Risk of progression to active tuberculosis among foreign-born persons with latent tuberculosis

BACKGROUND: Increased risk for tuberculosis (TB) disease has been identified in foreign-born persons in the United States, particularly during the first 5 years after their arrival in the United States. This could be explained by undetected TB disease at entry, increased prevalence of latent TB infection (LTBI), increased progression from LTBI to TB, or a combination of these factors. METHODS: We performed a cluster analysis of TB cases in Boston and a case-control study of risk factors for TB with an unclustered isolate among Boston residents with LTBI to determine whether such persons have an increased risk for reactivation of disease. RESULTS: Of 321 case patients with TB seen between 1996 and 2000, 133 isolates were clustered and 188 were not. In multivariate analysis, foreign birth was associated with an unclustered isolate (odds ratio [OR], 2.2; 95% confidence interval [CI], 1.2 to 3.8; p < 0.01), while being a close contact of a TB case was negatively associated (OR, 0.22; 95% CI, 0.07 to 0.73; p = 0.02). When 188 TB patients with unclustered isolates were compared to 188 age-matched control subjects with LTBI, there was no association between the occurrence of TB and foreign birth (OR, 0.71; 95% CI, 0.42 to 1.3); among foreign-born persons, there was no association between the occurrence of TB and being in the United States 相似文献   

Viral hepatitis prevalence in patients with active and latent tuberculosis

AIM: To assess the prevalence of hepatitis B virus(HBV) and hepatitis C virus(HCV) infection and association with drug induced liver injury(DILI) in patients undergoing anti-tuberculosis(TB) therapy.METHODS: Four hundred and twenty nine patients with newly diagnosed TB- either active disease or latent infection- who were due to commence antiTB therapy between September 2008 and May 2011 were included. These patients were prospectively tested for serological markers of HBV, HCV and human immunodeficiency virus(HIV) infections- hepatitis B core antigen(HBc Ag), hepatitis B surface antigen(HBs Ag), hepatitis B e antigen, Ig G and Ig M antibody to HBc Ag(anti-HBc), HCV Ig G antibody and HIV antibody using a combination of enzyme-linked immunosorbent assay, Western blot assay and polymerase chain reaction techniques. Patients were reviewed at least monthly during the TB treatment initiation phase. Liver function tests were measured prior to commencement of antiTB therapy and 2-4 wk later. Liver function tests were also performed at any time the patient had significant nausea, vomiting, rash, or felt non-specifically unwell. Fisher's exact test was used to measure significance in comparisons of proportions between groups. A P value of less than 0.05 was considered statistically significant.RESULTS: Of the 429 patients, 270(62.9%) had active TB disease and 159(37.1%) had latent TB infection. 61(14.2%) patients had isolated anti-HBc positivity, 11(2.6%) were also HBs Ag positive and 7(1.6%) were HCV-antibody positive. 16/270 patients with active TB disease compared to 2/159 patients with latent TB infection had markers of chronic viral hepatitis(HBs Ag or HCV antibody positive; P = 0.023). Similarly the proportion of HBs Ag positive patients were significantly greater in the active vs latent TB infection group(10/43 vs 1/29, P = 0.04). The prevalence of chronic HBV or HCV was significantly higher than the estimated United Kingdom prevalence of 0.3% for each. We found no association between DILI and presence of serological markers of HBV or HCV. Three(5.3%) patients with serological markers of HBV or HCV infection had DILI compared to 25(9.5%) patients without; P = 0.04.CONCLUSION: Viral hepatitis screening should be considered in TB patients. DILI risk was not increased in patients with HBV/HCV.     

Cost-effectiveness of interferon-gamma release assay screening for latent tuberculosis infection treatment in Germany

OBJECTIVES: To assess the cost-effectiveness of the new QuantiFERON-TB Gold In-Tube (QFT-G) [Cellestis; Carnegie, VIC, Australia] assay for screening and treating of persons who have had close contact with tuberculosis (TB) patients and are suspected of having latent tuberculosis infection (LTBI) [hereafter called close-contacts] in Germany. METHODS: The health and economic outcomes of isoniazid treatment of 20-year-old close-contacts were compared in a Markov model over a period of 20 years, using two different cutoff values for the tuberculin skin test (TST), the QFT-G assay alone, or the QFT-G assay as a confirmatory test for the TST results. RESULTS: QFT-G assay-based treatment led to cost savings of $542.9 and 3.8 life-days gained per LTBI case. TST-based treatment at a 10-mm induration size cutoff gained $177.4 and 2.0 life-days gained per test-positive contact. When the cutoff induration size for the TST was reduced to 5 mm, the incremental cost-effectiveness ratio fell below the willingness-to-pay threshold ($30,170 per life-years gained) but resulted in unnecessary treatment of 77% of contacts owing to false-positive TST results. Combination with the 5-mm induration size TST cutoff value compared to the results of the QFT-G assay alone reduced the total costs per 1,000 contacts by 1.8% to $222,869. The number treated to prevent 1 TB case was 22 for the two QFT-G assay-based procedures, 40 for the TST at a cutoff induration size of 10 mm, and 96 for the TST at a cutoff induration size of 5 mm. When the sensitivity rates of the TST and the QFT-G assay were compounded, the QFT-G assay strategy alone was slightly less costly (0.6%) than the two-step approach. CONCLUSIONS: Using the QFT-G assay, but especially combining the QFT-G assay following the TST screening of close-contacts at a cutoff induration size of 5 mm before LTBI treatment is highly cost-effective in reducing the disease burden of TB.     

Discriminating between latent and active tuberculosis with multiple biomarker responses

We sought to identify biomarker responses to tuberculosis specific antigens which could 1) improve the diagnosis of tuberculosis infection and 2) allow the differentiation of active and latent infections. Seventy subjects with active tuberculosis (N = 12), latent tuberculosis (N = 32), or no evidence of tuberculosis infection (N = 26) were evaluated. We used the Luminex Multiplexed Bead Array platform to simultaneously evaluate 25 biomarkers in the supernatant of whole blood samples following overnight stimulation using the Quantiferon(?) Gold In-Tube kit. We defined the response to stimulation as the difference (within an individual patient) between the response to the pooled tuberculosis antigens and the negative control. IP-10 response was significantly higher in tuberculosis-infected (active or latent) subjects compared to the uninfected group (p < 0.0001). Among the 25 parameters, expression levels of IL-15 and MCP-1 were found to be significantly higher in the active tuberculosis group compared to the latent tuberculosis group (p = 0.0006 and 0.0030, respectively). When combined, IL-15 and MCP-1 accurately identified 83% of active and 88% of latent infections. The combination of IL-15 and MCP-1 responses was accurate in distinguishing persons with active tuberculosis from persons with latent tuberculosis in this study.     

Quantitative scoring of an interferon-gamma assay for differentiating active from latent tuberculosis.

The aim of this study was to assess the contribution of an interferon-gamma release assay (T-SPOT.TB) to the differentiation of active tuberculosis (TB) from latent TB infection by quantifying spot-forming units (sfu). The investigation was a prospective study of contacts exposed to a case of contagious TB and cases of HIV-negative culture-proven TB referred over a 16-month period. Tuberculin skin tests (TSTs) and T-SPOT.TB were performed in 310 contacts 8-12 weeks after exposure. In subjects with culture-proven TB, T-SPOT.TB was performed within 2 weeks of initiation of treatment. The analysis included all contacts with a positive T-SPOT.TB result and all subjects with TB. TB contacts (n = 127) and cases (n = 58) were included. Mean+/-sd T-SPOT.TB results were 107+/-56 (range 1-207) sfu for TB, 54+/-60 (7-239) sfu for contacts with positive T-SPOT.TB results and a TST induration diameter of >5 mm, and 19+/-27 (7-143) sfu for contacts with positive T-SPOT.TB results and a TST induration diameter of < or =5 mm. By receiver operating characteristic curve analysis, a threshold value of 49.5 sfu showed a sensitivity of 83% and specificity of 74% for distinguishing latent TB infection from TB. Although T-SPOT.TB results were significantly related to disease activity, the test cannot be recommended for the diagnosis of tuberculosis.     

New diagnostics for latent and active tuberculosis: state of the art and future prospects

Tuberculosis (TB) continues to be the world's most important infectious cause of morbidity and mortality among adults. Nearly 9 million people develop TB disease each year, and an estimated 1.6 million die from the disease. Despite this enormous global burden, case detection rates are low, posing serious hurdles for TB control. Conventional TB diagnosis continues to rely on antiquated tests such as sputum smear microscopy, culture, tuberculin skin test, and chest radiography. These tests have several limitations and perform poorly in populations affected by the HIV epidemic. Conventional tests for detection of drug resistance are time consuming, tedious, and inaccessible in most settings. In this review, we describe recent advances in the diagnosis of latent and active TB, and detection of drug resistance. Although the perfect test will not be ready for large-scale roll-out and integration into routine TB care services for some time, substantial progress has been made in expanding the TB diagnostic product pipeline. With the resurgence of interest in the development of new tools for TB control, and the recent influx of funding and political support, it is likely that the next few years will see the introduction of new diagnostic tools into routine TB control programs.     

Risk factors for active tuberculosis after antiretroviral treatment initiation in Abidjan

RATIONALE: In sub-Saharan Africa: (1) tuberculosis is the first cause of HIV-related mortality; (2) the incidence of tuberculosis in adults receiving highly active antiretroviral therapy (HAART) is lower than in untreated HIV-infected adults but higher than in HIV-negative adults; and (3) factors associated with the occurrence of tuberculosis in patients receiving HAART have never been described. OBJECTIVE: To look for the risk factors for active tuberculosis in HIV-infected adults receiving HAART in Abidjan. METHODS: Seven-year prospective cohort of HIV-infected adults, with standardized procedures for documenting morbidity. We analyzed the incidence of active tuberculosis in patients who started HAART and the association between the occurrence of tuberculosis and the characteristics of these patients at HAART initiation. MAIN RESULTS: A total of 129 adults (median baseline CD4 count 125/mm(3)) started HAART and were then followed for 270 person-years (P-Y). At HAART initiation, 31 had a history of tuberculosis and none had current active tuberculosis. During follow-up, the incidence of active tuberculosis was 4.8/100 P-Y (95% confidence interval [CI], 2.5-8.3) overall, 3.0/100 P-Y (95% CI, 1.1-6.6) in patients with no tuberculosis history, and 11.3/100 P-Y (95% CI, 4.1-24.5) in patients with a history of tuberculosis (adjusted hazard ratio, 4.64; 95% CI, 1.29-16.62, p = 0.02). CONCLUSION: The risk of tuberculosis after HAART initiation was significantly higher in patients with a history of tuberculosis than in those with no tuberculosis history. If confirmed by others, this finding could lead to assessment of new patterns of time-limited tuberculosis secondary chemoprophylaxis during the period of initiation of HAART in sub-Saharan African adults.     

中国农村结核潜伏感染人群五年发病特征及相关影响因素

<正>最新研究估算全球有近1/4的人感染结核分枝杆菌并长期处于潜伏感染状态,其中5%～10%可能会在一生中发展为活动性结核病。因此,潜伏感染人群是一个庞大的潜在患者库。研究证实,针对潜伏感染高危人群开展预防性治疗可使其发病风险降低60%～90%。因此,在短期内新疫苗研发难以实现突破的前提下,针对潜伏感染高危人群开展预防性治疗成为可以直接降低发病率的重要手段。在没有结核病高负担国家成功经验可循的现状下,我国结核潜伏感染     

痰涂片阳性肺结核患者成年家庭接触者患活动性结核病的风险

场所：土耳其伊斯坦布尔7个公共结核病防治所。 目的：调查伊斯坦布尔新诊断的痰涂片阳性肺结核患者成年家庭接触者（≥15岁）患活动性结核病的风险。 设计：对1997-2000年在伊斯坦布尔7家结防所登记的1570例结核病成年家庭接触者的回顾性分析。 结果：研究包括6188例家庭接触者（平均接触者／线索病例：3．9）,其中4114例（67％）大于15岁（平均接触者／线索病例：2．6）;3310例（80．5％）参加了接触者调查。平均随访时间2．2年（1～4年）;发现222例活动性结核病例（5．4％,95％可信区间5．2～5．6）,第一年发现171例。活动性结核发病率为2491／100000（15～34岁年龄组发病率3555／100000,大于35岁年龄组发病率1195／100000,P〈0．0001）。活动性结核病发病率最高的在15～24岁（8．5％）和25～34岁（6．5％）年龄组。 结论：涂片阳性肺结核患者的成年家庭接触者活动性结核发病率高。这样的高发病率说明化学预防治疗对于所有接触者,特别是年龄为15～34岁的接触者都是必要的,而不应仅仅用于儿童。     

Risk of developing tuberculosis under anti-TNF treatment despite latent infection screening

BackgroundIn patients treated with TNF-antagonists, incident cases of tuberculosis (TB) after a negative screening have been reported, leading to the suggestion that improved TB testing is necessary.AimThe aim of the current study is to establish the incidence of TB and its characteristics in patients with inflammatory bowel disease (IBD) under TNF antagonists to design improved prevention strategies.MethodsIBD patients from a single center treated with anti-TNF therapy between January 2000 and September 2011 were identified through a database that prospectively records clinical data, treatments and adverse events.ResultsDuring the study period 423 patients received anti-TNF therapy. Screening for latent TB infection (LTBI) previous to anti-TNF treatment was positive in 30 patients (6.96%). Seven patients (1.65%) developed TB while under anti-TNF treatment. Six patients (five under immunosuppressant treatment) had a negative LTBI screening. TST was positive in one patient not receiving immunosuppressants, and was treated with isoniazid before starting anti-TNF therapy. In 4 patients TB was diagnosed within the first 16 weeks after starting anti-TNF therapy. Three cases had pulmonary TB and 4 extrapulmonary disease.ConclusionsIn the IBD population under study, incidence of TB infection associated with anti-TNF therapy is higher than that reported in controlled trials and occurs early after treatment initiation. False negative results of LTBI despite appropriate measures may occur, suggesting that more effective screening strategies are needed.