Active Tuberculosis In Children Research Articles

Retrospective evaluation of the results of immunodiagnostics for tuberculosis in children

Introduction. For early immunodiagnostics of tuberculosis (TB) in Russia, the Mantoux test (MT) has been used for decades; since 2013, the recombinant tuberculosis antigen (RTA) test has seen widespread use.
 The objective of this retrospective analytic observational cohort study was to evaluate the results of immunodiagnostics for TB in children with newly diagnosed active TB.
 Materials and methods. We studied data from Russian TB institutions on the results of MT and RTA assay in children with active and inactive TB first detected in 2013–2018, as well as children with active TB first detected in Moscow in 2017–2022.
 Results and discussion. In 2013–2018, out of 12,902 examined children with active TB, 11,673 (90.5%) had positive results of both skin tests and 198 (1.5%) had negative results. A negative RTA assay result with positive MT was found in 861 (6.7%) patients, and a positive RTA assay result with negative MT in 170 (1.3%). The sensitivity of the RTA assay in detecting active TB was 91.3%, while the sensitivity of MT was 97.2% (p 0.01). Similar data were obtained in the same regions in 14,127 children with inactive TB: the sensitivity of MT was higher than that of the RTA assay — 97.2% versus 95.2% (p 0.01). In Moscow, due to the small number of observations in 2022, it was not possible to show statistical reliability of the difference between the sensitivity of MT and RTA assay in detecting active TB in 2017–2022 (95.8% and 92.1% respectively; p 0.5). For the results obtained in 2017–2021, the difference was significant (p 0.05).
 Conclusion. The sensitivity of MT is higher than that of the RTA assay in screening children for TB. It is recommended to use the more sensitive MT test for screening children; screening with the RTA assay will increase the number of undetected and undiagnosed cases of active TB in children. Currently, MT cannot be excluded from the algorithm of early TB diagnosis in children.

Utility of interferon-gamma releasing assay for the diagnosis of active tuberculosis in children: A systematic review and meta-analysis

IntroductionThe accurate diagnosis of tuberculosis (TB) in children is essential for its effective management and control. Reliable diagnostic tools that are currently available for identifying TB infection include the in vivo tuberculosis skin test (TST) and ex vivo interferon-gamma release assays (IGRAs). This systematic review and meta-analysis aimed to evaluate the diagnostic accuracy of IGRAs in children. MethodsOf the 768 screened studies, 47 met the eligibility criteria. Data from 9065 patients, including 1086 (12.0 %) with confirmed TB, were included in the analysis. The overall quality of the included studies, assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool, was unclear. ResultsThe calculated pooled sensitivity and specificity of IGRAs in children were 0.85 (95 % confidence interval [CI]: 0.79–0.89) and 0.94 (95 % CI: 0.88–0.97), respectively. Subpopulation analysis revealed that the sensitivities and specificities were as follows: QuantiFERON tests: 0.83 (95 % CI: 0.74–0.89) and 0.93 (95 % CI: 0.87–0.96), T-SPOT: 0.87 (95 % CI: 0.79–0.91) and 0.99 (95 % CI: 0.85–1.00), IGRAs in children under 15 years: 0.77 (95 % CI: 0.43–0.94) and 0.96 (95 % CI: 0.84–0.97), and IGRAs in children under 5 years: 0.85 (95 % CI: 0.52–0.97) and 0.94 (95 % CI: 0.90–0.99), respectively. ConclusionsThis study demonstrated that the sensitivity and specificity of the IGRAs in children were moderate and high, respectively. Therefore, the IGRAs may be useful for detecting TB infection in children. Clinical trial registrationThe review protocol was prospectively registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000046737).

Assessment of ferroptosis-associated gene signatures as potential biomarkers for differentiating latent from active tuberculosis in children.

Ferroptotic cell death is a regulated process that is governed by iron-dependent membrane lipid peroxide accumulation that plays a pathogenic role in several disease-related settings. The use of ferroptosis-related genes (FRGs) to distinguish active tuberculosis (ATB) from latent tuberculosis infection (LTBI) among children, however, remains to be analysed. Tuberculosis-related gene expression data and FRG lists were obtained, respectively, from Gene Expression Omnibus (GEO) and FerrDb. Differentially expressed FRGs (DE-FRGs) detected when comparing samples from paediatric ATB and LTBI patients were explored using appropriate bioinformatics techniques, after which enrichment analyses were performed for these genes and hub genes were identified, with these genes then being used to explore potential drug interactions and construct competing endogenous RNA (ceRNA) networks. The GSE39939 dataset yielded 124 DE-FRGs that were primarily related to responses to oxidative, chemical and extracellular stimulus-associated stress. In total, the LASSO and SVM-RFE algorithms enabled the identification of nine hub genes (MAPK14, EGLN2, IDO1, USP11, SCD, CBS, PARP8, PARP16, CDC25A) that exhibited good diagnostic utility. Functional enrichment analyses of these genes suggested that they may govern ATB transition from LTBI through the control of many pathways, including the immune response, DNA repair, transcription, RNA degradation, and glycan and energy metabolism pathways. The CIBERSORT algorithm suggested that these genes were positively correlated with inflammatory and myeloid cell activity while being negatively correlated with the activity of lymphocytes. A total of 50 candidate drugs targeting 6 hub DE-FRGs were also identified, and a ceRNA network was used to explore the complex interplay among these hub genes. The nine hub FRGs defined in this study may serve as valuable biomarkers differentiating between ATB and LTBI in young patients.

The dynamics of incidence of active tuberculosis in children in Bukovina, the impact of the COVID-19 pandemic

Ukraine remains one of the leaders in the global ranking of morbidity and mortality from tuberculosis (TB) and, according to WHO, ranks 5th in the world and 2nd in Europe according to these indicators. Objective — to analyze the regional features of the epidemiology of tuberculosis among children in the Chernivtsi region. Materials and methods. The medical records of all pediatric patients with newly diagnosed TB for the period from January 2020 to December 2022 in the Chernivtsi Regional Clinical TB Dispensary were analyzed. Statistical processing of the data obtained during the research was carried out using the IBM SPSS Statistics v. 26.0 program. Results and discussion. An analysis of the dynamics by years, when Ukraine was in lockdown due to COVID-19, revealed an increase in the incidence of TB among children under the age of 14 — by 2.7 times compared to 2021 and almost 8 times compared to 2020. 2 cases (25 %) of extrapulmonary tuberculosis, one of which (meningoencephalitis) had an unfavorable prognosis and resulted in death. Indicators of the tuberculosis situation in the Chernivtsi Region in the age group of 15—17 years showed an increase in TB in the percentage ratio of almost 2 times, with an even gender distribution (50 % each) compared to 2020 and 2021. Conclusions. In Bukovina, for the period from 2020 to 2022, increase in the incidence of tuberculosis among children (almost in 2 times) was registered. In 2022, in 100 % of cases, TB was detected during referral, and in children living in rural areas, the majority were girls (62.5 %). In 87.5 % of cases, the diagnosis was confirmed bacterioscopically, in 50 % of children the presence of contact with a tuberculosis source was determined, in 12.5 % there was no BCG vaccination, in 25 % of children MDR-TB was registered.

Exploration of Lipid Metabolism Alterations in Children with Active Tuberculosis Using UHPLC-MS/MS.

Metabolic profiling using nonsputum samples has demonstrated excellent performance in diagnosing infectious diseases. But little is known about the lipid metabolism alternation in children with tuberculosis (TB). Therefore, the study was performed to explore lipid metabolic changes caused by Mycobacterium tuberculosis infection and identify specific lipids as diagnostic biomarkers in children with TB using UHPLC-MS/MS. Plasma samples obtained from 70 active TB children, 21 non-TB infectious disease children, and 21 healthy controls were analyzed by a partial least-squares discriminant analysis model in the training set, and 12 metabolites were identified that can separate children with TB from non-TB controls. In the independent testing cohort with 49 subjects, three of the markers, PC (15:0/17:1), PC (17:1/18:2), and PE (18:1/20:3), presented with high diagnostic values. The areas under the curve of the three metabolites were 0.904, 0.833, and 0.895, respectively. The levels of the altered lipid metabolites were found to be associated with the severity of the TB disease. Taken together, plasma lipid metabolites are potentially useful for diagnosis of active TB in children and would provide insights into the pathogenesis of the disease.

Relationship of specific and non-specific inflammation in children with respiratory tuberculosis and chronic lung diseases

The problem of the combination of tuberculosis and chronic nonspecific diseases of the bronchopulmonary system in children and adolescents has not been sufficiently studied to date and remains relevant.Purpose. The study aims at determination of predictors of tuberculosis infection to identify groups at high risk of developing tuberculosis among children with chronic nonspecific pathology.Materials and research methods. A prospective study of children and adolescents (n = 158) with isolated respiratory tuberculosis and its combination with various forms of chronic obstructive pulmonary disease (lung defects, chronic bronchitis, bronchial asthma) was conducted. These two groups were compared in respect of the medical history and physical examination data, as well as computed tomography findings.Results. The predictors of the development of tuberculosis included cases of pneumonia at an early age, acute respiratory infections 3 or more times a year, and the early age of children infected with Mycobacterium tuberculosis.Conclusion. These conditions increase the risk of developing active tuberculosis in children and cause its more severe course. In addition, chronic nonspecific lung diseases associated with tuberculosis often complicate the course of a specific process and are often characterized by recurrent attacks.

Tobacco Smoking and Second-Hand Smoke Exposure Impact on Tuberculosis in Children.

Little is known about whether second-hand smoke (SHS) exposure affects tuberculosis (TB). Here, we investigate the association of cigarette smoke exposure with active TB and latent TB infection (LTBI) in children, analyzing Interferon-Gamma Release Assays’ (IGRAs) performance and cytokine immune responses. A total of 616 children from contact-tracing studies were included and classified regarding their smoking habits [unexposed, SHS, or smokers]. Risk factors for positive IGRAs, LTBI, and active TB were defined. GM-CSF, IFN-γ, IL-2, IL-5, IL-10, IL-13, IL-22, IL-17, TNF-α, IL-1RA and IP-10 cytokines were detected in a subgroup of patients. Being SHS exposed was associated with a positive IGRA [aOR (95% CI): 8.7 (5.9–12.8)] and was a main factor related with LTBI [aOR (95% CI): 7.57 (4.79–11.94)] and active TB [aOR (95% CI): 3.40 (1.45–7.98)]. Moreover, IGRAs’ sensitivity was reduced in active TB patients exposed to tobacco. IL-22, GM-CSF, IL-5, TNF-α, IP-10, and IL-13 were less secreted in LTBI children exposed to SHS. In conclusion, SHS is associated with LTBI and active TB in children. In addition, false-negative IGRAs obtained on active TB patients exposed to SHS, together with the decrease of specific cytokines released, suggest that tobacco may alter the immune response.

Active Tuberculosis in Children Receiving Chemotherapy

Tuberculosis infections is a serious illness and can be life threatening for patients with hematologic malignancies. We are reporting the observations of two children aged 7 and 5 years undergoing anticancer treatment for hematological malignancies. The symptoms were, in the first case, cough, purulent sputum and signs of tuberculosis impregnation, for the second case, cervical adenopathies (PDA) with inflammatory signs. The evolution under antituberculosis treatment was favorable for both patients, with a 5-year follow-up for the first patient and one year for the second case. The tuberculosis did not affect chemotherapy. The goal of our work is to specify the etio-pathogenic mechanisms, the clinical, therapeutic and evolutionary particularities of this rare association.

Isoniazid versus alternative regimens for the treatment of latent tuberculosis in children: A systematic review and network meta-analysis

Background: Treatment of Latent Tuberculosis Infection (LTBI) is a therapeutic dilemma. The current systematic review has been conducted to differentiate the efficacy and safety of isoniazid (INH) versus alternative regimens for preventing active tuberculosis in children. Methods: A detailed analysis of the randomized controlled trials, methodology, interventions, and outcomes was done. Electronic searching was done through different databases. The dichotomous data (binary data) were reported as Odds ratios (ORs). Initially, a direct meta-analysis was performed that differentiated various interventions. The network meta-analysis was performed and ranking was done according to Surface under the cumulative ranking curve (SUCRA). Results: The systematic review included data from 4 randomized controlled trials, comprising 2978 participants for analyzing efficacy, treatment completion rate, and adverse effects. The most efficacious intervention for the treatment of LTBI included INH + Rifampin (RIF) ([OR], 0.44; 95% confidence interval [CI], 0.29-0.65). INH + RIF Rifampicin (OR, 0.30; 95% CI, 0.17-0.54) intervention reported a lesser number of adverse events in the experimental group compared to control group. All alternative regimens were superior in treatment completion rate compared to INH monotherapy. Ranking probability based on SUCRA reported that RIF + pyrazinamide (PZA) (SUCRA 61.3) had the probability of most efficacious intervention, RIF + PZA (SUCRA 46.8) in treatment completion rate and INH + Rifapentine (SUCRA 83.9) had the least adverse effects in LTBI. Conclusions: INH + RIF was found to be the most effective intervention for the LTBI treatment in respect of treatment efficacy and with tolerable adverse events. All alternative regimens were also effective.

The Diagnostic Value of Blood and Urine IP-10 Test in Children Having Active Tuberculosis or Latent Tuberculosis Infection

Abstract Objective This study aimed to investigate interferon-gamma-inducible protein-10 (IP-10) values in serum and urine in pediatric patients in the diagnosis of active tuberculosis (TB) or latent TB infection (LTBI). It also aimed to investigate whether it can be used as a biomarker to distinguish between active TB and LTBI. Methods Our study comprised active TB (25 patients), LTBI (25 patients), and the “infected” group (50 patients) formed by combining the two groups. As the control group, 37 healthy children were included in the study. TB skin test, plasma IP-10, and urine IP-10 measurements were performed in all patients included in the study. An additional QuantiFERON-TB Gold In-Tube (QFT-GIT) test was performed on patients evaluated as active TB or LTBI. Results Plasma IP-10 levels of the patients in the active TB, LTBI, and the “infected” groups were significantly higher than the control group (p = 0.022, p = 0.028, and p = 0.007, respectively). Urine IP-10 was successful in distinguishing the active TB and “infected” groups from the control group (p = 0.007 and p = 0.047, respectively). Also, in the combined use of the tests, when QFT-GIT and urine IP-10 were positive together, active TB and LTBI could be distinguished (p = 0.044). Urine IP-10 levels were found to be significantly higher in those with pulmonary TB than those with extrapulmonary TB (p = 0.012). Conclusion Our findings suggest that IP-10 can be used as a useful biomarker in the diagnosis of active TB in children.

Impact of the COVID-19 pandemic on tuberculosis management in Spain

BackgroundThe impact of COVID-19 on the diagnosis and management of tuberculosis (TB) patients is unknown. MethodsParticipating centres completed a structured web-based survey regarding changes to TB patient management during the COVID-19 pandemic. The study also included data from participating centres on patients aged ≥18 diagnosed with TB in 2 periods: March 15 to June 30, 2020 and March 15 to June 30, 2019. Clinical variables and information about patient household contacts were retrospectively collected. ResultsA total of 7 (70%) TB units reported changes in their usual TB team operations. Across both periods of study, 169 patients were diagnosed with active TB (90 in 2019, 79 in 2020). Patients diagnosed in 2020 showed more frequent bilateral lesions in chest X-ray than patients diagnosed in 2019 (P = 0.004). There was a higher percentage of latent TB infection and active TB among children in households of patients diagnosed in 2020, compared with 2019 (P = 0.001). ConclusionsThe COVID-19 pandemic has caused substantial changes in TB care. TB patients diagnosed during the COVID-19 pandemic showed more extended pulmonary forms. The increase in latent TB infection and active TB in children of patient households could reflect increased household transmission due to anti-COVID-19 measures.

Screening of potential biomarkers for distinguishing between latent and active tuberculosis in children using bioinformatics analysis.

Tuberculosis (TB) is one of the leading causes of childhood morbidity and death globally. Lack of rapid, effective non-sputum diagnosis and prediction methods for TB in children are some of the challenges currently faced. In recent years, blood transcriptional profiling has provided a fresh perspective on the diagnosis and predicting the progression of tuberculosis. Meanwhile, combined with bioinformatics analysis can help to identify the differentially expressed genes (DEGs) and functional pathways involved in the different clinical stages of TB. Therefore, this study investigated potential diagnostic markers for use in distinguishing between latent tuberculosis infection (LTBI) and active TB using children's blood transcriptome data.From the Gene Expression Omnibus database, we downloaded two gene expression profile datasets (GSE39939 and GSE39940) of whole blood-derived RNA sequencing samples, reflecting transcriptional signatures between latent and active tuberculosis in children. GEO2R tool was used to screen for DEGs in LTBI and active TB in children. Database for Annotation, Visualization and Integrated Discovery tools were used to perform Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analysis. STRING and Cytoscape analyzed the protein-protein interaction network and the top 15 hub genes respectively. Receiver operating characteristics curve was used to estimate the diagnostic value of the hub genes.A total of 265 DEGs were identified, including 79 upregulated and 186 downregulated DEGs. Further, 15 core genes were picked and enrichment analysis revealed that they were highly correlated with neutrophil activation and degranulation, neutrophil-mediated immunity and in defense response. Among them TLR2, FPR2, MMP9, MPO, CEACAM8, ELANE, FCGR1A, SELP, ARG1, GNG10, HP, LCN2, LTF, ADCY3 had significant discriminatory power between LTBI and active TB, with area under the curves of 0.84, 0.84, 0.84, 0.80, 0.87, 0.78, 0.88, 0.84, 0.86, 0.82, 0.85, 0.85, 0.79, and 0.88 respectively.Our research provided several genes with high potential to be candidate gene markers for developing non-sputum diagnostic tools for childhood Tuberculosis.

Dispensary observation of patients with increased risk of tuberculosis who are registered in antituberculosis institutions of Russian Federation

The provision of anti-tuberculosis care to the population of the Russian Federation has a largely preventive direction. Dispensary observation of population groups with an increased risk of tuberculosis is one of the most important sections of providing anti-tuberculosis care to the population. The materials on the organization and results of dispensary observation of patients with an increased risk of tuberculosis are presented: indicators of tuberculosis incidence and mortality and data on the reliability of some indicators. The factors influencing the results of dispensary observation of patients with an increased risk of tuberculosis in different groups of dispensary observation and the quality of preventive measures are considered. The data on the use of Diaskintest for the timely detection and diagnosis of active tuberculosis in children and the identification of children in the early period of tuberculosis infection are presented.

Latent tuberculosis infection in children in Bangui: about 524 cases exposed at home to index cases of positive microscopy pulmonary tuberculosis

Introductionmalgré la vaccination par le BCG, le risque de développer la tuberculose chez les jeunes enfants dans les régions endémiques reste plus élevé après exposition au cas de tuberculose chez l´adulte. Le but de cette étude était de réduire le risque de tuberculose active chez les enfants contacts des cas index adultes à domicile.Méthodesune étude transversale multisite (avril 2016-janvier 2019) a été réalisée sur des enfants de 0 à 59 mois, contacts des cas index à domicile, dépistés et suivis au centre pédiatrique de Bangui.Résultatscinq cent vingt- quatre (524) enfants ont été enregistrés. La moyenne d´âge était de 2 ans et 1 mois et le sex ratio garçon/fille de 1,02. Environ quatre-vingt-huit pourcent (88,5%) des contacts étaient vaccinés avec le BCG contre 11,5% non vaccinés. Dans plus de la moitié des cas (52%), les contacts et les cas index ont partagé la même chambre et le temps de contact journalier était supérieur à 12h dans 56% des ménages. Un peu plus de neuf pourcent (9,35%) des contacts avaient une IDR positive. Tous les enfants ont été mis sous chimioprophylaxie à base de Rifampicine + Isoniazide selon les directives nationales et malgré cela, 14 soit 2,67% ont développé une tuberculose active dont 13 formes pulmonaires et une forme ganglionnaire.Conclusionla chimio prophylaxie tuberculeuse a sans doute permis de réduire considérablement le risque de survenue de la tuberculose chez des enfants ayant été en contact avec les cas index à domicile.

Evaluation of QuantiFERON tuberculosis Gold In-Tube assay for diagnosis of active tuberculosis in children.

Tuberculin skin test (TST) is still used in diagnostic algorithms of childhood tuberculosis (TB). QuantiFERON TB Gold In-Tube assay (QFT-GIT) is an alternative test to TST based on the detection of interferon-gamma release upon in vitro induction of peripheral mononuclear cells by TB antigens. In this study, we aimed to determine the diagnostic value and performance of QFT-GIT for active childhood TB. This retrospective study was conducted between January 2005 and December 2011 in three referral hospitals in Turkey with 124 children who were diagnosed with definite active TB. Sensitivity values of TST and QFT-GIT were determined by accepting the microbiological confirmation as the gold standard of diagnosis of TB. In our study, sensitivity of QFT-GIT and TST was found to be 65 and 66% respectively. However, combined usage of QFT-GIT and TST was found to be more sensitive (85%) than TST or QFT-GIT alone (P < 0.0001). Although negative results of QFT-GIT or TST did not exclude the diagnosis of active TB in children, their positivity supported the diagnosis. Specificity could not be measured as only microbiologically confirmed cases of Mycobacterium tuberculosis disease were enrolled in the study. Although sensitivities of TST and QFT-GIT are too low to exclude active TB, their positivity supports diagnosis of active TB in children concomitant with signs and symptoms. QFT-GIT and TST should be used together to enhance diagnostic sensitivity and could help exclude a diagnosis of TB if the pretest probability is low.

A Model Based on the Combination of IFN-γ, IP-10, Ferritin and 25-Hydroxyvitamin D for Discriminating Latent From Active Tuberculosis in Children.

In recent years, pediatric research on tuberculosis (TB) has focused on addressing new biomarkers with the potential to be used as immunological non-sputum-based methods for the diagnosis of TB in children. The aim of this study was to characterize a set of cytokines and a series of individual factors (ferritin, 25-hydroxyvitamin D [25(OH)D], parasite infections, and nutritional status) to assess different patterns for discriminating between active TB and latent TB infection (LTBI) in children. The levels of 13 cytokines in QuantiFERON-TB Gold In-Tube (QFT-GIT) supernatants were analyzed in 166 children: 74 with active TB, 37 with LTBI, and 55 uninfected controls. All cytokines were quantified using Luminex or ELISA. Ferritin and 25(OH)D were also evaluated using CLIA, and Toxocara canis Ig-G antibodies were detected with a commercial ELISA kit. The combination of IP-10, IFN-γ, ferritin, and 25(OH)D achieved the best diagnostic performance to discriminate between active TB and LTBI cases in children in relation to the area under receiver operating characteristic (ROC) curve 0.955 (confidence interval 95%: 0.91–1.00), achieving optimal sensitivity and specificity for the development of a new test (93.2 and 90.0%, respectively). Children with TB showed higher ferritin levels and an inverse correlation between 25(OH)D and IFN-γ levels. The model proposed includes a combination of biomarkers for discriminating between active TB and LTBI in children to improve the accuracy of TB diagnosis in children. This combination of biomarkers might have potential for identifying the onset of primary TB in children.

Mucosal-Associated Invariant T Cell Levels Are Reduced in the Peripheral Blood and Lungs of Children With Active Pulmonary Tuberculosis.

Mucosal associated invariant T (MAIT) cells are unconventional, semi-invariant T lymphocytes that recognize microbial-derived vitamin B2 (riboflavin) biosynthesis precursor derivatives presented by the monomorphic MHC class 1-related (MR1) molecule. Upon microbial infection, MAIT cells rapidly produce cytokines and cytotoxic effectors, and are thus important players in anti-microbial defense. MAIT cells are protective in experimental models of infection and are decreased in the blood of adult patients with bacterial infections, including Mycobacterium tuberculosis (Mtb). In children, the risk of rapid progression to active tuberculosis (TB) following Mtb infection is higher than in adults. Whether MAIT cells influence the outcome of Mtb infection in children is therefore, an important issue. We analyzed MAIT cell numbers and phenotype in 115 children investigated for pulmonary TB and determined their potential correlation with disease progression. MAIT cells were reduced in numbers and activated in the peripheral blood of children with active TB as compared to those with latent TB infection (LTBI) and healthy children. Moreover, MAIT cells did not accumulate and did not proliferate in the lung of children with active TB. These results suggest that MAIT cells may be important in preventing progression of Mtb infection to active TB in children.

Mobile phone-based evaluation of latent tuberculosis infection: Proof of concept for an integrated image capture and analysis system

BackgroundThe tuberculin skin test is the most widely used method for detecting latent tuberculosis infection in adults and active tuberculosis in children. We present the development of a mobile-phone based screening tool for measuring the tuberculin skin test induration. MethodThe tool makes use of a mobile application developed on the Android platform to capture images of an induration, and photogrammetric reconstruction using Agisoft PhotoScan to reconstruct the induration in 3D, followed by 3D measurement of the induration with the aid of functions from the Python programming language. The system enables capture of images by the person being screened for latent tuberculosis infection. Measurement precision was tested using a 3D printed induration. Real-world use of the tool was simulated by application to a set of mock skin indurations, created by a make-up artist, and the performance of the tool was evaluated. The usability of the application was assessed with the aid of a questionnaire completed by participants. ResultsThe tool was found to measure the 3D printed induration with greater precision than the current ruler and pen method, as indicated by the lower standard deviation produced (0.3 mm versus 1.1 mm in the literature). There was high correlation between manual and algorithm measurement of mock skin indurations. The height of the skin induration and the definition of its margins were found to influence the accuracy of 3D reconstruction and therefore the measurement error, under simulated real-world conditions. Based on assessment of the user experience in capturing images, a simplified user interface would benefit wide-spread implementation. ConclusionsThe mobile application shows good agreement with direct measurement. It provides an alternative method for measuring tuberculin skin test indurations and may remove the need for an in-person follow-up visit after test administration, thus improving latent tuberculosis infection screening throughput.

Utility of the QuantiFERON-TB Gold In-Tube assay for the diagnosis of tuberculosis in Moroccan children.

The utility of interferon-gamma release assays (IGRAs), such as the QuantiFERON-TB Gold In-Tube (QFT-GIT) test, in diagnosing active tuberculosis (TB) in children is unclear and depends on the epidemiological setting. To evaluate the performance of QFT-GIT for TB diagnosis in children living in Morocco, an intermediate TB incidence country with high bacille Calmette-Gurin vaccination coverage. We prospectively recruited 109 Moroccan children hospitalised for clinically suspected TB, all of whom were tested using QFT-GIT. For 81 of the 109 children, the final diagnosis was TB. The remaining 28 children did not have TB. QFT-GIT had a sensitivity of 66% (95%CI 5277) for the diagnosis of TB, and a specificity of 100% (95%CI 88100). The tuberculin skin test (TST) had lower sensitivity, at 46% (95%CI 3360), and its concordance with QFT-GIT was limited (69%). Combining QFT-GIT and TST results increased sensitivity to 83% (95%CI 6992). In epidemiological settings such as those found in Morocco, QFT-GIT is more sensitive than the TST for active TB diagnosis in children. Combining the TST and QFT-GIT would be useful for the diagnosis of active TB in children, in combination with clinical, radiological and laboratory data.

Childhood tuberculosis: a unified response to a global problem.

If we were to stack all the pills required to treat one child with tuberculosis (TB), they would exceed the height of the Taj Mahal. Childhood TB to date has been a hidden epidemic, and the estimated incidence figures may not fully represent the true burden, given the multiple obstacles in reporting, diagnosing and treating TB in children in resource-poor settings. Children and adolescents are at a higher risk than adults for progression from infection to TB disease, with most cases progressing within 2 to 12 months of initial infection. The timeframe to act is limited, and with new paediatric formulations being released, the emphasis should be on implementation as well as translating research into policy. The European and Developing Countries Clinical Trials Partnership (EDCTP) 1 has so far invested nearly E71 million in TB research on treatment, vaccines and diagnostics, and with particular attention to vulnerable populations, including children and human immunodeficiency virus co-infected patients. Successful EDCTP TB paediatric studies include TB CHILD, which developed TAM-TB, the first reliable sputum-independent immunodiagnostic assay to detect active TB in children in a TB-endemic setting. 2 This was done through a close collaboration between multiple research teams in different African and European countries, and the aim is now to make TAM-TB ready for global uptake. The reversal of the childhood TB epidemic needs more of these international collaborations to accelerate the development and introduction of new or improved drugs, vaccines and diagnostics, and efforts must be made to involve policy makers, end-users and communities from the moment of inception of research activities and on to delivery to patients. The End TB Strategy demands a 95% reduction in TB deaths by 2035, 3 but with the introduction of the Sustainable Development Goals (SDG) the research community, industry, funders and policy makers have been given a new and even more ambitious target in the longstanding battle against TB. SDG target 3.3 seeks to end the epidemic of tuberculosis by 2030. To succeed in this mission, a global collaborative effort must be mobilised whereby each stakeholder plays to their strengths and overlaps in investments are avoided to circumvent resource constraints. Results from EDCTP prove that aligning research agendas, pooling financial resources and supporting collaboration across borders can deliver innovative solutions and contribute to the elimination of this centuries old disease.