Diagnostic Yield of Xpert MTB/RIF in Bronchoalveolar Lavage in Children with Probable Pulmonary Tuberculosis

Objective

To evaluate utility of Xpert MTB/RIF in bronchoalveolar lavage fluid in children with probable pulmonary tuberculosis.

Methods

Children with probable pulmonary tuberculosis with negative smear and Xpert on induced sputum/gastric aspirate were subjected to bronchoalveolar lavage (BAL) for Xpert assay and mycobacterial liquid culture. Data of children <14 y undergoing bronchoscopy for suspected MDR-TB (n=12) were also analyzed. The sensitivity of Xpert in BAL fluid for diagnosis of probable and confirmed pulmonary tuberculosis was calculated with clinico-radiological diagnosis and culture as gold standards, respectively.

Results

Of 41 enrolled children, 24 (58.5%) had Xpert positive in BAL fluid and 11 (26.8%) had culture confirmed tuberculosis (BAL fluid;10; sputum,1). The sensitivity of Xpert in BAL fluid among probable and culture confirmed tuberculosis cases was 58.5% (24/41) and 81.8% (9/11), respectively.

Conclusion

Xpert in bronchoalveolar lavage fluid has good sensitivity in both probable and confirmed pulmonary tuberculosis in children.

     

儿童肺结核支气管肺泡灌洗液Xpert MTB/RIF检测的诊断准确性研究

目的探讨支气管肺泡灌洗液的Xpert MTB/RIF检测对儿童肺结核的诊断价值。方法有疑似活动性结核病的临床症状和体征，行纤维支气管镜检查并留取了支气管肺泡灌洗液的患儿为研究对象。以支气管肺泡灌洗液作为病原学检测标本，分别以病原学诊断活动性结核病和临床诊断活动性结核病为金标准，以Xpert MTB/RIF为待测标准，考察Xpert MTB/RIF对病原学和临床诊断结核的诊断价值。基于样本中结核分枝杆菌（MTB）的Ct值反映所检测样本中MTB的载量；通过对利福平耐药位点的检测，对MTB菌株进行药物敏感性检测。结果符合本文纳入标准的疑似结核病患儿351例，男198例，女153例，年龄（5.9±3.9）岁。肺结核患儿125例，其中病原学诊断结核43例（34.4%），临床诊断结核82例（65.6%）；肺结核合并支气管结核51例（40.8%），单纯肺结核74例（59.2%）；非结核呼吸道感染性疾病226例，肺炎支原体肺炎187例（82.7%），细菌性肺炎39例（17.3%）。Xpert MTB/RIF在病原学诊断和临床诊断结核的敏感度分别为79%(95%CI：63%~89%)和51%(95%CI：40%~62%)，差异有统计学意义（χ2=9.18，P=0.002）；肺结核合并支气管结核的敏感度为80%（66%~90%),单纯肺结核的敏感度47%(35%~59%)；病原学诊断和临床诊断结核、合并支气管结核和单纯肺结核特异度均为100%(95% CI：97.9%~100%)。Xpert MTB/RIF检测病原学诊断结核敏感度高于临床诊断结核，肺结核合并支气管结核敏感度高于单纯肺结核，差异有统计学意义（χ2=13.88，P<0.001）；支气管肺泡灌洗液的MTB核酸检出载量病原学诊断结核高于临床诊断结核，差异有统计学意义（χ2=7.37，P=0.025）。76例Xpert MTB/RIF检测阳性患儿中，利福平耐药2例（2.6%）。结论支气管肺泡灌洗液的Xpert MTB/RIF检测在儿童肺结核诊断中具有较高价值，可在缺乏细菌学诊断证据的临床诊断结核病儿童中发现MTB，具有较高的敏感度，有助于提高儿童结核病病原学检出率。     

Xpert结核分枝杆菌/利福平试验对结核病及耐多药结核病诊断价值的Meta分析

目的 评估Xpert结核分枝杆菌/利福平（MTB/RIF）试验对结核病的诊断价值。方法 检索PubMed、Medline、中国知网、万方数据库等,收集Xpert MTB/RIF试验对结核病诊断价值的文献,检索起止时间均为建库至2012年6月。2名研究者独立进行资料提取和文献质量评估。采用Meta-Disc 1.4软件进行Meta分析。结果 共纳入26篇文献,其中2篇文献涉及儿童病例,包含了13 270例来自临床患者的检测标本。Meta分析结果显示,Xpert MTB/RIF试验诊断结核病的汇总敏感度为87%（95％CI:86%~88%）、特异度为97%（95％CI:97%~97%）。按照结核病的类型和患者年龄进行亚组分析,Xpert MTB/RIF试验诊断肺结核的敏感度高于肺外结核病,90%（95％CI:89%~91%） vs 76%（95％CI:72%~79%）;诊断涂阴菌阳性和涂阳菌阳性结核病的敏感度分别为74%（95％CI:71%~76%）和99％(95%CI:98%~99%);对儿童肺结核的诊断敏感度比成人肺结核低,74%（95％CI:65%~83%） vs 90%（95％CI:89%~92%）。Xpert MTB/RIF试验诊断耐多药结核病的敏感度为96%（95％CI:94%~97%）,特异度为98%（95％CI:98%~99%）。结论 Xpert MTB/RIF试验诊断结核病的价值较高,尤其是成人结核病及耐多药结核病。Xpert MTB/RIF试验在儿童结核病中的诊断价值由于纳入文献较少,尚待进一步研究。     

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??Objective??To evaluate the clinical value of fiberoptic bronchoscopy in diagnosis of active pulmonary tuberculosis. Methods??Clinical data of 5 children with tuberculosis confirmed by fiberoptic bronchoscopy was collected??who were treated in Tianjin Children’s Hospital from Oct. 2013 to Apr. 2016. The clinical features and treatment procedure of the 5 cases were analyzed. Results??The age of the 5 cases??3 male and 2 female?? ranged from 1 to 13 years old with the disease course of 12-35 days. The immune function of the 5 cases were normal. All of the cases were with abrupt onset. 3 cases had fever??2 cases had recurrent cough. Three cases misdiognosed as pneumonia and infant wheezing. One case was misdiagnosed as pulmonary abscess. One case was misdiagnosed as pneumonia. All of the 5 cases denied having tuberculosis contact history and all the patients received regular BCG vaccination. Lesion invased the lung and pleural with 3 cases diagnosed as lung tuberculosis??1 case with secondary left main bronchial stenosis?? and 2 cases as tuberculosis of bronchus. All of the cases received regular anti-tuberculosis treatment and were discharged with the hospitalization of 11 days. The outcome was good. Conclusion??The clinical symptom?? sign and bronchoscopic features were not typical in children with tuberculosis. For children with the symptom of persisting cough who don’t respond to conventional anti infection treatment??fiberoptic bronchoscopy examination is recommended to help make clinical diagnosis.     

Management of multidrug-resistant tuberculosis in children: a survival guide for paediatricians

WHO estimated that of 9.4 million cases of tuberculosis (TB) worldwide in 2008, 440,000 (3.6%) had multidrug-resistant (MDR)-TB. Childhood TB is estimated at 10-15% of the total burden, but little is known about the burden of MDR-TB in children. Children in close contact with MDR-TB cases are likely to become infected with the same resistant strains and are vulnerable to develop disease. Although MDR-TB is a microbiological diagnosis, children should be treated empirically according to the drug susceptibility result of the likely source case, as often cultures cannot be obtained from the child. MDR-TB treatment in children is guided by the same principles, using the same second-line drugs as in adults, with careful monitoring for adverse effects. Co-infection with HIV poses particular challenges and requires early initiation of antiretroviral therapy. Preventive therapy for high-risk MDR-TB contacts is necessary, but no consensus guidance exists on how best to manage these cases. Pragmatic and effective Infection control measures are essential to limit the spread of MDR-TB.     

诊断性抗结核治疗在鉴别儿童克罗恩病与肠结核时评估工具和时点的诊断准确性研究

目的 探讨诊断性抗结核治疗在鉴别儿童克罗恩病(CD)与肠结核(ITB)中评估工具及其合适的鉴别时点。 方法 回顾性收集临床和病理难以判断CD或ITB且明确结核或抗酸染色阳性的病例,剔除入院前曾经抗结核治疗或应用免疫抑制剂和先天免疫缺陷合并结核感染。活检干酪样坏死,或病理抗酸染色阳性,或肠外活动性结核,或 PPD皮试强阳性,或细菌涂片阳性者,接受诊断性抗结核治疗,于诊断性抗结核治疗前（基线）,治疗后3、6和12个月时,行儿童CD活动指数（PCDAI)评分、肠镜评估。诊断性抗结核治疗ITB确诊依据Logan修订的per Paustian标准。抗结核均采用2~3HRZE/7~10HR方案。 结果 26例难以判断CD或ITB的患儿完成了基线、3、6和12个月时的PCDAI评分和肠镜评估进入本文分析,ITB 组17例,CD 组9例,2组一般情况、临床表现、实验室检测指标、肠镜表现、小肠MRE表现、病理组织学表现、抗结核治疗时间和抗结核治疗方案差异无统计学意义。ITB组治疗3、6和12个月较基线PCDAI评分下降≥12.5分或不同时点PCDAI评分≤10分分别为6、14和16例;其中3个月较基线、6个月较3个月 、12个月较6个月PCDAI评分下降≥12.5分分别为6、4、4例。CD组治疗3、6和12个月较基线PCDAI评分下降≥12.5分或不同时点PCDAI评分≤10分分别为1、2、1例。ITB组和CD组,6个月时肠镜评估痊愈＋明显好转分别为76.5%（13/17）和22.2%（2/9）,12个月时痊愈＋明显好转分别为94.1%（16/17）和11.1%（1/9）,差异有统计学意义（Fisher精确检验,P=0.000）。以诊断性抗结核治疗ITB确诊标准作为金标准,3和6个月时PCDAI评分阳性预测值分别为85.7%和86.7%,6个月时肠镜评估阳性预测值86.7%;6个月时PCDAI评分+肠镜评估特异度88.9%,阳性预测值92.9%;12个月时PCDAI评分+肠镜评估阳性预测值（94.1%）比6个月时提高了1.2%。 结论 诊断性抗结核治疗过程中,难以判断有ITB或CD患儿临床症状好转较肠镜好转快,PCDAI评分+肠镜评估可作为难以判断ITB或CD患儿评估工具,诊断性抗结核治疗6个月时为最佳时点。     

Detection of Mycobacterium tuberculosis in gastric aspirate and sputum collected from Ethiopian HIV-positive and HIV-negative children in a mixed in- and outpatient setting

AIM: To investigate, through a prospective study, the detection rate of Mycobacterium tuberculosis in sputa and gastric aspirate from tuberculous children in a low-income country with high prevalence of tuberculosis and an increasing HIV epidemic. METHODS: Gastric aspirates and/or sputum samples were collected from 355 children with pulmonary tuberculosis as follows: from 136 children under 5 y only gastric aspirate was taken, for 159 children aged 5 to 9 y both methods were used, and for 60 children over 10 y only sputum was analysed. The diagnosis of tuberculosis was based on clinical data, tuberculin test and chest radiography. All children were tested for HIV infection. RESULTS: Direct microscopy for acid-fast bacilli was positive for 55 (15%) and mycobacterial culture for 183 (52%) children. The proportion of positive cultures was similar in all age groups. Among the 5 to 9 year-old children who could produce a sputum sample, sputum gave just as good culture yield of M. tuberculosis as gastric aspirate. Of the clinical or radiological findings only weight loss was associated with a higher yield. Repeat gastric aspirate increased the culture yield by 6%. Mycobacterial culture from HIV-positive children gave lower yield compared with HIV-negative children. CONCLUSION: Our data suggest that one gastric aspirate for children less than 6 y and three sputum samples for the older children collected at an outpatient TB clinic, is enough to provide a close to 50% yield of M. tuberculosis available for culture and further analyses. However, with an increasing prevalence of HIV, this detection rate may be reduced.     

Drug-resistant tuberculosis in two children in Greece: Report of the first extensively drug-resistant case

Extensively drug-resistant (XDR) tuberculosis (TB) represents a serious and growing problem in both endemic and non-endemic countries. We describe a 2.5-year-old girl with XDR-pulmonary TB and an 18-month-old boy with pre-XDR-central nervous system TB. Patients received individualized treatment with second-line anti-TB agents based on genotypic and phenotypic drug susceptibility testing results. Both children achieved culture conversion 3 months and 1 month after treatment initiation, respectively. The child with XDR-pulmonary TB showed evidence of cure while treatment adverse events were managed without treatment interruption. The child with pre-XDR-central nervous system TB after 6-month hospitalization with multiple infectious complications had a dismal end due to hepatic insufficiency possibly related to anti-TB treatment. This is the first report of children with pre-XDR and XDR TB in Greece, emphasizing the public health dimensions and management complexity of XDR TB.     

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??Objective??To explore the value of clinical manifestations and routine examinations for the diagnosis of intrathoracic tuberculosis in children. Methods??The medical records of children under 16 years of age due to intrathoracic diseases in Shanghai Pulmonary Hospital affiliated to Tongji University School of Medicine from January 2009 to December 2011 were collected. According to the final diagnosis??the patients were divided into 2 groups??intrathoracic tuberculosis and non tuberculosis. The clinical manifestations and routine auxiliary examination results of the 2 groups were retrospectively analyzed. The children were divided according to age??10 years and over 10 years old in 2 groups??and the clinical data were also compared. Results????1??Pathological diagnoses were confirmed at 72.30% of proportion at whole patients??70.73% in TB group. The positive rate of tuberculosis bacteriology was 21.85% in TB group. ??2??The middle course of history accounted for 56.30% in TB children. At the onset of illess??the proportion of fever and predisposition to tuberculosis??positivity of tuberculin skin test??TST?? and serumal tuberculosis antibody??and average value of ESR??CRP??PLT and D-Dier in blood were significantly higher in TB group than those in non-TB group. ??3??About 59% of patients in the non-TB group were cured or were markedly improved by antibiotic treatment??which was effective in 10% of the TB group. ??4??Diagnostic accordance rate by radiology was 53.36% and the rate of misdiagnosis as tuberculosis accounted for 11.71% in non-TB group. Conclusion??Clinical features combined with medical history and laboratory results are helpful for the identification of tuberculosis in children under 16 years old.     

Diagnosis of pediatric tuberculosis in the modern era

BACKGROUND: Correctly diagnosing tuberculosis (TB) in children is critical to provide appropriate treatment and to detect undiagnosed source cases. However, diagnosing TB in children may be difficult. OBJECTIVE: We sought to determine whether Amplicor, a Food and Drug Administration-approved polymerase chain reaction (PCR) assay used to detect Mycobacterium tuberculosis in sputum and computerized tomography (CT) would facilitate the diagnosis of TB in children. We also examined the applicability of the Centers for Disease Control and Prevention clinical case definition for TB. SETTING: A university-affiliated pediatric hospital in New York City. SUBJECTS: From March, 1995, to November, 1997, 27 children < 15 years of age (mean age, 3.9 years) were evaluated for suspected TB. RESULTS: M. tuberculosis was cultured from 5 of 76 (6.6%) gastric aspirate specimens, and PCR detected M. tuberculosis DNA in 3 (4.1%) of these specimens. There was poor correlation between culture and PCR because 6 specimens were discordant. CT scans were diagnostic of mediastinal or hilar adenopathy in 6 children with equivocal or negative chest radiographs and confirmed adenopathy in 8 others. Six children received alternative diagnoses. CONCLUSIONS: We conclude that the commercially available PCR technology had very limited utility in detecting M. tuberculosis from gastric aspirates, but CT scans were useful in assessing pediatric patients with suspected TB.