The Kynurenine/Tryptophan Ratio Is a Sensitive Biomarker for the Diagnosis of Pediatric Tuberculosis Among Indian Children

ObjectivesPediatric tuberculosis (TB) remains difficult to diagnose. The plasma kynurenine to tryptophan ratio (K/T ratio) is a potential biomarker for TB diagnosis and treatment response but has not been assessed in children.MethodsWe performed a targeted diagnostic accuracy analysis of four biomarkers: kynurenine abundance, tryptophan abundance, the K/T ratio, and IDO-1 gene expression. Data were obtained from transcriptome and metabolome profiling of children with confirmed tuberculosis and age- and sex-matched uninfected household contacts of pulmonary tuberculosis patients. Each biomarker was assessed as a baseline diagnostic and in response to successful TB treatment.ResultsDespite non-significant between-group differences in unbiased analysis, the K/T ratio achieved an area under the receiver operator characteristic curve (AUC) of 0.667 and 81.5% sensitivity for TB diagnosis. Kynurenine, tryptophan, and IDO-1 demonstrated diagnostic AUCs of 0.667, 0.602, and 0.463, respectively. None of these biomarkers demonstrated high AUCs for treatment response. The AUC of the K/T ratio was lower than biomarkers identified in unbiased analysis, but improved sensitivity over existing commercial assays for pediatric TB diagnosis.ConclusionsPlasma kynurenine and the K/T ratio may be useful biomarkers for pediatric TB. Ongoing studies in geographically diverse populations will determine optimal use of these biomarkers worldwide.

Child Contact Case Management—A Major Policy-Practice Gap in High-Burden Countries

The 2021 Global Tuberculosis (TB) report shows slow progress towards closing the pediatric TB detection gap and improving the TB preventive treatment (TPT) coverage among child and adolescent contacts. This review presents the current knowledge around contact case management (CCM) in low-resource settings, with a focus on child contacts, which represents a key priority population for CCM and TPT. Compelling evidence demonstrates that CCM interventions are a key gateway for both TB case finding and identification of those in need of TPT, and their yield and effectiveness should provide a strong rationale for prioritization by national TB programs. A growing body of evidence is now showing that innovative models of care focused on community-based and patient-centered approaches to household contact investigation can help narrow down the CCM implementation gaps that we are currently facing. The availability of shorter and child-friendly TPT regimens for child contacts provide an additional important opportunity to improve TPT acceptability and adherence. Prioritization of TB CCM implementation and adequate resource mobilization by ministries of health, donors and implementing agencies is needed to timely close the gap.

Adolescents in a tuberculosis hospital: Qualitative study of how relationships with doctors, caregivers, and peers mediate their mental wellbeing

Lengthy hospitalization can impact adolescents’ mental wellbeing in a number of negative ways. Scholarship has indicated that a young patient’s relationships play an important role in reducing the amount of stress felt and in improving emotional state. In this article we turn to the experiences of adolescents with tuberculosis [TB] in Russia to explore how exactly hospitalization together with the TB diagnosis itself impact their mental wellbeing and how relationships with others mediate these impacts. We conducted a qualitative, interview-based study in Tomsk pediatric TB clinic. Interviews were conducted with three groups relevant for reaching the aim of this research: adolescent patients, their adult caregivers, and their treating physicians [17 informants in total]. Interview data were complemented with prolonged observations in the same clinic. The results of our study highlight that threats to mental wellbeing of adolescents with TB are multiple. Adolescents who are about to enter the in-patient treatment feel apprehensive and anxious about their future. They tend to have a hard time accepting their diagnosis, which they often feel is something shameful, and, consequently, may develop a negative attitude towards themselves. Most importantly, many undergo painful loss of personal relationships and expect or actually experience rejection by peers because of having tuberculosis. However, relationships with physicians, caregivers, and other patients in the clinic mediate negative impacts of TB diagnosis and hospitalization on adolescents’ mental wellbeing and can open ways for providing support. Supportive practices include physicians leaving it up to adolescents to decide what they want to discuss and when, caregivers remaining available for contact and keeping regular communication, and other adolescents with TB proactively seeking contact with the newcomers and behaving in a non-judgmental way. These results can inform design of adolescent-friendly TB services.

Treatment success using novel and adapted treatment regimens in registered DR-TB children in Dushanbe, Tajikistan, 2013-2019

Introduction: Approximately 3% of all pediatric TB cases develop MDR-TB, with only 3–4% of such children receiving MDR-TB treatment. In Tajikistan, children as a proportion of all DR-TB in the country increased from 4.3 to 7.5% during 2013-2018. Despite limited evidence on the use of new anti-TB drugs in children, WHO has updated its guidelines for DR-TB treatment for children, and Tajikistan did so in 2013 and 2017. Novel and adapted regimens included individual regimens for RR/MDR, XDR (with and without Bedaquiline and Delamanid) and short treatment regimens with and without injectables. It is important to document the outcomes of the treatment regimens. Therefore, the aim of this study was to describe characteristics of children receiving different treatment regimens for DR-TB, the culture conversion and treatment outcomes. Methodology: Cohort study of children enrolled in DR-TB treatment by the National Tuberculosis Program in Dushanbe, Tajikistan, January 2013 to July 2019. Results: The study included 60 DR-TB children. The male to female ratio was 1:2 and mean age 13.6 years. Median time to culture conversion was 66 days [IQR:31-103; Range:2-232]. In children with treatment outcomes (N = 58), 93% had favorable outcomes. There were four children (7%) with unfavorable treatment outcomes, all of whom were female 15-17 years, on standard (RR/MDR) treatment during 2013-2015. Favorable outcomes by DR-TB type were 91%, 90%, and 100% in RR/MDR, PreXDR, and XDR-TB patients, respectively. Conclusions: All children enrolled after the introduction of modified guidelines for novel and adapted regimens for DR-TB showed positive TB treatment outcomes.

Challenges Perceived by Health Care Providers for Implementation of Contact Screening and Isoniazid Chemoprophylaxis in Karnataka, India

Background: In India, challenges in pediatric TB contact screening and chemoprophylaxis initiation are still underexplored. Elucidating these challenges will help in better implementation of the programme at the grass-roots level thereby helping in early detection of pediatric cases and timely initiation of preventive therapy. This study aimed at exploring the challenges faced by the health care provider in contact screening and chemoprophylaxis initiation implementation of the pediatric household contacts. Methods: A qualitative study was conducted in the districts of Bengaluru and Udupi and in-depth interviews of key participants were adopted to explore the challenges. Qualitative data analysis was done after developing transcripts by generating themes and codes. Results: The key challenges were identified as stigma towards the disease, migrant patients with changing address, difficulty in sample collection, anxiety among parents due to long duration of the prophylactic treatment and adherence to IPT is not well documented, inadequate transportation from rural areas, and the ongoing COVID-19 pandemic. Conclusions: It is important for the National TB programme to address these challenges efficiently and effectively. Innovative solutions, feasible engagements, and massive efforts are to be taken by the programme to improve contact screening and isoniazid chemoprophylaxis implementation.

Gambaran Sistem Skoring Tuberkulosis Anak di Rumah Sakit Bhayangkara Indramayu Tahun 2019

Indonesia menjadi negara endemis tb dengan prevalensi tb paru anak yang cukup tinggi. Tuberkulosis merupakan penyakit yang disebabkan oleh Mycobacterium tuberculosis. Kepadatnya penduduk, tingkat pendidikan rendah, pola hidup bersih dan sehat, serta status gizi buruk menjadi risiko tinggi penularan penyakit ini terutama pada anak. Terdapat kesulitan dalam penegakan diagnosis disebabkan oleh kesulitan pengambilan sampel dahak pada anak. Ikatan Dokter Anak Indonesia (IDAI) menggunakan pendekatan sistem skoring dalam mendiagnosis TB paru pada anak. Penelitian ini bertujuan untuk mengetahui gambaran sistem skoring tuberklosis pada pasien rawat jalan di Rumah Sakit Bhayangkara Indramayu bulan Januari-Desember tahun 2019. Penelitian ini menggunakan data sekunder yang diperoleh dari 69 rekam medis pasien TB anak mengenai parameter sistem skoring. Hasil menunjukkan bahwa sebanyak 74% pasien didiagnosis TB anak dengan skoring TB ≥6 dan 26% skoring TB <6. Hal ini kemungkinan karena sebagian besar anak yang didiagnosis mengalami gizi buruk. Imunitas yang belum matur juga menjadi salah satu faktor risiko sistem skoring rendah. Simpulan, sistem skoring masih dapat menjadi pendekatan diagnosis TB pada anak. Overview of the Children's Tuberculosis Scoring System at the Bhayangkara Indramayu Hospital in 2019Indonesia is one of the endemic countries for tuberculosis, with a high prevalence of pulmonary tuberculosis in children. Tuberculosis is a chronic disease caused by Mycobacterium tuberculosis. The density of population, low level of education, low hygiene and healthy lifestyle, and poor nutritional status are the cause of transmission of this disease, especially in children. Diagnosis of tuberculosis in children is quite difficult due to the difficulty of taking sputum samples in children. For this reason, the Indonesian Pediatrician Association (IDAI) uses a scoring system approach in diagnosing pulmonary TB in children. This study aims to determine the tuberculosis scoring system in outpatients at the Bhayangkara Indramayu Hospital in January-December 2019. This study used secondary data obtained from 69 medical records of pediatric TB patients regarding the scoring system parameters. The results showed that patients were diagnosed with TB in children with TB scoring ≥6 (74%) and TB scoring <6 (26%). These are presumed because most children which diagnosed with TB have malnutrition. Immature immunity is also a risk factor for low scoring system parameters. Conclusion, the scoring can still be a diagnostic approach for TB in children.

Pediatric Tuberculosis Disease during Years of High Refugee Arrivals: A 6-Year National Prospective Surveillance Study

<b><i>Background:</i></b> In Europe, surveillance and monitoring of pediatric tuberculosis (TB) remains important, particularly in the light of migration in recent years. The aim of the study was to evaluate incidence rates of childhood TB and detailed diagnostic pathways and treatment. <b><i>Methods:</i></b> Data were collected through the Swiss Pediatric Surveillance Unit (SPSU) from December 2013 to November 2019. Monthly ­notifications are obtained from the 33 pediatric hospitals in the SPSU, and a detailed questionnaire was sent out upon notification. Inclusion criteria were children and adolescents aged up to 15 years with culture- or molecular-confirmed TB disease or for whom a treatment with ≥3 antimycobacterial drugs had been initiated. Data were compared with age-matched notification data from the Swiss Federal Office of Public Health (FOPH). <b><i>Results:</i></b> Of the 172 cases notified to SPSU, a detailed questionnaire was returned for 161 (93%) children, of which 139 met the inclusion criteria. Reasons for exclusion were age &#x3e;15 years, double reporting, and not fulfilling the criteria for TB disease. During the same time period, 172 pediatric TB cases were reported to the FOPH, resulting in an incidence of 2.1 per 100,000, ranging from 1.4 to 2.8 per year, without a clear trend over time. In the 64 (46.0%) foreign-born children, incidence rates were higher and peaked in 2016, with 13.7 per 100,000 (<i>p</i> = 0.018). The median interval between arrival in Switzerland and TB diagnosis was 5 (IQR 1–21) months, and 80% were diagnosed within 24 months of arrival. In 58% of the cases, TB disease was confirmed by culture or molecular assays. Age &#x3e;10 years, presence of fever, or weight loss were independent factors associated with confirmed TB. <b><i>Conclusion:</i></b> The annual pediatric TB incidence rate only varied among foreign-born children and was highest in 2016 when refugee influx peaked in Europe. Importantly, most foreign-born children with TB were diagnosed within 2 years after arrival in Switzerland. Thus, the early period after arrival in Switzerland is associated with a higher risk of TB disease in children, and this should be considered for screening guidance in refugees.

Using a mobile application to improve pediatric presumptive TB identification in western Kenya

BACKGROUND: Early recognition of TB symptoms in children is critical in order to link children to appropriate testing and treatment. Healthcare workers (HCWs) in high TB burden countries are often overburdened with competing clinical priorities, leading to incomplete presumptive TB screening. We assessed if implementing a community health volunteer (CHV) led presumptive pediatric TB mobile android application (PPTBMAPP) in pediatric outpatient, primary care clinics in western Kenya would be feasible, appropriate, and effective.METHODS: We used a mixed-methods participatory, iterative approach to design and implement the PPTBMAPP during a 6-month period. We compared the proportion of children identified in presumptive TB and active TB disease registers out of all patients before and after the implementation of the intervention.RESULTS: Of the 1787 children aged ≤15 years screened using the PPTBMAPP, 376 (21%) met the criteria for presumptive TB. There was a statistically significant increase in the proportion of children to all patients in the presumptive TB registers (97/908, 10.7% vs. 160/989, 16.2%; P = 0.0005), and a trend towards an increase in the proportion of children to all patients in the TB case register (17/117, 14.5% vs. 15/83, 18.1%; P = 0.5). HCWs interviewed commented that the application sped up the presumptive TB screening process.CONCLUSION: Our CHV-led mobile screening intervention significantly increased presumptive TB notification. HCWs reported that the mobile screening intervention was feasible, appropriate, and effective.

Evaluation of a serum-based antigen test for tuberculosis in HIV-exposed infants: a diagnostic accuracy study

Background Non-sputum methods are urgently needed to improve tuberculosis diagnosis and treatment monitoring in children. This study evaluated the ability of a serum assay quantifying a species-specific peptide of the Mycobacterium tuberculosis CFP-10 virulence factor via nanotechnology and matrix-assisted laser desorption ionization time-of-flight mass spectrometry to diagnose tuberculosis in HIV-infected and HIV-uninfected infants. Methods Serum CFP-10 peptide signal was blinded evaluated in cryopreserved sera of 519 BCG-immunized, HIV-exposed infants (284 HIV-infected, 235 HIV-uninfected) from a multi-center randomized placebo-controlled isoniazid prophylaxis trial conducted in southern Africa between 2004 and 2008, who were followed up to 192 weeks for Mtb infection and TB. Children were classified as confirmed, unconfirmed, or unlikely tuberculosis cases using 2015 NIH diagnostic criteria for pediatric TB. Results In HIV-infected infants, CFP-10 signal had 100% sensitivity for confirmed TB (5/5, 95% CI, 47.8–100) and 83.7% sensitivity for unconfirmed TB (36/43, 95% CI 69.3–93.2), with 93.1% specificity (203/218, 95% CI 88.9–96.1). In HIV-uninfected infants, CFP-10 signal detected the single confirmed TB case and 75.0% of unconfirmed TB cases (15/20; 95% CI 50.9–91.3), with 96.2% specificity (177/184, 95% CI, 92.3–98.5). Serum CFP-10 achieved 77% diagnostic sensitivity for confirmed and unconfirmed TB (13/17, 95% CI, 50–93%) at ≤ 24 weeks pre-diagnosis, and both CFP-10-positivity and concentration declined following anti-TB therapy initiation. Conclusions Serum CFP-10 signal exhibited high diagnostic sensitivity and specificity for tuberculosis in HIV-infected and HIV-uninfected infants and potential utility for early TB detection and monitoring of anti-TB treatment responses.