BACKGROUND & AIMS: :The genotypic characteristics and drug susceptibility profiles of clinical isolates of Mycobacterium tuberculosis recovered from prison hospital patients in the Tula region (central Russia) during 2001 and 2002 are reported. The emergence of multi-drug-resistant tuberculosis (TB) poses a major health risk to the population, with economic implications for TB control. Prisons serve as a continuous source of TB transmission. The results showed that members of the LAM and Beijing families are major contributors to the epidemiological picture of TB in the population studied. The two families of strains accounted for most of the drug-resistant TB in the population. The genotypic characteristics of the M. tuberculosis predominant LAM strain that was responsible for 31 % of TB cases in this setting are presented.

背景与目标： : 报告了从图拉地区 (俄罗斯中部) 2001年和2002的监狱医院患者中回收的结核分枝杆菌临床分离株的基因型特征和药物敏感性。耐多药结核病 (TB) 的出现对人口构成重大健康风险，对结核病控制具有经济影响。监狱是结核病传播的持续来源。结果表明，LAM和北京家庭的成员是研究人群中结核病流行病学状况的主要贡献者。这两个菌株家族占人群中耐药性结核病的大部分。介绍了在这种情况下导致结核病病例31% 的结核分枝杆菌主要LAM菌株的基因型特征。

BACKGROUND & AIMS: :Six different secretory proteins of molecular weights (15, 26, 30, 41, 55 and 70 kDa) were isolated from 8-day-old culture filtrate of Mycobacterium tuberculosis H37Ra using different column chromatography techniques. These proteins were further examined for their ability to induce cell mediated (T-cell proliferation assay) and humoral immune response (ELISA) in mice immunized with total culture filtrate proteins. Out of six proteins, three proteins showed good reactivity. However, the activity was at a maximum with 30 kDa antigen. The immune response induced by 30 kDa antigen emulsified in Freund's incomplete adjuvant (FIA) was investigated and was found to be dose dependent. The T-cell response induced by this protein was skewed towards T-helper (Th1) cells as determined by the pronounced secretion of interleukin-2 (IL-2) and gamma-interferon (IFN-gamma). The protective activity of the 30 kDa protein was also evaluated and compared with reference to Bacillus Calmette Guerin (BCG) vaccine in the mice challenged with virulent M. tuberculosis H37Rv. The degree of protection afforded by the 30 kDa antigen on the basis of mortality and the significant decrease in c.f.u.'s recovered from different organs (lung, liver, spleen) after 30 days of challenge with LD50 of M. tuberculosis H37Rv was significantly higher in comparison to BCG vaccinated animals. However, the degree of immunity induced by this antigen decreased with time (when challenged 8 and 12 weeks post-immunization) but it was still comparable with BCG. These findings suggest that 30 kDa secretory protein of M. tuberculosis is the key immunoprotective antigen and may be a suitable candidate for the development of an alternative subunit vaccine against tuberculosis.

背景与目标： : 使用不同的柱色谱技术从8天大的结核分枝杆菌H37Ra培养滤液中分离出六种分子量不同的分泌蛋白 (15、26、30、41、55和70 kDa)。进一步检查了这些蛋白质在用总培养滤液蛋白免疫的小鼠中诱导细胞介导的 (T细胞增殖测定) 和体液免疫反应 (ELISA) 的能力。在六种蛋白质中，三种蛋白质显示出良好的反应性。然而，30 kDa抗原的活性最大。研究了在弗氏不完全佐剂 (FIA) 中乳化的30 kDa抗原诱导的免疫反应，并发现其具有剂量依赖性。由该蛋白诱导的T细胞反应向T辅助 (Th1) 细胞倾斜，这是由interleukin-2 (IL-2) 和 γ-干扰素 (IFN-γ) 的明显分泌决定的。还评估了30 kDa蛋白的保护活性，并将其与卡介苗 (BCG) 疫苗进行了比较，该疫苗在用强毒力结核分枝杆菌H37Rv攻击的小鼠中进行了比较。30 kDa抗原在死亡率的基础上提供的保护程度，以及在用结核分枝杆菌H37Rv的LD50攻击30天后从不同器官 (肺，肝，脾) 恢复的c.f.u.的显着降低与BCG接种的动物相比更高。然而，该抗原诱导的免疫程度随时间而降低 (预防接种后8周和12周受到攻击时)，但仍与BCG相当。这些发现表明，结核分枝杆菌的30 kDa分泌蛋白是关键的免疫保护性抗原，并且可能是开发针对结核病的替代亚单位疫苗的合适候选者。

BACKGROUND & AIMS: AIM:To report the patterns and sites of 18-FDG uptake in patients of presumed ocular tuberculosis. MATERIALS AND METHODS:The clinical and investigational findings of 11 patients were reviewed retrospectively. These included 6 males and 5 females with a mean age of 46.2 years. 21 eyes were included in the data analysis. Clinical presentations include 15 eyes with anterior uveitis, 2 eyes with retinal vasculitis, 2 eyes with panuveitis and 2 eyes with multifocal choroidopathy. RESULTS:Two distinct patterns of systemic uptake emerged. Pattern 1: No detectable systemic uptake (4 patients). Pattern 2: Detectable systemic uptake. a. Chest disease only (2 patients). b. Disseminated pattern, uptake seen at multiple sites (4 patients). c. Extrapulmonary only (1 patient). CONCLUSIONS:Ocular tuberculosis may often be part of a wider disseminated disease.

背景与目标：

BACKGROUND & AIMS: :Novel treatment strategies for tuberculosis are urgently needed. Many different preclinical models assessing anti-tuberculosis drug activity are available, but it is yet unclear which combination of models is most predictive of clinical treatment efficacy. The aim of this study was to determine the role of our in vitro time kill-kinetics assay as an asset to a predictive preclinical modeling framework assessing anti-tuberculosis drug activity. The concentration- and time-dependent mycobacterial killing capacities of six anti-tuberculosis drugs were determined during exposure as single drugs or in dual, triple and quadruple combinations towards a Mycobacterium tuberculosis Beijing genotype strain and drug resistance was assessed. Streptomycin, rifampicin and isoniazid were most active against fast-growing M. tuberculosis. Isoniazid with rifampicin or high dose ethambutol were the only synergistic drug combinations. The addition of rifampicin or streptomycin to isoniazid prevented isoniazid resistance. In vitro ranking showed agreement with early bactericidal activity in tuberculosis patients for some but not all anti-tuberculosis drugs. The time-kill kinetics assay provides important information on the mycobacterial killing dynamics of anti-tuberculosis drugs during the early phase of drug exposure. As such, this assay is a valuable component of the preclinical modeling framework.

背景与目标： 迫切需要新的结核病治疗策略。有许多不同的评估抗结核药物活性的临床前模型，但尚不清楚哪种模型组合最能预测临床治疗效果。这项研究的目的是确定我们的体外时间杀伤动力学测定法作为评估抗结核药物活性的预测性临床前建模框架的资产的作用。在暴露于结核分枝杆菌北京基因型菌株的过程中，确定了六种抗结核药物的浓度和时间依赖性的分枝杆菌杀伤能力，并评估了耐药性。链霉素，利福平和异烟肼对快速生长的结核分枝杆菌最有效。异烟肼与利福平或高剂量乙胺丁醇是唯一的协同药物组合。在异烟肼中添加利福平或链霉素可防止异烟肼耐药性。体外排名显示，对于某些 (但不是所有) 抗结核药物，结核病患者的早期杀菌活性一致。时间杀伤动力学测定法提供了有关药物暴露早期抗结核药物的分枝杆菌杀伤动力学的重要信息。因此，该测定是临床前建模框架的有价值的组成部分。

BACKGROUND & AIMS: :We have investigated the relationship between cortisol and dehydroepiandrosterone (DHEA) levels and the immune response to mycobacterial antigens in peripheral venous blood, from a male population of active tuberculosis patients and age-matched healthy controls of the same sex (HCo). Peripheral blood mononuclear cells were cultured for 36 or 96 h with whole sonicated Mycobacterium tuberculosis (WSA) for measurement of proliferation, interferon gamma (IFN-gamma) and interleukin-10 (IL-10) in culture supernatants. Comparisons on the in vitro mycobacterial-driven immune responses demonstrated that TB patients had a higher IL-10 production, a decreased lymphoproliferation and a trend to reduced IFN-gamma synthesis, in relation to HCo. Active disease was also characterized by increases in the plasma levels of glucocorticoids (GC) and reduced concentrations of DHEA which resulted in a higher cortisol/DHEA ratio respect the HCo group. Plasma DHEA levels were positively correlated with IFN-gamma values. An inverse correlation was found between the cortisol/DHEA ratio and IFN-gamma levels. Novel evidence is provided showing that the balance between cortisol and DHEA is partly responsible for the immune perturbations seen in TB patients.

背景与目标： : 我们已经调查了来自活跃的结核病患者和年龄匹配的同性健康对照 (HCo) 的男性人群的皮质醇和脱氢表雄酮 (DHEA) 水平与外周静脉血中分枝杆菌抗原的免疫反应之间的关系。将外周血单核细胞与全超声结核分枝杆菌 (WSA) 一起培养36或96小时，以测量培养上清液中的增殖，干扰素 γ (IFN-γ) 和interleukin-10 (IL-10)。对体外分枝杆菌驱动的免疫反应的比较表明，与HCo相比，结核病患者具有更高的IL-10产生，淋巴增殖减少以及IFN-γ 合成减少的趋势。活动性疾病的特征还在于血浆糖皮质激素 (GC) 水平升高和DHEA浓度降低，这导致HCo组的皮质醇/DHEA比率更高。血浆DHEA水平与IFN-γ 值呈正相关。皮质醇/DHEA比率与IFN-γ 水平之间呈负相关。提供了新的证据，表明皮质醇和DHEA之间的平衡是结核病患者免疫紊乱的部分原因。

BACKGROUND & AIMS: BACKGROUND:Tuberculosis is curable, but community surveys documenting epidemiological impact of the WHO-recommended DOTS strategy on tuberculosis prevalence have not been published. We used active community surveillance to compare the impact of DOTS with earlier programmes. METHODS:We conducted tuberculosis disease surveys using random cluster sampling of a rural population in South India approximately every 2.5 years from 1968 to 1986, using radiography as a screening tool for sputum examination. In 1999, DOTS was implemented in the area. Prevalence surveys using radiography and symptom screening were conducted at the start of DOTS implementation and after 2.5 years. RESULTS:From 1968 to 1999, culture-positive and smear-positive tuberculosis declined by 2.3 and 2.5% per annum compared with 11.9 and 5.6% after DOTS implementation. The 2.5 year period of DOTS implementation accounted for one-fourth of the decline in prevalence of culture-positive tuberculosis over 33 years. Multivariate analysis showed that prevalence of culture-positive tuberculosis decreased substantially (10.0% per annum, 95% CI: 2.8-16.6%) owing to DOTS after only slight declines related to temporal trends (2.1% annual decline, 95% CI: 1.1-3.2%) and short-course chemotherapy (1.5% annual decline, 95% CI: -9.7% to 11.5%). Under DOTS, the proportion of total cases identified through clinical care increased from 81 to 92%. CONCLUSIONS:Following DOTS implementation, prevalence of culture-positive tuberculosis decreased rapidly following a gradual decline for the previous 30 years. In the absence of a large HIV epidemic and with relatively low levels of rifampicin resistance, DOTS was associated with rapid reduction of tuberculosis prevalence.

背景与目标：

BACKGROUND & AIMS: -2

背景与目标： -2

BACKGROUND & AIMS: :Previous studies have suggested that isolates of Mycobacterium tuberculosis responsible for tuberculosis outbreaks grow more rapidly within human mononuclear phagocytes than do other isolates. Clinical scenarios suggesting virulence of specific M. tuberculosis isolates are readily identified. Determination of appropriate "control" isolates for these studies is more problematic, but equally important for validating these assays and, ultimately, for identifying biologic differences between M. tuberculosis strains that contribute to virulence. We utilized the database from a study of Ugandan tuberculosis patients and their household (HH) contacts to identify M. tuberculosis isolates transmitted within HH and nontransmitted control isolates. Isolate pairs were evaluated from matched HH in each of three clinical scenarios: (i) coprevalent disease and no disease, (ii) incident disease and no disease, and (iii) M. tuberculosis infection (purified protein derivative [PPD] positive) and no infection (PPD negative). Intracellular growth of paired organisms was determined in a blinded fashion using two models of intracellular infection in which we have previously demonstrated correlation between intracellular growth and strain virulence, primary human monocytes (MN) and THP-1 human macrophage-like cells. In both models, transmitted isolates from coprevalent disease HH displayed more rapid growth than nontransmitted control isolates. In the THP-1 model, this was also true of transmitted isolates from HH with incident disease and their controls. Differences in production of tumor necrosis factor alpha and interleukin-10 by matched isolates showed correlation with growth patterns in the THP-1 cells but not in MN. Paired isolates characterized in this manner may be of particular interest for further investigations of the virulence of M. tuberculosis.

背景与目标： : 先前的研究表明，负责结核病暴发的结核分枝杆菌分离株在人类单核吞噬细胞内的生长速度比其他分离株更快。提示特定结核分枝杆菌分离株毒力的临床情景很容易确定。为这些研究确定适当的 “对照” 分离株是更成问题的，但对于验证这些测定以及最终确定有助于毒力的结核分枝杆菌菌株之间的生物学差异同样重要。我们利用乌干达结核病患者及其家庭 (HH) 接触者的研究数据库来确定在HH内传播的结核分枝杆菌分离株和非传播的对照分离株。在三种临床情况下，从匹配的HH评估分离对 :( i) 共价疾病和无疾病，(ii) 突发疾病和无疾病，以及 (iii) 结核分枝杆菌感染 (纯化的蛋白衍生物 [PPD] 阳性) 和无感染 (PPD阴性)。使用两种细胞内感染模型以盲方式确定配对生物的细胞内生长，其中我们先前已经证明了细胞内生长与菌株毒力，原代人单核细胞 (MN) 和THP-1人巨噬细胞样细胞之间的相关性。在这两个模型中，来自共价疾病HH的传播分离株比未传播的对照分离株显示出更快的生长。在THP-1模型中，具有突发疾病的HH传播分离株及其对照也是如此。匹配的分离株在肿瘤坏死因子 α 和interleukin-10产生方面的差异显示出与THP-1细胞中的生长模式相关，而与MN中的生长模式无关。以这种方式表征的成对分离株对于进一步研究结核分枝杆菌的毒力可能特别感兴趣。

BACKGROUND & AIMS: :Bovine tuberculosis (bTB) is a chronic disease of cattle that is difficult to control and eradicate in part due to the costly nature of surveillance and poor sensitivity of diagnostic tests. Like many countries, bTB prevalence in Uruguay has gradually declined to low levels due to intensive surveillance and control efforts over the past decades. In low prevalence settings, broad-based surveillance strategies based on routine testing may not be the most cost-effective way for controlling between-farm bTB transmission, while targeted surveillance aimed at high-risk farms may be more efficient for this purpose. To investigate the efficacy of targeted surveillance, we developed an integrated within- and between-farm bTB transmission model utilizing data from Uruguay's comprehensive animal movement database. A genetic algorithm was used to fit uncertain parameter values, such as the animal-level sensitivity of skin testing and slaughter inspection, to observed bTB epidemiological data. Of ten alternative surveillance strategies evaluated, a strategy based on eliminating testing in low-risk farms resulted in a 40% reduction in sampling effort without increasing bTB incidence. These results can inform the design of more cost-effective surveillance programs to detect and control bTB in Uruguay and other countries with low bTB prevalence.

背景与目标： : 牛结核病 (bTB) 是一种牛的慢性疾病，由于监测的成本高昂和诊断测试的敏感性差，很难控制和根除。与许多国家一样，由于过去几十年来的密集监测和控制工作，乌拉圭的bTB患病率逐渐下降到较低水平。在低流行率的环境中，基于常规测试的基础广泛的监测策略可能不是控制农场间bTB传播的最具成本效益的方法，而针对高风险农场的针对性监测可能为此目的更有效。为了研究目标监测的有效性，我们利用乌拉圭综合动物运动数据库中的数据开发了一个集成的农场内和农场间bTB传播模型。使用遗传算法将不确定的参数值 (例如皮肤测试和屠宰检查的动物级敏感性) 拟合到观察到的bTB流行病学数据。在评估的十种替代监测策略中，基于消除低风险农场测试的策略导致采样工作量40% 减少，而不会增加bTB发生率。这些结果可以为设计更具成本效益的监测计划提供信息，以检测和控制乌拉圭和其他bTB患病率较低的国家的bTB。

BACKGROUND & AIMS: :We report the synthesis of 5'-modified thymidines (16, 18, 21, 23) and 5,5'-bis-substituted 2'-deoxyuridine analogues (30, 47) as inhibitors of thymidine monophosphate kinase of Mycobacterium tuberculosis (TMPKmt). These analogues were evaluated for their capacity to inhibit TMPKmt and solely two 5'-modified thymidines were found to possess moderate inhibitory activity. In addition, a feasibility study of protecting groups for the 5-CH(2)OH moiety of 2'-deoxyuridines is described that enables to introduce the desired 5'-modification.

背景与目标： : 我们报告了5 '-修饰的胸苷 (16,18，21,23) 和5,5'-双取代的2 '-脱氧尿苷类似物 (30,47) 作为结核分枝杆菌 (TMPKmt) 的胸苷单磷酸激酶抑制剂的合成。评估了这些类似物抑制TMPKmt的能力，仅发现两种5 '修饰的胸苷具有中等抑制活性。此外，描述了保护2 '-脱氧尿苷的5-CH(2)OH部分的基团的可行性研究，该研究能够引入所需的5'-修饰。

BACKGROUND & AIMS: :Organized bacterial communities, or biofilms, provide an important reservoir for persistent cells that are inaccessible or tolerant to antibiotics. Curli pili are cell-surface structures produced by certain bacteria and have been implicated in biofilm formation in these species. In order to determine whether these structures, which were suggested to be encoded by the Rv3312A (mtp) gene, have a similar role in Mycobacterium tuberculosis, we generated a Δmtp mutant and a mtp-complemented strain of a clinical isolate of M. tuberculosis and analyzed these strains for their ability to produce pili in comparison to the wild-type strain. Phenotypic analysis by transmission electron microscopy proved the essentiality of mtp for piliation in M. tuberculosis. We then compared biofilm formation of the derived strains in detergent-free Sauton's media. Biofilm mass was quantified spectrophotometrically using crystal violet. Furthermore, we examined mtp gene expression by quantitative real-time PCR in wild-type cells grown under biofilm versus planktonic growth conditions. We found a 68.4 % reduction in biofilm mass in the mutant compared to the wild-type strain (P = 0.002). Complementation of the mutant resulted in a restoration of the wild-type biofilm phenotype (P = 0.022). We, however, found no significant difference between mtp expression in cells of the biofilm to those growing planktonically. Our findings highlight a crucial, but non-specific, role of pili in the biofilm lifestyle of M. tuberculosis and indicate that they may represent an important target for the development of therapeutics to attenuate biofilm formation, thereby potentially reducing persistence.

背景与目标： : 有组织的细菌群落或生物膜为无法接触或耐受抗生素的持久性细胞提供了重要的储库。Curli菌毛是由某些细菌产生的细胞表面结构，并与这些物种的生物膜形成有关。为了确定这些被建议由Rv3312A (mtp) 基因编码的结构在结核分枝杆菌中是否具有类似的作用，我们产生了结核分枝杆菌临床分离株的 Δ mtp突变体和mtp补充株，并分析了这些菌株与野生型菌株相比产生菌毛的能力。透射电子显微镜的表型分析证明了mtp对结核分枝杆菌的重要性。然后，我们比较了不含洗涤剂的Sauton培养基中衍生菌株的生物膜形成。使用结晶紫分光光度法定量生物膜质量。此外，我们通过定量实时PCR检查了在生物膜与浮游生长条件下生长的野生型细胞中mtp基因的表达。我们发现与野生型菌株相比，突变体的生物膜质量68.4% 减少 (P = 0.002)。突变体的互补导致野生型生物膜表型的恢复 (P = 0.022)。然而，我们发现生物膜细胞中的mtp表达与浮游生长的细胞之间没有显着差异。我们的发现强调了菌毛在结核分枝杆菌的生物膜生活方式中至关重要但非特异性的作用，并表明它们可能是发展减少生物膜形成的疗法的重要目标，从而可能减少持久性。

BACKGROUND & AIMS: :A series of 14 patients suffering from tuberculosis of the sternum with a mean follow-up of 2.8 years (2 to 3.6) is presented. All were treated with antitubercular therapy: ten with primary therapy, two needed second-line therapy, and two required surgery (debridement). All showed complete healing and no evidence of recurrence at the last follow-up. MRI was useful in making the diagnosis at an early stage because atypical presentations resulting from HIV have become more common. Early adequate treatment with multidrug antitubercular therapy avoided the need for surgery in 12 of our 14 patients.

背景与目标： : 介绍了14例胸骨结核患者，平均随访2.8年 (2至3.6年)。所有患者均接受抗结核治疗: 10例接受主要治疗，2例需要二线治疗，2例需要手术 (清创术)。所有患者均显示完全愈合，并且在最后一次随访中没有复发的迹象。MRI可用于早期诊断，因为HIV引起的非典型表现已变得越来越普遍。在我们的14例患者中，有12例通过多药抗结核治疗进行早期的适当治疗避免了手术的需要。

BACKGROUND & AIMS: :The malonyl coenzyme A (CoA)-acyl carrier protein (ACP) transacylase (MCAT) plays a key role in cell wall biosynthesis in Mycobacterium tuberculosis and other bacteria. The M. tuberculosis MCAT (MtMCAT) is encoded by the FabD gene and catalyzes the transacylation of malonate from malonyl-CoA to holo-ACP. Malonyl-ACP is the substrate in fatty acid biosynthesis and is a by-product of the transacylation reaction. This ability for fatty acid biosynthesis enables M. tuberculosis to survive in hostile environments, and thus understanding the mechanism of biosynthesis is important for the design of new anti-tuberculosis drugs. The 2.3 A crystal structure of MtMCAT reported here shows that its catalytic mechanism differs from those of ScMCAT and EcMCAT, whose structures have previously been determined. In MtMCAT, the C(beta)-O(gamma) bond of Ser91 turns upwards, resulting in a different orientation and thus an overall change of the active pocket compared to other known MCAT enzymes. We identify three new nucleophilic attack chains from the MtMCAT structure: His90-Ser91, Asn155-Wat6-Ser91 and Asn155-His90-Ser91. Enzyme activity assays show that His90A, Asn155A and His90A-Asn155A mutants all have substantially reduced MCAT activity, indicating that M. tuberculosis MCAT supports a unique means of proton transfer. Furthermore, His194 cannot form part of a His-Ser catalytic dyad and only stabilizes the substrate. This new discovery should provide a deeper insight into the catalytic mechanisms of MCATs.

背景与目标： : 丙二酰辅酶a (CoA)-酰基载体蛋白 (ACP) 转酰基酶 (MCAT) 在结核分枝杆菌和其他细菌的细胞壁生物合成中起关键作用。结核分枝杆菌MCAT (MtMCAT) 由FabD基因编码，可催化丙二酸从丙二酰辅酶a转酰化为holo-ACP。丙二酰-ACP是脂肪酸生物合成中的底物，是转酰化反应的副产物。这种脂肪酸生物合成的能力使结核分枝杆菌能够在恶劣的环境中生存，因此了解生物合成的机理对于设计新的抗结核药物很重要。本文报道的MtMCAT的2.3 A晶体结构表明其催化机理不同于ScMCAT和EcMCAT的催化机理，ScMCAT和EcMCAT的结构先前已经确定。在MtMCAT中，与其他已知的MCAT酶相比，Ser91的C (β)-O (γ) 键向上旋转，导致不同的方向，从而导致活性口袋的整体变化。我们从MtMCAT结构中识别出三个新的亲核攻击链: His90-Ser91，Asn155-Wat6-Ser91和Asn155-His90-Ser91。酶活性测定表明His90A，Asn155A和His90A-Asn155A突变体均具有显着降低的MCAT活性，表明结核分枝杆菌MCAT支持质子转移的独特手段。此外，His194不能形成His-Ser催化二联体的一部分，只能稳定底物。这一新发现将为MCATs的催化机制提供更深入的了解。

BACKGROUND & AIMS: :Tuberculosis (TB) is an enormous global public health problem. Cases of extensively drug-resistant TB (XDR-TB) are being reported in increasing numbers across the globe. A large outbreak of XDR-TB associated with rapid and nearly universal mortality has been reported among patients with human immunodeficiency virus infection or acquired immunodeficiency disease in South Africa who have been receiving standard TB therapy and antiretrovirals. Epidemiologic features of this outbreak make it highly suspicious for health care-associated transmission. We urge the Infectious Diseases Society of America and its members to increase involvement in ongoing international TB prevention and treatment efforts and to develop a registry of experts in infection control and laboratory and disease management. We urge advocacy for increased funding for domestic and global TB control programs, including expanded access to sputum culture and drug susceptibility testing, as well as funding for TB clinical trials and research capacity. We believe that substandard TB diagnostic tests are not acceptable for TB control in resource-poor countries. We urge the development of shorter, less toxic TB treatment and prevention regimens. Funding of TB control and research should be reassessed to prevent budget cuts at a time when the disease is killing as many as 2 million people a year.

背景与目标： : 结核病 (TB) 是一个巨大的全球公共卫生问题。全球范围内广泛耐药结核病 (xdr-tb) 的病例越来越多。据报道，在南非接受标准结核病治疗和抗逆转录病毒药物治疗的人类免疫缺陷病病毒感染或获得性免疫缺陷性疾病患者中，广泛耐药结核病的大规模爆发与快速和几乎普遍的死亡率相关。这次疫情的流行病学特征使其高度怀疑与医疗保健相关的传播。我们敦促美国传染病学会及其成员更多地参与正在进行的国际结核病预防和治疗工作，并建立感染控制、实验室和疾病管理专家登记册。我们敦促倡导增加对国内和全球结核病控制计划的资助，包括扩大对痰培养和药物敏感性测试的获取，以及对结核病临床试验和研究能力的资助。我们认为，在资源匮乏的国家，不合格的结核病诊断测试对于结核病控制是不可接受的。我们敦促开发更短、毒性更小的结核病治疗和预防方案。应该重新评估结核病控制和研究的资金，以防止在该疾病每年造成多达200万人死亡的时候削减预算。

BACKGROUND & AIMS: :Laboratory diagnosis of tuberculosis (TB) traditionally relies on smear microscopy and culture of Mycobacterium tuberculosis from clinical samples. With recent advances in technology, there have been numerous efforts to develop new diagnostic tests for TB that overcome the low sensitivity and specificity and long turnover time associated with current diagnostic tests. Molecular biological tests based on nucleic acid amplification have brought an unprecedented opportunity for the rapid and specific detection of M. tuberculosis from clinical specimens. With automated sequencing analysis, species identification of mycobacteria is now easier and more accurate than with conventional methods, and rapid detection of mutations in the genes associated with resistance to TB drugs provides early information on the potential drug resistance for each clinical isolate or for clinical samples. In addition, immunological tests for the detection of M. tuberculosis antigens and antibodies to the antigens have been explored to identify individuals at risk of developing TB or with latent TB infection (LTBI). The recent introduction of commercial IFN-gamma assay kits for the detection of LTBI provides a new approach for TB control even in areas with a high incidence of TB. However, these molecular and immunological tools still require further evaluation using large scale cohort studies before implementation in TB control programs.

背景与目标： : 结核病 (TB) 的实验室诊断传统上依赖于涂片显微镜检查和临床样本中结核分枝杆菌的培养。随着技术的最新发展，已经做出了许多努力来开发新的结核病诊断测试，以克服与当前诊断测试相关的低敏感性和特异性以及长周转时间。基于核酸扩增的分子生物学检测为从临床标本中快速、特异性地检测结核分枝杆菌带来了前所未有的机遇。通过自动测序分析，与传统方法相比，分枝杆菌的物种鉴定现在更容易，更准确，并且快速检测与结核病药物耐药性相关的基因突变，可以为每种临床分离株或临床样本提供有关潜在耐药性的早期信息。此外，已经探索了用于检测结核分枝杆菌抗原和抗原抗体的免疫学测试，以识别有发展结核病或潜伏性结核感染 (LTBI) 风险的个体。最近推出的用于检测LTBI的商用IFN-γ 测定试剂盒为结核病控制提供了一种新方法，即使在结核病高发地区也是如此。然而，在实施结核病控制计划之前，这些分子和免疫学工具仍需要使用大规模队列研究进行进一步评估。