Chest X-Ray-Based Telemedicine Platform for Pediatric Tuberculosis Diagnosis in Low-Resource Settings: Development and Validation Study.

BACKGROUND: Tuberculosis (TB) remains a major cause of morbidity and death worldwide, with a significant impact on children, especially those under the age of 5 years. The complex diagnosis of pediatric TB, compounded by limited access to more accurate diagnostic tests, underscores the need for improved tools to enhance diagnosis and care in resource-limited settings. OBJECTIVE: This study aims to present a telemedicine web platform, BITScreen PTB (Biomedical Image Technologies Screen for Pediatric Tuberculosis), aimed at improving the evaluation of pulmonary TB in children based on digital chest x-ray (CXR) imaging and clinical information in resource-limited settings. METHODS: The platform was evaluated by 3 independent expert readers through a retrospective assessment of a data set with 218 imaging examinations of children under 3 years of age, selected from a previous study performed in Mozambique. The key aspects assessed were the usability through a standardized questionnaire, the time needed to complete the assessment through the platform, the performance of the readers to identify TB cases based on the CXR, the association between the TB features identified in the CXRs and the initial diagnostic classification, and the interreader agreement of the global assessment and the radiological findings. RESULTS: The platform's usability and user satisfaction were evaluated using a questionnaire, which received an average rating of 4.4 (SD 0.59) out of 5. The average examination completion time ranged from 35 to 110 seconds. In addition, the study on CXR showed low sensitivity (16.3%-28.2%) but high specificity (91.1%-98.2%) in the assessment of the consensus case definition of pediatric TB using the platform. The CXR finding having a stronger association with the initial diagnostic classification was air space opacification (χ21>20.38, P<.001). The study found varying levels of interreader agreement, with moderate/substantial agreement for air space opacification (κ=0.54-0.67) and pleural effusion (κ=0.43-0.72). CONCLUSIONS: Our findings support the promising role of telemedicine platforms such as BITScreen PTB in enhancing pediatric TB diagnosis access, particularly in resource-limited settings. Additionally, these platforms could facilitate the multireader and systematic assessment of CXR in pediatric TB clinical studies.

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.

Background: 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. Methods: 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. Results: 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. Conclusions: 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. Clinical Trials Registration: NCT06239337.

Feasibility and utility of a combined nasogastric-tube-and-string-test device for bacteriologic confirmation of pulmonary tuberculosis in young children.

For microbiological confirmation of pediatric pulmonary tuberculosis (PTB), gastric aspirates (GA) are often operationally unfeasible without hospitalization, and the encapsulated orogastric string test is not easily swallowed in young children. The Combined-NasoGastric-Tube-and-String-Test (CNGTST) enables dual collection of GA and string specimens. In a prospective cohort study in Kenya, we examined its feasibility in children under five with presumptive PTB and compared the bacteriological yield of string to GA. Paired GA and string samples were successfully collected in 95.6 % (281/294) of children. Mycobacterium tuberculosis was isolated from 7.0 % (38/541) of GA and 4.3 % (23/541) of string samples, diagnosing 8.2 % (23/281) of children using GA and 5.3 % (15/281) using string. The CNGTST was feasible in nearly all children. Yield from string was two-thirds that of GA despite a half-hour median dwelling time. In settings where the feasibility of hospitalisation for GA is uncertain, the string component can be used to confirm PTB.

Pediatric tuberculosis in Mexico and the COVID-19 phenomenon: Past and present.

In endemic regions, tuberculosis in children constitutes a bigger fraction of total cases as compared to those in low endemic regions, regardless of the implications, this phenomenon has been historically neglected. Pediatric tuberculosis has an insidious onset and quickly develops into disseminated disease and the young are at a special risk for dissemination. Some studies suggest that measures to contain adult tuberculosis are not enough to manage tuberculosis in children, meaning that pediatric tuberculosis needs dedicated attention. Children are harder to diagnose than adults, because collecting samples is difficult, and their bacterial yield is low. In endemic countries, such as Mexico, where contact with Mycobacterium tuberculosis is common, immunological tests are inconsistent, especially in immunocompromised children. With the disruption of Mexican healthcare services by the COVID-19 pandemic, there is an uncertainty of how the situation has evolved, current data about tuberculosis indicates a drop in the national report of cases: 15.4 per 100,000 persons in 2021, compared with pre-COVID 2019 17.7 per 100,000 persons, a small increase in mortality: 1.7 per 100,000 in 2021 compared with 2019 1.6 per 100,000, a drop in treatment success: 80.4% in 2021 compared with 85.4% in 2019, and a decrease in national vaccination rates: an estimate of 86.6% children between 1 and 2 years-old were vaccinated in 2021 compared with 97.3% reported national rate in 2018-2019. There is a need for new research on regions with high tuberculosis incidence, to clarify the current situation of pediatric tuberculosis and improve epidemiological surveillance.

Tuberculous Pericarditis in Childhood: A Case Report and a Systematic Literature Review.

Tuberculous pericarditis (TBP) is an important cause of pericarditis worldwide while being infrequent in childhood, especially in low-TB-incidence countries. We report a case of TBP and provide a systematic review of the literature, conducted by searching PubMed, Scopus, and Cochrane to find cases of TBP in pediatric age published in the English language between the year 1990 and the time of the search. Of the 587 search results obtained, after screening and a backward citation search, 45 studies were selected to be included in this review, accounting for a total of 125 patients. The main signs and symptoms were fever, cough, weight loss, hepatomegaly, dyspnea, and increased jugular venous pressure or jugular vein turgor. A definitive diagnosis of TBP was made in 36 patients, either thanks to microbiological investigations, histological analysis, or both. First-line antitubercular treatment (ATT) was administered in nearly all cases, and 69 children underwent surgical procedures. Only six patients died, and only two died of TBP. TBP in childhood is relatively uncommon, even in high-TB-prevalence countries. Clinical manifestations, often suggestive of right-sided cardiac failure, are subtle, and diagnosis is challenging. TBP has an excellent prognosis in childhood; however, in a significant proportion of cases, invasive surgical procedures are necessary.

Leptin levels in childhood tuberculosis and its correlation with body mass index, IFN-γ, and TNF-α in an Indonesian population.

BACKGROUND: Leptin plays a key role in the regulation of energy and inflammation in tuberculosis (TB). However, its correlation in children with TB remains unclear. Therefore, this study aimed to evaluate the correlations between body mass index, IFN-γ, TNF-α, and leptin levels in children with TB. METHODS: This was a cross-sectional study of children aged 2-14 years with TB. Sputum examination, chest radiography, and tuberculin skin test findings and clinical symptoms were considered for TB diagnosis. Data on body weight; height; mid-upper arm circumference (MUAC); body mass index (BMI); food intake; and IFN-γ, TNF-α, and leptin levels were collected and analyzed. RESULTS: Of the 64 diagnosed TB subjects, 2 subjects had positive bacteriological results. The median age was 6 (2-14) years, body weight was 17.7 (9.45-55) kg, height was 114 ± 21.46 cm, and Z score BMI was -0.85 ± 1.14 kg/m2. Malnourished was observed in 17.2% of the subjects. The median calorie intake was 1448.5 (676-4674) kcal, carbohydrate intake was 182.5 (63-558) g, protein intake was 57.9 (15.8-191.0) g, and fat intake was 81.6 (23.6-594.1) g. The median leptin level was 1.2 (0.2-59) ng/mL, IFN-γ was 2.5 (0.9-161) pg/mL, and TNF-α was 13.0 (5.7-356) pg/mL. Correlations were observed between leptin and MUAC (r = 0.251, p = 0.02), Z score (r = 0.453, p = 0.00), and IFN-γ (r = 0.295, p = 0.018). CONCLUSION: There were positive correlations between BMI and leptin levels, whereas IFN-γ and MUAC showed weak correlations.

Efficacy and safety of the all-oral bedaquiline-containing regimen as treatment for pediatric multidrug/rifampicin-resistant tuberculosis: a multicenter, retrospective, cohort study.

OBJECTIVE: The study aimed to observe the efficacy and safety of an all-oral bedaquiline (BDQ)-containing regimen for pediatric multidrug/rifampicin-resistant tuberculosis (MDR/RR-TB) through a multicenter, retrospective study in China. METHODS: In the study, pediatric patients receiving all-oral BDQ-containing regimen (BDQ group) with clinical matched control group were included, the control group received an injection-containing regimen. The treatment outcomes and the incidence of adverse events (AEs) were compared and analyzed. RESULTS: 79 pediatric patients were enrolled, including 37 cases in BDQ group and 42 cases in the control group, the median age was 12 {8-16} and 11 {9-15} in both groups respectively. Favorable treatment outcome and cure rate in BDQ group were significantly higher than those in control group (100%vs 83.3%, p 0.03; 94.6%vs 63.3%, p 0.00). Median time of sputum culture conversion in BDQ group was significantly shorter than that in the control group (4 weeks vs 8 weeks, p 0.00). The incidence of AEs in the BDQ group was significantly less than that in the control group (48.6% vs 71.4%, p 0.03). No AEs leading to treatment discontinuation of BDQ occurred. CONCLUSIONS: The all-oral BDQ-containing regimens may be effective and safe in the Chinese pediatric population.

Shortened Treatment Regimens for Drug Sensitive TB.

Tuberculosis (TB) has remained a global health challenge despite the availability of effective anti-tubercular drugs and various treatment strategies. Apart from the complications related to TB disease per se, adverse effects of antitubercular therapy (ATT) also contribute to morbidity. In addition to the adverse effects, the long duration of the treatment regimen also reduces the patient's acceptability of ATT. The available "short-course treatment regimens" are still relatively long, thereby adversely affecting treatment compliance. There is a need for effective, safe, short and intensive regimens for TB which can reduce the treatment cost and adverse effects, thereby improving its acceptance. With the emergence of new evidence, the World Health Organization (WHO) has recently endorsed 4 mo short duration ATT regimen for non-severe, drug-sensitive cases of tuberculosis. Even in severe forms of disease like tubercular meningitis (TBM), trials are underway evaluating efficacy and safety of shorter regimens. Inclusion of fluroquinolones and rifapentine help shorten the regimens. These shortened regimens, however, need more close monitoring for adverse effects and may need to be converted to longer course if there is inadequate clinical response. Thus, shorter regimens for pediatric TB are likely to not only decrease the burden on patients and healthcare but also improve compliance and lower the side effects of the drugs due to prolonged exposure. This article reviews the current evidence and the guidelines pertaining to the shortened, intensive regimens for drug-sensitive tuberculosis.

Tuberculosis in Spain: An opinion paper / Tuberculosis en España: Un documento de opinión

This document is the result of the deliberations of the Committee on Emerging Pathogens and COVID-19 of the Il lustrious Official College of Physicians of Madrid (ICOMEM) regarding the current situation of tuberculosis, particularly in Spain. We have reviewed aspects such as the evolution of its incidence, the populations currently most exposed and the health care circuits for the care of these patients in Spain. We have also discussed latent tuberculosis, the reality of extrapul monary disease in the XXI century and the means available in daily practice for the diagnosis of both latent and active forms. The contribution of molecular biology, which has changed the perspective of this disease, was another topic of discussion. The paper tries to put into perspective both the classical drugs and their resistance figures and the availability and indications of the new ones. In addition, the reality of direct observa tion in the administration of antituberculosis drugs has been discussed. All this revolution is making it possible to shorten the treatment time for tuberculosis, a subject that has also been reviewed. If everything is done well, the risk of relapse of tuberculosis is small but it exists. On the other hand, many special situations have been discussed in this paper, such as tuberculosis in pediatric age and tuberculosis as a cause for concern in surgery and intensive care. The status of the BCG vaccine and its present indications as well as the future of new vaccines to achieve the old dream of eradicating this disease have been discussed. Finally, the ethical and medicolegal impli cations of this disease are not a minor issue and our situation in this regard has been reviewed (AU)

El presente documento es el resultado de las deliberacio nes del Comité sobre Patógenos Emergentes y COVID-19 del Ilustre Colegio Oficial de Médicos de Madrid (ICOMEM) en re lación a la situación actual de la tuberculosis, particularmente en España. Hemos revisado aspectos tales como la evolución de su incidencia, las poblaciones actualmente más expuestas y los circuitos sanitarios para la atención a estos pacientes en España. Se ha discutido también la tuberculosis latente, la rea lidad de la enfermedad extrapulmonar en el siglo XXI y los me dios de que en la práctica diaria se dispone para el diagnóstico tanto de las formas latentes como de las activas. La aportación de la biología molecular que ha cambiado la perspectiva de es ta enfermedad ha constituido otro de los temas de debate. El documento trata de poner en perspectiva tanto los fármacos clásicos y sus cifras de resistencia como la disponibilidad e in dicaciones de los nuevos. Junto a esto, se ha discutido la rea lidad de la observación directa en la administración de fárma cos antituberculosos. Toda esta revolución está posibilitando el acortamiento del tiempo de tratamiento de la tuberculosis tema que ha sido igualmente revisado. Si todo se hace bien, el riesgo de recaída de la tuberculosis es pequeño pero existen te. Por otra parte, muchas situaciones especiales han merecido discusión en este documento como por ejemplo la tuberculosis en edad pediátrica y la tuberculosis como causa de preocupa ción en cirugía y cuidados intensivos. Se ha discutido tanto la situación de la vacuna BCG y sus indicaciones presentes, co mo el futuro de nuevas vacunas que permitan alcanzar el viejo sueño de erradicar esta enfermedad. Finalmente, las implica ciones éticas y medicolegales que esta enfermedad plantea no son un tema menor y se ha revisado nuestra situación en este particular (AU)

Tuberculosis in Spain: An opinion paper.

This document is the result of the deliberations of the Committee on Emerging Pathogens and COVID-19 of the Illustrious Official College of Physicians of Madrid (ICOMEM) regarding the current situation of tuberculosis, particularly in Spain. We have reviewed aspects such as the evolution of its incidence, the populations currently most exposed and the health care circuits for the care of these patients in Spain. We have also discussed latent tuberculosis, the reality of extrapulmonary disease in the XXI century and the means available in daily practice for the diagnosis of both latent and active forms. The contribution of molecular biology, which has changed the perspective of this disease, was another topic of discussion. The paper tries to put into perspective both the classical drugs and their resistance figures and the availability and indications of the new ones. In addition, the reality of direct observation in the administration of antituberculosis drugs has been discussed. All this revolution is making it possible to shorten the treatment time for tuberculosis, a subject that has also been reviewed. If everything is done well, the risk of relapse of tuberculosis is small but it exists. On the other hand, many special situations have been discussed in this paper, such as tuberculosis in pediatric age and tuberculosis as a cause for concern in surgery and intensive care. The status of the BCG vaccine and its present indications as well as the future of new vaccines to achieve the old dream of eradicating this disease have been discussed. Finally, the ethical and medicolegal implications of this disease are not a minor issue and our situation in this regard has been reviewed.

Diagnostic Accuracy of Cartridge Based Nucleic Acid Amplification Test (CBNAAT) in Stool Samples in Pediatric Tuberculosis.

OBJECTIVES: To find out the diagnostic accuracy of stool Cartridge-based nucleic acid amplification test (CBNAAT) as an alternate method as compared to CBNAAT in gastric aspirate (GA) samples in pediatric tuberculosis (TB). METHODS: This cross-sectional study was performed at Department of Pediatrics of a tertiary care hospital. Children aged 0-18 y diagnosed as presumptive tuberculosis were consecutively enrolled. Gastric aspirate and corresponding stool sample was subjected to CBNAAT and its performance was compared in both samples using appropriate statistical tests. RESULTS: Total 100 patients were enrolled in the study. Diagnostic accuracy of CBNAAT was 81% and 80% in gastric aspirate and stool sample respectively. On comparing gastric aspirate with corresponding stool sample there was 97% agreement, with Cohen's kappa value of 0.94. There was a statistically significant association observed between gastric aspirate CBNAAT and stool CBNAAT p <0.001 using chi square test. Sensitivity of gastric aspirate CBNAAT and stool CBNAAT was 75% and 73% respectively and specificity was 100% for both the samples compared against Composite Reference Standard (CRS). CONCLUSIONS: The diagnostic accuracy of stool CBNAAT is comparable to GA CBNAAT in children and can be used as a good alternative to gastric aspirate for diagnosis of pulmonary and disseminated tuberculosis in children.

Quantitation of Circulating Mycobacterium tuberculosis Antigens by Nanopore Biosensing in Children Evaluated for Pulmonary Tuberculosis in South Africa.

Nanopore sensing of proteomic biomarkers lacks accuracy due to the ultralow abundance of targets, a wide variety of interferents in clinical samples, and the mismatch between pore and analyte sizes. By converting antigens to DNA probes via click chemistry and quantifying their characteristic signals, we show a nanopore assay with several amplification mechanisms to achieve an attomolar level limit of detection that enables quantitation of the circulating Mycobacterium tuberculosis (Mtb) antigen ESAT-6/CFP-10 complex in human serum. The assay's nonsputum-based feature and low-volume sample requirements make it particularly well-suited for detecting pediatric tuberculosis (TB) disease, where establishing an accurate diagnosis is greatly complicated by the paucibacillary nature of respiratory secretions, nonspecific symptoms, and challenges with sample collection. In the clinical assessment, the assay was applied to analyze ESAT-6/CFP-10 levels in serum samples collected during baseline investigation for TB in 75 children, aged 0-12 years, enrolled in a diagnostic study conducted in Cape Town, South Africa. This nanopore assay showed superior sensitivity in children with confirmed TB (94.4%) compared to clinical "gold standard" diagnostic technologies (Xpert MTB/RIF 44.4% and Mtb culture 72.2%) and filled the diagnostic gap for children with unconfirmed TB, where these traditional technologies fell short. We envision that, in combination with automated sample processing and portable nanopore devices, this methodology will offer a powerful tool to support the diagnosis of pulmonary TB in children.

Insight into Population Structure and Drug Resistance of Pediatric Tuberculosis Strains from China and Russia Gained through Whole-Genome Sequencing.

This study aimed to determine phenotypic and genotypic drug resistance patterns of Mycobacterium tuberculosis strains from children with tuberculosis (TB) in China and Russia, two high-burden countries for multi/extensively-drug resistant (MDR/XDR) TB. Whole-genome sequencing data of M. tuberculosis isolates from China (n = 137) and Russia (n = 60) were analyzed for phylogenetic markers and drug-resistance mutations, followed by comparison with phenotypic susceptibility data. The Beijing genotype was detected in 126 Chinese and 50 Russian isolates. The Euro-American lineage was detected in 10 Russian and 11 Chinese isolates. In the Russian collection, the Beijing genotype and Beijing B0/W148-cluster were dominated by MDR strains (68% and 94%, respectively). Ninety percent of B0/W148 strains were phenotypically pre-XDR. In the Chinese collection, neither of the Beijing sublineages was associated with MDR/pre-XDR status. MDR was mostly caused by low fitness cost mutations (rpoB S450L, katG S315T, rpsL K43R). Chinese rifampicin-resistant strains demonstrated a higher diversity of resistance mutations than Russian isolates (p = 0.003). The rifampicin and isoniazid resistance compensatory mutations were detected in some MDR strains, but they were not widespread. The molecular mechanisms of M. tuberculosis adaptation to anti-TB treatment are not unique to the pediatric strains, but they reflect the general situation with TB in Russia and China.

Effect of time, temperature and pH on Mycobacterium tuberculosis culture positivity of gastric aspirate: An experimental study.

BACKGROUND: The culture of gastric aspirate (GA) has been used for bacteriological confirmation of pulmonary tuberculosis in children and patients who are unable to expectorate. Sodium bicarbonate neutralization of gastric aspirates is commonly recommended to increase culture positivity. We aim to study Mycobacterium tuberculosis (MTB) culture positivity of GA collected from confirmed case of pulmonary tuberculosis after storing it at different temperature, pH & time. METHODS: GA specimens from 865 patients of either sex predominately non-expectorating children/adults with suspected pulmonary TB were collected. Gastric lavage was performed in the morning after an overnight fasting (at least 6hrs fasting). The GA specimens were tested by CBNAAT (GeneXpert) and AFB microscopy & those who were positive on CBNAAT were further processed with MTB culture on Growth Indicator Tube (MGIT™) culture. pH neutralized and non-neutralized CBNAAT positive GA specimens were culture within 2 hours of collection and 24 hours after storage at 4 °C & room temperature. RESULTS: MTB was detected in 6.8% of collected GA specimens by CBNAAT. Culture positivity of neutralized GA specimens when processed within 2 hours of collection, was higher compared to paired non-neutralized GA specimens. Neutralized GA specimens had higher contamination rate than non-neutralized GA specimens. Storage of GA specimens at $Deg C had better culture yield than those stored at room temperature. CONCLUSION: Early neutralization of acid in Gastric aspirate (GA) is essential for better culture positivity of M. tuberculosis (MTB). If there is a delay in processing GA, it should be kept at 4 °C after neutralization; however, positivity decreases with time.

Standardization of a stool concentration method for Mycobacterium tuberculosis detection in the pediatric population.

Background: The inability of young children to expectorate sputum and paucibacillary status of Mycobacterium tuberculosis (MTB) increases its diagnostic complexity. In this study, we aimed to standardize a stool concentration method for the detection of MTB and its drug resistance by line probe assay (LPA). Methods: The stool from 10 healthy children spiked with H37Rv in five different dilutions (1:1, 1:10, 1:100, 1:1000, and 1:10,000), and stool from 10 confirmed TB and 54 clinically diagnosed TB children were subjected to an in-house stool concentration protocol. All the processed filtrates were subjected to smear microscopy, solid culture, Xpert ultra testing, and LPA. Results: Of 10 control samples, growth was seen in four samples (neat 1:1). In smear microscopy, bacilli could be seen in eight samples (1:1 and 1:10). Xpert ultra testing could detect MTB in eight samples in all dilutions with different loads. LPA could detect MTB in all samples and dilutions. In microbiologically confirmed children, seven out of 10 stool samples tested were positive. Out of 54 children with clinically diagnosed TB, 4 (7.4%) could be confirmed by microbiological diagnosis. Conclusion: The protocol standardized in this study proves to be better working in the molecular detection of MTB.

Indoor Urban Environment and Conventional Risk Factors for Pediatric Tuberculosis Among 1-12 Years Old Children in a Megacity in Pakistan: A Matched Case-Control Study.

Background: Estimated 1.1 million children developed tuberculosis (TB) globally in 2020. Household air pollution has been associated with increased respiratory tract infections among children. Nonetheless, there are scarce data regarding the association of indoor environment with pediatric TB. Objectives: To determine the association of indoor urban environment and conventional risk factors for pulmonary TB among children 1-12 years and to discern the differences of these factors among younger (1-5 years) and older children (6-12 years). Materials and Methods: We conducted an age-matched case-control study among children in 2 hospitals (tertiary and secondary care) in megacity, Karachi, Pakistan. A total of 143 pulmonary TB cases, diagnosed on Pakistan Paediatric Association Scoring Chart for Diagnosis of Tuberculosis (PPASCT), were compared with 286 age-matched controls (ratio 1:2). Indoor urban environment and other conventional risk factors were ascertained through a questionnaire and analyzed by conditional logistic regression. Results: Overall, being a female child [matched odds ratio (mOR): 2.03, 95% confidence interval (CI): 1.16-3.53], having household TB contact (mOR: 8.64, 95% CI: 4.82-15.49), open kitchen for cooking in household (mOR: 1.99, 95% CI: 1.59-5.66), and poorly ventilated house (mOR: 2.37, 95% CI: 1.09-3.65) increased the risk of TB among children (1-12 years). Open kitchen was a risk factor for younger children (1-5 years), whereas poorly ventilated house and being female child was a risk factor for older children (6-12 years), respectively. Conclusions: This study strengthens the evidence that a poor indoor environment increases the risk for childhood TB. Concerted efforts are needed to improve the indoor air environment in urban areas for prevention of TB in addition to addressing the conventional risk factors.

Treatment outcome of pediatric tuberculosis in eastern Ethiopia.

Background: Children are more vulnerable to developing active Mycobacterium tuberculosis infection which causes significant morbidity and mortality. However, the contribution of childhood tuberculosis and its treatment outcomes have not been well documented, and no research has been conducted in eastern Ethiopia. Objective: This study aimed to assess the treatment outcome and its predictors of pediatric tuberculosis in eastern Ethiopia from September 1, 2017 to January 30, 2018. Methods: A retrospective study was conducted in eight selected hospitals in eastern Ethiopia. Data on 2002 children with tuberculosis was extracted by using the standard checklist of the national tuberculosis treatment format. Treatment outcomes were determined according to the standard definitions of the National Tuberculosis and Leprosy Control Programme. Data were entered into Epi Data software version 3.1 and exported to Statistical Package for Social Science (SPSS) version 20 for analysis. Bivariable and multivariable regression analyses were carried out to examine the associations between dependent and independent variables. A P-value of <0.05 was considered statistically significant. Result: The overall successful treatment rate was 1,774 (88.6%) [95% confidence interval (CI): (80.59-97.40)]. A total of 125 (6.2%), 1,648 (82.3%), 59 (2.9%), and 19 (0.9%) children with tuberculosis (TB) were cured, completed, defaulted, and died, respectively. A high number of defaulters and deaths were reported in the age group <10 years. More children with smear-positive pulmonary TB (74.4%) were cured, while smear-negative tuberculosis had higher treatment completion rates. Being male in sex (adjusted odds ratio (AOR): 0.71, 95% CI: 0.53, 0.96) and those with human immunodeficiency virus (HIV) positive sero status (AOR: 0.51, 95% CI: 0.29, 0.90) had a lower chance of a successful treatment outcome. Conclusion: In this study, thee treatment success rate was higher than the recent World Health Organization report. Those males and HIV seropositive status were less likely to have a successful treatment outcome. Therefore, efforts should be made by each health institution in eastern Ethiopia by giving emphasis on male and HIV-positive individuals.

A Prospective Observational Study of Hepatic Dysfunction in Children on Antitubercular Drugs.

The frequency, risk factors, and prognosis of antitubercular drug-induced liver injury (TB-DILI) was assessed in this prospective observational study. All consecutive children < 18 y put on antitubercular therapy (ATT) for pulmonary or extrapulmonary tuberculosis between July 2019 and December 2020 were included. Liver function tests (LFTs) were done at baseline and at 2, 4, 6 wk, and then 2 monthly after initiation of therapy till completion of ATT regimen. A total of 81 children [14.27 ± 3.38 y, 34 (42%) males] were included. Out of the patients enrolled, 10 (12.3%) developed TB-DILI at a median of 8.5 (3-18) d of starting ATT. All patients were symptomatic with the most common symptoms being anorexia and nausea (80%). A higher baseline ALT was independently associated with DILI with adjusted OR 2.1 (95% CI 1.3-3.4), p = 0.01. Eight patients tolerated reintroduction of ATT in a sequential manner, 9-24 d after discontinuation.

Delamanid Added to an Optimized Background Regimen in Children with Multidrug-Resistant Tuberculosis: Results of a Phase I/II Clinical Trial.

Delamanid has been demonstrated to be safe and effective for treatment of adult multidrug-resistant tuberculosis (MDR-TB) and has been approved by the European Commission for treatment of pediatric MDR-TB patients at least 10 kg in weight, making the drug no longer limited to adults. A 10-day phase I age deescalation study was conducted, followed by a 6-month phase II extension study, to assess the pharmacokinetics, safety, tolerability, and preliminary efficacy of delamanid when combined with optimized background regimen (OBR) in children (birth to 17 years) with MDR-TB. Delamanid administered at 100 mg twice-daily (BID), 50 mg BID, and 25 mg BID resulted in exposures in 12- to 17- (n = 7), 6- to 11- (n = 6), and 3- to 5-year-olds (n = 12), respectively, comparable with those in adults at the approved adult dosage (100 mg BID). Exposures in 0- to 2-year-olds (n = 12) following a weight-based dosing regimen (5 mg once daily [QD] to 10 mg BID) were lower than predicted from pharmacokinetic modeling of the older three age groups and below target exposures in adults. Overall, the safety profile of delamanid in children 0 to 17 years of age was similar to the adult profile. At 24 months after the first delamanid dose, 33/37 children (89.2%) had favorable treatment outcomes, as defined by the World Health Organization (15/37 [40.5%] cured and 18/37 [48.6%] completed treatment). A new pediatric delamanid formulation used in 0- to 2-year-olds and 3- to 5-year-olds was palatable per child/parent and nurse/investigator reports. Data from initial phase I/II studies inform our understanding of delamanid use in children and support its further assessment in the setting of pediatric MDR-TB. (This study has been registered at ClinicalTrials.gov under identifiers NCT01856634 [phase I trial] and NCT01859923 [phase II trial].).