have analysed the results of re-evaluating TB contacts and have identified risk factors associated with missing re-evaluation.

Our study was a retrospective cohort study of pulmonary TB contacts screened between January 1 and June 30, 2009, at the Chest Disease Centre of Vila Nova de Gaia, Porto, Portugal, an outpatient TB clinic. All individuals were administered a symptom questionnaire and underwent a tuberculin skin test (TST)/interferon-γ release assay (IGRA) and chest radiograph. The first TST was performed upon identification of the index case, with individuals testing negative being offered a second TST 12 weeks later. Individuals testing positive were offered an IGRA test (QuantiFERON®-TB Gold; Cellestis Ltd, Melbourne, Victoria, Australia). Individuals positive on both TST and IGRA were offered preventive treatment, after exclusion of risk factors for hepatotoxicity. Individuals with symptoms or chest radiograph abnormalities were assessed for active TB.

Active TB was defined as positivity for M. tuberculosis in biological samples, either by culture or nuclei-amplification tests. LTBI was defined, in patients not having active TB, as TST ≥10 mm with positive IGRA.

Demographic, social and clinical data were collected and the results of the first and second screenings were reviewed.

Statistical analyses were performed using Epi Info (version 3.5.1; Centre for Diesease Control and Prevention (www.cdc.gov)). Chi-squared, Kruskal-Wallis, ANOVA and Fisher's exact tests were performed for univariate analysis, with logistic regression performed for multivariate analysis. A p-value <0.05 was considered statistically significant.

Screening of TB contacts was offered as part of the National Tuberculosis Program guidelines [2]. We evaluated 226 TB contacts, 150 females (66.4%) and 76 males (33.6%), of mean age 44.6±17.2 yrs.

The results of the first evaluation of the TB contacts are presented in figure 1. Of the 226 contacts, two (0.9%) were diagnosed with active TB, and 40 (17.7%) were diagnosed with LTBI. The remaining 161 TB contacts tested negative and were therefore eligible for the second evaluation. Of these 161 individuals, 56 (34.8%) missed the second evaluation.

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Figure 1–

Results of the first evaluation of 226 tuberculosis (TB) contacts. LTBI: latent TB infection.

Of the 105 re-evaluated individuals, none had active TB, whereas nine (8.6%) were diagnosed with LTBI. Thus re-evaluation led to the diagnosis of LTBI in 18.4% of all individuals diagnosed with LTBI.

Male sex and period of re-evaluation during the summer months (July, August and September) were associated with missing re-evaluation (table 1).

LTBI screening 10–12 weeks after exposure has been shown to be important, with 13.2–22.9% of all individuals with LTBI diagnosed at second evaluation. A negative result before this window period is considered unreliable for excluding infection [1]. We found that re-evaluation led to a diagnosis of LTBI in 8.6% of patients screened, suggesting that some individuals who were not re-evaluated were positive for LTBI.

This two-step evaluation can confound a booster phenomenon with a true conversion. Searching for boosting may not be useful because of the small number of patients identified in this way, and because this distinction is also difficult in two-step TST. Although a single evaluation performed ≥8 weeks after exposure may also be diagnostic, the first evaluation has been shown to be important in diagnosing active TB [1].

Compliance with re-evaluation was 65.2%, slightly higher than previously described (53–63%) [3]. Although no studies have determined factors associated with noncompliance with re-evaluation, male sex and seasonality have been associated with noncompliance in other clinical situations. For example, male sex has been associated with noncompliance during diagnosis in individuals suspected of TB [4] and in treatment for TB [5], and seasonality has been found to be associated with noncompliance for appointments at outpatient clinics [6].

The main limitation of our study was its retrospective design, which did not allow us to test the effectiveness of strategies to improve adherence. Future prospective studies should test different strategies, including oral and written information about the importance of TB screening and particularly of the second evaluation, using reminder telephone calls and other reminder strategies to encourage attendance.

• ©ERS 2011