OBJECTIVEThis study aimed to review the available literatures on control of latent tuberculosis (TB) infection and propose a new control strategy to shorten the course of TB chemotherapy.

DATA SOURCESThe data used in this review were mainly obtained from articles listed in PubMed. The search terms were "therapy (treatment) of tuberculosis," "therapy (treatment) of latent TB infection," and "vaccine of TB."

STUDY SELECTIONArticles regarding treatment and vaccine of TB were selected and reviewed.

RESULTSThe most crucial reason causing the prolonged course of TB chemotherapy is the dormant state of Mycobacterium tuberculosis (M. tuberculosis). Nevertheless, there are, to date, no effective drugs that can directly kill the dormant cells of M. tuberculosis in clinical therapy. In accordance with the growth cycle of dormant M. tuberculosis in the body, the methods for controlling dormant M. tuberculosis include direct killing with drugs, prevention of dormant M. tuberculosis resuscitation with vaccines, and resuscitating dormant M. tuberculosis with preparations or drugs and then thoroughly killing these resuscitated M. tuberculosis by using anti-TB therapy.

CONCLUSIONSThe comprehensive analysis of the above three methods suggests that the drugs directly killing dormant cells are in clinical trials, TMC207 is the most beneficial for controlling TB. Because the side effect of vaccines is less and their action period is long, prevention of dormant cells resuscitation with vaccines is promising. The last control method makes it probable that when a huge number of active cells of M. tuberculosis have been killed and eradicated after 1-month short chemotherapy, only a strong short-term subsequent chemotherapy can completely kill and eradicate the remaining M. tuberculosis. This control strategy is expected to significantly shorten the course of TB chemotherapy and bring a new change and breakthrough in TB treatment.

Antitubercular Agents ; therapeutic use ; Diarylquinolines ; therapeutic use ; Humans ; Latent Tuberculosis ; drug therapy ; Mycobacterium tuberculosis ; pathogenicity ; Tuberculosis ; drug therapy

Preventive treatment has an essential effect on latent tuberculosis infection (LTBI) [purified protein derivative (PPD) induration ⋝ 15 mm]. Between 2010 and 2013, there were 6 tuberculosis (TB) outbreaks in the universities in Dalian, China. So far, in Dalian, the directly observed therapy (DOT) and full course management (FCM) were widely used in the preventive treatment of LTBI. However, it is yet to be determined which one of them has better efficacy. Therefore, the purpose of our study was to explore the performance of these two strategies for LTBI preventive treatment. The chi-square test and exact test were used to perform statistical analysis. In total, 794 LTBI patients were enrolled in this study, of which 443 were included in the DOT group and 351 in the FCM group. In 287 students who said ditto to take prophylactic treatment (DOT 149 and FCM 79), the compliance rate for the DOT group was 90.3% (149/165), while that for the FCM group was 64.8% (79/122). This difference between the two groups was statistically significant (χ²=28.03, P=1.19E-07). The DOT group showed an effective intervention rate of 81.5%, while that for the FCM group was 28.5%. Again, this difference was significant (χ²=56.17, P=6.63E-14). Further, in 228 students who truly started taking treatment, 26 cases exhibited various adverse reactions (11.4%, 26/228), the most frequent one being elevated liver enzyme levels (6.6%, 15/228). In addition, the major reason for the treatment interruption was adverse reactions in the DOT group, and 6 (28.6%) LTBI patients discontinued treatment due to the adverse reactions of the anti-TB drugs. We also performed a one-year follow-up after the completion of the 3-month treatment. Out of the 794 close contacts, a total of 9 cases (1.1%) developed active TB. These results show that DOT is an effective preventive treatment for LTBI and would play an irreplaceable role in improving preventive treatment adherence and treatment outcomes.
Adult ; Antitubercular Agents ; therapeutic use ; China ; Directly Observed Therapy ; Female ; Humans ; Latent Tuberculosis ; drug therapy ; Male ; Patient Compliance ; Young Adult

Tuberculosis (TB) prophylactic therapy for latent infection, which can reduce the risk for the development of active TB, is an important measure in TB control. China recommends prophylactic therapy for latent tuberculosis infection (LTBI) in some key populations to reduce the risk for TB. Contacts of patients with multi-drug and rifampicin-resistant TB (MDR/RR-TB) are at high risk for the infection with drug-resistant pathogen, however, no unified prophylactic therapy regimen has been recommended for LTBI due to exposure to MDR/RR-TB patients. This paper summarizes the current MDR/RR-TB prophylactic therapy regimen and its protection effect based on the results of the retrieval of literature, guidelines, expert consensus and technical specifications to provide reference for the prevention and control of LTBI.
Humans ; Rifampin/therapeutic use* ; Tuberculosis, Multidrug-Resistant/prevention & control* ; Tuberculosis/drug therapy* ; Latent Tuberculosis/chemically induced* ; China ; Antitubercular Agents/therapeutic use*

One fourth of the global population has been infected with Mycobacterium tuberculosis, and about 5%-10% of the infected individuals with latent tuberculosis infection (LTBI) will convert to active tuberculosis (ATB). Correct diagnosis and treatment of LTBI are important in ending the tuberculosis epidemic. Current methods for diagnosing LTBI, such as tuberculin skin test (TST) and interferon-γ release assay (IGRA), have limitations. Some novel biomarkers, such as transcriptome derived host genes in peripheral blood cells, will help to distinguish LTBI from ATB. More emphasis should be placed on surveillance in high-risk groups, including patients with HIV infection, those using biological agents, organ transplant recipients and those in close contact with ATB patients. For those with LTBI, treatment should be based on the risk of progression to ATB and the potential benefit. Prophylactic LTBI regimens include isoniazid monotherapy for 6 or 9 months, rifampicin monotherapy for 4 months, weekly rifapentine plus isoniazid for 3 months (3HP regimen) and daily rifampicin plus isoniazid for 3 months (3HR regimen). The success of the one month rifapentine plus isoniazid daily regimen (1HP regimen) suggests the feasibility of an ultra-short treatment strategy although its efficacy needs further assessment. Prophylactic treatment of LTBI in close contact with MDR-TB patients is another challenge, and the regimens include new anti-tuberculosis drugs such as bedaquiline, delamanid, fluoroquinolone and their combinations, which should be carefully evaluated. This article summarizes the current status of diagnosis and treatment of LTBI and its future development direction.
Humans ; Rifampin/therapeutic use* ; Isoniazid/therapeutic use* ; Latent Tuberculosis/drug therapy* ; HIV Infections/epidemiology* ; Antitubercular Agents/therapeutic use*

Student contacts of tuberculosis (TB) cases are susceptible to latent tuberculosis infection (LTBI), and chemo-prophylaxis can reduce the risk of active TB among them. This study aimed to assess the acceptance of chemo-prophylaxis for LTBI among students, and their concerns regarding TB and its preventive treatment. A total of 560 students contacts were included in the investigation. The extent of contact was categorized from high to low (4 levels) with 12.9% of the students being close contacts. About 87.0% of the students were willing to receive chemo-prophylaxis if diagnosed with, LTBI, whereas 73 students declined. Students with a higher level of knowledge about TB (aOR = 1.11) or close contact with TB patients (aOR = 4.30) were more likely to accept treatment. To conclude, education regarding TB transmission is necessary. Moreover, LTBI detection should be integrated into the current school-based TB contact investigation.
Adolescent ; Adult ; Antitubercular Agents ; administration & dosage ; therapeutic use ; China ; epidemiology ; Contact Tracing ; Female ; Humans ; Latent Tuberculosis ; drug therapy ; epidemiology ; Male ; Students ; Tuberculosis, Pulmonary ; drug therapy ; epidemiology ; prevention & control ; transmission ; Universities ; Young Adult

The aims of this study were to assess the risk of tuberculosis (TB) and the status of latent tuberculosis infection (LTBI) in Korean patients with inflammatory bowel disease (IBD) receiving tumor necrosis factor (TNF)-alpha blockers. We reviewed medical records of 525 Korean IBD patients (365 TNF-alpha blocker naive and 160 TNF-alpha blocker exposed) between January 2001 and December 2013. The crude incidence of TB was significantly higher in IBD patients receiving TNF-alpha blockers compared to TNF-alpha-blocker-naive patients (3.1% vs. 0.3%, P=0.011). The mean incidence of TB per 1,000 patient-years was 1.84 for the overall IBD population, 4.89 for TNF-alpha blocker users, and 0.45 for TNF-alpha-blocker-naive patients. The adjusted risk ratio of TB in IBD patients receiving TNF-alpha blocker was 11.7 (95% confidence interval, 1.36-101.3). Pulmonary TB was prevalent in patients treated with TNF-alpha blockers (80.0%, 4/5). LTBI was diagnosed in 17 (10.6%) patients, and none of the 17 LTBI patients experienced reactivation of TB during treatment with TNF-alpha blockers. Treatment with TNF-alpha blockers significantly increased the risk of TB in IBD patients in Korea. De novo pulmonary TB infection was more prevalent than reactivation of LTBI, suggesting an urgent need for specific recommendations regarding TB monitoring during TNF-alpha blocker therapy.
6-Mercaptopurine/adverse effects/analogs & derivatives/therapeutic use ; Adult ; Anti-Inflammatory Agents, Non-Steroidal/adverse effects/therapeutic use ; Antibodies, Monoclonal/adverse effects/therapeutic use ; Cohort Studies ; Colitis, Ulcerative/*drug therapy ; Crohn Disease/*drug therapy ; Female ; Humans ; Latent Tuberculosis/chemically induced/diagnosis/*epidemiology ; Male ; Mycobacterium tuberculosis/isolation & purification ; Republic of Korea ; Retrospective Studies ; Tuberculosis, Pulmonary/chemically induced/diagnosis/*epidemiology ; Tumor Necrosis Factor-alpha/*antagonists & inhibitors

The aims of this study were to assess the risk of tuberculosis (TB) and the status of latent tuberculosis infection (LTBI) in Korean patients with inflammatory bowel disease (IBD) receiving tumor necrosis factor (TNF)-alpha blockers. We reviewed medical records of 525 Korean IBD patients (365 TNF-alpha blocker naive and 160 TNF-alpha blocker exposed) between January 2001 and December 2013. The crude incidence of TB was significantly higher in IBD patients receiving TNF-alpha blockers compared to TNF-alpha-blocker-naive patients (3.1% vs. 0.3%, P=0.011). The mean incidence of TB per 1,000 patient-years was 1.84 for the overall IBD population, 4.89 for TNF-alpha blocker users, and 0.45 for TNF-alpha-blocker-naive patients. The adjusted risk ratio of TB in IBD patients receiving TNF-alpha blocker was 11.7 (95% confidence interval, 1.36-101.3). Pulmonary TB was prevalent in patients treated with TNF-alpha blockers (80.0%, 4/5). LTBI was diagnosed in 17 (10.6%) patients, and none of the 17 LTBI patients experienced reactivation of TB during treatment with TNF-alpha blockers. Treatment with TNF-alpha blockers significantly increased the risk of TB in IBD patients in Korea. De novo pulmonary TB infection was more prevalent than reactivation of LTBI, suggesting an urgent need for specific recommendations regarding TB monitoring during TNF-alpha blocker therapy.
6-Mercaptopurine/adverse effects/analogs & derivatives/therapeutic use ; Adult ; Anti-Inflammatory Agents, Non-Steroidal/adverse effects/therapeutic use ; Antibodies, Monoclonal/adverse effects/therapeutic use ; Cohort Studies ; Colitis, Ulcerative/*drug therapy ; Crohn Disease/*drug therapy ; Female ; Humans ; Latent Tuberculosis/chemically induced/diagnosis/*epidemiology ; Male ; Mycobacterium tuberculosis/isolation & purification ; Republic of Korea ; Retrospective Studies ; Tuberculosis, Pulmonary/chemically induced/diagnosis/*epidemiology ; Tumor Necrosis Factor-alpha/*antagonists & inhibitors

Adult ; Antitubercular Agents ; therapeutic use ; Contact Tracing ; Counseling ; Female ; Humans ; Latent Tuberculosis ; drug therapy ; prevention & control ; Male ; Multivariate Analysis ; Odds Ratio ; Pamphlets ; Practice Patterns, Nurses' ; Prospective Studies ; Singapore ; Smoking Cessation ; methods

We evaluated the utility of follow-up interferon-gamma release assays (IGRAs) for the diagnosis of reactivation of latent tuberculosis infection (LTBI) or new tuberculosis in ankylosing spondylitis (AS) patients receiving anti-tumor necrosis factor alpha (anti-TNFalpha). The study participants (n=127) had a negative IGRA screening before receiving anti-TNFalpha and were evaluated by follow-up IGRA. We retrospectively examined data of the subjects according to age, gender, tuberculosis prophylaxis, concomitant medications, IGRA conversion and anti-TNFalpha, including type and treatment duration. The median duration of anti-TNFalpha was 21.5 months, and the median age was 35.3 yr. Of the 127 patients, IGRA conversion was found in 10 patients (7.9%). There was no significant variation between IGRA conversion rate and any risk factors except for age. IGRA conversion rate was not significantly different between AS and rheumatoid arthritis (P=0.12). IGRA conversion was observed in AS patients receiving anti-TNFalpha in Korea. A follow-up IGRA test can be helpful for identifying LTBI or new tuberculosis in AS patients receiving anti-TNFalpha.
Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal/*adverse effects/*therapeutic use ; Antirheumatic Agents/adverse effects/therapeutic use ; Female ; Follow-Up Studies ; Humans ; Interferon-gamma/*blood ; Latent Tuberculosis/*blood/*chemically induced/diagnosis ; Longitudinal Studies ; Male ; Middle Aged ; Prognosis ; Reproducibility of Results ; Sensitivity and Specificity ; Spondylitis, Ankylosing/blood/*drug therapy ; Treatment Outcome ; Tumor Necrosis Factor-alpha/antagonists & inhibitors

BACKGROUND: We assessed the efficacy of serial interferon-gamma release assays (IGRAs) for the diagnosis of latent tuberculosis infection (LTBI) in patients receiving immunosuppressive agents for treatment of rheumatic diseases in Korea. METHODS: Of 276 patients who underwent consecutive screening with one of two IGRAs [QuantiFERON-TB Gold or QuantiFERON-TB Gold In-Tube], 66 patients were evaluated by the serial IGRA for detection of LTBI during therapy with immunosuppressive agents. Information on clinical diagnosis, medication, previous TB, blood cell count, tuberculin skin test, and interferon-gamma (IFN-gamma) level measured by IGRA was collected. RESULTS: Of the 66 patients, the initial IGRA was positive in 24.2%, negative in 65.2%, and indeterminate in 10.6%. Forty-six patients (69.7%) showed consistent IGRA results during follow-up, and 13 patients (19.7%) had consistently positive results. IGRA conversion rate was 12.1% (8/66) and reversion rate was 4.5% (3/66). Conversion of IGRA results was only observed in ankylosing spondylitis patients, and the median interval between the two tests in patients with conversion was 8.5 months. The mean IFN-gamma level in the group of patients with consistently positive IGRA results was higher than that in the group with inconsistently positive results, although this trend was not statistically significant (P=0.293). Indeterminate results were observed most frequently in patients with systemic lupus erythematosus. CONCLUSIONS: In patients receiving immunosuppressive agents, both IGRA conversions and reversions were observed. Serial IGRA testing may not be needed in patients with a positive initial IGRA result showing high IFN-gamma levels, because of high consistency in the test results.
Adult ; Blood Cell Count ; Female ; Follow-Up Studies ; Humans ; Immunosuppressive Agents/*therapeutic use ; Interferon-gamma/*analysis ; *Interferon-gamma Release Tests ; Latent Tuberculosis/complications/*diagnosis/metabolism ; Lupus Erythematosus, Systemic/complications/diagnosis/metabolism ; Male ; Middle Aged ; Rheumatic Diseases/complications/diagnosis/drug therapy ; Spondylitis, Ankylosing/complications/diagnosis/metabolism ; Tuberculin Test