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Tuberculosis (TB) survivors, especially children and adolescents, can develop chronic respiratory problems called post-tuberculosis lung disease (PTLD). We conducted a scoping review to identify the current knowledge gaps on PTLD definitions, measuring tools, and research specific to this age group. We searched MEDLINE, EMBASE, Global Health, CINAHL, and Web of Science for studies published between January 1, 2000, and March 1, 2024, and identified 16 studies. Our review found that no consistent definition of PTLD was used in the studies, and the measurement tools used varied widely. Moreover, there was a lack of research on children under five years old, who are disproportionately affected by TB. Also, symptom screening tools designed for adults were frequently used in these studies, raising concerns about their accuracy in detecting PTLD in children and adolescents. Several critical research gaps require attention to improve our understanding and treatment of PTLD. Firstly, the use of inconsistent definitions of PTLD across studies makes it challenging to compare research findings and gain a clear understanding of the condition. Therefore, we need to include an objective measurement of respiratory health, such as a comprehensive post-TB lung function assessment for children and adolescents. It is also crucial to determine the optimal timing and frequency of post-TB assessments for effective PTLD detection. Furthermore, we need more knowledge of the modifiable risk factors for PTLD. The scarcity of prospective studies makes it difficult to establish causality and track the long-term course of the disease in children and adolescents. Finally, current approaches to PTLD management often fail to consider patient-reported outcomes and strategies for social support. Addressing these research gaps in future studies can improve our understanding and management of paediatric PTLD, leading to better long-term health outcomes for this vulnerable population.

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BACKGROUND: Comorbidities complicate the management of tuberculosis (TB) and have become an essential part of the end TB strategy to eradicate TB. However, pulmonary TB has received the most attention, and little is known about the impact of comorbidities and other factors on outcomes in patients with extrapulmonary tuberculosis (EPTB). OBJECTIVES: Our aim was to analyze the factors associated with hospitalization and mortality in EPTB at a hospital in Central India, using non-TB patients with similar clinical presentations as a comparison. METHODS: Patients with presumptive EPTB were prospectively enrolled and followed up until the end of treatment or for at least 6 months. Detailed demographic and clinical information was collected for all participants, and patients were categorized as TB or non-TB using a composite reference standard. Multivariate logistic regression was used to analyze the impact of various clinical findings and risk factors on hospitalization and mortality. RESULTS: A total of 276 patients were categorized as TB cases and 175 as non-TB cases. Factors associated with hospitalization in children were younger age and non-adenitis site of disease. In adults, factors associated with mortality were older age, non-adenitis site of disease and HIV infection regardless of TB diagnosis, while diabetes mellitus increased the odds of mortality in EPTB patients. CONCLUSION: Our results show that comorbidities increase the odds of death in both TB and non-TB patients in low-resource settings. This argues for a shift away from the traditional vertical management of diseases in these areas and supports a continued focus on building robust healthcare systems.

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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.

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Diagnosing extrapulmonary tuberculosis (EPTB) is challenging. Immunohistochemistry or immunocytochemistry has been used to diagnose tuberculosis (TB) by detection of MPT64 antigen from various extrapulmonary specimens and has shown good diagnostic performance in our previous studies. The test can distinguish between disease caused by Mycobacterium tuberculosis (Mtb) complex and nontuberculous mycobacteria and can be applied on formalin-fixed paraffin-embedded tissue. As the antibodies previously used were in limited supply, a new batch of polyclonal antibodies was developed for scale-up and evaluated for the first time in this study. Our aim was to assess the diagnostic accuracy of the MPT64 test with reproduced antibodies in the high burden settings of Pakistan and India. Patients were enrolled prospectively. Samples from suspected sites of infection were collected and subjected to histopathologic and/or cytologic evaluation, routine TB diagnostics, GeneXpert MTB/RIF (Xpert), and the MPT64 antigen detection test. Patients were followed until the end of treatment. Based on a composite reference standard (CRS), 556 patients were categorized as TB cases and 175 as non-TB cases. The MPT64 test performed well on biopsies with a sensitivity and specificity of 94% and 75%, respectively, against a CRS. For cytology samples, the sensitivity was low (36%), whereas the specificity was 81%. Overall, the MPT64 test showed higher sensitivity (73%) than Xpert (38%) and Mtb culture (33%). The test performed equally well in adults and children. We found an additive diagnostic value of the MPT64 test in conjunction with histology and molecular tests, increasing the yield for EPTB. In conclusion, immunochemical staining with MPT64 antibodies improves the diagnosis of EPTB in high burden settings and could be a valuable addition to routine diagnostics.

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BACKGROUND: Although post-tuberculosis lung disease (PTLD) is a known consequence of pulmonary tuberculosis (pTB), few studies have reported the prevalence and spectrum of PTLD in children and adolescents. METHODS: Children and adolescent (≤19 years) survivors of pTB in the Western Regions of The Gambia underwent a respiratory symptom screening, chest X-ray (CXR) and spirometry at TB treatment completion. Variables associated with lung function impairment were identified through logistic regression models. RESULTS: Between March 2022 and July 2023, 79 participants were recruited. The median age was 15.6 years (IQR: 11.8, 17.9); the majority, 53/79 (67.1%), were treated for bacteriologically confirmed pTB, and 8/79 (10.1%) were children and adolescents living with HIV. At pTB treatment completion, 28/79 (35.4%) reported respiratory symptoms, 37/78 (47.4%) had radiological sequelae, and 45/79 (57.0%) had abnormal spirometry. The most common respiratory sequelae were cough (21/79, 26.6%), fibrosis on CXR (22/78, 28.2%), and restrictive spirometry (41/79, 51.9%). Age at TB diagnosis over ten years, undernutrition and fibrosis on CXR at treatment completion were significantly associated with abnormal spirometry (p = .050, .004, and .038, respectively). CONCLUSION: Chronic respiratory symptoms, abnormal CXR, and impaired lung function are common and under-reported consequences of pTB in children and adolescents. Post-TB evaluation and monitoring may be necessary to improve patient outcomes.

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Background: One of the global key indicators for monitoring the implementation of the World Health Organization's End Tuberculosis (TB) Strategy is the treatment outcome rate. Objective: This study aims to assess the magnitude of unfavorable treatment outcomes and estimate their relationship with baseline undernutrition and sustained undernutrition among children receiving TB treatment in central Ethiopia. Methods: This retrospective cohort study included children treated for drug-susceptible TB between June 2014 and February 2022. The study comprised children aged 16 and younger who were treated in 32 randomly selected healthcare facilities. A log-binomial model was used to compute adjusted risk ratios (aRR) with 95% confidence intervals (CIs). Results: Of 640 children, 42 (6.6%; 95% CI = 4.8-8.8%) had an unfavorable TB treatment outcomes, with 31 (73.8%; 95% CI = 58.0-86.1%) occurring during the continuation phase of TB treatment. We confirmed that baseline undernutrition (aRR = 2.68; 95% CI = 1.53-4.71), age less than 10 years (aRR = 2.69; 95% CI = 1.56-4.61), HIV infection (aRR = 2.62; 95% CI = 1.50-4.59), and relapsed TB (aRR = 3.19; 95% CI = 1.79-4.71) were independent predictors of unfavorable TB treatment outcomes. When we looked separately at children who had been on TB treatment for two months or more, we found that sustained undernutrition (aRR = 3.76; 95% CI = 1.90-7.43), age below ten years (aRR = 2.60; 95% CI = 1.31-5.15), and HIV infection (aRR = 2.26; 95% CI = 1.11-4.59) remained predictors of unfavorable outcomes, just as they had in the first two months. However, the effect of relapsed TB became insignificant (aRR = 2.81; 95% CI = 0.96-8.22) after the first two months TB treatment. Conclusions: The magnitude of unfavorable TB treatment outcomes among children in central Ethiopia met the World Health Organization's 2025 milestone. Nearly three-quarters of unfavorable TB treatment outcomes occurred during the continuation phase of TB treatment. Baseline undernutrition, sustained undernutrition, younger age, HIV infection, and relapsed TB were found to be independent predictors of unfavorable TB treatment outcomes among children receiving TB treatment in central Ethiopia.

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BACKGROUND: Inadequate numbers of children under five years of age who are exposed to tuberculosis (TB) in the home (child contact) are initiated on TB preventive treatment (TPT) in South Africa. We assessed barriers of initiating isoniazid preventive therapy (IPT) in this age group. METHODS: We conducted a qualitative study at two primary health clinics in the Ekurhuleni district in Gauteng Province. Between April and July 2019, we enrolled facility managers, TB staff and parents or legal guardians of child contacts (caregivers) attending for care, at the two facilities. Semi-structured questionnaires, facility observations and in-depth interviews using a semi-structured interview guide were used to collect data. Findings from the semi-structured questionnaires with facility staff and facility observations were summarized. Thematic analysis with a deductive approach was used to analyse the data from the in-depth interviews with caregivers. RESULTS: Two facility managers took part in the study and were assisted to complete the semi-structured questionnaires by TB staff. Fifteen caregivers aged between 18 and 43 years were interviewed of which 13 (87%) were female. Facility managers and TB staff (facility staff) felt that even though caregivers knew of family members who were on TB treatment, they delayed bringing their children for TB screening and TPT. Facility staff perceived caregivers as not understanding the purpose and benefits of TB prevention strategies such as TPT. Caregivers expressed the desire for their children to be screened for TB. However, caregivers lacked knowledge on TB transmission and the value of TB prevention in children at high risk of infection. CONCLUSION: While facility staff perceived caregivers to lack responsibility, caregivers expressed limited knowledge on the value of screening their children for TB as reasons for not accessing TB preventive services. Health education on TB transmission, screening, and TB prevention strategies at a community level, clinics, creches, schools and via media are important to achieve the global end TB goal of early detection and prevention of TB.

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Tuberculosis and malignancy are major public health problems in developing countries like India and causes significant morbidity and mortality. Mycobacterium tuberculosis is an aerobic acid-fast bacilli which is an important pathogen especially complicating clinical status of paediatric oncology patients and treatment of infection with this bacilli is challenging in this subpopulation of patients because of ongoing immunosuppression and relative lack of published guidelines. Atypical presentations of tuberculosis in children also complicate the diagnosis and management. All the more, in tuberculosis endemic area lung cancer may be mistakenly diagnosed as tuberculosis or vice versa and this wrong diagnosis increases the burden on country's health status. It is noted that tuberculosis prevalence is high in children with haematological malignancy and head and neck tumours compared to other solid organ tumours. Moreover, it is found that morbidity and mortality from tuberculosis is more in children from WHO listed high TB burden countries who undergo hematopoietic stem cell and solid organ transplantation. Use of immune checkpoint inhibitors as novel therapy in treatment of childhood malignancies has led to modification of the body's immunological response and has resulted in increased latent tuberculosis infection reactivation as one immune-related infectious consequence. Latent TB infection screening is important concept in management of paediatric oncology patients. Currently, the tests employed as screening diagnostics for LTBI are interferon-gamma release assay (IGRA) blood test and the tuberculin skin test (TST). Various regimens have been suggested for the treatment of LTBI. But, after a positive IGRA or TST and prior to latent TB treatment, active tuberculosis should be ruled out by detailed history taking, examination and appropriate investigations so as to minimize the risk of drug resistance with anti-tuberculosis monotherapy used in LTBI treatment. To add on to literature, Non tuberculous mycobacteria are universally present environmental organisms. However, in immunocompromised children especially in subpopulation of malignancy, NTM is known to cause infections which needs protocol based management. Also importance has to given to implementation of adequate preventive and corrective measures to prevent such opportunistic infection in paediatric oncology subpopulation. In this review, we provide an overview of tuberculosis in paediatric oncology patients and summarize the expansive body of literature on the tuberculosis mimicking carcinoma, tuberculosis burden in transplantation patients and those receiving immune check point inhibitors, latent TB infection screening and management, and NTM infection in children with malignancy.

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BACKGROUND: 1.2 million children under 15 years are estimated to have developed tuberculosis (TB) in 2021. 85% of paediatric patients achieve successful treatment outcomes if treated for the first episode of TB. However, despite so-called successful treatment, TB leaves many survivors with permanently destroyed or damaged lungs. Data from prospective paediatric cohorts to establish the burden and evolution of post-TB lung disease (PTLD) are still absent. The Childhood TB Sequel study aims to describe respiratory consequences associated with pulmonary TB in Gambian children, describe the evolution of these sequelae, and determine associated epidemiological risk factors. METHODS: We aim to recruit up to 80 subjects aged 19 years and below who have recently completed treatment for pulmonary TB. Recruitment started in April 2022 and is expected to continue until June 2024. Clinical assessment, chest X-ray, and comprehensive lung function assessment are carried out at treatment completion and again six and 12 months later. DISCUSSION: The Childhood TB Sequel study will address existing research gaps to enhance our knowledge and understanding of the burden of PTLD in Gambian children. The study will also contribute to formulating a plan for post-TB evaluation and long-term follow-up strategies. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05325125, April 13, 2022.

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BACKGROUND: Childhood tuberculosis (TB) was poorly studied in Ethiopia. This study aimed to describe the epidemiology of childhood TB and identify predictors of death among children on TB treatment. METHODS: This is a retrospective cohort study of children aged 16 and younger who were treated for TB between 2014 and 2022. Data were extracted from TB registers of 32 healthcare facilities in central Ethiopia. Phone interview was also conducted to measure variables without a space and not recorded in the registers. Frequency tables and a graph were used to describe the epidemiology of childhood TB. To perform survival analysis, we used a Cox proportional hazards model, which was then challenged with an extended Cox model. RESULTS: We enrolled 640 children with TB, 80 (12.5%) of whom were under the age of two. Five hundred and fifty-seven (87.0%) of the enrolled children had not had known household TB contact. Thirty-six (5.6%) children died while being treated for TB. Nine (25%) of those who died were under the age of two. HIV infection (aHR = 4.2; 95% CI = 1.9-9.3), under nutrition (aHR = 4.2; 95% CI = 2.2-10.48), being under 10 years old (aHR = 4.1; 95% CI = 1.7-9.7), and relapsed TB (aHR = 3.7; 95% CI = 1.1-13.1) were all independent predictors of death. Children who were found to be still undernourished two months after starting TB treatment also had a higher risk of death (aHR = 5.64, 95% CI = 2.42-13.14) than normally nourished children. CONCLUSIONS: The majority of children had no known pulmonary TB household contact implying that they contracted TB from the community. The death rate among children on TB treatment was unacceptably high, with children under the age of two being disproportionately impacted. HIV infection, baseline as well as persistent under nutrition, age < 10 years, and relapsed TB all increased the risk of death in children undergoing TB treatment.

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Drug-resistant tuberculosis (DR-TB) in children is a growing global health concern, This review provides an overview of the current epidemiology of childhood TB and DR-TB, including prevalence, incidence, and mortality. We discuss the challenges in diagnosing TB and DR-TB in children and the limitations of current diagnostic tools. We summarize the challenges associated with treating multi-drug resistance TB in childhood, including limitations of current treatment options, drug adverse effects, prolonged regimens, and managing and monitoring during treatment. We highlight the urgent need for improved diagnosis and treatment of DR-TB in children. The treatment of children with multidrug-resistant tuberculosis will be expanded to include the evaluation of new drugs or new combinations of drugs. Basic research is needed to support the technological development of biomarkers to assess the phase of therapy, as well as the urgent need for improved diagnostic and treatment options.

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BACKGROUND: Latent tuberculosis (TB) infection has been known as a seedbed for TB disease later in life. The interruption from latent TB infection to TB disease can be done through TB preventive treatment (TPT). In Cambodia, only 40.0% of children under five years old who were the household contacts to bacteriologically confirmed TB cases were initiated with TPT in 2021. Scientific studies of context-specific operational challenges in TPT provision and uptake among children are scarce, particularly in high TB-burden countries. This study identified challenges in TPT provision and uptake among children in Cambodia from the perspective of healthcare providers and caregivers. METHODS: Between October and December 2020, we conducted in-depth interviews with four operational district TB supervisors, four clinicians and four nurses in charge of TB in referral hospitals, four nurses in charge of TB in health centers, and 28 caregivers with children currently or previously on TB treatment or TPT, and those who refused TPT for their eligible children. Data were audio recorded along with field notetaking. After verbatim transcription, data analyses were performed using a thematic approach. RESULTS: The mean age of healthcare providers and caregivers were 40.19 years (SD 12.0) and 47.9 years (SD 14.6), respectively. Most healthcare providers (93.8%) were male, and 75.0% of caregivers were female. More than one-fourth of caregivers were grandparents, and 25.0% had no formal education. Identified key barriers to TPT implementation among children included TPT side effects, poor adherence to TPT, poor understanding of TPT among caregivers, TPT risk perception among caregivers, TPT's child-unfriendly formula, TPT supply-chain issues, caregivers' concern about the effectiveness of TPT, being non-parental caregivers, and poor community engagement. CONCLUSION: Findings from this study suggest that the national TB program should provide more TPT training to healthcare providers and strengthen supply chain mechanisms to ensure adequate TPT drug supplies. Improving community awareness of TPT among caregivers should also be intensified. These context-specific interventions will play a crucial role in expanding the TPT program to interrupt the development from latent TB infection to active and ultimately lead to ending TB in the country.

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Background: The burden of tuberculosis (TB) in Nigeria remains high, and diagnosis in children, a challenge. We aimed to document yield from Xpert Mycobacterium tuberculosis/rifampicin (MTB/RIF) as a mode of diagnosis for children and the variables associated with a positive result. Methods: This was a retrospective review of TB treatment cards of children aged 0-15 years managed from January 2017 to December 2021 across six public tertiary institutions in Nigeria. The data obtained were analyzed using the descriptive and inferential statistics. Statistical significance was set at P < 0.05. Results: Of 1489 children commenced on TB treatment, 1463 (97.9%) had sufficient data for analysis the median age of study participants was 60 months (interquartile range [IQR]: 24, 120), and 814 (55.6%) were males. Xpert MTB/RIF test was performed in 862 (59%) participants and MTB was detected in 171 (19.8%) participants, of which 6.4% (11/171) had RIF resistance reported. The use of Xpert MTB/RIF rose from 56.5% in 2017 to 64% in 2020 but fell to 60.9% in 2021. We found that older age (> 10 years), the presence of pulmonary TB (PTB), and a negative human immunodeficiency virus (HIV) status were associated with positive Xpert MTB/RIF tests (P = 0.002, 0.001, and 0.012, respectively). Conclusion: The utilization of Xpert MTB/RIF in children increased in the years before the COVID-19 pandemic. Factors associated with MTB detection by Xpert MTB/RIF include older age, the presence of PTB, and a negative HIV status. Clinical and radiological evaluation continues to play vital roles in the diagnosis of childhood TB in Nigeria.

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El compromiso ocular es una forma extrapulmonar de tuberculosis. Puede comprometer cualquier componente del sistema visual. Las manifestaciones oculares pueden ser causadas por una infección activa que invade el ojo o por una reacción inmunológica de hipersensibilidad retardada. Las presentaciones clínicas más comunes son uveítis anterior crónica, coroiditis y esclero-queratitis. A pesar de la existencia de herramientas moleculares altamente sensibles, arribar al diagnóstico de formas poco frecuentes o no pensadas como la TB ocular en un niño sigue siendo un gran reto y se basa en la presentación clínica, evaluación sistémica y la respuesta terapéutica. El tratamiento implica el uso de antifímicos y, muchas veces, esteroides. El objetivo fue presentar una forma de tuberculosis endoftálmica, pulmonar miliar y meníngea, en el marco de la drogorresistencia.

Eye engagement is an extrapulmonary form of tuberculosis. It can compromise any component of the visual system. Eye manifestations can be caused by an active infection that invades the eye or by a delayed hypersensitivity immune reaction. The most com mon clinical presentations are: chronic anterior uveitis, choroiditis and sclero-keratitis. Despite the existence of highly sensitive molecular tools, arriving at diagnosis in rare or undeceived ways with eye tuberculosis in a child remains a major challenge, based on clinical presentation, systemic evaluation and therapeutic response. Treatment involves the use of antiphymics and often steroids. The objective was to present a form of endophthalmic tuberculosis, miliary pulmonary and meningeal, in the framework of drug resistance.

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BACKGROUND: Diagnosis and treatment of tuberculosis (TB) in children remain challenging, particularly in resource-limited settings. Healthcare providers and caregivers are critical in improving childhood TB screening and treatment. This study aimed to determine the barriers to childhood TB detection and management from the perspectives of healthcare providers and caregivers in Cambodia. METHOD: We conducted this qualitative study between November and December 2020. Data collection included in-depth interviews with 16 healthcare providers purposively selected from four operational districts and 28 caregivers of children with TB and children in close contact with bacteriologically confirmed pulmonary TB residing in the catchment areas of the selected health centers. Data were analyzed using thematic analyses. RESULTS: Mean ages of healthcare providers and caregivers were 40.2 years (standard deviation [SD] 11.9) and 47.9 years (SD 14.6), respectively. Male was predominant among healthcare providers (93.8%). Three-fourths of caregivers were female, and 28.6% were grandparents. Inadequate TB staff, limited knowledge on childhood TB, poor collaboration among healthcare providers in different units on TB screening and management, limited quality of TB diagnostic tools, and interruption of supplies of childhood TB medicines due to maldistribution from higher levels to health facilities were the key barriers to childhood TB case detection and management. Caregivers reported transportation costs to and from health facilities, out-of-pocket expenditure, time-consuming, and no clear explanation from healthcare providers as barriers to childhood TB care-seeking. Aging caregivers with poor physical conditions, lack of collaboration from caregivers, ignorance of healthcare provider's advice, and parent movement were also identified as barriers to childhood TB case detection and management. CONCLUSIONS: The national TB program should further invest in staff development for TB, scale-up appropriate TB diagnostic tools and ensure its functionalities, such as rapid molecular diagnostic systems and X-ray machines, and strengthen childhood TB drug management at all levels. These may include drug forecasting, precise drug distribution and monitoring mechanism, and increasing community awareness about TB to increase community engagement.

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BACKGROUND: We describe tuberculosis (TB) disease among antiretroviral treatment (ART) eligible children living with HIV (CLHIV) in South Africa to highlight TB prevention opportunities. METHODS: In our secondary analysis among 0- to 12-year-old ART-eligible CLHIV in five Eastern Cape Province health facilities from 2012 to 2015, prevalent TB occurred 90 days before or after enrollment; incident TB occurred >90 days after enrollment. Characteristics associated with TB were assessed using logistic and Cox proportional hazards regression with generalized estimating equations. RESULTS: Of 397 enrolled children, 114 (28.7%) had prevalent TB. Higher-income proxy [adjusted odds ratio (aOR) 1.8 [95% confidence interval (CI) 1.3-2.6] for the highest, 1.6 (95% CI 1.6-1.7) for intermediate]; CD4+ cell count <350 cells/µl [aOR 1.6 (95% CI 1.1-2.2)]; and malnutrition [aOR 1.6 (95% CI 1.1-2.6)] were associated with prevalent TB. Incident TB was 5.2 per 100 person-years and was associated with delayed ART initiation [hazard ratio (HR) 4.7 (95% CI 2.3-9.4)], malnutrition [HR 1.8 (95% CI 1.1-2.7)] and absence of cotrimoxazole [HR 2.3 (95% CI 1.0-4.9)]. Among 362 children with data, 8.6% received TB preventive treatment. CONCLUSIONS: Among these CLHIV, prevalent and incident TB were common. Early ART, cotrimoxazole and addressing malnutrition may prevent TB in these children.

BACKGROUND: We describe tuberculosis (TB) in children living with HIV (CLHIV) eligible for HIV treatment in South Africa to highlight opportunities to prevent TB. METHODS: We analyzed additional data from our original study of CLHIV who were 0­12 years old and due to start HIV treatment in five health facilities in Eastern Cape Province from 2012 to 2015 and assessed characteristics associated with existing and new TB. RESULTS: Of 397 enrolled children, 114 (28.7%) had existing TB. Children with a higher measure of household income had higher odds of existing TB. CD4+ cell count <350 cells/µl and malnutrition were also associated with existing TB. There were 5.2 new cases of TB for every 100 child-years. New TB was 4.7 times more likely for children with delayed HIV treatment start, 1.8 times more likely for children with malnutrition and 2.3 times more likely for children who did not get cotrimoxazole. Among 362 children with data, 8.6% received treatment to prevent TB. CONCLUSIONS: Among these CLHIV, existing and new TB were common. Early HIV treatment, cotrimoxazole and addressing malnutrition may prevent TB in these children.

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Background The prevalence of tuberculosis (TB) disease among household contacts of adult TB patients is very high. Contact screening and isoniazid preventive therapy (IPT) are recommended for household contacts, but their uptake by families and implementation by the national TB program are poor. This study was performed to estimate the yield of tuberculosis disease, risk factors associated with disease development, and coverage of IPT in household contacts of sputum-positive pulmonary tuberculosis patients in the Aurangabad district of Maharashtra. Methods A cross-sectional study was conducted at MGM Medical College Hospital Aurangabad. Sputum-positive adult TB patients were enrolled in the study. Their household contacts were screened for TB disease, and the status of IPT in eligible contacts was studied. Serial screening and follow-up of these contacts were performed for one year. Results A total of 82 contacts of 55 index cases were studied. At the one-year follow-up, 15 (18%) patients developed TB disease. Twelve had pulmonary TB, and three had extrapulmonary TB. The mean age of diseased contacts was 5.5 years. The disease was more common in contacts under six years of age. Sixty-four percent of eligible contacts received IPT. There was a statistically significant association between disease development and noncompliance with IPT (p-value 0.005913). Conclusions The yield of tuberculosis disease is high in children contacts with sputum-positive pulmonary TB cases. IPT implementation is inadequate in child contact.

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Background: Microbiological confirmation of pulmonary tuberculosis (PTB) in children is a well-documented challenge. This study evaluated Xpert Mycobacterium Tuberculosis (MTB)/Rifampicin (RIF) Ultra (Ultra) and mycobacterial cultures in routine clinical care at a tertiary paediatric hospital. Methods: Children treated for PTB and who had at least one respiratory specimen investigated by Ultra and mycobacterial culture before tuberculosis (TB) treatment was commenced were included. The findings of this retrospective study were summarised using descriptive and inferential statistics. Results: A total of 174 children were included. The median age was 2.5 years. Microcytic anaemia, airway compression, cavitary disease and miliary TB were significantly observed in children with microbiologically confirmed TB (cTB). Tuberculosis was microbiologically confirmed in 93 (53.4%) children. The positive yield from testing the first respiratory specimens was 68/174 (39.1%) on Ultra and 82/174 (47.1%) on combined Ultra and mycobacterial culture. In the subset of children (n = 70) tested with Ultra on two sequential respiratory specimens, the incremental yield from the second specimen was 30.3%. In the subset of children (n = 16) tested with Ultra on three sequential respiratory specimens, the incremental yield from the second and third specimens was 16.7% and 0.0%, respectively. When Ultra and mycobacterial culture results were combined, the incremental yield in children who had two sequential respiratory specimens tested was 24.4% and 3.1% on Ultra and mycobacterial culture, respectively. Conclusion: Ultra and mycobacterial culture on a single respiratory specimen resulted in a high microbiological yield. Ultra-testing on a second respiratory specimen increased the yield of microbiologically cTB. Additional diagnostic testing may require further study.

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BACKGROUND: This study assesses the impact of the Xpert MTB/RIF in the diagnosis of childhood tuberculosis (TB) in a rural hospital in a resource-constrained setting. METHODS: Retrospective cross-sectional study in children evaluated for presumptive TB from 1 June 2016 to 31 May 2017 at the Gambo General Hospital in rural Southern Ethiopia. Children were evaluated according to a defined protocol based on national guidelines. Samples were submitted for Xpert MTB/RIF assay to the nearest reference laboratory. RESULTS: Of the 201 children assessed for presumptive TB, 46.3% (93/201) were diagnosed with TB. Of these, 49.5% (46/93) were microbiologically confirmed, mostly by Xpert MTB/RIF (only one patient was diagnosed by smear alone). The rest were clinically diagnosed. Microbiologically confirmed patients had a higher mean age, longer duration of fever and cough and lymphadenopathy more frequently than those clinically diagnosed. Gastric aspirates were Xpert MTB/RIF-positive in 18.2% of the samples (26/143); none were smear-positive (0/140). Sputum samples were Xpert MTB/RIF-positive in 27.1% (13/35) of the samples and smear-positive in 8.6% (3/35). There were no HIV-positive patients and just one case of rifampicin-resistant TB. A long delay (median 15 days) was detected in returning the results. CONCLUSION: Xpert MTB/RIF serves as an important adjunctive test for diagnosing childhood TB in rural settings, with microbiological confirmation in up to half the TB cases. Processes need to be optimized to achieve an early diagnosis. The diagnosis of childhood TB in high-burden countries such as Ethiopia still relies largely upon diagnostic algorithms and the clinician's skills.Lay summaryWorld Health Organization recommends the use of Xpert MTB/RIF to improve the microbiological diagnosis of childhood tuberculosis (TB) since 2014, but the impact of this test under real conditions in rural areas of low-income countries is not clear. We conducted a cross-sectional study in children evaluated for presumptive TB from 1 June 2016 to 31 May 2017 at the Gambo General Hospital in rural Southern Ethiopia. Children were evaluated according to a clinical protocol based on national guidelines and samples were submitted for Xpert MTB/RIF assay to the nearest reference laboratory.Of the 201 children assessed, 46.3% (93/201) were diagnosed with tuberculosis. Of these, 48.4% (45/93) were microbiologically confirmed by Xpert MTB/RIF [smear microscopy only diagnosed the 5.4% (5/93)]. Patients with microbiologically confirmed tuberculosis had a higher mean age, longer duration of fever and cough and had lymphadenopathy more frequently than those clinically diagnosed. A long delay in returning the results (median 15 days) was detected. Xpert MTB/RIF serves as an important test for diagnosing childhood TB in rural settings, with microbiological confirmation in up to half the cases. Processes need to be optimized to achieve an early diagnosis. The diagnosis of childhood TB in high-burden countries still relies largely upon diagnostic algorithms and the clinician's skills.

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