The impact of human single nucleotide polymorphisms on Bacillus Calmette-Guérin responses

The influence of genetic variability on human immune responses has major implications for the understanding of disease mechanisms and host-pathogen interactions. Bacillus Calmette-Guérin (BCG) vaccine, which is given globally to protect against tuberculosis, has high variability in its protective efficacy against mycobacteria and its beneficial off-target (heterologous) effects. Single nucleotide polymorphisms (SNPs) are major cause of genetic variation and have been strongly associated with susceptibility to tuberculosis and outcomes following BCG immunotherapy for cancer. This review discusses the contribution of SNPs to the variability in mycobacterial-specific and off-target BCG responses, and the implications for this on development of novel TB vaccines and strategies to harness the beneficial off-target effects of BCG.     

提高新发涂阳肺结核病人发现率方法的研究

目的 促进肺结核登记报告,提高病人发现率?方法 根据新发涂阳登记率,采用分层单纯随机抽样方法在山东省确定6个县作为调查点?采取积极的干预措施,进行广泛深入地宣教,并在采取措施前后对健康人群?肺结核病人及综合医院进行调查?对比?结果 通过采取措施,有症状主动到结核病防治所就诊者,由干预前的29%增加到干预后的270%;综合医院收住肺结核由030%下降到014%,漏报率由282%下降到159%?1995年新发涂阳登记率为1345/10万,较干预前1994年的1194/10万有明显提高(P<0.01)?采取干预措施后的4年(1994~1997)登记的新发涂阳病人,比干预前的4年(1990~1993)增加434%(2940/2050)?结论 加强宣教,强调依法归口管理?综合医院建立胸透登记?转诊,可以有效地提高新发涂阳病人发现率?     

Retrospective evaluation of the efficacy of the BCG vaccination campaign of newborns in Barcelona,Spain

The efficacy of the BCG vaccination campaign of neonates in Barcelona, carried out in the period 1966–1974, was evaluated with a study of cases and controls made during the period 1978–1988 in patients between the ages of 4 and 21 years. It shows that the efficacy of this vaccination campaign was 32%, that it was greater in men than women and that it decreased with the passage of time. The number of cases of tuberculosis prevented by this campaign is calculated at 13.4%.Given that the vaccine used offered maximum guarantees, the authors consider that this poor efficacy must be attributed to operational deficiencies in the vaccination campaign itself.     

The safety,effectiveness and cost‐effectiveness of cytisine in achieving six‐month continuous smoking abstinence in tuberculosis patients—protocol for a double‐blind,placebo‐controlled randomized trial

Background and aims

Tuberculosis (TB) patients who quit smoking have much better disease outcomes than those who continue to smoke. In general populations, behavioural support combined with pharmacotherapy is the most effective strategy in helping people to quit. However, there is no evidence for the effectiveness of this strategy in TB patients who smoke. We will assess the safety, effectiveness and cost‐effectiveness of cytisine—a low‐cost plant‐derived nicotine substitute—for smoking cessation in TB patients compared with placebo, over and above brief behavioural support.

Design

Two‐arm, parallel, double‐blind, placebo‐controlled, multi‐centre (30 sites in Bangladesh and Pakistan), individually randomized trial.

Setting

TB treatment centres integrated into public health care systems in Bangladesh and Pakistan.

Participants

Newly diagnosed (in the last 4 weeks) adult pulmonary TB patients who are daily smokers (with or without dual smokeless tobacco use) and are interested in quitting (n = 2388).

Measurements

The primary outcome measure is biochemically verified continuous abstinence from smoking at 6 months post‐randomization, assessed using Russell Standard criteria. The secondary outcome measures include continuous abstinence at 12 months, lapses and relapses; clinical TB outcomes; nicotine dependency and withdrawal; and adverse events.

Comments

This is the first smoking cessation trial of cytisine in low‐ and middle‐income countries evaluating both cessation and TB outcomes. If found effective, cytisine could become the most affordable cessation intervention to help TB patients who smoke.     

住院肺结核患者结核病知识知晓率状况

目的了解住院肺结核患者确诊前结核病知识知晓状况。方法对武汉市结核病防治所登记确诊的住院肺结核患者,进行结核病防治知识结构式问卷调查。结果 60.0%以上的住院肺结核患者基本掌握了咳嗽、咳痰、咯血、痰中带血为肺结核病的主要症状。肺结核患者结核病防治知识总体知晓率为60.1%,市区、郊区和外地住院肺结核患者总体正答率之间,差异有统计学意义（P〈0.05）,市区患者结核病知识知晓率高于郊区,郊区患者知晓率高于外地。结论住院肺结核患者在确诊前具有一定的结核病防治知识知晓水平,但与国家结控项目要求还有一定差距。     

Changing Epidemiology of Pulmonary Nontuberculous Mycobacteria Infections

Nontuberculous mycobacteria (NTM) disease is a notifiable condition in Queensland, Australia. Mycobacterial isolates that require species identification are forwarded to the Queensland Mycobacterial Reference Laboratory, providing a central opportunity to capture statewide data on the epidemiology of NTM disease. We compared isolates obtained in 1999 and 2005 and used data from the Queensland notification scheme to report the clinical relevance of these isolates. The incidence of notified cases of clinically significant pulmonary disease rose from 2.2 (1999) to 3.2 (2005) per 100,000 population. The pattern of disease has changed from predominantly cavitary disease in middle-aged men who smoke to fibronodular disease in elderly women. Mycobacterium intracellulare is the main pathogen associated with the increase in isolates speciated in Queensland.Worldwide, pulmonary disease caused by nontuberculous mycobacteria (NTM) appears to be increasing (1–4), yet accurate data to support this assumption are difficult to produce. Patients traditionally described are middle-aged men with underlying chronic lung disease, such as chronic obstructive pulmonary disease, who have upper lobe cavity formation and nodules of various sizes. An increasing number of patients have nodules, bronchiolitis, and bronchiectasis involving the middle lobe and lingula. These patients are more commonly female nonsmokers and have no preexisting lung disease (5,6).NTM disease is not a reportable condition in most countries because no evidence of human-to-human transmission exists; therefore, it is not considered a public health concern. However, the organisms are ubiquitous in the environment, and substantial evidence shows that the environmental niche for Mycobacterium intracellulare (the most common pulmonary pathogen) is in biofilms lining suburban water pipes. Many NTM pathogens have been isolated from drinking water (7). Some clinicians believe the condition should be classified as an environmental health concern, similar to that caused by Legionella spp.Globally, geographic variability in environmental exposure and prevalence of NTM disease is significant (8). Without detailed clinical information, differentiating between contamination of specimens, colonization/infection, and disease is difficult; laboratory reports of isolates do not always reflect the true incidence of disease. To determine if disease is present, sputum specimens and often a bronchoscopic sample of a patient’s lower respiratory tract must be collected. In addition, computed tomography scanning and clinical appointments with primary care providers and specialists are needed. Because this investigative process is costly to the healthcare system and the patient, accurate epidemiologic data on this condition should be of interest to public health experts.Studies of avian versus human Mantoux testing in schoolchildren have shown that exposure to NTM organisms is common in Queensland (9–11). Therefore, since the introduction of TB control services, disease caused by NTM in Queensland has been notifiable. This practice has been continued primarily to avoid confounding of smear-positive cases with TB. The notification process provides a unique opportunity to study the clinical significance of isolates positive for NTM and the features such as age and sex, symptoms, underlying conditions, and radiology results of patients with disease, avoiding the inherent bias that occurs in case series that are reported by tertiary and quaternary referral centers. The incidence of clinically reported cases of pulmonary disease caused by M. avium complex (MAC) in Queensland has been increasing (1985, 0.63/100,000 population; 1994, 1.21/100,000; and 1999, 2.2/100,000). In 2005, the Queensland Tuberculosis Control Centre (QTBCC) revised the notification process to ensure collection of meaningful clinical data and follow-up of clinically significant NTM cases.     

Notified tuberculosis among Singapore residents by ethnicity, 2002–2011

Setting:

The National Tuberculosis Programme in Singapore where, among resident cases, higher tuberculosis (TB) rates have been reported in ethnic Malays.

Objective:

To describe the socio-demographic and clinical characteristics of resident TB cases by ethnicity, and to assess whether Malays differ from other groups in terms of the above parameters.

Design:

Cross-sectional review of records from the tuberculosis registry’s electronic database.

Results:

Among 15 622 resident cases notified, 72.2% were Chinese, 18.7% Malay, 5.8% Indian and 2.9% were from other minorities. Compared to other ethnicities, Malays were more likely to be incarcerated at the time of notification (odds ratio [OR] 3.70, 95%CI 3.03–4.52) and clustered at the same residential address (OR 1.65, 95%CI 1.44–1.89), but were less likely to be aged ≥65 years (OR 0.61, 95%CI 0.54–0.70) or to reside in high-cost housing (OR 0.11, 95%CI 0.07–0.17). In terms of disease characteristics, more Malays had diabetes mellitus (OR 1.54, 1.37–1.73), a highly-positive acid-fast bacilli smear (OR 1.64, 95%CI 1.47–1.83) and cavitary disease on chest X-ray (OR 1.41, 95%CI 1.28–1.55).

Conclusion:

Compared to other ethnicities, reported TB cases among Malays were more severe and were likely to be more infectious. Increased vigilance in case management and contact investigations, as well as an improvement in the socio-economic conditions of this community, are required to reduce TB rates in this ethnic group.