Pediatric Tuberculosis Research Articles

ТУБЕРКУЛЕЗ ОРГАНОВ ДЫХАНИЯ У ПОДРОСТКОВ ПОД «МАСКОЙ» ВНЕБОЛЬНИЧНОЙ ПНЕВМОНИИ: КЛИНИЧЕСКИЕ НАБЛЮДЕНИЯ

Absence of pathognomonic signs of tuberculosis (TB) of the respiratory system and the diversity of its clinical manifestations reduce the alertness of primary health care (PHC) physicians to this problem, which in its turn leads to belated TB diagnosis. Most often initial diagnosis is “community-acquired pneumonia” at the onset of the disease. An algorithm for interdisciplinary interaction between pediatricians and TB specialists in cases of suspected TB of the respiratory system is proposed. The reasons for untimely detection of TB and diagnostic errors in PHC units are presented using the clinical cases. Absence of suspicion of TB in the presence of its predictors (contact with a TB patient, results of skin immunological tests); development of pulmonary disease outside the season of viral infections in patients who are not included in the risk group according to their frequency and in patients from socially problematic living conditions; incorrect interpretation of the clinical and radiological picture and the course of the disease at its onset are the main reasons for late diagnosis. Conclusion: identifying TB in children and adolescents when seeking medical help is the final part of the diagnostic journey of patients, since opportunities to diagnose the disease at earlier stages of its development were missed. The results of the presented observations indicate the need for interdisciplinary interaction between pediatric physicians and TB specialists for timely diagnosis of TB.

Newer perspectives - Diagnosis and management of pediatric tuberculosis

Pediatric tuberculosis is a proxy indicator for the tuberculosis (TB) burden in the community. Although there has been a decline in the incidence, it is inadequate to meet the global goals for complete eradication of the disease. Childhood TB remains a challenge for clinicians and program managers. Advances in the diagnosis and treatment of pediatric tuberculosis are discussed in this review.

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

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). 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. 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). 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.

Impairments in pulmonary functions in paediatric spinal tuberculosis: a cross-sectional study.

This study aimed to investigate the impact of vertebral column destruction and kyphotic deformity due to spinal tuberculosis on pulmonary functions in paediatric patients. A cross-sectional study was conducted, involving 30 patients diagnosed with healed spinal tuberculosis, aged 7-18years. Detailed radiographic measurements, including the level of involvement, kyphosis angle, Spinal Deformity Index (SDI), and drug-resistance status, were compared with various pulmonary function parameters. The mean age of the study group was 12.8 ± 2.7years (range 7-17years), consisting of 11 males and 19 females. Fourteen patients were managed conservatively and 16 were managed operatively. The mean SDI was 5.2 ± 4.7. The mean kyphotic angle was 31.3° ± 25.3. The average number of involved vertebrae was 2.6 ± 1.5. Pulmonary functions were classified as restrictive in 24 patients, normal in 4 patients, obstructive in 1 patient, and mixed in 1 patient. Multidrug-resistant tuberculosis (MDR-TB) was detected in 5 (16.7%) patients, while the remaining 25 (83.3%) patients were sensitive to conventional antitubercular drugs. The correlation coefficients between the percentage reduction in forced vital capacity (FVC) and kyphosis angle, SDI, and number of vertebrae were 0.4 (p = 0.026), 0.4 (p = 0.028), and 0.19 (p = 0.295), respectively. The mean percentage reduction in FVC and total lung capacity (TLC) were 35.8 ± 15.7 and 6.2 ± 2.3, respectively. No significant association was observed between pulmonary functions and drug sensitivity status (p = 0.074). Paediatric spinal tuberculosis can lead to thoracic insufficiency due to progressive destruction and shortening of the spinal column, spinal growth inhibition, and kyphotic deformity. Management of these cases should focus on promoting normal lung development while ensuring disease resolution and deformity correction. Further research should explore growth conserving or growth guiding systems to address or prevent growth retardation and simultaneously provide spinal stabilization.

Area-Based Sociodemographic Factors Associated with Latent Tuberculosis Infection in a Low-Prevalence Setting.

Area-based sociodemographic markers, such as census tract foreign-born population, have been used to identify individuals and communities with a high risk for tuberculosis (TB) infection in the United States. However, these markers have not been evaluated as independent risk factors for TB infection in children. We evaluated associations between census tract poverty, crowding, foreign-born population, and the CDC's Social Vulnerability Index (CDC-SVI) ranking and TB infection in a population of children tested for TB infection in Boston, Massachusetts. After adjustment for age, crowding, and foreign-born percentage, increasing census tract poverty was associated with increased odds of TB infection (adjusted odds ratio [aOR] per 10% increase in population proportion living in poverty: 1.20 [95% CI, 1.04-1.40]; P = 0.01), although this association was attenuated after further adjustment for preferred language. In separate models, increasing CDC-SVI ranking was associated with increased odds of TB infection, including after adjustment for age and language preference (aOR per 10-point increase in CDC-SVI rank: 1.08 [95% CI, 1.02-1.15]; P = 0.01). Our findings suggest area-based sociodemographic factors may be valuable for characterizing TB infection risk and defining the social ecology of pediatric TB infection in low-burden settings.

Cost-effectiveness analysis of interventions to improve diagnosis and preventive therapy for paediatric tuberculosis in 9 sub-Saharan African countries: A modelling study.

Over 1 million children aged 0 to 14 years were estimated to develop tuberculosis in 2021, resulting in over 200,000 deaths. Practical interventions are urgently needed to improve diagnosis and antituberculosis treatment (ATT) initiation in children aged 0 to 14 years and to increase coverage of tuberculosis preventive therapy (TPT) in children at high risk of developing tuberculosis disease. The multicountry CaP-TB intervention scaled up facility-based intensified case finding and strengthened household contact management and TPT provision at HIV clinics. To add to the limited health-economic evidence on interventions to improve ATT and TPT in children, we evaluated the cost-effectiveness of the CaP-TB intervention. We analysed clinic-level pre/post data to quantify the impact of the CaP-TB intervention on ATT and TPT initiation across 9 sub-Saharan African countries. Data on tuberculosis diagnosis and ATT/TPT initiation counts with corresponding follow-up time were available for 146 sites across the 9 countries prior to and post project implementation, stratified by 0 to 4 and 5 to 14 year age-groups. Preintervention data were retrospectively collected from facility registers for a 12-month period, and intervention data were prospectively collected from December 2018 to June 2021 using project-specific forms. Bayesian generalised linear mixed-effects models were used to estimate country-level rate ratios for tuberculosis diagnosis and ATT/TPT initiation. We analysed project expenditure and cascade data to determine unit costs of intervention components and used mathematical modelling to project health impact, health system costs, and cost-effectiveness. Overall, ATT and TPT initiation increased, with country-level incidence rate ratios varying between 0.8 (95% uncertainty interval [UI], 0.7 to 1.0) and 2.9 (95% UI, 2.3 to 3.6) for ATT and between 1.6 (95% UI, 1.5 to 1.8) and 9.8 (95% UI, 8.1 to 11.8) for TPT. We projected that for every 100 children starting either ATT or TPT at baseline, the intervention package translated to between 1 (95% UI, -1 to 3) and 38 (95% UI, 24 to 58) deaths averted, with a median incremental cost-effectiveness ratio (ICER) of US$634 per disability-adjusted life year (DALY) averted. ICERs ranged between US$135/DALY averted in Democratic of the Congo and US$6,804/DALY averted in Cameroon. The main limitation of our study is that the impact is based on pre/post comparisons, which could be confounded. In most countries, the CaP-TB intervention package improved tuberculosis treatment and prevention services for children aged under 15 years, but large variation in estimated impact and ICERs highlights the importance of local context. This evaluation is part of the TIPPI study, registered with ClinicalTrials.gov (NCT03948698).

SCREENING FOR TUBERCULOSIS DISEASE AMONG CHILDREN: A SYSTEMATIC REVIEW

Introduction : One of the top 10 causes of death worldwide is tuberculosis (TB). An estimated 10 million new cases of TB, including 1.2 million in children, were reported in 2019. Due to the symptoms of pediatric tuberculosis (TB) being similar to those of other juvenile illnesses and the difficulty in obtaining lung samples due to children's propensity to swallow sputum, diagnosing pediatric TB is challenging. Methods : This systematic review's objective was to find reliable screening techniques for paediatric tuberculosis diagnosis. The Cochrane Central Register of Controlled Trials, ScienceDirect, PubMed, and Web of Science databases were all searched in accordance with PRISMA standards.The words "screening" and "(Tuberculosis) OR (TB) OR (TB)" and "(Children")" were used. Result : This investigation covered a total of five studies. TST and IGRA are recommended by the Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC) as techniques for diagnosing M. tuberculosis infection, with certain preferences and considerations. For testing children younger than 5 years old, TST is preferred over IGRA. Conclusion :Testing BCG recipients (either as a therapy or a vaccine) or patients with subpar TST findings is preferred to be done with IGRAs.

Predictors of mortality in Ugandan children with TB, 2016-2021.

BACKGROUND: The burden of pediatric TB is high in Uganda. Our objective was to evaluate predictors of mortality during TB treatment among children at an urban and a rural referral hospital.METHODS: We designed a historical cohort study of TB cases at Mulago National Referral Hospital, Kampala; and Fort Portal Regional Referral Hospital, Fort Portal, Uganda, in children aged <15 years from 2016 to 2021. We used Kaplan-Meier models to estimate survival and fit multivariable Cox regression models to determine mortality hazards during TB treatment.RESULTS: We identified 1,658 children diagnosed with TB from 2016 to 2021. Of 1,623 children with known treatment outcomes, 127/1,623 (7.8%) died during TB treatment, 1,298/1,623 (78.3%) completed treatment, 150/1,623 (9.2%) were lost to follow-up, and two children failed treatment. Using Kaplan-Meier functions, the median time to death was 27 days following treatment initiation. In adjusted Cox models, predictors of mortality included HIV (aHR 1.68, 95% CI 1.01-2.81), moderate malnutrition (aHR 2.22, 95% CI 1.18-4.16), and severe malnutrition (aHR 2.92, 95% CI 1.75-4.87).CONCLUSION: Mortality was high at an urban and a rural referral hospital among children who initiated TB treatment from 2016 to 2021, with the majority of deaths occurring during the intensive phase of TB treatment. Malnutrition and HIV were significant predictors of death during treatment.

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.

Pediatric Tuberculosis In Turkey: A Review of 5-years Period In A Tertiary Care Hospital

Tüberküloz gelişmiş ve gelişmekte olan tüm ülkelerde halen önemi koruyan bir halk sağlığı sorunudur. Çocukluk çağı tüberkülozunda erişkinden farklı olarak klasik bulguların daha az görülmesi ve mikrobiyolojik yöntemlerle etkenin gösterilme oranının düşük olması tanıdaki zorlukları oluşturur. Bu çalışma ile kliniğimizde tüberküloz hastalığı tanısı ile takip edilen hastaların klinik, laboratuvar ve radyolojik bulgularının değerlendirilmesi amaçlanmıştır. Çalışmaya kliniğimizde Ocak 2014-Aralık 2019 tarihleri arasında tüberküloz hastalığı tanısı ile izlenen 34 hasta dahil edilmiş olup hastaların dosyaları retrospektif olarak incelenmiştir. Hastaların %50’si (n:17) erkek olup tanı yaşı ortancası 153.5 aydır (aralık 17-218 ay). On üç hasta pulmoner, 8 hasta dissemine, 6 hasta gastrointestinal tüberküloz tanısı alırken; 6 hasta lenf nodu, 1 hasta eklem tüberkülozu tanısı almıştır. Tüberküloz temas öyküsü 8 (%23.5) hastada bulunmakta iken en sık başvuru şikayeti öksürük, karın ağrısı, kilo kaybı ve ateşti. Sekiz (%23.5) hastada başvuru sırasında patolojik muayene bulgusu saptanmamıştır. On yedi (%50) hastada tüberkülin deri testi pozitifliği mevcut iken yedi hastada tüberküloz basili mikrobiyolojik yöntemlerle gösterilmiştir. Bir hastada tedaviye verdiği olumlu yanıt ve diğer hastalıkların dışlanması ile tüberküloz hastalığı tanısı konulmuştur. Dört (%11.8) hastada yan etki nedeniyle tedaviye kısa süreli ara verilirken hiçbir hastada ciddi yan etki gözlenmemiştir. Tanı klinik, laboratuvar ve radyolojik bulguların bir araya getirilmesi ile konulmakta olup, kimi zaman hastanın tedaviye verdiği olumlu cevap ile hastalar tanı alabilmektedir.

Characteristics of Pediatric Tuberculosis Patients at Simpang Lima Gumul Hospital, Kediri, East Java

Introduction: Pediatric tuberculosis can cause a variety of problems, including growth failure, disability, and death. In 2021, WHO recorded 10.6 million individuals had tuberculosis globally, with pediatric tuberculosis accounting for 11% of these cases. Indonesia is the second highest high-burden country for tuberculosis, according to the WHO. Children with tuberculosis often present non-specific and uncommon symptoms, making diagnosis challenging and frequently delayed. This study aims to present an overview of the characteristics of pediatric tuberculosis patients at Simpang Lima Gumul Hospital in Kediri, East Java. Material and Methods: This was a descriptive retrospective study with a cross-sectional method. Pediatric tuberculosis patients who received treatment at the Simpang Lima Gumul Hospital in Kediri, East Java, were the subject of research. We compiled pediatric tuberculosis patients' demographic data and clinical characteristics using medical records. Results: Sixty-one children included in the study. Most of them were male (56%) between 1 to 5 years old (52%). Seventy-two percent had a positive tuberculin skin test; chronic cough was noted in 69% of cases. An adult contact history of tuberculosis was reported in 64% of cases, while 61% had radiographic findings from TB. 52% also had fever, 51% had lymphadenopathy, and 72% had good nutritional status. Conclusion: Tuberculosis occurs most commonly in male children 1 to 5 years of age. The most common symptoms of pediatric tuberculosis include a positive tuberculin skin test, chronic cough, contact with adults with tuberculosis, positive radiographic findings, fever, and lymphadenopathy.

Original Research Paper, Paediatrics Impact of Vitamin D Supplementation on Nutritional Status and Treatment Results in Pediatric and Adolescent Tuberculosis Patients

Original Research Paper, Paediatrics Impact of Vitamin D Supplementation on Nutritional Status and Treatment Results in Pediatric and Adolescent Tuberculosis Patients

Public Health Impact and Cost-Effectiveness of Screening for Active Tuberculosis Disease or Infection Among Children in South Africa.

Although tuberculosis disease is a leading cause of global childhood mortality, there remain major gaps in diagnosis, treatment, and prevention in children because tuberculosis control programs rely predominantly on presentation of symptomatic children or contact tracing. We assessed the public health impact and cost-effectiveness of age-based routine screening and contact tracing in children in South Africa. We used a deterministic mathematical model to evaluate age-based routine screening in 1-year increments from ages 0 to 5 years, with and without contact tracing and preventive treatment. Screening incorporated symptom history and tuberculin skin testing, with chest x-ray and GeneXpert Ultra for confirmatory testing. We projected tuberculosis cases, deaths, disability-adjusted life years (DALYs), and costs (in 2021 U.S. dollars) and evaluated the incremental cost-effectiveness ratios comparing each intervention. Routine screening at age 2 years with contact tracing and preventive treatment averted 11 900 tuberculosis cases (95% confidence interval [CI]: 6160-15 730), 1360 deaths (95% CI: 260-3800), and 40 000 DALYs (95% CI: 13 000-100 000) in the South Africa pediatric population over 1 year compared with the status quo. This combined strategy was cost-effective (incremental cost-effectiveness ratio $9050 per DALY; 95% CI: 2890-22 920) and remained cost-effective above an annual risk of infection of 1.6%. For annual risk of infection between 0.8% and 1.6%, routine screening at age 2 years was the dominant strategy. Routine screening for tuberculosis among young children combined with contact tracing and preventive treatment would have a large public health impact and be cost-effective in preventing pediatric tuberculosis deaths in high-incidence settings such as South Africa.

Clinical standards for drug-susceptible TB in children and adolescents.

BACKGROUND: These clinical standards aim to provide guidance for diagnosis, treatment, and management of drug-susceptible TB in children and adolescents.METHODS: Fifty-two global experts in paediatric TB participated in a Delphi consensus process. After eight rounds of revisions, 51/52 (98%) participants endorsed the final document.RESULTS: Eight standards were identified: Standard 1, Age and developmental stage are critical considerations in the assessment and management of TB; Standard 2, Children and adolescents with symptoms and signs of TB disease should undergo prompt evaluation, and diagnosis and treatment initiation should not depend on microbiological confirmation; Standard 3, Treatment initiation is particularly urgent in children and adolescents with presumptive TB meningitis and disseminated (miliary) TB; Standard 4, Children and adolescents should be treated with an appropriate weight-based regimen; Standard 5, Treating TB infection (TBI) is important to prevent disease; Standard 6, Children and adolescents should receive home-based/community-based treatment support whenever possible; Standard 7, Children, adolescents, and their families should be provided age-appropriate support to optimise engagement in care and clinical outcomes; and Standard 8, Case reporting and contact tracing should be conducted for each child and adolescent.CONCLUSION: These consensus-based clinical standards, which should be adapted to local contexts, will improve the care of children and adolescents affected by TB.

The use of clinical laboratory and radiologic data in the assessment of pediatric extrapulmonary tuberculosis cases in Kisumu County Kenya

Extrapulmonary tuberculosis is detected more frequently in children than adults since the risk of lymphohematogen spread is high in young children. Tuberculosis may attack any organ in the body, including the lymph nodes and the central nervous system. In children, it is difficult to detect tuberculosis since most signs and symptoms are not easily detected in young children. However, it has been documented to be the most crucial cause of mortality in the childhood age group. It has also been found to be non-specific, with low sensitivity to diagnostic tests amongst pediatric patients. This is partly because of its ability to mimic many other disease manifestations. This study evaluated the clinical, laboratory, and radiologic observations and treatment outcomes in pediatric patients followed up in the TB clinic.

Differences in epidemiological and clinical features between adult and pediatric tracheobronchial tuberculosis patients in Southwest China.

Tracheobronchial tuberculosis (TBTB) is a common form of extrapulmonary tuberculosis that affects the tracheobronchial tree. However, the mechanism has not been fully elucidated. Comparisons of clinical characteristics in various age groups can aid in the understanding of TBTB. This retrospective study was conducted at the Public Health Clinical Center of Chengdu between July 2017 and December 2021, including adults and children with TBTB. Clinical data were extracted from medical records. T/T' test, Mann-Whitney U test, Chi-square test, or Fisher's exact test were used in this study. This study enrolled 347 patients with TBTB (175 adults and 172 children). Adult females were more susceptible to TBTB, whereas gender-based differences were not observed in children. Children had a higher occurrence of irritant dry cough and fever, and acute hematogenous disseminated PTB, and specific types of EPTB, but a shorter interval before diagnosis, and lower diagnostic yields compared to adults (P < 0.05). Adults presented more extensive lung lesions and cavitations as compared to children. Granulation hyperplasia and lymph fistula were more frequently observed in children, as well as airway stenosis, but less severe. The study revealed important variations exist in multiple respects between adults and children with TBTB.

The use of clinical, laboratory, and radiologic data in the assessment of pediatric extra pulmonary tuberculosis cases in Kisumu County, Kenya

Extrapulmonary tuberculosis is detected more frequently in children than adults since the risk of lymphohematogen spread is high in young children. Tuberculosis may attack any organ in the body, including the lymph nodes and the central nervous system

Securing accelerated access to long-acting injectable cabotegravir for HIV prevention in low- and middle-income countries.

Reductions in HIV acquisition have slowed, and the global community is significantly off track from global goals. Oral pre-exposure prophylaxis (PrEP) alone cannot address the diverse needs of the millions of people at risk of HIV acquisition. Long-acting injectable cabotegravir (CAB-LA) received United States Food and Drug Administration approval for HIV prevention in December 2021. When studied, CAB-LA demonstrated high effectiveness, provides months of protection versus daily use, is preferred by some users and has the potential to achieve commodity cost reduction. These factors position CAB-LA to catalyse transformation in HIV prevention. Significant work must be undertaken to ensure at-scale uptake in low- and middle-income countries. Leveraging decades of product introduction experience, Clinton Health Access Initiative (CHAI) has developed an innovative roadmap to support equitable CAB-LA introduction, comprising tightly executed market-shaping, product development, regulatory, and programmatic and implementation action. Proven models exist (e.g. long-acting reversible contraceptives, paediatric tuberculosis treatment and antiretrovirals (ARVs), such as paediatric dolutegravir and tenofovir disoproxil fumarate, lamivudine, and dolutegravir) for partnership-driven, accelerated, impactful product introduction. Based on learnings from these models and needs in the prevention space, CHAI developed a roadmap to maximize the near-term impact of CAB-LA and accelerate the development of, access to and impact of quality-assured, low-cost generic CAB-LA. This roadmap is intended to inform introduction planning and investment decision-making across a range of stakeholders, including donors, governments, manufacturers and other partners working in the HIV prevention space. Elements include (1) ensuring coordination and alignment across partners, and avoiding redundancy experienced during oral PrEP introduction; (2) preparing national programmes and providing support to maximize impact, including the development of national policies, guidelines and introduction plans; system strengthening; quantification and procurement; and addressing evidence needs, among other areas; (3) supporting community engagement, ensuring that demand generation and delivery approaches are person-centred and community-led; (4) incentivizing generic product development through, for example, milestone-based commercialization incentives and product development cost-sharing; and (5) expediting regulatory reviews. Accelerating access to affordable, generic CAB-LA can transform progress towards HIV epidemic control. This vision of impact at scale in prevention is achievable, if informed by results-backed approaches to introduction.

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.

Duration of Symptoms Prior to Pediatric and Adolescent Tuberculosis Diagnosis and Its Impact on Schooling in Tanzania: A Mixed Methods Study.

At least a third of tuberculosis (TB) cases remain undiagnosed, disproportionately so in children and adolescents, which is hampering global elimination goals. Prolonged symptom duration presents a high-risk scenario for childhood TB in endemic areas, but the prolonged period of symptoms and its impact on educational attainment are rarely documented. Using a mixed method approach, we aimed to quantify the duration of respiratory symptoms and describe their impact on education among children from a rural area of Tanzania. We used data from a prospectively enrolled cohort of children and adolescents aged 4-17 years in rural Tanzania at the start of active TB treatment. We report on the cohort's baseline characteristics and explore the correlation between duration of symptoms and other variables. In-depth qualitative interviews were designed on the basis of a grounded theory approach to explore the impact of TB on educational attainment among school-aged children. In this cohort, children and adolescents diagnosed with TB experienced symptoms for a median of 85 days (interquartile range: 30, 231 days) prior to treatment initiation. In addition, 56 participants (65%) had a TB exposure in the household. Of the 16 families with school-aged children who were interviewed, 15 (94%) reported a significant negative impact of TB on the schooling of their children. Children in this cohort experienced a long duration of TB symptoms; the extent of illness impacted absenteeism at school. Screening initiatives for households affected by TB may lead to a shortened duration of symptoms and may minimize the impact on school attendance.