Diagnosis Of Pediatric Tuberculosis Research Articles

Prevalence, diagnosis and treatment status of pediatric drug-resistant tuberculosis

Tuberculosis is a chronic infectious disease caused by Mycobacterium tuberculosis, which threats the health of children worldwide.Accompany with the increase of drug-resistance tuberculosis, great challenging has arose in the prevention and treatment of tuberculosis.Nowadays, the diagnosis and treatment of drug-resistance tuberculosis is still difficult in pediatric patients.Based on molecular diagnosis, fast detect as well as reliable treatment of drug-resistance tuberculosis become available.Currently, the principle of drug-resistant tuberculosis treatment in children is essentially similar to adults.In this review, the mechanism, diagnosis and treatment of pediatric drug resistance tuberculosis were discussed. Key words: Child; Drug-resistance tuberculosis; Prevalence; Mechanisms of drug-resistance; Diagnosis; Treatment

Use of procalcitonin in the diagnosis of tuberculosis in infants and preschool children.

In our study, PCT was not a useful diagnostic test for TB in young children. In a low-burden TB setting, PCT may be of some value in distinguishing pulmonary TB from pneumococcal pneumonia. What is Known: • Diagnosis of pediatric tuberculosis on clinical evidence is difficult, particularly in infants and small children. • Studies in adults with tuberculosis have mostly reported normal procalcitonin levels at diagnosis. What is New: • In pre-scholars with tuberculosis, erythrocyte sedimentation rate and white blood cell counts were higher than in healthy controls, but procalcitonin was not. • Procalcitonin may be useful in the differential diagnosis of intrathoracic tuberculosis and pneumococcal pneumonia.

Prevalence of rifampicin-resistant pediatric tuberculosis by cartridge-based nucleic acid amplification test at the intermediate reference laboratory under revised national tuberculosis control program India: A multidimensional approach

Background: Tuberculosis (TB) still remains the major public health threat in India. Early diagnosis, so as to initiate early treatment is a priority as any delay, may complicate the prognosis further leading to the failure of an effective control. India accounts for 6% incidence of pediatric TB cases in a population that has 40% as estimated latent TB cases. Implementation of cartridge-based nucleic acid amplification tests (CBNAATs) in diagnosis of pediatric TB has augmented the detection rates. The study involves a retrospective multidimensional analysis of the increased pediatric TB case detection by CBNAAT at the Intermediate Reference laboratory, State TB Demonstration and Training Centre in West Bengal, India. A total of 14,088 samples from pediatric patients coming from all the districts were tested from May 2014 to April 2018. This included pulmonary (sputum, bronchoalveolar lavage, gastric lavage, and gastric aspirate) and extrapulmonary (cerebrospinal fluid [CSF], pus, ascitic fluid, pericardial fluid, lymph node aspirate) samples. Although detection levels showed variation in the nature of the samples, the study explored percentage contribution of the types of samples and the proportion positive rates among them. Percentage-wise propensity with regard to age, clinical presentations, type of samples, and smear result were observed. The predominant geographical location in terms of incidences and periodic prevalence were studied. The resistant cases were retested with line probe assay by MTBDRplus and V2 Hains for concordance analysis. This was done based on the parameters in the erstwhile evaluations. Methods: Pulmonary and extrapulmonary pediatric samples were tested on CBNAAT by Xpert Mycobacterium tuberculosis rifampicin (RIF) (Cepheid) based on the manufacturer's instruction. All necessary aseptic measures were taken. The data were captured in the Xpert software automatically during the tests and exported to the Microsoft Excel sheets for further analysis. A defined study design against each and every objective was set up. Results: It was found that a point prevalence of 6%–7% of pediatric TB exists among the tested specimens every quarter. The periodic prevalence was found to be 5%, the incidence rates ranged from 4.5% to 5%. RIF resistance detection showing a seasonal variation ranged from 13% to 15% among the CBNAAT-positive cases. Gastric lavage showed a major detection in children below 6 months of age of whom collecting sputum samples were difficult. This prompted suboptimal detection levels due to the dearth of sample collection modalities at the peripheries. CSF accounted for 2.37% of positivity. Conclusions: The study concluded that more skilled collection centers for biological specimens are required to address the undetected pulmonary TB cases among the pediatric age group, especially below the 6 months of age. About 5% prevalence and around 4.9% incidence is an alarming situation in the TB control scenario of West Bengal. Focus on the universal drug-susceptibility testing is a prerequisite.

A comparison of tuberculosis diagnostic systems in a retrospective cohort of HIV-infected children in Rio de Janeiro, Brazil

Objectives:The diagnosis of pediatric tuberculosis (TB) presents many challenges, and is further complicated in HIV-infected patients. While many diagnostic systems have been proposed, there is no pediatric TB diagnosis gold standard. The outcomes of four TB diagnostic systems in HIV-infected children were compared in this study.Methods:A retrospective cohort study was conducted at a TB/HIV reference hospital in Rio de Janeiro. HIV-infected pediatric patients evaluated for TB from 1998 to 2010 were reassessed using four diagnostic systems: Kenneth Jones, 1969; Tidjani, 1986; Ben Marais, 2006; Brazilian Ministry of Health, 2010. Results were compared to standardized diagnoses made by an expert panel of physicians.Results:Of the 121 patients in the study cohort, the expert panel diagnosed 64 as TB and 57 as not TB cases. The Tidjani system showed the highest diagnostic accuracy, with and without the inclusion of microbiological data. The Tidjani and Kenneth Jones systems produced fewer false-positives, and the Ben Marais and Ministry of Health fewer false-negatives. Across systems, there was little agreement between TB diagnoses.Conclusions:In HIV-infected pediatric patients, the Ben Marais and Ministry of Health systems are useful for TB diagnostic screening, whereas the Tidjani and Kenneth Jones systems are best used in a reference center setting.

19.146 Point of care urine lipoarabinomannan antigen detection for diagnosis of tuberculosis in Pediatric population

Purpose: Due to pauci-bacillary nature of disease, difficulties in obtaining good quality specimen, low sensitivity of smear-microscopy and poor access to culture; rapid diagnosis of tuberculosis in children is challenging. To expedite diagnosis of pediatric tuberculosis, we evaluated Urine Lipoarabinomannan antigen(LAM) detection for its diagnostic accuracy. Young children with pulmonary tuberculosis develop disseminated disease more frequently than adults, which may increase the chances of mycobacterial antigen secretion. Methods & Materials: Based on microbiological and clinical findings, 381 children including 280 and 101 of suspected pulmonary tuberculosis(PTB) and suspected tubercular lymphadenitis(LNTB) were categorized as Confirmed, sixty eight(17.9%) & 25(24.7%); Probable, 66(23.5%) & 20(19.8%); Possible, four(1.4%) & 13(12.8%); and No-TB, 142(50.7%) & 43(42.5%) respectively. In case of PTB, either expectorated sputum or Induced sputum were taken while fine needle aspiration cytology was collected in LNTB. Samples were subjected to Ziehl-Neelsen stain, MGIT-960 culture and GeneXpert. For LAM antigen detection from urine, lateral-flow assay was performed as per manufacturer's instructions. Results: Among the PTB and LNTB cases, Eight(2.8%) and three children(2.9%) were positive by smear, 51(18.2%) and 23(22.7%) by GeneXpert, 48(17.1%) and 9(8.9%) by culture respectively. GeneXpert detected 20 and 16 cases more than culture in PTB & LNTB cases respectively and it detected 31 of 48 culture confirmed PTB cases (sensitivity 74%, specificity 91%) and 7 of 9 culture confirmed LNTB cases (sensitivity 82%, specificity 82%). On analysis of LAM assay with microbiological confirmation (either culture or GeneXpert Positive), sensitivity was 79% & 80%, specificity 71% & 67%, PPV 55% & 52%, NPV 89% & 88% in PTB & LNTB cases respectively. On adding the cases which were started with anti-tubercular therapy irrespective of microbiological confirmation, specificity of LAM assay improved to 92% & 93% and PPV to 93% & 92% in PTB & LNTB cases respectively. Conclusion: GeneXpert assay & Urinary LAM antigen detection led to early detection of TB cases. Nevertheless, neither negative LAM antigen test completely rule out TB nor positive LAM test fully indicates towards tuberculosis. But these limitations were circumvented by good clinical, radiological & histopathological correlation which is needed for treatment initiation and culture continues to be gold standard

Utility of Novel Plasma Metabolic Markers in the Diagnosis of Pediatric Tuberculosis: A Classification and Regression Tree Analysis Approach.

Although tuberculosis (TB) has been the greatest killer due to a single infectious disease, pediatric TB is still hard to diagnose because of the lack of sensitive biomarkers. Metabolomics is increasingly being applied in infectious diseases. But little is known regarding metabolic biomarkers in children with TB. A combination of a NMR-based plasma metabolic method and classification and regression tree (CART) analysis was used to provide a broader range of applications in TB diagnosis in our study. Plasma samples obtained from 28 active TB children and 37 non-TB controls (including 21 RTIs and 16 healthy children) were analyzed by an orthogonal partial least-squares discriminant analysis (OPLS-DA) model, and 17 metabolites were identified that can separate children with TB from non-TB controls. CART analysis was then used to choose 3 of the markers, l-valine, pyruvic acid, and betaine, with the least error. The sensitivity, specificity, and area under the curve (AUC) of the 3 metabolites is 85.7% (24/28, 95% CI, 66.4%, 95.3%), 94.6% (35/37, 95% CI, 80.5%, 99.1%), and 0.984(95% CI, 0.917, 1.000), respectively. The 3 metabolites demonstrated sensitivity of 82.4% (14/17, 95% CI, 55.8%, 95.3%) and specificity of 83.9% (26/31, 95% CI, 65.5%, 93.9%), respectively, in 48 blinded subjects in an independent cohort. Taken together, the novel plasma metabolites are potentially useful for diagnosis of pediatric TB and would provide insights into the disease mechanism.

Digital platform for improving non-radiologists' and radiologists' interpretation of chest radiographs for suspected tuberculosis - a method for supporting task-shifting in developing countries.

Shifting X-ray interpretation to non-radiologists can help to address radiologist shortages in developing countries. To determine the change in accuracy of non-radiologists and radiologists for the radiographic diagnosis of paediatric tuberculosis after a short skill-development course. Participants interpreted 15 paediatric chest radiographs before and after a 30-minute course using three possible responses: (1) diagnostic for tuberculosis, (2) abnormal but inconclusive for diagnosis of tuberculosis and (3) normal. We compared proportions of correct diagnoses, sensitivity, and specificity, before and after the course. We included 256 participants comprising 229 non-radiologists (134 radiographers, 32 paediatricians, 39 Médecins Sans Frontières clinicians and 24 physicians including paediatricians) and 27 radiologists. Mean change proportions of correct diagnosis ranged from -27% to 53% for individuals and 9% to 20% for groups. All groups showed a statistically significant improvement. Mean change in diagnostic sensitivity ranged from -38% to 100% for individuals and from 16% to 41% for groups. All groups showed a statistically significant improvement. Mean change in specificity ranged from -57% to 57% for individuals and from -15% to -4% for groups. The decrease was statistically significant for physicians, paediatricians and radiographers. The course resulted in increased correct diagnoses and improved sensitivity at the expense of specificity.

Drug-resistant tuberculosis in children less than 5 years old with culture positive mycobacterium tuberculosis

Background: Diagnosis of paediatric tuberculosis remains a challenge due to the difficulty in obtaining samples from children and the low sensitivity of culture confirmation. Drug resistance in TB continues to be a significant challenge in South Africa. Microbiologic confirmation of tuberculosis in children is necessary to exclude drug-resistant tuberculosis in face of the high multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) rates reported in the adult population. We describe the rates of drug-resistant TB in children less than 5 years old from KwaZulu Natal – a province in South Africa with the highest burden of both TB and HIV disease. Methods & Materials: A retrospective descriptive analysis was done of specimens from children less than 5 years old submitted to TB reference laboratory in KwaZulu-Natal, South Africa. Data was collected from 2012 to 2014. Specimens cultured included respiratory samples, lymph node aspirates, pleural and peritoneal fluid, cerebrospinal fluid, bone and tissue samples. Cultures were performed using the automated Mycobacterial Growth Indicator Tube 960 system (Becton Dickinson) and identification and susceptibility was confirmed with the line probe MTBDR plus assay (Hain-Life Science). From 2012 the Xpert MTB/RIF was introduced into the diagnostic algorithm for MTB detection and Rifampicin resistance. Results: 903 children were found to have culture-confirmed TB during this 3 year period. Drug susceptibility testing showed susceptible MTB ranging from 71-82% in the various age groups. Overall the resistance to isoniazid and rifampicin (MDR) rates ranged from 11-16% with the highest rates found in 2 year old age group. Extensively drug-resistant TB (0-2.1%) was present in all age groups. INH mono-resistance was 3,4% and Rifampicin mono-resistance was 2.8%. Conclusion: High rates of Mycobacterium tuberculosis including extensively drug resistant TB were found in children less than one, which indicates the burden of TB infection among woman during childbearing years. INH mono-resistance is of concern as this will not be detected by the current diagnostic algorithm that includes the Xpert MTB/RIF for MTB detection and Rifampicin resistance. Children with INH mono-resistance may benefit from high-dose isoniazid therefore bacteriological confirmation through culture is important in management of childhood TB.

Approaching a diagnostic point-of-care test for pediatric tuberculosis through evaluation of immune biomarkers across the clinical disease spectrum.

The World Health Organization (WHO) calls for an accurate, rapid, and simple point-of-care (POC) test for the diagnosis of pediatric tuberculosis (TB) in order to make progress “Towards Zero Deaths”. Whereas the sensitivity of a POC test based on detection of Mycobacterium tuberculosis (MTB) is likely to have poor sensitivity (70–80% of children have culture-negative disease), host biomarkers reflecting the on-going pathological processes across the spectrum of MTB infection and disease may hold greater promise for this purpose. We analyzed transcriptional immune biomarkers direct ex-vivo and translational biomarkers in MTB-antigen stimulated whole blood in 88 Indian children with intra-thoracic TB aged 6 months to 15 years, and 39 asymptomatic siblings. We identified 12 biomarkers consistently associated with either clinical groups “upstream” towards culture-positive TB on the TB disease spectrum (CD14, FCGR1A, FPR1, MMP9, RAB24, SEC14L1, and TIMP2) or “downstream” towards a decreased likelihood of TB disease (BLR1, CD3E, CD8A, IL7R, and TGFBR2), suggesting a correlation with MTB-related pathology and high relevance to a future POC test for pediatric TB. A biomarker signature consisting of BPI, CD3E, CD14, FPR1, IL4, TGFBR2, TIMP2 and TNFRSF1B separated children with TB from asymptomatic siblings (AUC of 88%).

Recommendations for the diagnosis of pediatric tuberculosis.

Tuberculosis (TB) is still the world's second most frequent cause of death due to infectious diseases after HIV infection, and this has aroused greater interest in identifying and managing exposed subjects, whether they are simply infected or have developed one of the clinical variants of the disease. Unfortunately, not even the latest laboratory techniques are always successful in identifying affected children because they are more likely to have negative cultures and tuberculin skin test results, equivocal chest X-ray findings, and atypical clinical manifestations than adults. Furthermore, they are at greater risk of progressing from infection to active disease, particularly if they are very young. Consequently, pediatricians have to use different diagnostic strategies that specifically address the needs of children. This document describes the recommendations of a group of scientific societies concerning the signs and symptoms suggesting pediatric TB, and the diagnostic approach towards children with suspected disease.

Are TB control programmes in South Asia ignoring children with disease? A situational analysis

Paediatric tuberculosis (TB) has long been an evasive entity for public health practitioners striving to control the disease. Owing to difficulty in diagnosis of paediatric TB, incidence estimates based on...

Assessment of the novel T-cell activation marker–tuberculosis assay for diagnosis of active tuberculosis in children: a prospective proof-of-concept study

The diagnosis of paediatric tuberculosis is complicated by non-specific symptoms, difficult specimen collection, and the paucibacillary nature of the disease. We assessed the accuracy of a novel immunodiagnostic T-cell activation marker-tuberculosis (TAM-TB) assay in a proof-of-concept study to identify children with active tuberculosis. Children with symptoms that suggested tuberculosis were prospectively recruited at the NIMR-Mbeya Medical Research Center in Mbeya, and the Ifakara Health Institute in Bagamoyo, Tanzania, between May 10, 2011, and Sept 4, 2012. Sputum and peripheral blood mononuclear cells were obtained for Mycobacterium tuberculosis culture and performance assessment of the TAM-TB assay. The children were assigned to standardised clinical case classifications based on microbiological and clinical findings. Among 290 children screened, we selected a subgroup of 130 to ensure testing of at least 20 with culture-confirmed tuberculosis. 17 of 130 children were excluded because of inconclusive TAM-TB assay results. The TAM-TB assay enabled detection of 15 of 18 culture-confirmed cases (sensitivity 83·3%, 95% CI 58·6-96·4). Specificity was 96·8% (95% CI 89·0-99·6) in the cases that were classified as not tuberculosis (n=63), with little effect from latent tuberculosis infection. The TAM-TB assay identified five additional patients with highly probable or probable tuberculosis, in whom M tuberculosis was not isolated. The median time to diagnosis was 19·5 days (IQR 14-45) for culture. The sputum-independent TAM-TB assay is a rapid and accurate blood test that has the potential to improve the diagnosis of active tuberculosis in children. European and Developing Countries Clinical Trials Partnership, German Federal Ministry of Education and Research, and Swiss National Science Foundation.

Laboratory diagnosis of paediatric tuberculosis in the European Union/European Economic Area: analysis of routine laboratory data, 2007 to 2011

Laboratory confirmation of paediatric tuberculosis (TB) is frequently lacking. We reviewed the range of routine laboratory tests and their performance in different biological samples used to diagnose active TB in children. A questionnaire-based survey was conducted among the European Reference Laboratory Network for TB followed by collection of routine laboratory data on 10,549 paediatric samples tested in 2007 to 2011 at six reference laboratories (in Croatia, Germany, Italy, Latvia, Lithuania and the United Kingdom (UK)). The questionnaire showed that all laboratories used rapid assays. Non-respiratory samples were collected more often in Germany (135/275, 49.1%) and the UK (490/2,140, 22.9%) compared with Croatia (138/2,792, 4.9%), Latvia (222/2,401, 9.2%) and Lithuania (76/1,549, 4.9%). Overall laboratory positivity rates (isolation of Mycobacterium tuberculosis complex and/or identification of its nucleic acids in a sample) were higher in lymph node and gastric aspirate samples (14/203 (6.9%) and 43/1,231 (3.5%)) than in sputum samples (89/4,684 (1.9%)). Pooled sensitivity, specificity, positive and negative predictive values and accuracy of molecular assays assessed against solid or liquid culture were 79.2%, 93.6%, 67.1%, 96.5% and 91.6%, respectively. A more intensive approach in obtaining gastric aspirate and non-respiratory samples may increase laboratory confirmation of paediatric TB. Major effort is needed in optimisation and validation of molecular tests in these samples.

The Sensitivity of T-SPOT.TB Assay in Diagnosis of Pediatric Tuberculosis

This study was performed aiming to evaluate the sensitivity of T-SPOT.TB assay in diagnosis of pediatric TB and investigate the association between age and results of T-SPOT.TB assay. Between March 2012 and September 2013, 102 patients, who aged ≤15 years old, were enrolled in this retrospective study and then were grouped into three age categories: Group 1, aged ≤2 years; Group 2, aged 3 to 12 years; and Group 3, aged 13 to 15 years. The χ2 test was used to compare the sensitivities of T-SPOT.TB between groups with different ages. The overall sensitivity of T-SPOT.TB assay was 58.8% (95% confidence interval: 49.1–67.9%) and low in diagnosis of pediatric TB. Although the sensitivities varied in the three groups, the difference did not reach statistical significance (p > 0.05). Therefore, in high burden countries, T-SPOT.TB assay wasn't accurate in diagnosis of pediatric TB, and age was not associated with the results of T-SPOT.TB

Chest Radiographs for Pediatric TB Diagnosis: Interrater Agreement and Utility.

The chest radiograph (CXR) is considered a key diagnostic tool for pediatric tuberculosis (TB) in clinical management and endpoint determination in TB vaccine trials. We set out to compare interrater agreement for TB diagnosis in western Kenya. A pediatric pulmonologist and radiologist (experts), a medical officer (M.O), and four clinical officers (C.Os) with basic training in pediatric CXR reading blindly assessed CXRs of infants who were TB suspects in a cohort study. C.Os had access to clinical findings for patient management. Weighted kappa scores summarized interrater agreement on lymphadenopathy and abnormalities consistent with TB. Sensitivity and specificity of raters were determined using microbiologically confirmed TB as the gold standard (n = 8). A total of 691 radiographs were reviewed. Agreement on abnormalities consistent with TB was poor; k = 0.14 (95% CI: 0.10–0.18) and on lymphadenopathy moderate k = 0.26 (95% CI: 0.18–0.36). M.O [75% (95% CI: 34.9%–96.8%)] and C.Os [63% (95% CI: 24.5%–91.5%)] had high sensitivity for culture confirmed TB. TB vaccine trials utilizing expert agreement on CXR as a nonmicrobiologically confirmed endpoint will have reduced specificity and will underestimate vaccine efficacy. C.Os detected many of the bacteriologically confirmed cases; however, this must be interpreted cautiously as they were unblinded to clinical features.

Childhood Tuberculosis in Kermanshah, Iran, During 10 Years

Background:: Tuberculosis in children still remains as one of the main causes of morbidity and mortality throughout the world. Objectives:: The aim of this study was to evaluate the epidemiological aspects of childhood tuberculosis in Kermanshah, Iran. Patients and Methods:: Medical records of all 150 patients aged 0-18 in Kermanshah district who were diagnosed according to WHO criteria for 10 years were retrospectively reviewed. As well as presenting demographic and clinical aspects of patients, we calculated notification rate. Results:: 35% of cases were male and 65% were female. Of total 150 tuberculosis cases, 56% were pulmonary and 44% were extra pulmonary. The most common symptoms were fever and cough. About 16% were asymptomatic. About 17% of patients had adult pulmonary tuberculosis in their families. The mean of the number of people living in a family (5.5) was similar in both pulmonary and extra pulmonary types. Except for year 2002, for all years the notification rate in girls was higher than that in boys. Over 10 years of study, the notification rate was 3.75/100,000 with no significant trend. Conclusions:: Based on our results, rate of diagnosis seemed under the expected range, in particular in children under 5. Therefore, we recommend that authorities come up with programs that aim at raising awareness about the importance of diagnosis of pediatric tuberculosis.

Evaluation of Xpert MTB/RIF and MODS assay for the diagnosis of pediatric tuberculosis

BackgroundTuberculosis (TB) in children is rarely confirmed due to the lack of effective diagnostic tools; only 10 to 15% of pediatric TB is smear positive due to paucibacillary samples and the difficulty of obtaining high-quality specimens from children. We evaluate here the accuracy of Xpert MTB/RIF in comparison with the Micoroscopic observation drug susceptibility (MODS) assay for diagnosis of TB in children using samples stored during a previously reported evaluation of the MODS assay.MethodsNinety-six eligible children presenting with suspected TB were recruited consecutively at Pham Ngoc Thach Hospital in Ho Chi Minh City Viet Nam between May to December 2008 and tested by Ziehl-Neelsen smear, MODS and Mycobacterial growth Indicator (MGIT, Becton Dickinson) culture. All samples sent by the treating clinician for testing were included in the analysis. An aliquot of processed sample deposit was stored at −20°C and tested in the present study by Xpert MTB/RIF test. 183 samples from 73 children were available for analysis by Xpert. Accuracy measures of MODS and Xpert were summarized.ResultsThe sensitivity (%) in detecting children with a clinical diagnosis of TB for smear, MODS and Xpert were 37.9 [95% CI 25.5; 51.6], 51.7 [38.2; 65.0] and 50.0 [36.6; 63.4], respectively (per patient analysis). Xpert was significantly more sensitive than smear (P=0.046). Testing of additional samples did not increase case detection for MODS while testing of a second sputum sample by Xpert detected only two additional cases. The positive and negative predictive values (%) of Xpert were 100.0 [88.0; 100.0] and 34.1 [20.5; 49.9], respectively, while those of MODS were 96.8 [83.3; 99.9] and 33.3 [19.6; 49.5].ConclusionMODS culture and Xpert MTB/RIF test have similar sensitivities for the detection of pediatric TB. Xpert MTB RIF is able to detect tuberculosis and rifampicin resistance within two hours. MODS allows isolation of cultures for further drug susceptibility testing but requires approximately one week to become positive. Testing of multiple samples by xpert detected only two additional cases and the benefits must be considered against costs in each setting. Further research is required to evaluate the optimal integration of Xpert into pediatric testing algorithms.

Diagnosis of paediatric tuberculosis: the culture conundrum

Diagnosis of paediatric tuberculosis: the culture conundrum

Evaluation of QuantiFERON microtube, using 0.9 mL blood, for diagnosing tuberculosis infection

The performance of QuantiFERON microtube (QFT-MT), using 0.9 mL blood, and QuantiFERON-TB Gold in-tube test (QFT-IT) (3 mL blood), for diagnosing tuberculosis (TB) was compared in children and adults in an endemic setting. In 152 children with suspected TB and 87 adults with confirmed TB, QFT-IT was compared with two QFT-MT concentrations (QFT-MT A and B). Proportions of positive and indeterminate results, interferon (IFN)-γ responses, interassay agreement and sensitivity were assessed. We found similar proportions of indeterminate results, levels of IFN-γ and comparable sensitivity. The interassay agreement was moderate in all children (QFT-IT versus QFT-MT A: 85%, k=0.44 and QFT-IT versus QFT-MT B: 88%, k=0.50) and adults (QFT-IT versus QFT-MT A: 88%, k=0.50 and QFT-IT versus QFT-MT B: 89%, k=0.49). Sensitivity was low (QFT-IT 23%, QFT-MT A 18% and B 19%) in children with confirmed or highly probable TB compared with adults (83%, 86% and 88%, respectively). The QFT-MT test can be reliably performed using less than one-third of the blood volume used in QFT-IT. The reduced volume may be useful for research and future diagnosis of paediatric TB. The poor sensitivity and high indeterminate rate of both IFN-γ release assays in severely ill children, with immature or impaired immunity in an endemic setting, warrants further investigations.

Update on laboratory diagnosis of pediatric tuberculosis: New and more rapid methods

Update on laboratory diagnosis of pediatric tuberculosis: New and more rapid methods