How can we achieve better prevention of progression to tuberculosis among contacts?

Abstract

Strategies for control and elimination of tuberculosis (TB) in low-incidence settings are directed toward treatment of recently acquired latent tuberculosis infection (LTBI) in TB contacts [1]. To identify this target population for preventive treatment the development of more specific, in vitro assays for LTBI, the interferon (INF)-c release assays (IGRAs), has offered an alternative method for LTBI diagnosis. Although IGRAs are increasingly recommended in national guidelines, evidence that positive IGRA results are prognostic for developing TB is still limited [2,3], especially outside of prospective studies with welldefined inclusion criteria. Therefore, we investigated progression towards active TB among IGRA positive contacts of active TB cases under routine field conditions and calculated the positive predictive value (PPV) for progression and the number needed to treat (NNT) with preventive treatment to prevent one incident TB case. Additionally, we introduced different cut-off values for IGRA positivity and compared the computed progression rates. Among all contacts with a positive tuberculosis-specific IGRA we describe the uptake of preventive treatment.Our study covered a population of 3.2 million with a reported TB incidence of 7.5 cases per 100 000 population in 2008. From 2008 to 2010, we prospectively recruited all IGRA-positive contacts of newly detected sputum smear and/or culture positive notified TB cases at 12 local public health authorities (LPHAs) in Hesse, Germany. Only contacts with a history of TB disease were excluded.

Serial QuantiFERON testing and tuberculosis disease risk among young children: an observational cohort study

“…16 Whether higher interferon-γ values represent more recent M tuberculosis exposure, greater aerosolised inoculum, or sustained infection-or simply reflect heterogeneity in human immune responses to M tuberculosis-is unclear. Importantly, evidence for whether higher QFT conversion interferon-γ values are associated with increased risk of progression to active disease is conflicting, 19,[21][22][23] and current management algorithms do not distinguish between interferon-γ values above the QFT manufacturer's recommended test threshold of 0·35 IU/mL.…”

Numbers needed to treat to prevent tuberculosis

“…To provide guidance in this area, the World Health Organization (WHO) has recently issued guidelines on LTBI management [4].…”

“…More recently, it has become evident that the risk of the development of tuberculosis among patient groups classically considered at risk is highly variable, and is not necessarily associated with the results of immunodiagnostic testing by the TST or IGRAs [2][3][4][5]. More detailed knowledge of groups at actual risk of tuberculosis and on immunodiagnostic test performance in these risk groups may provide better guidance for physicians on priorities for targeting tuberculosis testing and LTBI treatment in low-incidence countries.…”

“…Although not selected by a systematic approach, we made use of the fact that several studies with large sample sizes from low-incidence countries of tuberculosis were recently published from three major groups classically considered at risk for progression. In these studies, tuberculosis contacts [2,4,5], immunocompromised hosts [3] and healthcare workers [6][7][8] were evaluated for LTBI and subsequent progression. We have calculated the number needed to treat to prevent one case of tuberculosis (table 1), and found that the number needed to treat was very similar across three studies evaluating 1579, 5020 and 4774 tuberculosis contacts, respectively, with a positive TST or IGRA, ranging from 30 to 37 [2,4,5] (table 1).…”

“…In these studies, tuberculosis contacts [2,4,5], immunocompromised hosts [3] and healthcare workers [6][7][8] were evaluated for LTBI and subsequent progression. We have calculated the number needed to treat to prevent one case of tuberculosis (table 1), and found that the number needed to treat was very similar across three studies evaluating 1579, 5020 and 4774 tuberculosis contacts, respectively, with a positive TST or IGRA, ranging from 30 to 37 [2,4,5] (table 1). In immunocompromised individuals with a positive test (n=1537) [3], the number needed to treat to prevent a case was higher and ranged from approximately 50 to 80 (table 1).…”