儿童潜伏结核感染的诊断与治疗

1　潜伏结核感染的概念在 2 0 0 0年美国胸科协会制定的成人和儿童结核病诊断标准以及分类指南中 ,将结核纯蛋白衍化物 (PPD)皮肤试验阳性 ,但临床和放射学检查无活动性结核病证据 ,称为潜伏结核感染 (latenttuberculosisinfection) [1] 。潜伏结核感染及其潜伏结核感染治疗的概念其实是对既往所谓的结核感染和预防性治疗或化学预防的更改。预防性治疗指对已知或可能感染结核杆菌者 ,使用简单的药物 (通常是异烟肼 )治疗 ,以预防发展为活动性结核病。这一治疗 ,很难达到真正的初级预防 ,即不能预防与传染性结核患者接触者的感染 ,为了更准…     

Consensus document on treatment of tuberculosis exposure and latent tuberculosis infection in children

INTRODUCTION: The most important causes of the current tuberculosis pandemic are poverty, HIV infection, drug resistance, and the spread of infection by patients with latent tuberculosis infection. In industrialized countries, the main reasons for the increase of this disease are immigration from developing countries and the lack of effective surveillance programs. The situation of children is even more serious as they are more vulnerable to the disease than adults. The children most at risk are those who live with adults at risk for tuberculosis, immigrant children, and adoptees from developing countries. Although children are bacilliferous only exceptionally, the appropriate management of bacilliferous tuberculosis exposure and latent tuberculosis infection in children contributes to the creation of close surveillance of nuclear families and rigorous study of contacts. Moreover, it could prevent serious forms of the disease, which are more frequent in children. OBJECTIVE: The principal objective of this second consensus document of the Spanish Society of Pediatric Infectious Diseases (Sociedad Espa?ola de Infectología Pediátrica [SEIP]) is to unify the criteria for the treatment of tuberculosis exposure and latent tuberculosis infection in children. A further aim is to increase awareness of the need for strict detection measures in high-risk populations among health authorities.     

干扰素释放试验对儿童隐性结核感染的诊断价值

隐性结核感染是指已经感染结核杆菌,但尚未出现临床症状和胸片异常表现者,常用结核菌素皮肤试验(TST)来进行诊断。但TST在卡介苗接种者或非结核分枝杆菌感染者中会出现假阳性,而免疫低下或婴幼儿中常出现假阴性,因此急需寻找敏感性及特异性更高的方法进行隐性结核感染的判断。最近,干扰素释放试验越来越受到人们的关注,并在有些国家已经作为TST诊断隐性结核感染的替代或确认方法。该方法比TST特异性高,不受卡介苗接种和其他非结核分枝杆菌感染的影响;其敏感性在免疫正常者与结核菌素试验相似,在免疫抑制的患者中敏感性高于TST。提示干扰素释放试验在诊断隐性结核感染中有很好的应用前景,但还不能完全替代TST。     

γ干扰素释放试验诊断儿童潜伏结核菌感染的Meta分析

目的以结核菌素皮肤试验(TST)为参考试验,评价QuantiFERON-TB Gold test(QFT)和T-SPOT.TB两种IFN-γ释放试验诊断儿童潜伏结核菌感染的准确性。方法计算机检索EMBASE、PubMed、Cochrane图书馆、中文科技期刊全文数据库、中国期刊全文数据库和万方数字化期刊群等数据库,检索时间均为建库至2010年3月。全面检索IFN-γ释放试验诊断儿童潜伏结核菌感染的文献,按照诊断试验的纳入标准筛选文献,提取纳入文献的特征信息(研究背景、设计信息和诊断参数信息)。根据QUADAS质量评价标准评价纳入文献的质量。采用Meta-Disc1.4软件进行Meta分析,检验异质性,并根据异质性结果选择相应的效应模型。对纳入文献予以加权定量合并,计算汇总敏感度、特异度、阳性似然比、阴性似然比和诊断优势比及其95%CI,绘制汇总受试者工作特征(SROC)曲线,并计算曲线下面积(AUC)。结果共检出相关文献285篇,按照文献纳入标准,最终纳入13篇文献(英文文献12篇和中文文献1篇)。10篇文献报道了QFT试验对儿童潜伏结核菌感染的诊断价值,汇总敏感度为0.40(95%CI:0.37~0.44)、汇总特异度为0.87(95%CI:0.85~0.88)、汇总阳性似然比为6.21(95%CI:3.07~12.54)、汇总阴性似然比为0.46(95%CI:0.31~0.68)、汇总诊断优势比为15.58(95%CI:7.47~32.48),SROC AUC为0.8931。4篇文献报道了T-SPOT.TB试验对儿童潜伏结核菌感染的诊断价值,汇总敏感度为0.74(95%CI:0.68~0.79)、汇总特异度为0.84(95%CI:0.81~0.87)、汇总阳性似然比为4.66(95%CI:1.27~17.12)、汇总阴性似然比为0.42(95%CI:0.18~0.99)、汇总诊断优势比为13.71(95%CI:3.71~50.72),SROCAUC为0.8306。结论 IFN-γ释放试验适用于进一步鉴别诊断儿童是否处于潜伏结核菌感染,不适合儿童潜伏结核菌感染的筛查。     

结核分枝杆菌特异性效应T细胞斑点数鉴别儿童活动性结核病与潜伏结核感染的价值

目的 通过γ干扰素释放试验探讨结核分枝杆菌特异性效应T细胞斑点数（简称T细胞斑点数）鉴别儿童活动性结核病（TB）与潜伏结核感染（LTBI）的价值。方法 纳入T细胞斑点试验（T.SPOT.TB）阳性且未经过抗结核治疗的93例活动性TB（重症TB 27例,非重症TB 66例）和47例LTBI儿童,根据T.SPOT.TB结果对T细胞斑点数进行比较分析。结果 活动性TB组T细胞斑点数中位数84（6～710）显著高于LTBI组17（6～316）,P=0.000;非重症TB患儿的T细胞斑点数中位数为99（6～710）,显著高于重症TB的44（6～268）,P=0.011,也显著高于LTBI组17（6～316）,P=0.000;重症TB儿童T细胞斑点数中位数高于LTBI组儿童（44 vs 17）,但差异无统计学意义（P=0.084）,T细胞斑点数分布在活动性TB、重症TB、非重症TB和LTBI之间均有较大范围重叠。受试者工作特征曲线分析显示以T细胞斑点数43.5作为区分活动性TB与LTBI的最佳界值,其敏感度与特异度分别为69.9%和70.2%。结论 T细胞斑点数在活动性TB尤其是非重症TB患儿显著高于LTBI儿童;T细胞斑点数的数量可反映体内的结核分枝杆菌负荷,但不能用于区分儿童活动性TB与LTBI。     

小儿隐性结核感染最佳治疗方案探讨

全世界有20亿人口感染隐性结核,是世界范围内结核病流行的最危险根源。85%~90%新被诊断的活动性肺结核,系由PPD阳性的隐性结核感染(LTBI)演变而来。海地1例30岁妇女怀孕前2年PPD硬结直径20mm,胸片(-),无结核中毒症状,未按LTBI给予抗结核治疗。2年后产一男婴,出生44d后出现发热被诊为先天性结核病。母产前1周出现惊厥,诊为脑结核,母与其子均经结核菌检阳性证明为结核,因为母亲未及时治疗LTBI所致[1]。结核病防治最有效的措施是早期治疗LTBI,从而减少活动性结核病的发生[2,3]。美国公共健康服务机构采用随机对照选用INH治疗7万各种…     

Serial diffusion-weighted MRI correlates with clinical course and treatment response in children with intracranial pus collections

Background Accurate assessment of treatment response in children with intracranial pus collections is vital to guide appropriate therapy and reduce morbidity and mortality. Objective To correlate serial MR-measurable changes in diffusion-weighted imaging (DWI) with clinical response to treatment. Materials and methods We retrospectively reviewed clinical notes, conventional MR sequences and DWI in eight children with intracranial pus collections. Trace DWI signal intensity and apparent diffusion coefficient (ADC) values were compared at three time points: at initial diagnosis (eight children, 13 collections), at follow-up during continued clinical infection (three children, sp collections), and at follow-up when clinical infection had resolved (seven children, 12 collections). Results At initial diagnosis all patients were septic and collections showed restricted diffusion (mean ADC 0.61±0.15×10⁻³mm²/s). Patients with persistent clinical sepsis at follow-up DWI had collections with persistent low ADC values (0.66±0.21×10⁻³mm²/s), significantly (P<0.001) below normal cortical gray matter values. Successful resolution of the infection was associated with a significant rise in ADC values (1.57±0.57×10⁻³mm²/s, P<0.01) compared both to patients with signs of continued sepsis and to normal gray matter values. Conclusion Persistent restricted diffusion in pus collections correlates with continued sepsis. Treatment response is associated with clinical resolution of sepsis and ADC value elevation significantly above normal gray matter values. Presented at ESPR 2005, Dublin, Ireland     

Predictors of virologic response to Lamivudine treatment in children with chronic hepatitis B infection

BACKGROUND: Some children with chronic hepatitis B develop advanced liver disease. Lamivudine, an oral nucleoside, is a therapeutic option. A recent large, multicenter study demonstrated that lamivudine was superior to placebo in eliciting loss of hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV) DNA from serum in children (2 to 17 years) treated for 52 weeks. OBJECTIVE: To identify pretreatment factors that predict the likelihood of response to lamivudine in children with chronic hepatitis B infection. STUDY DESIGN: Data from the multicenter trial in 297 children (191 lamivudine, 96 placebo) were analyzed for the effects of baseline factors on the likelihood of responses. These responses included virologic response, defined as loss of HBeAg and HBV DNA, and HBeAg seroconversion, defined as loss of HBeAg and development of antibody to HBeAg. Univariate and multivariate analyses examined the effects of lamivudine treatment, age, gender, race, body weight, body mass index, previous interferon treatment and baseline alanine aminotransferase (ALT), histologic activity index (HAI) score and HBV DNA on the virologic responses. RESULTS: In the univariate analysis higher baseline ALT, higher HAI score and lower HBV DNA level predicted a greater likelihood of virologic responses to lamivudine. In the multivariate model only baseline ALT and HAI score were predictive of responses. There was no effect of age or ethnicity on response. CONCLUSIONS: Children with higher pretreatment ALT and HAI scores are most likely to respond to lamivudine. Age, ethnicity and other factors do not significantly influence the frequency of virologic responses in children with chronic hepatitis B infection.     

Breath holding spells in 91 children and response to treatment with iron.

To evaluate the prognosis of breath holding spells (BHS) after iron treatment, 91 children (56 boys, 35 girls) aged between 6 months and 40 months (median, 17) were followed prospectively for a median of 45 months (range, 6-89). In 49 of the children, the frequency of BHS was less than 10 each month, in 22 it was 10-30 each month, and in 20 more than 30 each month. The spells were cyanotic in 60 children. All patients were evaluated initially and during follow up for haematological indices. Electroencephalographic and electrocardiographic abnormalities were also recorded. Sixty three patients were found to have iron deficiency anaemia and were treated with iron (6 mg/kg/day) for three months. Other patients were not given any treatment. After three months, there was a significant difference for correction of cyanotic spells between children who had been treated with iron and those who had not (84.1% v 21.4%). During further follow up, febrile convulsions occurred in 10 children (six were on iron treatment initially). It appears that treating iron deficiency anaemia is effective in reducing the frequency of BHS.     

Mycobacterium tuberculosis in children with human immunodeficiency virus type 1 infection.

A retrospective study was conducted at the Childrens Hospital Center at Jackson Memorial Hospital in Miami, FL, to evaluate the natural history of Mycobacterium tuberculosis infection in nine children with vertically acquired human immunodeficiency virus type 1 infection. The patients' ages ranged from 6 months to 7 years (median age, 42 months). Common presenting symptoms included prolonged fever, cough and anorexia. Only one patient had a positive tuberculin test. Five patients evidenced only pulmonary disease, three patients had pulmonary and extrapulmonary disease and one patient developed extrapulmonary tuberculosis (mastoiditis) and pulmonary interstitial disease that could not be attributed to mycobacterial infection because of lack of information. Organisms isolated before January, 1989, were susceptible to isoniazid and rifampin whereas isolates from three patients cultured after that time were resistant to multiple antituberculosis drugs. The median survival time after M. tuberculosis diagnosis for all children was 20 months. Our study suggests that children with human immunodeficiency virus type 1 infection who have tuberculosis have an increased risk for extrapulmonary disease. A high index of suspicion for the diagnosis of M. tuberculosis should be maintained in human immunodeficiency virus type 1-infected children with prolonged fever and respiratory symptoms. In areas of high endemicity of multidrug-resistant organisms, therapy with a broader panel of drugs may need to be instituted until susceptibility testing becomes available.     

Serial chest radiographs in the management of children with a clinical suspicion of pulmonary tuberculosis.

The aim of the study was to define the role of serial chest radiographs (SCR) in the management of children with a clinical suspicion of pulmonary tuberculosis (PTB) and to determine the interval at which they should be taken. Eighty children with a clinical suspicion of PTB were studied and followed-up for a duration of 18 months. SCR during the time of treatment were taken at monthly intervals for the first 3 months, then at 2-monthly intervals up to the end of therapy, and finally 2 months post-therapy. These were reviewed and the changes while on treatment noted and correlated with the clinical picture. Lung opacities were observed in 73 children (91 per cent) and were the most common radiological finding on the initial chest X-ray. These were followed by reduced chest wall muscle bulk present in 66 children (83 per cent). Mediastinal and/or hilar lymphadenopathy was noted in 47 children with a significant occurrence in the 0-4 age group (p = 0.004). Pleural effusions, cavities and calcification were rare. Human immunodeficiency virus (HIV) seropositive children with PTB accounted for 87 per cent and carried a poor prognosis (p = 0.0007). The common chest radiographic findings in children with PTB include lung opacities with hilar/mediastinal lymphadenopathy. Pleural effusions, cavitation, calcifications, miliary spread and normal chest X-rays were rare. SCR are useful in monitoring response to treatment, detection of onset of secondary infections and complications. HIV positive patients carry a poor prognosis. Based on the results of this study, pre-treatment, 2 months after onset of treatment, and end of therapy radiographs are recommended as routine in children with a clinical suspicion of PTB.     

Risk factors for human immunodeficiency virus infection in Ethiopian children with tuberculosis.

BACKGROUND: Separate risk factors for HIV infection and for tuberculosis (TB) are well-studied, but it is unclear whether these risk factors still apply in the new epidemiologic situation of dual infection. This study examines risk factors associated with seropositivity for HIV in Ethiopian children with clinical TB. METHODS: A prospective, controlled study of children with TB diagnosed in Addis Ababa from December 11, 1995, to January 28, 1997, in which HIV-positive children were compared with HIV-negative children with regard to sociodemographic background, previous medical history and vaccination. RESULTS: HIV prevalence among children with clinical TB was 11.2%. High educational status of mothers, low age, loss of one or two parents and earlier Calmette-Guérin bacillus (BCG) vaccination of the child were factors independently related to HIV infection. CONCLUSION: Factors associated with HIV infection among children with clinical TB include higher education of parents, higher income and better living conditions. The HIV epidemic might thus modify traditional risk factors for tuberculosis. It might also decrease the overall effect of BCG vaccination given that BCG did not provide protection in children infected with HIV. An expected increase of dually infected children who are younger, more in need of hospitalization and often lacking one or both parents will put an additional burden on the Ethiopian health care system.