Publications by authors named "Anna Mandalakas"

Background: Tuberculosis vaccine trials using disease as the primary endpoint are large, time consuming, and expensive. An earlier immunological measure of the protection against disease would accelerate tuberculosis vaccine development. We aimed to assess whether the effectiveness of the Bacillus Calmette-Guérin (BCG) vaccine for prevention of Mycobacterium tuberculosis infection was consistent with that for prevention of tuberculosis disease.

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Introduction: Global migration has increased in recent decades due to war, conflict, persecutions, and natural disasters, but also secondary to increased opportunities related to work or study. Migrants' risk of tuberculosis (TB) differs by reasons for migration, socioeconomic status, mode of travel and TB risk in transit, TB incidence and healthcare provision in country of origin. Despite advances in TB care for migrants and new treatment strategies, decisions for the management of migrants at risk of TB often rely on expert opinions, rather than clinical evidence.

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Background: There has been a global pursuit to improve the diagnosis of tuberculosis in young children by applying diagnostic methods on accessible biospecimens such as stool. We aimed to conduct a systematic review on the accuracy of stool-based molecular tests for tuberculosis diagnosis in children and to assess the impact of the available pre-processing methods and other design characteristics.

Methods: In this systematic review and meta-analysis, we evaluated studies in children younger than 16 years with presumptive tuberculosis that were published in English, Spanish, French, and Portuguese from Jan 1, 2000, to May 3, 2024, in MEDLINE, Embase, and Embase Classic, comparing the molecular detection of Mycobacterium tuberculosis DNA in stool with microbiological tests on other samples or a clinical diagnosis.

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Severe and chronic infections, including pneumonia, sepsis, and tuberculosis (TB), induce long-lasting epigenetic changes that are associated with an increase in all-cause postinfectious morbidity and mortality. Oncology studies identified metabolic drivers of the epigenetic landscape, with the tricarboxylic acid (TCA) cycle acting as a central hub. It is unknown if the TCA cycle also regulates epigenetics, specifically DNA methylation, after infection-induced immune tolerance.

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Introduction: People living with HIV (PLHIV) have a 20-fold risk of tuberculosis (TB) disease compared to HIV-negative people. In 2021, the uptake of TB preventive treatment among the children and adolescents living with HIV at the Baylor-Uganda HIV clinic was 45%, which was below the national target of 90%. Minimal evidence documents the enablers and barriers to TB preventive treatment (TPT) initiation and completion among children and adolescents living with HIV(CALHIV).

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Article Synopsis
  • Acute lower respiratory infections (ALRI) are a major cause of death in children under 5, especially prevalent in low- and middle-income countries.
  • The WHO defines serious hypoxemia in children as having an oxygen saturation (SpO2) below 90%, but recent studies suggest that even levels between 90% and 92% may be linked to mortality.
  • Evidence indicates that some pulse oximeters may inaccurately overestimate oxygen saturation in children with dark skin tones, highlighting the need for further research while emphasizing the lifesaving potential of pulse oximetry.
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Background: Recently, face mask sampling (FMS) confirmed detection of Mycobacterium tuberculosis DNA from exhaled breath in adults with tuberculosis. To date, no study has evaluated the use of FMS to detect pulmonary tuberculosis in children. We developed a method for FMS of M.

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Background: Differentiated service delivery (DSD) for children and adolescents living with HIV can improve targeted resource use. We derived a mortality prediction score to guide clinical decision making for children and adolescents living with HIV.

Methods: Data for this retrospective observational cohort study were evaluated for all children and adolescents living with HIV and initiating antiretroviral therapy (ART); aged 0-19 years; and enrolled at Baylor clinics in Eswatini, Malawi, Lesotho, Tanzania, and Uganda between 2005 and 2020.

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Background: Tuberculosis is a preventable disease. However, there is debate regarding which individuals would benefit most from tuberculosis preventive treatment and whether these benefits vary in settings with a high burden and low burden of tuberculosis. We aimed to compare the effectiveness of tuberculosis preventive treatment in exposed individuals of differing ages and Mycobacterium tuberculosis infection status while considering tuberculosis burden of the settings.

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Background: Despite increasing availability of rapid molecular tests for the diagnosis of tuberculosis in high-burden settings, many people with tuberculosis are undiagnosed. Reliance on sputum as the primary specimen for tuberculosis diagnostics contributes to this diagnostic gap. We evaluated the diagnostic accuracy and additive yield of a novel stool quantitative PCR (qPCR) assay for the diagnosis of tuberculosis in three countries in Africa with high tuberculosis burdens.

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Background: Tuberculosis (TB) is a major cause of mortality worldwide. Children and people living with HIV (PLHIV) have an increased risk of mortality, particularly in the absence of rapid diagnosis. The main challenges of diagnosing TB in these populations are due to the unspecific and paucibacillary disease presentation and the difficulty of obtaining respiratory samples.

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Background: An estimated one fourth of the world's population is infected with Mycobacterium tuberculosis, and 5-10% of those infected develop tuberculosis in their lifetime. Preventing tuberculosis is one of the most underutilized but essential components of curtailing the tuberculosis epidemic. Moreover, current evidence illustrates that tuberculosis manifestations occur along a dynamic spectrum from infection to disease rather than a binary state as historically conceptualized.

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Background: Disparities in scholarship exist between authors in low- or middle-income countries (LMIC) and high-income countries. Recognizing these disparities in our global network providing pediatric, adolescent, and maternal healthcare to vulnerable populations in LMIC, we sought to improve access and provide resources to address educational needs and ultimately impact the broader scholarship disparity.

Methods: We created a virtual community of practice (CoP) program underpinned by principles from starling murmuration to promote interdisciplinary scholarship.

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Delivery of tuberculosis preventive therapy (TPT) for children with household exposure to tuberculosis is a globally supported intervention to reduce the impact of tuberculosis disease (TB) in vulnerable children; however, it is sub-optimally implemented in most high-burden settings. As part of a community-based household contact management program, we evaluated predictors of adherence to community based TPT in children and performed qualitative assessments of caregiver experiences. The Vikela Ekhaya (Protect the Home) project was a community-based household contact management program implemented between 2019 and 2020 in the Hhohho Region of Eswatini.

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Article Synopsis
  • - The study addresses the issue of undiagnosed pulmonary tuberculosis in children, aiming to improve diagnostic algorithms and prediction models to assist in treatment decisions at primary health-care centers.
  • - Researchers conducted a meta-analysis using data from WHO and various studies to evaluate the effectiveness of existing treatment-decision algorithms and develop new multivariable prediction models.
  • - The analysis included data from 4718 children under 10 years old across 12 countries, resulting in the creation of two scoring systems for tuberculosis classification that aim for high sensitivity in clinical settings.
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Drug-resistant tuberculosis is a substantial health-care concern worldwide. Despite culture-based methods being considered the gold standard for drug susceptibility testing, molecular methods provide rapid information about the Mycobacterium tuberculosis mutations associated with resistance to anti-tuberculosis drugs. This consensus document was developed on the basis of a comprehensive literature search, by the TBnet and RESIST-TB networks, about reporting standards for the clinical use of molecular drug susceptibility testing.

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The WHO has endorsed the use of stool samples for diagnosis of tuberculosis (TB) in children, and targeted next-generation sequencing (tNGS) of stool has been shown to support diagnosis and provide information about drug susceptibility (DS). Optimizing extraction of DNA from stool for sequencing is critical to ensure high diagnostic sensitivity and accurate DS information. Human stool samples were spiked with various concentrations of Mycobacterium bovis bacillus Calmette-Guérin (BCG), and DNA was extracted from the samples using four different DNA extraction kits.

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