Recurrent tuberculosis in the pre-elimination era

Abstract

Recurrent tuberculosis (TB), defined as TB that recurs after a patient has been considered cured, constitutes a challenge to TB control. In low TB burden countries, the underlying causes and consequences of recurrent TB are poorly understood. We conducted a literature review to summarise the evidence of recurrent TB in low-burden settings and to address current gaps in knowledge. We included peer-reviewed publications on studies conducted in countries with an estimated TB incidence of <100 cases per 100 000 population. The Newcastle-Ottawa scale was used to assess study quality. The review yielded 44 manuscripts, 39 of which were reports of observational studies and 5 of clinical trials. The median percentage of TB patients experiencing an episode of recurrent TB after treatment completion was 3.4% (interquartile range [IQR] 1.6-6.0, range 0.4-16.7) in studies with a median follow-up of 7.8 years (IQR 5-12, range 2-33). The median percentage of recurrences attributable to endogenous reactivation (rather than exogenous reinfection) was 81% (IQR 73.1-85.5, range 49-100). Commonly identified risk factors for recurrence in low-burden settings included infection by the human immunodeficiency virus, low socio-economic status, foreign birth and infection with drug-resistant TB. Current understanding of recurrence in low-burden settings is limited, in part due to substantial methodological differences between studies. Further research is required to delineate the mechanisms of TB recurrence, its health and clinical impact, as well as the implications for TB elimination efforts in low-burden countries.

Tuberculosis recurrences and predictive factors in a vulnerable population in Catalonia

“…A review by Rosser et al also indicates that patients cured of a TB episode have a higher risk of TB than those without prior infection. These authors estimated that the TB rate was 31.5 times higher in recurrences than in new TB cases [5].…”

“…Other studies performed in areas with a low burden of the disease have concluded that relapses of a prior infection continue to be the most common cause of TB recurrences. Infections with new Mycobacterium tuberculosis strains are possible but infrequent in low endemic areas [5,12,23,25,26]. Nevertheless, two studies conducted in Spain highlight the importance of TB infections in contexts with a low or moderate incidence [27,28].…”

“…Although considerable progress has been made in the last few years, the main obstacles to controlling the infection are human immunodeficiency virus (HIV), the increase in antibiotic resistance, and the problem of TB in large cities associated with socially vulnerable populations at risk of social exclusion, such as drug users, alcoholics, and economic immigrants [1][2][3][4]. Interest in TB recurrences has been growing because, despite efforts to control the disease globally, long-term cure is not maintained in all successfully treated patients [5,6]. Compared with patients without a prior TB episode, those with a history of TB are at higher risk of contracting the disease again [7].…”

“…In areas with a low incidence of TB, most recurrences are attributed to reactivation or incomplete cure of the first TB episode, instead of a new infection due to repeat exposure. In contrast, the latter is more common in countries with a high burden of the disease, where transmission is highly frequent [5,[11][12][13].…”

“…While the factors associated with poor treatment adherence are well known, there are few reports of recurrence rates and their associated factors in vulnerable populations in countries with a medium or low incidence [5,6,14,15]. Such knowledge would help to identify the populations that are most susceptible and which have the highest risk of recurrent TB.…”