Diagnosis Of Pediatric Tuberculosis Research Articles

Assessing capacity for diagnosing tuberculosis in children in sub-Saharan African HIV care settings [Short communication

Research on the prevalence of pediatric-specific tuberculosis (TB) diagnostics in sub-Saharan Africa is scarce. We assessed the availability of pediatric TB diagnostic tests at 651 pediatric human immunodeficiency virus care and treatment sites across nine African countries: 54% of the sites had access to sputum culture capacity and 51% to chest X-ray services. While 87% of sites had access to smear microscopy, only 6% had the capacity to perform sputum induction and 5% to perform gastric aspirate. These findings confirm that diagnostic resources for the accurate diagnosis of pediatric TB are limited. Capacity-building initiatives to improve sputum collection in children are urgently required.

Interferon gamma release assay in diagnosis of pediatric tuberculosis: a meta-analysis

Although interferon gamma release assays (IGRAs) have been widely used for the diagnosis of latent and active tuberculosis in adults, a relative lack of validation studies in children has led to caution in their clinical interpretation. This meta-analysis systematically evaluated two IGRAs (ELISA and ELISPOT) and the tuberculin skin test (TST). We searched databases (PubMed, MEDLINE, Ovid) between January 2000 and January 2011 using search terms of latent tuberculosis infection or tuberculosis and interferon gamma release assay, or T-SPOT.TB test, or QuantiFERON-TB Gold, or ESAT-6, or CFP-10, and child, or childhood, or pediatrics. We also collected data by performing a manual search of references from relevant articles and communicating with selected authors. The meta-analysis was conducted with random effects models to account for heterogeneity between selected studies. The sensitivities of all three tests in active tuberculosis were similar. The pooled sensitivity was 70% for ELISA studies, 62% for ELISPOT studies and 71% for TST. Calculated sensitivities for IGRAs and the TST differ in culture-confirmed tuberculosis [ELISA (85%) vs. ELISPOT (76%) vs. TST (85%)] and clinical diagnosed cases [ELISA (64%) vs. ELISPOT (58%) vs. TST (66%)]. The pooled specificity was 100% for ELISA and 90% for ELISPOT, but was much lower for TST [56% in all included studies and 49% in children with bacillus Calmette-Guerin (BCG) vaccination]. The agreement between the TST and IGRAs in non-BCG-vaccinated children is higher than that in BCG-vaccinated children. In the diagnosis of active tuberculosis in children, the TST and IGRAs have similar sensitivity. By contrast, the specificity of IGRAs is far greater than the TST, particularly in children with previous BCG vaccination.

Diagnosing tuberculosis with urine lipoarabinomannan: systematic review and meta-analysis

Lipoarabinomannan (LAM) is a potential marker of active tuberculosis (TB). We performed a systematic review and meta-analysis regarding use of urinary LAM assays for diagnosing active TB. We systematically searched for published and unpublished studies that evaluated urinary LAM for active TB diagnosis. Extracted data were pooled using bivariate random effects models and hierarchical summary receiver operating characteristic curves. Heterogeneity was explored through subgroup analysis and meta-regression. Quality was assessed according to standardised QUADAS (Quality Assessment of Diagnostic Accuracy Studies) criteria. In seven studies that assessed test accuracy in microbiologically confirmed cases only, estimates of sensitivity ranged from 13% to 93%, while specificity ranged from 87% to 99%. In five studies that assessed accuracy in clinical and confirmed TB cases, sensitivity ranged from 8% to 80%, while specificity ranged from 88% to 99%. In five studies with results stratified by HIV status, sensitivity was 3-53% higher in HIV-positive than HIV-negative subgroups; sensitivity was highest with advanced immunosuppression. The LAM urinary assay has several characteristics that make it attractive for diagnosing active TB, but has suboptimal sensitivity for routine clinical use. Further studies are needed to evaluate the potential value of the LAM assay in individuals with advanced HIV or for diagnosis of paediatric TB.

Evaluation of Latent Class Analysis and Decision Thresholds to Guide the Diagnosis of Pediatric Tuberculosis in a Rwandan Reference Hospital

A pediatric ward of a university hospital in Kigali, Rwanda, a region with a high HIV seroprevalence. To estimate the diagnostic accuracy of symptoms, signs, and paraclinical investigations for tuberculosis in children, and to propose a clinical rule based on the results. During a 2-year period all children with cough for more than 2 weeks and/or fever for more than 2 weeks and/or reported weight loss were prospectively included. A set of clinical and paraclinical data were analyzed with latent class analysis. Comparison of post-test probability based on this analysis with a therapeutic threshold for TB was used to develop a guideline. In the 309 children HIV prevalence was 56%, bacteriology was positive in 9%, and the tuberculin skin test (TST) was >10 mm in 20%. TB prevalence was 32%. Bacteriology and TST had a specificity of 97% and cough had a sensitivity of 91%. Decision analysis suggests treating children presenting one of the inclusion criteria, combined with positive bacteriology or TST >10 mm or contact with a TB patient. Latent class analysis confirmed earlier identified predictors for TB and allowed development of an easy to use clinical rule, applicable in reference hospitals of countries with high HIV endemicity.

Detection of Antibodies Secreted from CirculatingMycobacterium tuberculosis-Specific Plasma Cells in the Diagnosis of Pediatric Tuberculosis

Diagnosis of tuberculosis (TB) in children is difficult because symptoms are often nonspecific or absent in infected children, diagnostic specimens are difficult to obtain from younger children, and >50% have negative TB cultures. Thus, there is an urgent need for improved diagnosis of pediatric TB. This study aimed to evaluate the diagnostic value of a new serological method, the ALS (antibodies in lymphocyte supernatant) assay, for the diagnosis of active TB in children with clinically identified TB. The ALS test is based on the concept that antigen-specific plasma cells are present in the circulation only at times of acute infection and not in latency. A cross-sectional study of pediatric patients (age range, 11 to 167 months) who were clinically identified as TB (n = 58) or non-TB (n = 16) patients was conducted, and they were monitored for 6 months. Healthy children (n = 58) were enrolled as controls. Spontaneous release of TB antigen-specific antibodies by in vitro-cultured, unstimulated peripheral blood mononuclear cells was assessed by an enzyme-linked immunosorbent assay using Mycobacterium bovis bacillus Calmette-Guérin (BCG) as the detecting antigen. Of the patients clinically diagnosed with TB, 15% had culture-confirmed TB, 64% were positive for TB by clinically established scoring charts (K. Edwards, P. N. G. Med. J. 30: 169-178, 1987; G. Stegen, K. Jones, and P. Kaplan, Pediatrics 43: 260-263, 1969; and stop TB Partnership, Childhood TB subgroup, World Health Organization, Int. J. Tuberc. Lung Dis. 10: 1091-1097, 2006), and 91% were TB positive by the ALS method. All TB patients had significantly higher BCG-specific ALS titers at enrollment (optical density [OD], 1.06 +/- 0.32) than healthy-control children (OD, 0.18 +/- 0.06) and non-TB children (OD, 0.21 +/- 0.10) (P = 0.001). The ALS titers declined in children with active disease from enrollment through 6 months following anti-TB therapy (P = 0.001). The ALS assay is a novel diagnostic method with potential applications in the diagnosis of pediatric TB and in subsequent monitoring of treatment effectiveness.

Tuberculosis and pericarditis in children.

With the rapid spread of tuberculosis (TB) in Zimbabwe the disease is becoming a major paediatric health problem. Children are at high risk of TB, are prone to disseminated disease and the diagnosis of paediatric TB may be difficult, since complaints often are unspecific and contacts may not been known. Data from 265 children, aged between 2 weeks and 12 years, being treated for TB in Gweru Hospital in 1995, are analysed. In 72% pericardial effusion was found as a sign of early dissemination. Cultures of gastric aspirates for Mycobacterium tuberculosis were positive in 31%. In optimal circumstances the yield for isolates of M. tuberculosis is less than 50%, and these results under limited conditions are acceptable, and may reflect the true incidence. Given the epidemiology of TB in Zimbabwe, pericardial effusions should be considered indicative of TB until proven otherwise.

Diagnosis of pediatric tuberculosis in the modern era.

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