Updates on the risk factors for latent tuberculosis reactivation and their managements

Abstract

The preventive treatment of latent tuberculosis infection (LTBI) is of great importance for the elimination and control of tuberculosis (TB) worldwide, but existing screening methods for LTBI are still limited in predicting the onset of TB. Previous studies have found that some high-risk factors (including human immunodeficiency virus (HIV), organ transplantation, silicosis, tumor necrosis factor-alpha blockers, close contacts and kidney dialysis) contribute to a significantly increased TB reactivation rate. This article reviews each risk factor's association with TB and approaches to address those factors. Five regimens are currently recommended by the World Health Organization, and no regimen has shown superiority over others. In recent years, studies have gradually narrowed down to the preventive treatment of LTBI for high-risk target groups, such as silicosis patients, organ-transplantation recipients and HIV-infected patients. This review discusses regimens for each target group and compares the efficacy of different regimens. For HIV patients and transplant recipients, isoniazid monotherapy is effective in treating LTBI, but for others, little evidence is available at present.

MTBVAC from discovery to clinical trials in tuberculosis-endemic countries

“…In adult and newborn C57BL/6 mice MTBVAC confers significantly greater protection than BCG SSI as measured by significant CFU reduction (>0.5 log) in lung bacterial burden [39,71]. Of note, in the well-established guinea pig model at PHE, BCG is given at a lower 5×10 4 CFU dose, and in those studies MTBVAC and SO2 administration normally followed the same vaccination regimen as that of BCG to allow for data comparison. Importantly, preclinical efficacy data in mice and guinea pigs have demonstrated that efficacy of BCG and MTBVAC vaccines is dose independent by the SC route, at least in short-term protection experiments [39,77].…”

“…However, BCG remains one of most reactogenic (local skin reaction) vaccines known today [20,21], which possibly explains in part why it has been removed from the vaccination calendar in low-burden developed countries [4]. Given the limitations of BCG and the WHO declaration in 1993 of TB as a global health emergency, the past 20 years have seen an intensive upsurge in the research and discovery of new TB vaccine candidates.…”

“…Because of the rising globalization and emergence of multidrug-resistant (MDR) and extensively drugresistant TB (XDR) strains, TB is increasingly becoming a serious threat for the entire world. Today TB has reached alarming proportions of 10.4 million incidence cases and 1.8 million deaths attributed to the disease as reported by the latest World Health Organization (WHO) global TB report 2016 [4]. Globally, some 50 million individuals are already latently infected with MDR M. tuberculosis strains creating a remarkable resource for future cases of active TB with insufficient treatment options [3].…”

“…Globally, some 50 million individuals are already latently infected with MDR M. tuberculosis strains creating a remarkable resource for future cases of active TB with insufficient treatment options [3]. Nevertheless, the WHO End TB Strategy has vowed to reduce TB morbidity by 90% and TB mortality by 95% by 2035 and recognizes the urgent need for more accessible diagnostic tools that are rapid and reliable, new less toxic and more efficacious antibiotics to shorten therapy and ultimately new vaccines to prevent pulmonary TB in order to achieve this ambitious goal [4].…”

“…The incidence of TB is increasing worldwide due to poverty and inequity and is aggravated with the HIV/AIDS pandemic, which greatly increases risk of infection proceeding to active disease [3]. Diabetes, metabolic syndrome, smoking and more recently vitamin deficiencies due to malnutrition and poor socioeconomic conditions are emerging as important risk factors for TB [4,5]. Importantly, how these factors can influence efficacy evaluation of new TB vaccines requires specific attention when defining clinical trial designs that involve study or patient populations with a variety of such risk factors.…”