Delays in the Diagnosis and Treatment of Tuberculous Lymphadenitis in Low-Incidence Countries: A Systematic Review

Abstract

Early detection and treatment of tuberculosis (TB) is essential to achieve the goals appointed in the WHO End TB Strategy. Tuberculous lymphadenitis (TBLA) is the most common manifestation of extrapulmonary TB, but the diagnosis can be challenging in low-incidence countries due to sparse and inconsistent clinical features, resulting in delay. We aimed to summarize and discuss the current literature on patient delay, health care delay, and total delay (i.e., time to first health care contact, diagnosis, and treatment) in patients with TBLA in TB low-incidence countries. A systematic review using PubMed was conducted, searching for studies set in TB low-incidence countries (defined as <20 per 100,000 citizens) that reported on health care seeking behaviour, patient delay, health care delay, and/or total delay. Studies were categorized by type of delay and compared. We identified 11 heterogeneous studies with highly variable observations. Mean patient delay varied from 55 to 154 days (range, 14–1,461), mean health care delay from 44 to 94 days (range, 7–224) and median total delay from 77.5 to 122 days (range, 0–2,820). Evidently, more comprehensive insights into the diagnostic pathway and delay in TBLA patients are warranted.

Clinical features of tuberculous lymphadenitis in a low-incidence country

“…As mentioned, it is assumed that the diagnosis of TBLA in Denmark is often delayed and not considered before late into the course of disease. The disease is rare, and a high index of suspicion is required (Mathiasen et al, 2019a;Mathiasen et al, 2019b). This is also supported by the substantial health care delay of a median of 42 days (IQR 16-82), which is comparable to a recent systematic review (Mathiasen et al, 2019b).…”

“…The disease is rare, and a high index of suspicion is required (Mathiasen et al, 2019a;Mathiasen et al, 2019b). This is also supported by the substantial health care delay of a median of 42 days (IQR 16-82), which is comparable to a recent systematic review (Mathiasen et al, 2019b). It is important that all patients with TBLA are screened for pulmonary symptoms and examined with chest radiographs to preclude contagious TB.…”

“…The most common extrapulmonary manifestation of tuberculosis (TB) is tuberculous lymphadenitis (TBLA) (Holden et al, 2019a), which is often attributed to reactivation of latent infection (Fontanilla et al, 2011;Mathiasen et al, 2019a). The diagnosis may be difficult in countries with a low incidence of TB, as the disease is rare, which may delay appropriate treatment (Mathiasen et al, 2019b). TBLA is often located in the cervical lymph nodes, and many benign and malignant conditions mimic the disease (e.g.…”

Epidemiology of tuberculous lymphadenitis in Denmark: A nationwide register-based study

“…In most low-incidence countries, TBLA is rare and the clinician not used to diagnose this disease manifestation. Our recent review suggests that TBLA patients experience delays in both presentation, diagnosis and treatment [5]. The diagnosis may be complicated due to difficulties in obtaining good samples for microbiological examination [36], e.g.…”

“…Consequently, this may result in delays in diagnosis which potentially increases the morbidity and mortality for the affected patients and constitutes sources of Mycobacterium tuberculosis (Mtb) transmission in undiagnosed patients with concurrent pulmonary infection [5,6]. In a recent systematic review, we demonstrated that TBLA patients have a mean health care delay of up to as many as 94 days in low-incidence, high-income countries [5]. Furthermore, EPTB has been associated with an increased long-term mortality [7,8].…”