Multidrug-resistant tuberculosis presenting as a solitary splenic mass in an immunocompetent patient

Here, we report a case of multidrug-resistant tuberculosis (TB) presenting as a solitary splenic mass in a 60-year-old immunocompetent patient. Splenic TB is unusual and, when present, is usually associated with disseminated disease in immunocompromised patients. A high level of suspicion is required for diagnosis, and, as occurred in our case, it may be an unexpected finding following surgery. Diagnosis was made by polymerase chain reaction, which showed the presence of Mycobacterium tuberculosis DNA. Interestingly, rifampicin- and isoniazid-resistant genes were detected in our analysis. Splenic TB diagnosis and treatment are reviewed.     

Sulfamethoxazole Susceptibility of Mycobacterium tuberculosis Isolates from HIV-Infected Ugandan Adults with Tuberculosis Taking Trimethoprim-Sulfamethoxazole Prophylaxis

Additional drugs are needed for the treatment of multidrug-resistant tuberculosis (TB). Sulfamethoxazole has been shown to have in vitro activity against Mycobacterium tuberculosis; however, there is concern about resistance given the widespread use of trimethoprim-sulfamethoxazole prophylaxis among HIV-infected patients in sub-Saharan Africa. Thirty-eight of 40 Mycobacterium tuberculosis isolates (95%) from pretreatment sputum samples from Ugandan adults with pulmonary TB, including HIV-infected patients taking trimethoprim-sulfamethoxazole prophylaxis, were susceptible with MICs of ≤38.4 μg/ml.     

Mycobacterium tuberculosis

The emergence and spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) has become an important health problem and threatens TB control worldwide. World Health Organization reported that there were an estimated 440,000 cases of MDR-TB in 2008. By July 2010, 58 countries and territories had reported at least one case of XDR-TB. The emergence of MDR/XDR-TB strains is reflection of poor tuberculosis management. To avoid the emergence of more resistant strains that may lead to almost untreatable TB, we must focus our efforts on the right management of drug susceptible TB.     

江西省安福县实施结核病控制项目5年效果分析

目的分析江西省安福县实施结核病控制效果。方法对安福县2003-2007年初诊患者登记本、结核患者登记本、实验室登记本及结核病防治工作季报表进行汇总分析。结果自2003年起实施结核病控制项目5年来,安福县肺结核患者的发现及治疗效果逐年提高,5年共接诊可疑肺结核患者4531例,发现活动性肺结核患者2291例,其中涂阳患者825例, 肺结核患者痰检阳性检出率、新发涂阳登记率及治愈率分别由2003年的24.24%、15.97/10万、93.54%上升到2007年的25.50%、45.90/10万、94.94%。结论安福县结核病控制项目的实施,使肺结核传染源得到有效控制,取得预期效果。     

Boarding issue in a commercial flight for patients with cavitary pulmonary tuberculosis: A case report

BACKGROUND Several studies have demonstrated that airborne transmission of Mycobacterium tuberculosis bacteria from patients with active pulmonary tuberculosis(TB) to other passengers or crew members can occur during long flights. As such, non-infectious TB patients are usually allowed to undertake air travel after taking the appropriate anti-TB drugs. However, the global guidelines for air travel for patients with TB are inconsistent and insufficiently detailed with respect to cavitary pulmonary TB(CPTB).CASE SUMMARY Here, we report a case in which a patient with multiple CPTB was permitted air travel, following negative sputum acid-fast bacilli smear tests after administration of proper anti-TB medication. The patient’s culture results were pending.CONCLUSION This case revealed that more specific guidelines regulating air travel for patients with CPTB are necessary.     

Prevalence and Genetic Characterization of Second-Line Drug-Resistant and Extensively Drug-Resistant Mycobacterium tuberculosis in Rural China

This study aimed to investigate the prevalence of resistance to second-line antituberculosis (anti-TB) drugs and its association with resistance-related mutations in Mycobacterium tuberculosis isolated in China. In the present study, we collected 380 isolates from a population-based study in China and tested the drug susceptibility to first- and selected second-line drugs. These results were compared with polymorphisms in the DNA sequences of genes associated with drug resistance and MIC values of the studied second-line drugs. Of 43 multidrug-resistant M. tuberculosis isolates, 13 showed resistance to fluoroquinolones or injectable second-line drugs (preextensively drug-resistant TB [pre-XDR-TB]), and 4 were resistant to both and thus defined as extensively drug-resistant TB (XDR-TB). Age and previous TB therapy, including use of second-line drugs, were two independent factors associated with increased resistance to both first- and second-line drugs. Molecular analysis identified the most frequent mutations in the resistance-associated genes: D94G in gyrA (29.1%) and A1401G in rrs (30.8%). Meanwhile, all 4 XDR-TB isolates had a mutation in gyrA, and 3 of them carried the A1401G mutation in rrs. Mutations in gyrA and rrs were associated with high-level resistance to fluoroquinolones and the second-line injectable drugs. In addition to the identification of resistance-associated mutations and development of a rapid molecular test to diagnose the second-line drug resistance, it should be a priority to strictly regulate the administration of second-line drugs to maintain their efficacy to treat multidrug-resistant TB.     

耐多药结核病护理的研究进展

目的 结核病仍然是一个全球公共卫生的巨大负担，特别是在发展中国家的情况更为严重。由于联合用药不合理、管理不完善和耐药菌株的流行等原因，结核病的发病率逐年上升，耐多药结核病也逐渐增多，给我国结核病的防控和人类健康带来严重威胁。在治疗耐多药结核病的过程中，临床护理工作发挥了重要作用。本文对近年来国内外比较优化的耐多药结核病护理模式进行了整理和阐述，旨在提高我国耐多药结核病的治愈率。结论 探索高效的耐多药结核病患者临床护理模式在我国结核病的防控过程中有着更积极的作用。     

Immunodiagnosis of tuberculosis: state of the art

Undiagnosed and mismanaged tuberculosis (TB) continues to fuel the global TB epidemic. Rapid, accurate and early diagnosis of TB is therefore a priority to improve TB case detection and interrupt transmission. Although considerable improvements have been made in TB diagnostics, there are two major gaps in the existing diagnostics pipeline: (1) lack of a simple accurate point-of-care test that can be used for rapid diagnosis at the primary care level; (2) lack of a biomarker (or combination of biomarkers) that can be used to identify latently infected individuals who will benefit most from preventive therapy. Currently available commercial serological (antibody detection) tests are inaccurate and do not improve patient outcomes. Despite this evidence, dozens of serological tests are sold and used in countries (e.g. India) with weak regulatory systems, especially in the private sector. Recognizing the threat posed by these suboptimal tests, a World Health Organization (WHO) Expert Group has strongly recommended against the use of serological tests for the diagnosis of pulmonary and extra-pulmonary TB. Another WHO Expert Group has discouraged the use of interferon-γ release assays for active pulmonary TB diagnosis in low- and middle-income countries. All existing tests for latent TB infection appear to have only modest predictive value and further research is needed to identify highly predictive biomarkers.     

2005-2011年网络直报系统和结核病专报系统报告肺结核患者比较分析

目的 了解网络直报系统和结核病专报系统登记报告肺结核患者情况的特征,比较两者之间的差异并探讨原因。 方法 对2005-2011年两大监测系统报告的肺结核患者进行描述和比较分析。 结果 2005-2011年两大监测系统登记报告肺结核患者和涂阳患者呈下降趋势,网络直报系统报告的涂阳比例有所下降,涂阴比例有所上升,未痰检比例明显下降但仍高于结核病专报系统;网络直报系统报告的肺结核患者数高于结核病专报系统,但是涂阳患者数低于结核病专报系统。 结论 由于监测系统的覆盖面,监测病例的定义和监测数据的统计时间不同,两大监测系统报告的肺结核患者数不完全一致。应进一步规范综合性医疗机构对结核病患者的诊断和报告工作,加强医防合作以及结核病的归口管理工作,两大监测系统报告数据的差异会逐步缩小。     

Discovery of Novel Oral Protein Synthesis Inhibitors of Mycobacterium tuberculosis That Target Leucyl-tRNA Synthetase

The recent development and spread of extensively drug-resistant and totally drug-resistant resistant (TDR) strains of Mycobacterium tuberculosis highlight the need for new antitubercular drugs. Protein synthesis inhibitors have played an important role in the treatment of tuberculosis (TB) starting with the inclusion of streptomycin in the first combination therapies. Although parenteral aminoglycosides are a key component of therapy for multidrug-resistant TB, the oxazolidinone linezolid is the only orally available protein synthesis inhibitor that is effective against TB. Here, we show that small-molecule inhibitors of aminoacyl-tRNA synthetases (AARSs), which are known to be excellent antibacterial protein synthesis targets, are orally bioavailable and effective against M. tuberculosis in TB mouse infection models. We applied the oxaborole tRNA-trapping (OBORT) mechanism, which was first developed to target fungal cytoplasmic leucyl-tRNA synthetase (LeuRS), to M. tuberculosis LeuRS. X-ray crystallography was used to guide the design of LeuRS inhibitors that have good biochemical potency and excellent whole-cell activity against M. tuberculosis. Importantly, their good oral bioavailability translates into in vivo efficacy in both the acute and chronic mouse models of TB with potency comparable to that of the frontline drug isoniazid.     

Multidrug-resistant tuberculosis meningitis: clinical problems and concentrations of second-line antituberculous medications

OBOFFTIVE: To describe a case of culture-proven multidrug-resistant tuberculous (MDR-TB) meningitis, in which the patient survived long enough for clinicians to adjust antituberculous therapy to second-line therapeutic agents. DESIGN: Case report. SETTING: Tertiary care hospital. PATIENT: Twenty-one-month-old girl with MDR-TB meningitis. INTERVENTIONS: Initial standard treatment failed. Subsequent treatment with second-line therapeutic agents including ciprofloxacin, cycloserine, ethambutol, ethionamide, and rifabutin were given for approximately two years. Concentrations of these drugs were measured in serum and cerebrospinal fluid in the presence and absence of meningeal inflammation. MAIN OUTCOME MEASURES/RESULTS: The patient survived for approximately two years after initiation of second-line anti-TB therapy. During this treatment, she developed a ventriculo-peritoneal shunt tunnel tract infection secondary to MDR-TB. CONCLUSIONS: All TB meningitis isolates for which the source case antibiotic susceptibility pattern is not known should be cultured and susceptibility tested using rapid broth techniques. Measurement and subsequent adjustment of therapeutic drug concentrations may optimize therapy with second-line anti-TB drugs in TB meningitis. Better pediatric formulations and pharmacokinetic data for second-line and anti-TB therapeutic agents are needed.     

2008-2013年浙江省诸暨市涂阳肺结核学生患者的密切接触者结核感染情况调查

目的调查分析涂阳肺结核学生患者的密切接触者感染情况及影响因素,为进一步防止结核病在学生中的扩散和蔓延提供依据。方法通过在诸暨市2008-2013年发生的涂阳肺结核学生患者的密切接触者的结核菌纯蛋白衍生物(purified protein derivative of tuberculin,PPD)筛查,以非密切接触者为感染情况作为本底对照;分层分析密切接触者感染情况的影响因素。结果调查28例涂阳肺结核学生患者密切接触者共1721人,强阳性400人,强阳性率为23.24%。同时调查非密切接触者1409人,强阳性39人,强阳性率为2.77%,密切接触者的强阳性率远高于非密切接触者(χ2=269.33,P=0.000)。影响密切接触者PPD试验结果的因素有发病季节、痰菌含量及就诊延误,通过分层分析,冬春季发病患者的密切接触者阳性率较高,特别是患者痰菌含量较高时(χ2=10.12,P=0.00;χ2=5.35,P=0.02);痰菌含量高的患者其密切接触者阳性率高,在春季发病患者的密切接触者中尤其明显(χ2=14.42,P=0.00;χ2=11.25,P=0.00);传染源诊断延误时间对密切接触者强阳性率的影响表现为患者痰菌含量较低时,冬春季发病患者的不同诊断延误患者的密切接触者强阳性率不同(χ2=4.60,P=0.03);而患者痰菌含量较高时,不同季节发病患者的密切接触者强阳性率差异无统计学意义。结论在影响涂阳肺结核学生患者PPD试验强阳性率的主要因素中,传染源的发病季节、痰菌含量和诊断延误各自起着一定的作用,其中以发病季节和痰菌含量的作用更为显著。     

Perianal tuberculosis: A case report and review of the literature

Tuberculosis(TB) is still a major health problem worldwide. We present a rare case of an immunocompetent patient with perianal TB. A 38-year-old man visited a clinic with pain, swelling, and redness in the perineum. He had been persistently coughing for the past 6 mo. The abscess had formed a fistula to the perianal region, indicating perianal abscess. Mycobacterium tuberculosis was found in sputum and perianal abscess. Surgical drainage was performed, and oral anti-tuberculous drugs were administered for 6 mo. The patient's clinical course was favorable. On review of the literature on 58 cases of perianal TB, we found that the duration of persistent perianal lesion was much longer in patients without active pulmonary TB(APTB) than in those with APTB(66.4 mo vs 8.3 mo; confidence interval, 0.0760-0.9620, P = 0.0380). Thus, in cases of non-healing or recurrent perianal lesions, TB should be considered.     

Factors influencing sputum smear and culture conversion time among patients with new case pulmonary tuberculosis

Sputum smear and culture conversion are important indicators for the effectiveness of treatment and the infectivity of the patient. The aim of this study was to identify the factors influencing both sputum smear and culture conversion time among patients with new case pulmonary tuberculosis (TB). The study was conducted in a reference hospital in Turkey in which 737 patients with pulmonary TB were hospitalised between January 2000 and 2005. We evaluated 306 (193 men and 113 women) human immunodeficiency virus-negative patients diagnosed with new case pulmonary TB. Factors associated with both sputum smear and culture conversion time (days) were investigated. Patients with diabetes mellitus (DM), cavitary disease, radiologically extensive disease had longer sputum smear and culture conversion time than the other groups. In addition, old age, male sex, smoking and thrombocytosis were found to be significantly associated with sputum smear conversion time. In the logistic regression analysis, the presence of DM and extensive disease were determined as independent factors associated with persistent sputum smear and culture positivity at the end of 2 months. The presence of DM and extensive disease were found to be independent risk factors influencing both sputum smear and culture conversion time in pulmonary TB. Sputum smear and culture examinations should be considered together to assess the poor prognosis.     

2004-2013年结核病专病监测系统登记肺结核患者的特征分析

目的了解结核病专病监测系统登记的肺结核患者特征。方法利用2004-2013年结核病专病监测系统收集的结核病患者登记报告资料进行分析。结果 2004-2013年,肺结核和涂阳登记率呈现先上升后下降的趋势。2008-2013年,肺结核患者登记率的年均降幅3.62%,2005-2013年涂阳登记率的年均降幅6.33%。2013年全国共登记肺结核患者855 307例,登记率为62.86/10万;其中涂阳患者312 071例,登记率为22.93/10万。除0~14岁组外,新涂阳患者登记数男性均高于女性,性别比随年龄增长逐渐增大。65岁以上组、55~64岁组和45~54岁组新涂阳患者所占比例较高,且该比例呈逐年上升趋势。结论肺结核患者登记率在2008年以前呈上升趋势,近几年开始下降,男性高于女性,中老年组患者所占比例较高。     

Molecular characterization of drug-resistant and -susceptible Mycobacterium tuberculosis isolated from patients with tuberculosis in Korea

We investigated the causal relationship between genotype and phenotype of drug-resistant Mycobacterium tuberculosis isolates obtained from patients with pulmonary tuberculosis (TB) in Korea. Of 80 isolates tested, 17, 20, 1, and 7 isolates were mono-resistant to ethambutol (EMB), isoniazid (INH), pyrazinamide (PZA), and rifampicin (RFP), respectively, and 31 isolates (38.8%) were multidrug-resistant (MDR). Sequencing analysis showed that 78% (32/41) of RFP-resistant strains had mutations in the rifampicin resistance-determining region (RRDR) of rpoB, and the mutation at rpoB531 (59.4%) was most abundant. In 52 INH-resistant strains, mutations were found mostly at C-15T (n = 21, 40.4%) in the inhA promoter region as well as at katG315 (n = 12, 23.1%). Mutations at embB306 were mostly found in 26.7% (12/45) of EMB-resistant isolates. New mutations found here in MDR isolates include rpoB523 (Gly523Glu) and embB319 (Tyr319Ser). Consequently, mutations in the rpoB531, C-15T in the inhA promoter region, embB306, and katG315 would be a useful marker for rapid detection of MDR M. tuberculosis isolates in Korea.     

Delayed diagnosis of active pulmonary tuberculosis in emergency department

Background and Purpose

Tuberculosis (TB) is a worldwide health challenge. Emergency department (ED) is the major public access to the health care system. Delayed diagnosis of active pulmonary TB was believed to precipitate mortality and morbidity. The study was designed to investigate clinical characteristics and factors in patients with delayed diagnosis of active TB in ED.

Methods

We used a retrospective chart review.

Patients

A total of 103 patients were enrolled between December 2003 and March 2006.

Results

Typical chest radiographic findings were noted in 79.8% of nondelayed TB group and 31.6% of delayed TB group (P < .001). Diagnosis of pneumonia was made at ED in 22.6% of nondelayed TB group and 68.4% of delayed TB group (P < .001). Length of initiation of TB treatment intervention was 0 days (0-1 days) and 9 days (6-16 days), respectively (P < .001). In-hospital mortality rate was 15.5% and 47.4%, respectively (P < .01).Age (odds ratio, 1.07; 95% confidence interval, 1.01-1.1) and intensive care unit admission (odds ratio, 5.01; 95% confidence interval, 1.18-21.3) were associated with lower in-hospital survival. Delayed ED diagnosis of TB was associated with mortality in results of univariate analysis (P = .002), but no statistical significance was noted in the final result of stepwise logistic regression analysis.

Conclusion

Intensive care unit admission and age are associated with mortality. Awareness of varying features of pulmonary TB by physicians is important.     

一起学校肺结核病聚集性感染疫情的调查

目的分析学生结核病聚集性感染的影响因素,为学校肺结核病防控提供依据。方法对出现病例所有班级学生进行胸透检查、X线胸部摄片,部分班级开展结核菌素(PPD)试验,对X线胸片检查异常者给予痰涂片检查,查抗酸杆菌。结果此次共发现肺结核病26例,首发病例被误诊为慢性咽炎3个多月,首发病例所在班级、寝室均有明显的聚集现象,P0.01。在筛查中胸透肺结核病发现率为0.10%,PPD试验结合X线胸片检查,发现率为40.48%。结论首发病例被误诊后没有及时隔离治疗,是造成本次聚集性感染的主要原因。加强学校对传染病的管理,建立学生及教师因病缺课登记及病因追踪登记制度,建立医院、学校、疾病预防控制中心为一体的防控网络,是预防学校肺结核病聚集性感染的有效方法 。     

Helminth-induced arginase-1 exacerbates lung inflammation and disease severity in tuberculosis

Parasitic helminth worms, such as Schistosoma mansoni, are endemic in regions with a high prevalence of tuberculosis (TB) among the population. Human studies suggest that helminth coinfections contribute to increased TB susceptibility and increased rates of TB reactivation. Prevailing models suggest that T helper type 2 (Th2) responses induced by helminth infection impair Th1 immune responses and thereby limit Mycobacterium tuberculosis (Mtb) control. Using a pulmonary mouse model of Mtb infection, we demonstrated that S. mansoni coinfection or immunization with S. mansoni egg antigens can reversibly impair Mtb-specific T cell responses without affecting macrophage-mediated Mtb control. Instead, S. mansoni infection resulted in accumulation of high arginase-1–expressing macrophages in the lung, which formed type 2 granulomas and exacerbated inflammation in Mtb-infected mice. Treatment of coinfected animals with an antihelminthic improved Mtb-specific Th1 responses and reduced disease severity. In a genetically diverse mouse population infected with Mtb, enhanced arginase-1 activity was associated with increased lung inflammation. Moreover, in patients with pulmonary TB, lung damage correlated with increased serum activity of arginase-1, which was elevated in TB patients coinfected with helminths. Together, our data indicate that helminth coinfection induces arginase-1–expressing type 2 granulomas, thereby increasing inflammation and TB disease severity. These results also provide insight into the mechanisms by which helminth coinfections drive increased susceptibility, disease progression, and severity in TB.     

Usefulness of gastric aspirate for the diagnosis of smear-negative pulmonary tuberculosis

IntroductionGastric aspirate can be useful for the diagnosis of pulmonary tuberculosis (TB) in patients with smear-negative pulmonary TB or without sputum production. The gastric aspirate smear technique has low sensitivity, and a previous report demonstrated that no patient was diagnosed by only gastric aspirate analysis. However, some patients with TB have been negative on sputum examination but positive on gastric aspirate examination, and the incidence of such cases is uncertain. Therefore, this study investigated the usefulness of gastric aspirate in the diagnosis of pulmonary TB.MethodsTo analyze the diagnostic accuracy of gastric aspirate examination, the data of 513 patients with negative sputum smears or a lack of sputum production, including 203 patients with pulmonary TB (39.6%) and 93 patients with nontuberculous mycobacteriosis who underwent gastric aspiration at Fukujuji Hospital from January 2016 to March 2021, were collected retrospectively.ResultsThe accuracy rates of gastric aspirate examination for the diagnosis of pulmonary TB were as follows: 21.2% sensitivity and 91.9% specificity for smear positivity, 55.8% sensitivity and 99.6% specificity for nucleic acid amplification test positivity, and 71.4% sensitivity and 100% specificity for culture positivity. Twenty-three patients (11.2%) were diagnosed by gastric aspirate examination alone. Among the 356 patients who underwent three repeated sputum examinations in addition to gastric aspirate examination, the cumulative diagnostic rate for the 3 mycobacterial examinations plus gastric aspirate examination was higher than that for only three sputum examinations.ConclusionsGastric aspirate is useful for the diagnosis of TB in patients with smear-negative pulmonary TB or without sputum production.