Diagnosis Of Tuberculosis In Children Research Articles

Addressing the challenges in laboratory confirmation of paediatric tuberculosis: the role of induced sputum specimen

Tuberculosis (TB) remained the single leading infectious cause of ill health and death globally until the COVID-19 pandemic occurred. Tuberculosis contributes significantly to childhood mortality of about 16% among HIV-negative children worldwide. Childhood tuberculosis is a significant epidemiological tool as childhood TB represents recent transmission in the community and reflects the presence of an infected adult. Previously clinical research, diagnostic methods, and therapeutic discoveries have focused on adult tuberculosis to the neglect of childhood tuberculosis. Limited pediatric surveillance data, poor case ascertainment, and limited resources and capabilities have hindered the attainment of the true burden of childhood tuberculosis in countries with high tuberculosis disease burden. The difficulty in characterising the true burden of tuberculosis is mainly from the difficulty in obtaining adequate and reliable diagnostic samples to confirm TB in children. Sputum induction has proven to be feasible and effective in several LMIC settings. Gene Xpert MTB/Rif; polymerase chain reaction, performed on induced sputum samples is more sensitive in the detection of paucibacillary TB in children as compared to sputum smear testing. This allows for early diagnosis and timely initiation of therapy. It is necessary that we continue to utilize the available tools to improve TB diagnosis in children and ensure we meet End TB and SDG goal 3 targets on time

Nutritional Deficiencies, Vitamin D Levels, and other Risk Factors in Pediatric Tuberculosis Patients

Background: Tuberculosis (TB) is a major world health challenge affecting more than 9 million people every year of which more than 1 million are children. It presents non-specific symptoms and for this reason has been described as a silent epidemic, especially in the diagnosis of childhood TB, especially in bacteriological confirmation. Understanding the risk factors of TB in children is therefore important. Objectives: to describe socio-economic, environmental, and health related characteristics of childhood TB patients in Nowshera, Pakistan, and their risk factors in order to propose public health interventions. Study design: A Cross-Sectional-Study Place and duration of study : This research study is proposed to be conducted in Nowshera Medical College / Nowshera Medical College / Qazi Hussain Ahmed Medical Complex situated in Nowshera, Khyber Pakhtunkhwa province of Pakistan over a period of eight months starting from the first of 03 March 2022 to 03 December 2022 Materials and Methods: A cross-sectional study was carried out at the DOTS-center of Nowshera Medical College / Qazi Hussain Ahmed Medical Complex Nowshera from 1st March to 31st October 2022 and comprised of 130 patients. In this study, Convenience sampling (Non probability) was used. The data was collected by a structured questionnaire and analyzed by statistical package for the social sciences (SPSS version 24). Quantitative data were described by measures of central tendencies; mean and standard deviation and qualitative data were described by frequencies and percentages. Chi-square test was used to test the relationship between variables where the level of statistical significant was set at P ≤ 0. 05. Results: Participants included mainly the study population of children aged 0-15 years, and the gender was equally split throughout boy 50% and girls 50%. A large percentage (69. 2%) were from low income earners’ homes, and 66. 9% of the respondents were from rural areas. Subjects’ Body Mass Index (BMI) varied from less than 18 to more than 25. Of special interest, 43. 8% of the children with TB had not been administered BCG vaccination. The source of infection, that is, contact with an adult TB patient, was reported in 43. 8% while the rest were in the 56. 2 % who had no such history. Conclusion: childhood TB in the population under study is significantly related with some factors namely; direct contact with TB patients, low economic status, crowded housing, poor ventilation and malnutrition

Sex-specific blood-derived RNA biomarkers for childhood tuberculosis

Confirmatory diagnosis of childhood tuberculosis (TB) remains a challenge mainly due to its dependence on sputum samples and the paucibacillary nature of the disease. Thus, only ~ 30% of suspected cases in children are diagnosed and the need for minimally invasive, non-sputum-based biomarkers remains unmet. Understanding host molecular changes by measuring blood-based transcriptomic markers has shown promise as a diagnostic tool for TB. However, the implication of sex contributing to disease heterogeneity and therefore diagnosis remains to be understood. Using publicly available gene expression data (GSE39939, GSE39940; n = 370), we report a sex-specific RNA biomarker signature that could improve the diagnosis of TB disease in children. We found four gene biomarker signatures for male (SLAMF8, GBP2, WARS, and FCGR1C) and female pediatric patients (GBP6, CELSR3, ALDH1A1, and GBP4) from Kenya, South Africa, and Malawi. Both signatures achieved a sensitivity of 85% and a specificity of 70%, which approaches the WHO-recommended target product profile for a triage test. Our gene signatures outperform most other gene signatures reported previously for childhood TB diagnosis.

Impact of the Stool-Based Xpert Test on Childhood Tuberculosis Diagnosis in Selected States in Nigeria.

In Nigeria, most children with tuberculosis (TB) present at primary health clinics where there are limited personnel skilled in collecting appropriate respiratory specimens from those who cannot produce sputum. KNCV Nigeria, in collaboration with the National Tuberculosis Control Program, implemented a modified simple, one-step (SOS), stool-based Xpert MTB/RIF method for diagnosis of TB in children who cannot expectorate sputum. We evaluated the impact of its implementation on childhood TB diagnosis. A cross-sectional study was conducted across 14 selected states using secondary data of children presumed to have TB. Stool was collected from children presumed to have TB and processed using Xpert. Out of 52,117 presumptive TB cases, 52% were male and 59.7% were under 5 years old. A total of 2440 (5%) cases were diagnosed with TB, and 2307 (95%) were placed on treatment. Annual TB notifications increased significantly after the introduction of the stool-based Xpert test when compared to those in the pre-implementation period. Increasing contributions from stool testing were observed throughout the implementation period, except in 2020 during the COVID-19 era. Overall, stool Xpert testing improved childhood TB notification in the studied states. Interventions aimed at awareness creation, capacity building, and active case finding improved the performance of the test.

Xpert-Ultra Assay in Stool and Urine Samples to Improve Tuberculosis Diagnosis in Children: The Médecins Sans Frontières Experience in Guinea-Bissau and South Sudan.

More than half of childhood tuberculosis cases remain undiagnosed yearly. The World Health Organization recommends the Xpert-Ultra assay as a first pediatric diagnosis test, but microbiological confirmation remains low. We aimed to determine the diagnostic performance of Xpert-Ultra with stool and urine samples in presumptive pediatric tuberculosis cases in 2 high-tuberculosis-burden settings. This Médecins Sans Frontières cross-sectional multicentric study took place at Simão Mendes Hospital, Guinea-Bissau (July 2019 to April 2020) and in Malakal Hospital, South Sudan (April 2021 to June 2023). Children aged 6 months to 15 years with presumptive tuberculosis underwent clinical and laboratory assessment, with 1 respiratory and/or extrapulmonary sample (reference standard [RS]), 1 stool, and 1 urine specimen analyzed with Xpert-Ultra. A total of 563 children were enrolled in the study, 133 from Bissau and 400 from Malakal; 30 were excluded. Confirmation of tuberculosis was achieved in 75 (14.1%), while 248 (46.5%) had unconfirmed tuberculosis. Of 553 with an RS specimen, the overall diagnostic yield was 12.4% (66 of 533). A total of 493 stool and 524 urine samples were used to evaluate the performance of Xpert-Ultra with these samples. Compared with the RS, the sensitivity and specificity of Xpert-Ultra were 62.5% (95% confidence interval, 49.4%-74%) and 98.3% (96.7%-99.2%), respectively, with stool samples, and 13.9% (7.5%-24.3%) and 99.4% (98.1%-99.8%) with urine samples. Nine patients were positive with stool and/or urine samples but negative with the RS. Xpert-Ultra in stool samples showed moderate to high sensitivity and high specificity compared with the RS and an added diagnostic yield when RS results were negative. Xpert-Ultra in stool samples was useful in extrapulmonary cases. Xpert-Ultra in urine samples showed low test performance. NCT06239337.

Increased tuberculosis case detection in Tanzanian children and adults using African giant pouched rats.

African giant pouched rats, trained by Anti-Persoonsmijnen Ontmijnende Product Ontwikkeling (APOPO), have demonstrated their ability to detect tuberculosis (TB) from sputum. We assessed rat-based case detection and compared the mycobacterium bacillary load (MTB-load) in children versus adults. From January-December 2022, samples were collected prospectively from 69 Directly Observed Therapy (DOT) facilities' presumed TB patients. Using an average of five rats, APOPO re-evaluated patients with bacteriologically negative (sputum-smear microscopy or Xpert MTB/RIF) results. Rat-positive samples were tested using concentrated smear light-emitting diode microscopy to confirm TB detection before treatment initiation. The rats' identification of pulmonary TB is based on smelling TB-specific volatile organic compounds (VOCs) in sputum. Using STATA, Chi-square for oddsratio and confidence interval was calculated and evaluated: (1) the yield of rat-based TB detection compared to that of the health facilities; (2) rat-based TB detection in children versus adults; and (3) rats' ability to detect TB across MTB-loads and between children and adults. From 35,766 patients, 5.3% (1900/35,766) were smear-positive and 94.7% (33,866/35,766) were smear or Xpert-negatives at DOTS facility. Of those with negative results, 2029 TB cases were detected using rats, contributing to 52% (2029/3929 of total TB identified), which otherwise would have been missed. Compared to DOT facilities, rats were six-fold more likely to detect TB among Acid Fast Bacilli (AFB) 1+/scanty [90% (1829/2029) versus 60% (1139/1900), odds ratio, OR = 6.11, 95% confidence interval, CI: 5.14-7.26]; twice more likely to identify TB cases among children [71% (91/129) versus 51% (1795/3542), OR = 2.3, 95% CI: 1.59-3.42]; and twice more likely to identify TB cases among children with AFB 1+/scanty than adults with the same MTB-load [5% (86/1703) versus 3% (28/1067), OR = 2.0, 95% CI: 1.28-3.03]. Rats contributed over half of the TB cases identified in program settings, and children, especially those with a lower MTB-load, were more likely to be diagnosed with TB by rats. The chemical signatures, VOCs, were only available for adults, and further research describing the characteristics of VOCs in children versus adults may pave the way to enhance TB diagnosis in children.

Paediatric pulmonary disease-are we diagnosing it right?

It has been reported that differential diagnosis of bacterial or viral pneumonia and tuberculosis (TB) in infants and young children is complex. This could be due to the difficulty in microbiological confirmation in this age group. In this study, we aimed to assess the utility of a real-time multiplex PCR for diagnosis of respiratory pathogens in children with pulmonary TB. A total of 185 respiratory samples [bronchoalveolar lavage (15), gastric aspirates (98), induced sputum (21), and sputum (51)] from children aged 3-12 years, attending tertiary care hospitals, Chennai, India, were included in the study. The samples were processed by N acetyl L cysteine (NALC) NAOH treatment and subjected to microbiological investigations for Mycobacterium tuberculosis (MTB) diagnosis that involved smear microscopy, Xpert® MTB/RIF testing, and liquid culture. In addition, DNA extraction from the processed sputum was carried out and was subjected to a multiplex real-time PCR comprising a panel of bacterial and fungal pathogens. Out of the 185 samples tested, a total of 20 samples were positive for MTB by either one or more identification methods (smear, culture, and GeneXpert). Out of these 20 MTB-positive samples, 15 were positive for one or more bacterial or fungal pathogens, with different cycle threshold values. Among patients with negative MTB test results (n = 165), 145 (87%) tested positive for one or more than one bacterial or fungal pathogens. The results suggest that tuberculosis could coexist with other respiratory pathogens causing pneumonia. However, a large-scale prospective study from different geographical settings that uses such simultaneous detection methods for diagnosis of childhood tuberculosis and pneumonia will help in assessing the utility of these tests in rapid diagnosis of respiratory infections.

Effect of decentralising childhood tuberculosis diagnosis to primary health centre versus district hospital levels on disease detection in children from six high tuberculosis incidence countries: an operational research, pre-post intervention study

Childhood tuberculosis (TB) remains underdiagnosed largely because of limited awareness and poor access to all or any of specimen collection, molecular testing, clinical evaluation, and chest radiography at low levels of care. Decentralising childhood TB diagnostics to district hospitals (DH) and primary health centres (PHC) could improve case detection. We conducted an operational research study using a pre-post intervention cross-sectional study design in 12 DHs and 47PHCs of 12 districts across Cambodia, Cameroon, Côte d'Ivoire, Mozambique, Sierra Leone and Uganda. The intervention included 1) a comprehensive diagnosis package at patient-level with tuberculosis screening for all sick children and young adolescents <15 years, and clinical evaluation, Xpert Ultra-testing on respiratory and stool samples, and chest radiography for children with presumptive TB, and 2) two decentralisation approaches (PHC-focused or DH-focused) to which districts were randomly allocated at country level. We collected aggregated and individual data. We compared the proportion of tuberculosis detection in children and young adolescents <15 years pre-intervention (01 August 2018-30 November 2019) versus during intervention (07 March 2020-30 September 2021), overall and by decentralisation approach. This study is registered with ClinicalTrials.gov, NCT04038632. TB was diagnosed in 217/255,512 (0.08%) children and young adolescent <15 years attending care pre-intervention versus 411/179,581 (0.23%) during intervention, (OR: 3.59 [95% CI 1.99-6.46], p-value<0.0001; p-value=0.055 after correcting for over-dispersion). In DH-focused districts, TB diagnosis was 80/122,570 (0.07%) versus 302/86,186 (0.35%) (OR: 4.07 [1.86-8.90]; p-value=0.0005; p-value=0.12 after correcting for over-dispersion); and 137/132,942 (0.10%) versus 109/93,395 (0.11%) in PHC-focused districts, respectively (OR: 2.92 [1.25-6.81; p-value=0.013; p-value=0.26 after correcting for over-dispersion). Decentralising and strengthening childhood TB diagnosis at lower levels of care increases tuberculosis case detection but the difference was not statistically significant. Unitaid, Grant number 2017-15-UBx-TB-SPEED.

Cost-effectiveness and budget impact of decentralising childhood tuberculosis diagnosis in six high tuberculosis incidence countries: a mathematical modelling study

The burden of childhood tuberculosis remains high globally, largely due to under-diagnosis. Decentralising childhood tuberculosis diagnosis services to lower health system levels could improve case detection, but there is little empirically based evidence on cost-effectiveness or budget impact. In this mathematical modelling study, we assessed the cost-effectiveness and budget impact of decentralising a comprehensive diagnosis package for childhood tuberculosis to district hospitals (DH-focused) or primary health centres (PHC-focused) compared to standard of care (SOC). The project was conducted in Cambodia, Cameroon, Côte d'Ivoire, Mozambique, Sierra Leone, and Uganda between August 1st, 2018 and September 30th, 2021. A mathematical model was developed to assess the health and economic outcomes of the intervention from a health system perspective. Estimated outcomes were tuberculosis cases, deaths, disability-adjusted life years (DALYs) and incremental cost-effectiveness ratios (ICERs). We also calculated the budget impact of nationwide implementation. The TB-Speed Decentralization study is registered with ClinicalTrials.gov, NCT04038632. For the DH-focused strategy versus SOC, ICERs ranged between $263 (Cambodia) and $342 (Côte d'Ivoire) per DALY averted. For the PHC-focused strategy versus SOC, ICERs ranged between $477 (Cambodia) and $599 (Côte d'Ivoire) per DALY averted. Results were sensitive to TB prevalence and the discount rate used. The additional costs of implementing the DH-focused strategy ranged between $12.8M (range 10.8-16.4) (Cambodia) and $50.4M (36.5-74.4) (Mozambique), and between $13.9M (12.6-15.6) (Sierra Leone) and $134.6M (127.1-143.0) (Uganda) for the PHC-focused strategy. The DH-focused strategy may be cost-effective in some countries, depending on the cost-effectiveness threshold used for policy making. Either intervention would require substantial early investment. Unitaid.

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.&#x0D; 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.&#x0D; 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.&#x0D; 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).&#x0D; 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.

Analysis of Determinants of Tuberculosis in Stunted Toddlers in Rambipuji, Jember

Tuberculosis (TB) and stunting remain serious health problems in Indonesia. Stunting can impact a child's ability to resist infections, including TB. Stunted toddlers are more vulnerable to contracting TB compared to those with normal nutritional status. This research aims to explore the relationship and influence of TB risk factors on the occurrence of TB in stunted toddlers. This research is an analytical descriptive research with a cross sectional design. The research sample consisted of 183 stunted toddlers from eight villages in the Rambipuji sub-district, Jember. The research procedures included interviews, direct observations, and TB examinations in children. Interviews were conducted with the parents/guardians of the child respondents. Observations and direct measurements were performed to determine the physical characteristics of the respondents' living environments, including household density, ventilation area, natural lighting, humidity, and room temperature. The diagnosis of TB in children was established based on a scoring table for childhood TB. From the research findings, 15 children tested positive for TB (8.2%). Bivariate analysis showed a value of p &lt;0.05 for nutritional status, close contact, household density, ventilation, and natural lighting factors. Multivariate analysis revealed significant results for close contact (p=0.000; OR=39.563), household density (p=0.015; OR=9.659), and nutritional status (p=0.029; OR=6.718) as risk factors. In conclusion, it can be inferred that the risk factors associated with TB occurrence in stunted toddlers include nutritional status, close contact history, household density, ventilation, and natural lighting. The factors influencing TB occurrence in stunted toddlers are close contact history, household density, and nutritional status. Keywords: risk factor, stunted toddler, tuberculosis

Evaluation of Gene Xpert Test of Stool Specimen with that of Induced Sputum as Gold Standard

Background: Globally Tuberculosis (TB) is a major infectious disease. In 2011, there were an estimated 8.7 million new cases with 6% childhood tuberculosis. The majority of the cases occurring in high TB burden countries worldwide. Confirmed diagnosis of childhood TB remains challenging for physicians. MT test and Chest X-ray usually has very little diagnostic value for the diagnosis of pulmonary tuberculosis in children who has symptom criteria suggestive of PTB. Objectives: This study was done to evaluate of Gene Xpert Test of Stool Specimen with that of Induced Sputum as Gold Standard. Methods: The cross-sectional study was conducted in the Department of Pediatrics, Sir Salimullah Medical College &amp; Mitford Hospital from January 2020 to June 2021. A total of 48 subjects of both sexes with the age range from 1 month to 59 months were included in the study. Data were collected over a period of eleven months and analyzed by appropriate computer based programmed software Statistical Package for the Social Sciences (SPSS), version 22. Results: In this study, most of the children 14 (29.2%) lies between 13 months to 24 months. About most of the children 28 (58.33%) were male and 20 (41.67%) children were female. According to the clinical presentation majority of the children present with fever 39(75.0%), followed by cough (72.9%) and weight loss (50%), history of contact was present in 15 (31.3%) children. Chest X-ray of 54% children was suggestive of PTB (as Consolidation, Milliary mottling, patchy opacity etc) 46% showed normal X-ray findings. Gene X-pert of Induced sputum could detect M.Tuberculosis in case of 12.5% children and in 87.5% cases Gene X-pert could not detect M.Tuberculosis in induced sputum. M.Tuberculosis was detected by Stool X-pert in 18% of children who were clinically diagnosed as PTB. In 82% of patient stool X-pert could not detect M.Tuberculosis. Conclusion: Gene Xpert test of stool specimen is a relatively easy test for the diagnosis ........

Diagnostic accuracy of Xpert MTB/RIF Ultra for childhood tuberculosis in West Africa – a multicenter pragmatic study

ObjectiveTo evaluate the performance of Xpert Mycobacterium Tuberculosis/rifampicin (MTB/RIF) Ultra (Ultra) for diagnosis of childhood tuberculosis (TB) within public health systems. MethodsIn this cross-sectional study, children aged <15 years with presumptive pulmonary TB were consecutively recruited and evaluated for TB at tertiary-level hospitals in Benin, Mali, and Ghana. Bivariate random-effects models were used to determine the pooled sensitivity and specificity of Ultra against culture. We also estimated its diagnostic yield against a composite microbiological reference standard (cMRS) of positive culture or Ultra. ResultsOverall, 193 children were included in the analyses with a median (interquartile range) age of 4.0 (1.1-9.2) years, 88 (45.6%) were female, and 36 (18.7%) were HIV-positive. Thirty-one (16.1%) children had confirmed TB, 39 (20.2%) had unconfirmed TB, and 123 (63.7%) had unlikely TB. The pooled sensitivity and specificity of Ultra verified by culture were 55.0% (95% confidence interval [CI]: 28.0–79.0%) and 95.0% (95% CI: 88.0–98.0%), respectively. Against the cMRS, the diagnostic yield of Ultra and culture were 67.7% (95% CI: 48.6–83.3%) and 70.9% (95% CI: 51.9–85.8%), respectively. ConclusionUltra has suboptimal sensitivity in children with TB that were investigated under routine conditions in tertiary-level hospitals in three West African countries.

What is New in the Diagnosis of Childhood Tuberculosis?

The fact that almost half of the 1 million cases of childhood tuberculosis (TB)globally remain undiagnosed jeopardizes the TB elimination goal. Fortunately, there are new advances in this fieldwhich have the potential to bridge this diagnostic gap. Advances in imaging include computer assisted interpretation of chest X-rays (CXRs), point of care ultrasound (POCUS) and faster and superior computed tomography/ magnetic resonance imaging (CT/ MRI) protocols. The urine lipoarabinomannan test has proved to be a good point of care test for diagnosing TB in Human immunodeficiency virus (HIV) infected children. Stool and nasopharyngeal aspirates are emerging as acceptable alternatives for gastric lavage and induced sputum for diagnosing intrathoracic tuberculosis. Xpert MTB/RIF Ultra has improved sensitivitycompared to Xpert MTB/RIF for diagnosing both pulmonary/ extrapulmonary TB. Xpert XDR is another commercially available accurate point of care test for detecting resistance to drugs other than rifampicin in smear positive samples. Other molecular methods including new line probe assays, pyrosequencing, whole genome sequencing, and targeted next generation sequencing are extremely promising but not available commercially at present. The C-Tb skin test isan acceptable alternative to the tuberculin skin test and interferon gamma release assays for diagnosis of latent infection. There is an urgent need to incorporate some of these advances in the existingdiagnostic algorithms of childhood TB.

Evaluation of Interferon-Gamma Release Assay Testing and Tuberculin Skin Test for Early Diagnosis of Tuberculosis in Children and Adolescents

Evaluation of Interferon-Gamma Release Assay Testing and Tuberculin Skin Test for Early Diagnosis of Tuberculosis in Children and Adolescents

Evaluation of Induced Sputum against Gastric Juice Aspirate in the Diagnosis of Tuberculosis in Children: A Cross-sectional Study

Introduction: Diagnosing Tuberculosis (TB) in children is difficult as they do not expectorate sputum on their own, and the sample is usually paucibacillary. Hence, alternative sampling methods like Gastric juice Aspiration (GA), which is the widely accepted method, and Induced Sputum (IS) collection, a more novel approach, are used. The IS method has several advantages, such as being less invasive, not requiring inpatient admission, causing less discomfort, and not necessitating overnight fasting, compared to the GA method. Aim: To evaluate IS against GA for diagnosing TB using XpertMTB/ RIF assay, as well as mycobacterial culture, in children aged between 2 and 15 years. Materials and Methods: This cross-sectional study was conducted in the Department of Paediatrics at Christian Medical College and Hospital, Vellore, Tamil Nadu, India from June 2019 to March 2020, involving 138 children aged between 2 and 15 years who were being evaluated for TB. GA samples were collected after an overnight fast, and on the same day, atleast two hours later, IS samples were collected by trained staff. Both samples underwent mycobacterial smear and culture using the Mycobacteria Growth Indicator Tube (MGIT) method and Xpert MTB/RIF assay. Confirmation of pulmonary TB was based on atleast one of these tests being positive. The ‘Wong-Baker’ Visual Analogue Scale (VAS) was individually administered to each patient to compare the discomfort associated with GA and IS procedures. The differences in yield between IS and GA were tested for significance using the Two-sample test of proportions with a significance level set at 5%. McNemar's χ2 test was employed to compare matched observations. The MannWhitney test was used for comparing continuous variables, and the Chi-Square test for categorical variables. Cohen’s Kappa (κ) was used to assess interobserver agreement between the sampling methods using the different tests. Results: Out of the 138 cases recruited with suspected pulmonary TB, the diagnosis was microbiologically confirmed in 13 cases (9.4%). The overall diagnostic yield was 12/138 (8.7%) for GA and 10/138 (7.2%) for IS. In children under 10 years, GA outperformed IS with all three cases being positive by GA and none by IS. For those aged 10 years and above, 10 children (100%) tested positive with IS, while nine children (90%) were positive with GA. According to the Wong-Baker VAS measuring discomfort during the procedure, IS was favoured over GA (p-value&lt;0.0001). Conclusion: IS performs similarly or better than GA in children over 10 years, while GA performs better than IS in children under 10 years of age. IS is reported to cause less discomfort than GA on the Wong-Baker VAS.

Diagnostic Accuracy of Clinical Diagnostic Scoring Systems for Childhood Tuberculosis: A Systematic Review and Meta-analysis.

Diagnosis of childhood tuberculosis (TB) poses several challenges. Therefore, point-based scoring systems and diagnostic algorithms have been developed to improve the diagnostic yields in this population. However, there are no updated systematic reviews of the existing childhood TB scoring systems and algorithms. Hence, we systematically reviewed the diagnostic accuracy of the childhood TB diagnostic scoring systems and algorithms. We systematically searched PubMed, CINAHL, Embase, Scopus, and Google Scholar databases for relevant articles published until 30 March 2023. QUADAS-2 was used to assess their study quality. Diagnostic accuracy measures (ie, sensitivity, specificity, diagnostic odds ratio, positive and negative likelihood ratios) were pooled using a random-effects model. We included 15 eligible studies, with a total of 7327 study participants aged <15 years, with 10 evaluations of childhood TB diagnostic scoring systems and algorithms. Among these algorithms and scoring systems, only 3 were evaluated more than once. These were the Keith Edwards scoring system with 5 studies (sensitivity, 81.9%; specificity, 81.2%), Kenneth Jones criteria with 3 studies (sensitivity, 80.1%; specificity, 45.7%), and the Ministry of Health-Brazil algorithm with 3 studies (sensitivity, 79.9%; specificity, 73.2%). We recommend using the Keith Edwards scoring system because of its high sensitivity and specificity. Further research is necessary to assess the effectiveness of scoring systems and algorithms in identifying TB in children with HIV and malnutrition.

Critical Review of Tuberculosis Diagnosis in Children from Papua New Guinea Presenting to Health Facilities in the Torres Strait Islands, Australia.

Paediatric tuberculosis can be challenging to diagnose, and various approaches are used in different settings. A retrospective review was conducted on Papua New Guinea (PNG) children with presumptive TB who presented for health care in the Torres Strait Islands, Australia, between 2016 and 2019. We compared diagnostic algorithms including the modified Keith Edwards TB Score, The Union Desk Guide, and the new World Health Organization (WHO) algorithm, with diagnostic practices used in the remote Torres Strait Islands. Of the 66 children with presumptive TB, 7 had bacteriologically confirmed TB. The majority (52%) were under 5 years (median age 61 months), and 45% were malnourished. There was moderate agreement across the diagnostic methods (K = 0.34; 95% CI 0.23-0.46), with the highest concordance observed between The Union Desk Guide and the WHO's algorithm (K = 0.61). Local TB physicians might have over-diagnosed presumed lymph node TB while under-diagnosing TB overall. Enhancing the precision and promptness of paediatric TB diagnosis using practical tools is pivotal to decrease TB-related child mortality, notably in isolated regions like the Torres Strait and the Western Province of PNG.

Orbital tuberculosis mimicking an ocular malignancy: a case report

Background: Tuberculosis (TB), a multi-systemic disease caused by Mycobacterium tuberculosis, is associated with a high burden of morbidity and mortality worldwide. The diagnosis of TB in children is challenging, particularly when it presents in rarer sites such as the eye. We present a case of a female Ghanaian toddler with a right orbital mass which mimicked an orbital malignancy and was confirmed as TB on histopathology. This case report highlights the need for a high index of suspicion for TB among children who present with orbital masses, especially in TB-endemic regions.

Issues of interdisciplinary interaction during detection and diagnosis of tuberculosis in children and adolescents: a literature review and comments

Interdisciplinary interaction between phthisiatricians and pediatricians on the issues of detection and diagnosis of tuberculosis provides basis for the reduction of duration of the diagnostic process and the early identification of disease progression. The purpose of this review and comments is to systematize the knowledge of pediatricians about the detection and diagnosis of tuberculosis in children and adolescents in primary health care (PHC) facilities to improve the diagnostic process. We have performed an analysis and systematization of the current directive and methodological documents, articles on the detection and diagnosis of tuberculosis in PHC facitlities. The significance of skin immunological tests (Mantoux test using 5 tuberculin units (TU) of purified protein derivative (PPD)-L and a test with recombinant tuberculosis allergen (RTA)) during mass and selective screening to form groups at high risk for Tuberculosis and detect the disease is emphasized. The doctor’s actions based on the current guiding documents and laws are presented for cases when parents/legal representatives or the patient himself refuses from immunological skin tests. Positions that determine the need for interdisciplinary interaction for pediatricians on the issues of detection, diagnosis and differential diagnosis of tuberculosis are clearly articulated. The pathway to diagnosis begins with the formation of groups at high risk for tuberculosis in PHC facilities and with seeking medical help from a pediatrician in the presence of clinical signs similar to those of tuberculosis. Particular attention is paid to the detection of the disease when patients with clinical symptoms similar to those of tuberculosis seek medical help, and the missed opportunities for its early diagnosis are presented. Predictors allowing pediatricians to suspect tuberculosis and promptly refer a patient to a phthisiatrician to confirm / exclude the disease are provided.