Contribution of the polymerase chain reaction to the diagnosis of tuberculous infections in children

Abstract The purpose of the study was to evaluate the contribution of polymerase chain reaction (PCR) to the diagnosis of tuberculous infection in children. Two different PCR techniques were compared to the standard bacteriological methods for the detection ofMycobacterium tuberculosis in 157 specimens obtained from the respiratory system of 51 children. Patients were classified in three groups: 12 patients with active disease (57 specimens), 12 patients with silent tuberculous infection (23 specimens) and 27 patients without tuberculosis (77 specimens). One PCR method (PCR/Ag85) used amplification of a fragment of the genes coding for the mycobacterial antigen 85 followed by hybridization of a probe specific forM. tuberculosis on the Southern blot of amplified DNA. The other PCR technique was a nested PCR (NPCR) using double amplification of a fragment of the insertion element IS6110 only present in theM. tuberculosis genome. The sensitivities of the different techniques, compared to the clinical diagnosis, were 7.0% for acid fast staining, 22.8% for culture, 24.6% for PCR/Ag85 and 44.9% for NPCR in active disease, 4.3% for culture, 8.7% for PCR/Ag85 and 28.6% for NPCR in silent tuberculous infection. The specificities were 100% for culture, 94.8% for PCR/Ag85 and 87.9% for NPCR. Among the 12 children clinically considered as having active tuberculosis, 1 had smear positive samples, 4 had at least one positive culture, 7 at least one positive PCR/Ag85 and 9 at least one NPCR positive sample. Among the 12 children having silent tuberculous infection, none had positive smears, 1 had one positive culture, 2 had at least one positive PCR/Ag85 and 5 at least one NPCR positive sample.Conclusion Our study suggests that both PCR techniques, and especially NPCR, are able to detectM. tuberculosis DNA in specimens containing few micro-organisms. PCR methods are more sensitive than culture and the results are available more quickly. Testing multiple samples from the same individual increased the sensitivity. In view of occasional false-positive results, cultures remain the gold standard to establish definitive diagnosis of primary tuberculous infection in children.     

Collapsing Glomerulopathy in a 16-Year-old Girl with Pulmonary Tuberculosis: The Role of Systemic Inflammatory Mediators

Idiopathic collapsing glomerulopathy is an aggressive variant of focal segmental glomerulosclerosis (FSGS) seen primarily in adults. Its etiology is unknown. Nearly identical pathology is seen in association with nephrotic syndrome in human immunodeficiency virus type 1 (HIV-1)-infected patients, raising the possibility that viral infection plays a role in pathogenesis. This is supported by the recent discovery of parvovirus B19 DNA in some cases of idiopathic collapsing glomerulopathy. We report a case of collapsing glomerulopathy in a 16-year-old girl who presented with steroid-resistant nephrotic syndrome and pulmonary tuberculosis. In the absence of the usual associations (adult age group, African-American race, or history of intravenous drug abuse), infection is the sole known risk factor in this case. This lends support to the hypothesis that immune dysregulation due to infection per se, rather than infection by specific viral agents, may lead to collapsing glomerulopathy in susceptible individuals.     

Antibiotic susceptibility of acute otitis media pathogens in otitis-prone Belgian children

A regional surveillance study was carried out in children with recurrent acute otitis media (AOM) to determine the antimicrobial susceptibility of three common AOM pathogens. Susceptibility to relevant antimicrobial agents was determined on 149 Streptococcus pneumoniae, 246 Haemophilus influenzae and 119 Moraxella catarrhalis strains isolated between January 1999 and January 2002, either from the nasopharynx or middle ear of 74 children with recurrent AOM, the majority (77%) being otitis-prone. Overall pneumococcal resistance to penicillin was 9.4% (6.7% penicillin-intermediate resistant, 2.7% penicillin-resistant), whereas cotrimoxazole and erythromycin resistance accounted for 25.5% and 38.9% respectively. The prevalence of antimicrobial-non-susceptible S. pneumoniae was the highest in middle ear isolates (P<0.05) and in otitis-prone children (P<0.01). Moreover, otitis-prone children harboured significantly more pneumococci resistant to at least two antimicrobial agents (24.3% versus 7.4%; P<0.01). No patient age related variation was observed. Five serogoups (6, 19, 23, 14 and 9) covered by the 7-valent pneumococcal conjugate vaccine, constituted most of the antibiotic resistant pneumococci. Among nasopharyngeal and middle ear H. influenzae isolates, 17.1% were resistant to ampicillin and 16.3% to cotrimoxazole. For M. catarrhalis, 92.4% of all isolates was ampicillin-resistant. Conclusion: this study confirms international and national differences in antimicrobial susceptibility profiles of three acute otitis media pathogens with relatively favourable antibiotic resistance rates in Belgian children with frequent acute otitis media. This at risk population of otitis-prone children is shown to harbour more antimicrobial resistant and multidrug resistant pneumococci. If antimicrobial therapy in this group of children is indicated, high dose amoxicillin is recommended whereas the use of macrolides is obsolete.Abbreviations AOM acute otitis media - MEF middle ear fluid - MIC minimal inhibitory concentration     

Non-traumatic colon perforation in children: a 10-year review

Colon perforation is an abdominal surgical emergency in the pediatric population, but is seldom reported when occurring from non-traumatic causes in children beyond the neonate. The goal of this study was to identify the clinical characteristics, management, and outcomes of non-traumatic colon perforation in children. Medical records for the 10-year period from September 1994 to September 2004 were reviewed for children beyond the neonate with non-traumatic colon perforation. Data gathered included age, gender, symptoms, duration of symptoms, physical findings, and length of postoperative hospital stay. Diagnostic information included laboratory data, radiographic imaging, and operative findings. Forty-four patients with non-traumatic colon perforation were recruited into this study. The mean age was 2.22 ± 1.87 years; 91.4% of cases were younger than 5 years old. The most common presenting symptom was fever (97.7%); the most common sign was abdominal distention (93.1%). The mean duration of symptoms prior to admission was 6.19 days. Pneumoperitoneum was presented in 86.3% of patients by plain abdominal radiograph. Ascending and transverse colon were the most common perforation sites. Non-typhoid salmonella was the leading pathogen isolated, causing 20.4% of episodes. One case died due to Clostridium speticum infection. Non-traumatic colon perforation most commonly affects children younger than 5 years of age. It may be secondary to infection, especially non-typhoid salmonella. Plain abdominal radiograph can be an adjuvant tool for the high index of suspicion for colon perforation in children with abdominal distention and history of fever or diarrhea for more than 5 days.     

Oophorectomy in children. Who and why: 13-year experience in a single centre

Aim: Oophorectomy performed in children is extremely uncommon. We aimed to investigate the disease pattern and the association between the underlying pathology and the clinical presentation among those patients who had their ovaries removed in their childhood. Methods: A retrospective study was performed on 41 consecutive children who underwent oophorectomy in a tertiary referral centre in the period between June 1995 and May 2008. Results: The median age was 11 years, ranged from 11 weeks to 15 years at the time of surgery. The primary presentations were acute lower abdominal pain (n= 20), progressive abdominal distension or abdominal mass (n= 13), chronic abdominal pain (n= 3), irregular menses (n= 1), antenatal diagnosis (n= 3) and incidental finding (n= 1). Ultrasound examination was performed in 31 patients and positive findings of ovarian pathology were found in all but one examination. Twenty cases of ovarian torsion were confirmed intra‐operatively. Patients presenting with acute abdominal pain were more likely to have torsion than other presentations (P < 0.01). Non‐neoplastic conditions and ovarian neoplasms were found in 11 and 30 patients, respectively. The most common neoplasm was mature teratoma (52%). Malignant neoplasms included immature teratoma (n= 3), dysgerminoma (n= 1), mixed dysgerminoma + yolk sac tumour (n= 2), yolk sac tumour (n= 2) and juvenile granulose cell tumour (n= 1). Malignant neoplasms were found to have more chronic presentation and less torsion than benign pathologies (P < 0.05). Conclusion: Although ovarian pathology is uncommon in children, a girl presenting with acute lower abdominal pain or progressive abdominal distension should raise the suspicion and prompt immediate investigation to rule out ovarian torsion or ovarian neoplasms.     

免疫缺陷患儿合并结核分枝杆菌感染的临床特征分析

目的 探讨继发性免疫缺陷病（SID）及原发性免疫缺陷病（PID）患儿合并结核分枝杆菌感染的临床特征。方法 回顾性分析合并结核分枝杆菌感染的免疫缺陷患儿（SID组36例、PID组52例）及非免疫缺陷患儿（对照组108例）的临床资料。结果 PID组患儿起病年龄低于对照组和SID组（P < 0.05）,男性比例高于对照组和SID组（P < 0.05）。SID组及PID组患儿其他结核中毒症状（盗汗、消瘦、乏力、食欲下降）及PPD试验阳性率均低于对照组（P < 0.05）,且更易出现肺叶受累≥ 3叶（P < 0.05）。PID患儿更易合并多器官受累（P < 0.05）。SID组肺部粟粒影发生率高于对照组和PID组（P < 0.05）,PID组γ-干扰素释放试验阳性率低于对照组和SID组（P < 0.05）。结核分枝杆菌感染在SID组表现为潜伏结核感染（36.1%）和活动性结核病（63.9%）;在PID组以卡介苗病（90.4%）为主,有2例（3.8%）同时合并结核病。结论 免疫缺陷患儿合并结核分枝杆菌感染的临床症状不典型,易出现播散性感染,PPD试验及γ-干扰素释放试验阳性率较低,容易出现误诊及漏诊。免疫缺陷患儿应常规进行结核相关筛查,早期识别及干预以改善预后。     

Complicated parapneumonic effusion in Belgian children: increased occurrence before routine pneumococcal vaccine implementation

An increased occurrence of complicated parapneumonic effusions in children has been reported from the UK and USA. Data from mainland Europe are scarce. We investigated the incidence of complicated parapneumonic effusion and empyaema in children admitted to the University Hospital of Leuven between 1993 and 2005, an era when pneumococcal conjugated vaccination had not yet been implemented. Sixty-eight cases were identified. The incidence increased from 20–55/100,000 hospital admissions to 120–130/100,000 hospital admissions in 2005, with 50% of the cases occurring from 2003 onwards (late cohort). This increase occurred later than that reported in the UK and US, but is of similar magnitude. The median patient age was 3.6 years (range 0.5–17 years). The median duration of symptoms before admission was 4 days (quartile values 3–7 days). The median white blood cell (WBC) count was 15,450 WBC/mm³ (quartile values 11,300–21,200 WBC/mm³) and the median C-reactive protein (CRP) level was 242 mg/L (quartile values 143–344 mg/L). Patients in the late cohort seemed to have worse disease compared to early cohort patients; significantly higher pleural lactate dehydrogenase (LDH) level (P = 0,02), higher pleural WBC, lower pleural glucose level and significantly longer duration of hospitalisation in the later cohort (P < 0,05), possibly reflecting more severe disease. In both cohorts, Streptococcus pneumoniae was the most frequently isolated pathogen, with serogroup 1 prevailing. The occurrence of complicated parapneumonic effusion increased in Belgian children before pneumococcal vaccination was added to routine childhood immunisations. This increase is pronounced from 2003 onwards (late cohort) and, thus, occurred later than that reported in the UK and USA; several parameters point towards the occurrence of more serious disease in the late cohort patients. Tine Van Ackere and Marijke Proesmans contributed equally to this paper and are the first authors.     

Inflammatory myofibroblastic tumor of the liver due to <Emphasis Type="Italic">Μycobacterium tuberculosis</Emphasis> in an immunocompetent girl

The case of a 9-year-old girl with a Mycobacterium tuberculosis inflammatory myofibroblastic tumor (IMT) of the left lobe of the liver is reported. The tumor was surgically excised and had histological features diagnostic of IMT, a positive Ziehl-Nielsen staining for acid-fast bacilli and a positive polymerase chain reaction for Mycobacterium tuberculosis. Surgical excision of the tumor followed by anti-tuberculosis treatment for 9 months resulted in full recovery. The patient had no apparent immune disorder, and there was no evidence of extrahepatic tuberculosis. These findings make this case exceptional because IMTs, due mostly to atypical mycobacteria, have been described only in immunocompromised patients.     

Epidemiology and clinical management of tuberculosis in children in Canada

Although often regarded as a foreign disease, latent tuberculosis or tuberculosis disease will be encountered in many clinical situations by the Canadian child health practitioner. There are key differences between tuberculosis in children and adults. In the present article, the changing epidemiology of tuberculosis in children in Canada and around the world, the pathogenesis of infection, diagnostic tests, and clinical management of childhood latent tuberculosis and tuberculosis disease are reviewed.     

Mycobacterium genavense invasive infection in two children with AIDS: Long-term followup

Mycobacterium genavense is a rare cause of opportunistic infection in immunocompromised hosts. Follow up of two cases ofM. genavense invasive infection in children with haemophilia A and AIDS are presented. One patient died 18 months after diagnosis ofM. genavense infection of an indirectly related cause, probably ofPneumocystis carinii pneumonia. The second patient still attends our outpatient clinic and the infection is under control. Both presented with abdominal lymphomas and pain and a wasting syndrome. A combination of several drugs against atypical mycobacteria is used for treatment.     

Centro-temporal spikes in non-epileptic children: a long-term follow up

OBJECTIVE: This study was undertaken in order to determine the natural evolution of centro-temporal spikes (CTS) in a healthy paediatric population. METHODOLOGY: Forty children and adolescents (mean age +/- SD: 9.9 +/- 4.1 years) with non-epileptic disturbances (tics, headache, pavor nocturnus, vertigo, etc), who showed CTS during routine EEG recordings were studied. No patient suffered from seizures. A clinical and electroencephalographic follow-up of at least 5.5 years was carried out in all subjects. RESULTS: At the follow-up examination, 33 of the 40 cases (82.5%) had no CTS or other epileptic discharges in awake and sleep EEGs, while six subjects continued to show CTS discharges in sleep EEG. Among those subjects who showed persistence of CTS in sleep EEG, rolandic epilepsy developed in two cases, while all other subjects continued to be seizure free. CONCLUSIONS: This study demonstrates that CTS can be present in non-epileptic children and adolescents; in the majority of subjects this EEG abnormality disappears spontaneously and only a small percentage of subjects who have persistence of this pattern develops rolandic epilepsy.     

Sacrococcygeal teratoma: the 13-year experience of a tertiary paediatric centre

Aim: To describe the management, morbidity and mortality of infants admitted to a tertiary paediatric hospital in New South Wales, Australia with a diagnosis of sacrococcygeal teratoma (SCT). Methods: All neonates admitted to the neonatal intensive care unit with a SCT between January 1996 and December 2008 were included in this retrospective review. Data collected included maternal and neonatal demographics, time of diagnosis, tumour characteristics, surgical treatment, operative complications and outcomes. Results: Seventeen infants with a diagnosis of SCT were included in the study. Of these infants, the majority (70%) were born at term, and eight had a prenatal diagnosis made during the second trimester. Associated anomalies were detected in seven infants (41.8%), with renal anomalies being the most common. Tumour histology included mature (50%, n= 8), yolk sac tumour (18.75%, n= 3), immature (6.25%, n= 1) and mature with mixed elements (25%, n= 4). Recurrent disease occurred in two infants within 4–18 months of the primary resection, with one infant suffering a second recurrence. Only one child died prior to surgery, giving a survival rate of 94%, and mean age at follow‐up was 32 months. Long‐term sequelae found in four babies included revision of scar, vesicoureteric reflux, post‐surgical neurogenic bladder and osteotomy for hip dysplasia. Conclusions: The overall survival of neonatal SCT is high. While this is a small series, our results are consistent with the literature. Important components of management include timely diagnosis, multidisciplinary planning, long‐term follow‐up and intervention for functional sequelae.     

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。     

Long-term results of delayed primary anastomosis for pure oesophageal atresia: a 27-year follow up

The management of a newborn with pure oesophageal atresia continues to be challenging. We started treating babies with pure oesophageal atresia by delayed primary anastomosis in 1977. The purpose of this study was to review the long-term outcome in infants with pure oesophageal atresia (EA) treated by delayed primary anastomosis with special emphasis on gastroesophageal reflux (GOR) related morbidity. The medical charts of all patients treated by delayed primary anastomosis between 1977 and 2004 were retrospectively reviewed. All survivors were followed up with completion of a questionnaire and personal/phone interviews. There were 26 patients in total admitted during the 27-year study period with the diagnosis of pure oesophageal atresia. Three died prior to surgery due to associated anomalies; two had almost no distal oesophageal segment and underwent oesophageal replacement surgery. The remaining 21 children were treated with delayed primary anastomosis and made up our study group. There were four deaths (19%) in this group, and all were prior to 1980. The median gestational age was 35.5 weeks and the median birth weight was 2.6 kg; median initial gap was 3.7 cm and median preoperative gap was 1.5 cm; median age at operation was 80 days and the median hospital stay was 5.5 months. The median follow-up period was 13.5 years. Fourteen children (66%) developed symptomatic gastroesophageal reflux and nine of these needed fundoplication (43%). Sixteen children developed strictures at the anastomotic site; ten responded to repeated dilatations while six needed resection and reanastomosis. At the time of this study, 15 out of the 17 survivors (88%) were on normal diet with no respiratory problems and 2 (12%) were dependent on gastrostomy feeds. Our long-term follow-up data shows that the delayed primary anastomosis provides excellent functional results in patients born with pure oesophageal atresia. The high incidence of gastroesophageal reflux and associated morbidity requires early intervention to prevent ongoing feeding problems due to oesophagitis and stricture formation.     

Iodine deficiency disorders in school children of Sikkim

Sikkim is a small state in the eastern Himalayas. A survey was conducted to determine the prevalence of iodine deficiency disorders in the state. A two stage sampling procedure was adopted. In stage one, all villages in the state were listed and 249 were randomly selected for the survey. In stage two, households, were randomly selected from the selected villages using the electoral lists. The basic sampling unit was a household and all members of the households were studied. A total of 17,837 subjects were studied from 3,197 households of 249 villages. Overall prevalence of goitre and cretinism in the community as a whole, were 54,03% and 3.46% respectively. Of the population studied, 5939 were children in the age group of 5 to 16 years. There were 3,005 boys and 2,934 girls. Goitre was detected in 3,381 (56.9%). Goitre prevalence in the boys was 55.4% and in girls it was 58.5% (p=<0.05). Grade I goitre was seen in 2,472 (73.1%), grade II in 888 (26.3%) and grade III in 21 (0.6%). Endemic cretinism was diagnosed in 175 subjects (2.9%). Cretinism prevalence in the boys was 3.1%, and in girls in was 2.8% and this difference was not significant. Neurological; cretinism was the predominant form (98.3%). Estimation of urinary iodine concentration in 167 subjects revealed the mean concentration to be 3.64 u/dl (SD 2.47). The median value was ug/dl indicating the skewed distribution of the urinary iodine concentration. The study shows the existence of severe iodine deficiency in the school-aged children of Sikkim. The iodine deficiency disorders status in this age group is representative of the community as a whole and can be used as the target group for surveys.     

An unusual case of recurrent hypoglycaemia: 10-year follow up of a child with insulin auto-immunity

We report the case of a child with hypoglycaemia due to insulin auto-immunity. Insulin autoimmunity is the third most frequent cause of hypoglycaemia in Japan where the first cases were described. The child has been followed for the past 10 years with recurrence of hypoglycaemic symptoms and high titres of insulin antibodies.     

孕期增重对婴幼儿体重和肥胖风险影响的随访研究

目的：研究孕期增重对子代0~24个月内体重和肥胖风险的影响。方法：对317名孕产妇进行孕前体重、分娩前体重和一般人口统计学信息调查,在子代出生时及3、6、9、12、18、24个月龄时进行体重、身高测量和母乳喂养调查。结果：Logistic回归分析显示,孕期增重过多会显著增加子代6月龄(RR=3.56, 95% CI: 1.31~8.35)和9月龄(RR=2.87, 95% CI:1.04~3.28)时肥胖的风险,但并未增加12月龄以后的肥胖风险。线性回归模型结果显示,孕期增重与子代在出生时(β=0.032, 95% CI:0.008~0.057)、3月龄(β=0.037, 95% CI: 0.013~0.062)、6月龄(β=0.043, 95% CI: 0.017~0.068)、9月龄(β=0.038, 95% CI: 0.013~0.063)和12月龄(β=0.034, 95% CI: 0.009~0.059)时体重的Z分值间存在显著的线性关联,但这种关联在子代12个月龄后均无统计学意义。结论：孕期增重过多对子代体重发育的影响可从胎儿期持续至整个婴儿期,这种影响在生后第2年会暂时消失。     

Clinical manifestations of appendiceal pinworms in children: an institutional experience and a review of the literature

The association of Enterobius vermicularis infestation with acute appendicitis varies from 0.2–41.8% worldwide. Our purpose was to determine the significance of Enterobius-associated appendicitis by retrospective review of appendectomies performed during a 5-year period at a major childrens hospital. The Surgical Pathology database at Childrens Hospital, Columbus, Ohio, was reviewed for appendiceal specimens found to have Enterobius infestation. Corresponding patient charts were evaluated for age, gender, presenting symptoms, laboratory data, operative findings, and clinical course. Of the 1,549 appendectomies performed from January 1998 through January 2003, 21 specimens (1.4%) were found to contain Enterobius vermicularis. Fifteen of the appendectomies were performed for symptoms of acute appendicitis; the remaining six were incidental appendectomies in conjunction with other operations. The mean age was 8.9 years. Ten patients were male; 11 were female. Of the 15 symptomatic children, nine presented with fever >99.0ºF, and 11 had a WBC count >10,000. Intra-operative appearance of the appendix ranged from normal to perforation. Pathologic evaluation showed neutrophil or eosinophil infiltration in 15 of the 21 specimens. Enterobius infestation is an uncommon cause of acute appendicitis in children in the United States. It may be associated with acute appendicitis, chronic appendicitis, ruptured appendicitis, or with no significant clinical symptoms.