Pediatric Pulmonary Tuberculosis Research Articles

A Meta-Analysis on GeneXpert Using Stool Samples in Diagnosing Pediatric Pulmonary Tuberculosis

Objectives: To find an alternative specimen for GeneXpert assay in the diagnosis of pediatric pulmonary tuberculosis (PTB). To determine the sensitivity and specificity of using stool samples as an alternative to sputum for GeneXpert assay. Methods: A systematic search was done using an electronic database (e.g. Pubmed). Using the keywords “GeneXpert”, “tuberculosis”, “Stool samples”. QUADAS-2 checklist was used in assessing the studies gathered. Revman 5.3 was used to determine the sensitivity and specificity of the study included in this meta-analysis. Results: A total of 185 stool samples were included in this review, which showed a median sensitivity of 77% (IQR 0.63-0.87) and median specificity of 98% (IQR 0.95-1.0). Conclusion: Despite the heterogeneous sensitivity, GeneXpert has a high specificity, which enabled rapid diagnosis of pulmonary tuberculosis promoting timely initiation of appropriate therapy.

Molecular clustering of patients with diabetes and pulmonary tuberculosis: A systematic review and meta-analysis.

IntroductionMany studies have explored the relationship between diabetes mellitus (DM) and tuberculosis (TB) demonstrating increased risk of TB among patients with DM and poor prognosis of patients suffering from the association of DM/TB. Owing to a paucity of studies addressing this question, it remains unclear whether patients with DM and TB are more likely than TB patients without DM to be grouped into molecular clusters defined according to the genotype of the infecting Mycobacterium tuberculosis bacillus. That is, whether there is convincing molecular epidemiological evidence for TB transmission among DM patients. Objective: We performed a systematic review and meta-analysis to quantitatively evaluate the propensity for patients with DM and pulmonary TB (PTB) to cluster according to the genotype of the infecting M. tuberculosis bacillus.Materials and methodsWe conducted a systematic search in MEDLINE and LILACS from 1990 to June, 2016 with the following combinations of key words “tuberculosis AND transmission” OR “tuberculosis diabetes mellitus” OR “Mycobacterium tuberculosis molecular epidemiology” OR “RFLP-IS6110” OR “Spoligotyping” OR “MIRU-VNTR”. Studies were included if they met the following criteria: (i) studies based on populations from defined geographical areas; (ii) use of genotyping by IS6110- restriction fragment length polymorphism (RFLP) analysis and spoligotyping or mycobacterial interspersed repetitive unit-variable number of tandem repeats (MIRU-VNTR) or other amplification methods to identify molecular clustering; (iii) genotyping and analysis of 50 or more cases of PTB; (iv) study duration of 11 months or more; (v) identification of quantitative risk factors for molecular clustering including DM; (vi) > 60% coverage of the study population; and (vii) patients with PTB confirmed bacteriologically. The exclusion criteria were: (i) Extrapulmonary TB; (ii) TB caused by nontuberculous mycobacteria; (iii) patients with PTB and HIV; (iv) pediatric PTB patients; (v) TB in closed environments (e.g. prisons, elderly homes, etc.); (vi) diabetes insipidus and (vii) outbreak reports. Hartung-Knapp-Sidik-Jonkman method was used to estimate the odds ratio (OR) of the association between DM with molecular clustering of cases with TB. In order to evaluate the degree of heterogeneity a statistical Q test was done. The publication bias was examined with Begg and Egger tests. Review Manager 5.3.5 CMA v.3 and Biostat and Software package R were used.ResultsSelection criteria were met by six articles which included 4076 patients with PTB of which 13% had DM. Twenty seven percent of the cases were clustered. The majority of cases (48%) were reported in a study in China with 31% clustering. The highest incidence of TB occurred in two studies from China. The global OR for molecular clustering was 0.84 (IC 95% 0.40–1.72). The heterogeneity between studies was moderate (I2 = 55%, p = 0.05), although there was no publication bias (Beggs test p = 0.353 and Eggers p = 0.429).ConclusionThere were very few studies meeting our selection criteria. The wide confidence interval indicates that there is not enough evidence to draw conclusions about the association. Clustering of patients with DM in TB transmission chains should be investigated in areas where both diseases are prevalent and focus on specific contexts.

Technical aspects of mediastinal ultrasound for pediatric pulmonary tuberculosis.

Diagnosing childhood pulmonary tuberculosis (TB) may be challenging due to difficulties in obtaining adequate sputum samples, paucibacillary disease and the low sensitivity of diagnostic tests. Chest radiography is an important diagnostic tool for pulmonary TB, but it involves radiation exposure, requires facilities that can house X-ray equipment and has poor inter-reader agreement. The cardinal radiologic finding of mediastinal lymphadenopathy may be detected using mediastinal ultrasound (US). We describe technical aspects of performing mediastinal US, which may assist diagnosis of paediatric pulmonary TB.

Predictable repeatability issues with GeneXpert-Xpert MTB/RIF (version 4) derived rifampicin resistant tuberculosis results from South India: Appreciating the limits of a technological marvel!

Background: GeneXpert MTB/RIF (Xpert), the fully automated cartridge-based nucleic acid amplification test for simultaneous identification of Mycobacterium tuberculosis complex and rifampicin resistance (RR), directly from samples is considered as a game changer for tuberculosis (TB) control programs worldwide. Methods: We are reporting serious issues with repeatability among a subgroup of Xpert (Version 4) identified RR results from South Indian state recently switched to Xpert by the National TB control program. Results: We have demonstrated that poor repeatability is frequently associated with those Xpert derived RR results, identified by detection of delayed amplification of any probe in the presence of positive analyte results for all probes. Another significant contributing factor was found to be lower bacterial loads in samples. The repeat tests were done by Xpert and/or by line probe assay depending on smear positivity. The finding is worrying as Xpert is recommended over other tests due to its reportedly better performance among low bacterial load samples such as pediatric, extra-pulmonary, HIV-TB co-infected, and smear negative pulmonary TB and the same samples, it seems are more likely to cause error prone RR results. Conclusions: We recommend for additional genotypic tests with specific mutant probes for detecting mutations at rpoB hot sites and growth based tests for all Xpert derived RR-TB cases identified by the above algorithm for confirmation of the presence of mutation, based on our available data.

Xpert<SUP>®</SUP> MTB/RIF assay for the diagnosis of pulmonary tuberculosis in children

A tertiary care teaching hospital in New Delhi, India. To determine the sensitivity and specificity of the Xpert(®) MTB/RIF assay in paediatric pulmonary tuberculosis (PTB) using MGIT™ culture as gold standard. After ethical approval had been obtained, 50 patients aged 0-14 years with suspected PTB were enrolled. Sputum/induced sputum and gastric lavage from the participants were sent for direct smear, MGIT culture and Xpert testing. Chest X-ray and tuberculin skin test (TST) were also performed. PTB diagnosis was made without considering Xpert results according to the Revised National Tuberculosis Control Programme (RNTCP) algorithm. The sensitivity and specificity of Xpert were calculated using culture as gold standard. Of 50 individuals with suspected PTB, 23 (46%) were diagnosed with PTB based on the RNTCP algorithm. Sixteen children from the PTB group (69.5%) were Xpert-positive. None in the 'not PTB' group were Xpert-positive. With culture as gold standard, Xpert sensitivity and specificity were respectively 91.6% (95%CI 59.7-99.5) and 86.8% (95%CI 71.1-95.05). In almost 70% of PTB cases, a definitive diagnosis could be made within 2 h using Xpert, establishing its role as a sensitive and specific point-of-care test.

Comparison of bronchial brushing and sputum in detection of pediatric pulmonary tuberculosis

The retrospective study aimed to evaluate the diagnostic value of bronchial brushing and sputum using acid fast bacilli smear, mycobacterial culture and real-time PCR in detection of pediatric pulmonary tuberculosis, sensitivity and specificity of bronchial brushing and sputum examined by the three methods were calculated and compared to each other. Data showed there were no significant difference in sensitivity between bronchial brushing and matched sputum using each method. But the specificity of real-time PCR on bronchial brushing was lower than on sputum. Compared with bronchial brushing, sputum was better specimen in detection of pediatric pulmonary tuberculosis.

Diagnosis of pediatric pulmonary tuberculosis with special reference to polymerase chain reaction based nucleic acid amplification test

ObjectiveTo determine the utility of polymerase chain reaction (PCR) for diagnosing pediatric pulmonary tuberculosis (PPTB). MethodA prospective cross-sectional study was carried out on 100 children less than 14years of age, with strong clinical suspicion and radiological evidence suggestive of pulmonary tuberculosis (TB). Sputum samples/gastric lavage were collected. Direct smears and culture on Lowenstein Jensen (LJ) media were performed. DNA extraction and amplification was performed using Genei™ Amplification Reagent set for Mycobacterium tuberculosis (MTB) (by Genei, Bangalore, India). This test is based on the principle of single-tube nested PCR which amplifies the repetitive insertion sequence IS6110. ResultsWhen compared with culture, sensitivity and specificity of PCR was 93.55% and 92.75%, respectively. The PPV was 85.29% and the NPV was 96.97%. When intention to treat (ITT) was used as the standard, sensitivity, specificity, PPV and NPV of PCR was 47.88%, 93.1%, 94.4%, and 42.19%, respectively, and that of culture was 40.85%, 100%, 100% and 40.85%, respectively. Against response to treatment (RTT), PCR demonstrated sensitivity, specificity, PPV and NPV of 50.9%, 93.1%, 93.33% and 50%, respectively, and for culture it was 43.64%, 100%, 100% and 48.33%, respectively. Conclusion/recommendationThe present study reinforces better case detection rate with PCR-based nucleic acid amplification test as compared with microscopy and culture in pediatric pulmonary TB. PCR showed a higher correlation with clinical diagnosis as compared with microscopy and solid culture. Hence, a molecular platform should be the test of choice for detecting PPTB.

Diagnostic values of microRNA-31 in peripheral blood mononuclear cells for pediatric pulmonary tuberculosis in Chinese patients.

We investigated the diagnostic values of microRNA-31 in peripheral blood mononuclear cells (PBMCs) for pediatric pulmonary tuberculosis in Chinese patients. Sixty-five children with TB were selected for this study, which was conducted at the Department of Infectious Diseases People's Hospital of Laiwu City between December 2013 and December 2014. Sixty healthy children, selected in parallel, served as the control group. Real-time PCR was used to detect miR-31 expression in PBMCs. Serum levels of IL-6, TNF-α, NF-κB, and IFN-γ was detected by ELISA. ROC curve was employed to evaluate the diagnostic value of miR-31 in pediatric TB. Results show that expression of miRNA-31 in pediatric TB patients was significantly lower than that in normal children (0.48 ± 0.15 vs 1.23 ± 0.36, P < 0.05). By contrast, serum levels of the innate immune response cytokines, IL-6, TNF-α, NF-κB, and IFN-γ, were significantly higher in pediatric TB patients compared with normal children (P < 0.05). Furthermore, miRNA-31 expression was negatively correlated with serum levels of IL-6 (t = 69.91, P < 0.001), TNF-α (t = 10.96, P < 0.001), NF-κB (t = 39.94, P < 0.001), and IFN -γ (t = 37.94, P < 0.001). The cut-off threshold of miR-31 for pediatric TB diagnosis is 0.835 with a sensitivity of 98.5% and a specificity of 86.7%. Therefore, miR-31 has the potential to be a diagnostic marker in pediatric TB patients.

Enhancing TB case detection: experience in offering upfront Xpert MTB/RIF testing to pediatric presumptive TB and DR TB cases for early rapid diagnosis of drug sensitive and drug resistant TB.

BackgroundDiagnosis of pulmonary tuberculosis (PTB) in children is challenging due to difficulties in obtaining good quality sputum specimens as well as the paucibacillary nature of disease. Globally a large proportion of pediatric tuberculosis (TB) cases are diagnosed based only on clinical findings. Xpert MTB/RIF, a highly sensitive and specific rapid tool, offers a promising solution in addressing these challenges. This study presents the results from pediatric groups taking part in a large demonstration study wherein Xpert MTB/RIF testing replaced smear microscopy for all presumptive PTB cases in public health facilities across India.MethodsThe study covered a population of 8.8 million across 18 programmatic sub-district level tuberculosis units (TU), with one Xpert MTB/RIF platform established at each study TU. Pediatric presumptive PTB cases (both TB and Drug Resistant TB (DR-TB)) accessing any public health facilities in study area were prospectively enrolled and tested on Xpert MTB/RIF following a standardized diagnostic algorithm.Results4,600 pediatric presumptive pulmonary TB cases were enrolled. 590 (12.8%, CI 11.8–13.8) pediatric PTB were diagnosed. Overall 10.4% (CI 9.5–11.2) of presumptive PTB cases had positive results by Xpert MTB/RIF, compared with 4.8% (CI 4.2–5.4) who had smear-positive results. Upfront Xpert MTB/RIF testing of presumptive PTB and presumptive DR-TB cases resulted in diagnosis of 79 and 12 rifampicin resistance cases, respectively. Positive predictive value (PPV) for rifampicin resistance detection was high (98%, CI 90.1–99.9), with no statistically significant variation with respect to past history of treatment.ConclusionUpfront access to Xpert MTB/RIF testing in pediatric presumptive PTB cases was associated with a two-fold increase in bacteriologically-confirmed PTB, and increased detection of rifampicin-resistant TB cases under routine operational conditions across India. These results suggest that routine Xpert MTB/RIF testing is a promising solution to present-day challenges in the diagnosis of PTB in pediatric patients.

Stool as Appropriate Sample for the Diagnosis of &amp;lt;i&amp;gt;Mycobacterium&amp;lt;/i&amp;gt; &amp;lt;i&amp;gt;tuberculosis&amp;lt;/i&amp;gt; by Gene Xpert Test

Background: Diagnosis of pediatric pulmonary tuberculosis (PTB) is a challenge. Symptoms are nonspecific. Young children are unable to expectorate sputum samples; the procedures for obtaining respiratory samples are invasive. Thus Mycobacterium tuberculosis cultures and smears often are not performed. Stool samples were used as an alternative to respiratory samples for the diagnosis of pediatric PTB using stool Xpert MTB/RIF and its sensitivity for detecting the DNA of MTB in stool was determined. Methods: The study was a laboratory-based cross-sectional prospective design. Stool specimen was collected from PTB suspected children (Mycobacterium tuberculosis DNA can be detected in stool using Xpert testing with a higher sensitivity. Therefore stool which can easily be obtained is an appropriate alternative sample for the diagnosis of PTB using Xpert assay for children unable to give respiratory samples. Furthermore Xpert turn round time is less than 2 hours.

Bronchoscopic Evaluation in Childhood Pulmonary Tuberculosis

We aimed to describe the risk factors of airway involvement and to investigate the contribution of bronchoscopy in the bacteriologic diagnosis of tuberculosis. Airway involvement was more often present in patients with resistance to tuberculosis therapy than in the patients having bronchoscopy performed at initial presentation. Addition of bronchoalveolar lavage to the diagnostic workup increased the mycobacteriologic yield statistically.

Rapid diagnosis of pulmonary tuberculosis in African children in a primary care setting by use of Xpert MTB/RIF on respiratory specimens: a prospective study.

In children admitted to hospital, rapid, accurate diagnosis of pulmonary tuberculosis with the Xpert MTB/RIF assay is possible, but no paediatric studies have been done in the primary care setting, where most children are given care, and where microbiological diagnosis is rarely available. We assessed the diagnostic accuracy of Xpert MTB/RIF in children in primary care. For this prospective study, we obtained repeat induced sputum and nasopharyngeal aspirate specimens from children (<15 years) with suspected pulmonary tuberculosis at a clinic in Khayeliwtsha, Cape Town, South Africa. We compared the diagnostic accuracy of Xpert MTB/RIF with a reference standard of culture and smear microscopy on induced sputum specimens. For the main analysis, specificity of Xpert MTB/RIF versus liquid culture, we included only children with two interpretable Xpert MTB/RIF and induced sputum culture results. Between Aug 1, 2010, and July 30, 2012, we enrolled 384 children (median age 38·3 months, IQR 21·2-56·5) who had one paired induced sputum and nasopharyngeal specimen, 309 (81%) of whom had two paired specimens. Five children (1%) tested positive for tuberculosis by smear microscopy, 26 (7%) tested positive by Xpert MTB/RIF, and 30 (8%) tested positive by culture. Xpert MTB/RIF on two induced sputum specimens detected 16 of 28 culture-confirmed cases (sensitivity of 57·1%, 95% CI 39·1-73·5) and on two nasopharyngeal aspirates detected 11 of 28 culture-confirmed cases (sensitivity of 39·3, 23·6-57·6; p=0·18). The specificity of Xpert MTB/RIF on induced sputum was 98·9% (95% CI 96·9-99·6) and on nasopharyngeal aspirates was 99·3% (97·4-99·8). Our findings suggest that Xpert MTB/RIF on respiratory secretions is a useful test for rapid diagnosis of paediatric pulmonary tuberculosis in primary care. National Institutes of Health, National Health Laboratory Services Research Trust, the Medical Research Council of South Africa, the National Research Foundation South Africa, the European and Developing Countries Clinical Trials Partnership.

“Induced sputum versus gastric lavage for the diagnosis of pulmonary tuberculosis in children”

BackgroundDiagnosis of pulmonary tuberculosis (PTB) is difficult in infants and young children. For microbiological confirmation of PTB children, sequential gastric lavage (GL) is recommended. Induced sputum (IS) may be an alternative or complementary tool, but the information is limited in children in developed countries. The aim of this study is to assess the safety and diagnostic yield from IS combined with GL for PTB diagnosis in non-HIV infected children.MethodsThe study involved 22 children with suspected PTB admitted to the Getafe Hospital from January 2007 to May 2011. IS and GL were performed on three consecutive days, according to a standardized protocol. In all samples, BK staining, culture and PCR were carried out, including Genotype MTBDR plus for resistance to INH-RIF (Isoniazid-Rifampin) since 2008. A preliminary analysis of an ongoing prospective study is presented.ResultsMedian age was 72 months (range 1 month to 14 years of age). Seven (33%) were ≤ 5 years of age. Seventeen were clinically diagnosed of PTB based on positive PPD and radiological criteria. Microbiological confirmation was achieved in 10 (58.8%) by either GL or IS. M. tuberculosis was identified by GL in 8 children (47.1%) and by IS in 7 (41.2%). One infant (2 IS samples) had transient oxygen desaturation recovered spontaneously.ConclusionsIS appears to be safe and well tolerated by children for diagnosis of PTB and is more convenient. Increasing the diagnostic yield of PTB in children with PTB may be a complementary technique. Largest studies are necessary to define the role of IS in paediatric PTB.

The hidden harm of home-based care: Pulmonary tuberculosis symptoms among children providing home medical care to HIV/AIDS-affected adults in South Africa

Millions of children in sub-Saharan Africa undertake personal and medical care for family members who are unwell with AIDS. To date, no research has investigated whether such care provision places children at heightened risk for pulmonary tuberculosis. This study aimed to address this gap by identifying risk factors for paediatric pulmonary tuberculosis symptomatology. In 2009–2011, 6002 children aged 10–17 years were surveyed using door-to-door household sampling of census enumeration areas. These were randomly sampled from six urban and rural sites with over 30% HIV prevalence, within South Africa's three highest tuberculosis-burden provinces. Validated scales and clinical tuberculosis symptom checklists were modelled in multivariate logistic regressions, controlling for socio-demographic co-factors. Findings showed that, among children, severe pulmonary tuberculosis symptomatology was predicted by primary caregiver HIV/AIDS-illness [odds ratio (OR): 1.63, confidence interval (CI): 1.23–2.15, p<0.001], and AIDS-orphanhood (OR: 1.44, CI: 1.04–2.00, p<0.029). Three-fold increases in severe tuberculosis symptoms were predicted by the child's exposure to body fluids through providing personal or medical care to an ill adult (OR: 3.12, CI: 1.96–4.95, p<0.001). Symptoms were also predicted by socio-economic factors of food insecurity (OR: 1.52, CI: 1.15–2.02, p<0.003) and household overcrowding (OR: 1.35, CI: 1.06–1.72, p<0.017). Percentage probability of severe tuberculosis symptoms rose from 1.4% amongst least-exposed children, to 18.1% amongst those exposed to all above-stated risk factors, independent of biological relationship of primary caregiver-child and other socio-demographics. Amongst symptomatic children, 75% had never been tested for tuberculosis. These findings identify the risk of tuberculosis among children providing home medical care to their unwell caregivers, and suggest that there are gaps in the health system to screen and detect these cases of paediatric tuberculosis. There is a need for effective interventions to reduce childhood risk, as well as further support for community-based contact-tracing, tuberculosis screening and anti-tuberculosis treatment for children caring for ill adults in contexts with a high burden of HIV and tuberculosis.

Rapid Molecular Diagnosis of Pulmonary Tuberculosis in Children Using Nasopharyngeal Specimens

A rapid diagnosis of pediatric pulmonary tuberculosis (PTB) using Xpert MTB/RIF (Mycobacterium tuberculosis/rifampicin) automated testing on induced sputum (IS) is possible, but the capacity for performing IS is limited. The diagnosis using a nasopharyngeal aspirate (NPA), which can be non-invasively obtained, is desirable. Paired specimens (NPA and IS) were tested using smear, liquid culture and Xpert. The diagnostic accuracy of Xpert and smear was compared with culture for different specimens in children with suspected PTB. There were 535 children [median age 19 months, 117 (21·9%) HIV-infected] who had one IS and one NPA specimen; 396 had two paired specimens. A positive smear, Xpert test or culture occurred in 30 (5.6%), 81 (15.1%) and 87 children (16.3%), respectively. The culture yield was higher from IS (84/87, 96.6%) vs NPA (61/87, 70.1%, P < .001). Amongst children with two paired specimens, 63 culture-confirmed cases occurred [60 (95.2%) IS vs 48 (76.2%) NPA, P = .002]. The sensitivity of two Xpert tests was similar for IS and NPAs [(45/63) 71% vs (41/63) 65%, P = .444)]; the sensitivity of smear was lower for IS (21/63, 33%) and NPA (16/63, 25%). The incremental yield from a second IS was 9 cases (17.6%) by culture and 9 (25%) by Xpert testing; a second NPA increased the culture yield by 10 (26.3%) and Xpert by 11 (36.7%). Xpert specificity was 99.1% (98.1-100) for IS and 98.2% (96.8-99.6) for NPAs. Xpert testing provided faster results than culture (median 0 vs 15 days, P < .001). Xpert testing on 2 NPAs is useful in children with suspected PTB, particularly in settings where IS and culture are not feasible.

Clinical Course of Endobrochial Tuberculosis Diagnosed by Flexible Bronchoscopy in Children

Purpose:The incidence of endobronchial tuberculosis in children is unknown, due to the incon- sistent implementation of bronchoscopy in pediatric patients with pulmonary tuberculosis. In this study, our aim was to determine the incidence and clinical course of endobronchial tuberculosis in children. Methods: We performed a retrospective chart review of patients less than 18 years of age, who was diagnosed with endobronchial tuberculosis via fiberoptic bronchoscopy. Results:Out of the 101 patients with pulmonary tuberculosis, 16 patients had endobronchial tuberculosis. The median age at diagnosis was 11.2 years (range, 5 months to 16.1 years). Tuberculin skin test was positive in 9 cases (56.2%), and 6 patients (37.5%) had a history of household contact with tuberculosis. Consolidation lesion was common in the simple chest radiographs of patients with endobronchial tuberculosis. According to the bronchoscopic finding, actively caseating type was most common (43.8%). Nine of the 16 patients of endobronchial tuber- culosis progressed to bronchial obstruction and 4 patients underwent pneumonectomy or lobec- tomy. Fibrostenotic and tumorous type tend to progress to endobronchial obstruction compared with actively caseating type. Conclusion:The incidence of endobronchial tuberculosis in pediatric pulmonary tuberculosis was 15.8%. Early detection and effective treatment of endobronchial tuberculosis are important to decrease the secondary complication, such as bronchial obstruction. (Pediatr Allergy Respir Dis(Korea) 2012;22:197-203)

Relationship between Toll-Like Receptor 8 Gene Polymorphisms and Pediatric Pulmonary Tuberculosis

Objectives:Genetic variants in Toll-like receptors (TLRs) are considered a potential indicator for host susceptibility to and outcome of several infectious diseases including tuberculosis. The aim of this study was to determine whether −129 C/G and Met1Val polymorphisms of TLR8 were associated with pediatric pulmonary tuberculosis in Turkish population.Methods:The −129 C/G and Met1Val polymorphisms were studied in 124 children with pulmonary tuberculosis compared to 150 age-matched healthy control subjects.Results:We did not identify any statistically significant differences between the patients with TB and control groups with regard to the frequency of genotypes GG or G/(−), CG, and CC or C/(−); and alleles G and C at rs3764879 (p&gt; 0.05). We found a strong association with genotype A/(−) at rs3764880 with susceptibility to pulmonary TB in males (OR 2.87, 95%CI 1.38–5.98,p= 0.007).Conclusions:Our results provide evidence, for the first time, of a role for the TLR8 gene in susceptibility to pulmonary TB in male children. Additional research to verify our results are necessary. Tuberculosis in children presents particularly difficult challenges, but research priorities and advances in pediatric tuberculosis could provide wider insights and opportunities for tuberculosis control.

Relationship between toll-like receptor 8 gene polymorphisms and pediatric pulmonary tuberculosis.

Objectives: Genetic variants in Toll-like receptors (TLRs) are considered a potential indicator for host susceptibility to and outcome of several infectious diseases including tuberculosis. The aim of this study was to determine whether −129 C/G and Met1Val polymorphisms of TLR8 were associated with pediatric pulmonary tuberculosis in Turkish population. Methods: The −129 C/G and Met1Val polymorphisms were studied in 124 children with pulmonary tuberculosis compared to 150 age-matched healthy control subjects. Results: We did not identify any statistically significant differences between the patients with TB and control groups with regard to the frequency of genotypes GG or G/(−), CG, and CC or C/(−); and alleles G and C at rs3764879 (p > 0.05). We found a strong association with genotype A/(−) at rs3764880 with susceptibility to pulmonary TB in males (OR 2.87, 95%CI 1.38–5.98, p = 0.007). Conclusions: Our results provide evidence, for the first time, of a role for the TLR8 gene in susceptibility to pulmonary TB in male children. Additional research to verify our results are necessary. Tuberculosis in children presents particularly difficult challenges, but research priorities and advances in pediatric tuberculosis could provide wider insights and opportunities for tuberculosis control.

Diagnosis of Pediatric Pulmonary Tuberculosis by Stool PCR

Pediatric pulmonary tuberculosis diagnosis is difficult because young children are unable to expectorate sputum samples. Testing stool for tuberculosis DNA from swallowed sputum may diagnose pulmonary tuberculosis. Hospitalized children with suspected tuberculosis had stool, nasopharyngeal, and gastric aspirates cultured that confirmed pulmonary tuberculosis in 16/236 patients. Twenty-eight stored stools from these 16 children were used to evaluate stool polymerase chain reaction (PCR) for tuberculosis diagnosis compared with 28 stool samples from 23 healthy control children. Two DNA extraction techniques were used: fast-DNA mechanical homogenization and Chelex-resin chemical extraction. DNA was tested for tuberculosis DNA with a hemi-nested IS6110 PCR. PCR after Fast-DNA processing was positive for 6/16 culture-proven tuberculosis patients versus 5/16 after Chelex extraction (sensitivity 38% and 31%, respectively). All controls were negative (specificity 100%). If sensitivity can be increased, stool PCR would be a rapid, non-invasive, and relatively bio-secure initial test for children with suspected pulmonary tuberculosis.

The Role of Flexible Bronchoscopy in Pediatric Pulmonary Tuberculosis

The Role of Flexible Bronchoscopy in Pediatric Pulmonary Tuberculosis