Aetiology of pleural effusions in children living in a high TB endemic setting.

Confirming the aetiology of pleural effusion in children may be difficult in TB-endemic settings. We investigated the role of polymerase chain reaction (PCR) and routine biochemical tests in discriminating pleural effusion caused by bacteria from other aetiologies.This is a cross-sectional post-hoc analysis among children with pleural effusion in a tertiary hospital in South Africa, incorporating new data from PCR testing of stored pleural fluid. Aetiological classification was defined by microbiological confirmation.Ninety-one children were enrolled; the median age 31 months (IQR 12-102). The aetiology of pleural effusion was 40% (36/91) bacteria, 11% (10/91) TB, 3% (3/91) viruses, 11% (10/91) polymicrobial and 35% (32/91) had no pathogen identified. The most common pathogen was Staphylococcus aureus (27/91, 30%) with similar yields on culture and PCR, followed by Streptococcus pneumoniae (12/91, 13%), detected more commonly by PCR. PCR reduced the number of children with unconfirmed aetiologies from 48 to 32. Characteristics of children with no pathogen most resembled those with TB. Pleural fluid lactate dehydrogenase ≥1,716 U/L best discriminated bacterial pleural effusion from other aetiologies (sensitivity of 86%; specificity 95%).PCR improved detection of pathogens and reduced number of children with unconfirmed aetiologies in presumed exudative pleural effusion..

Progress Toward Tuberculosis Elimination and Tuberculosis Program Performance - National Tuberculosis Indicators Project, 2016-2022.

Problem/Condition: Elimination of tuberculosis (TB) is defined as reducing TB disease incidence in the United States to less than 1 case per million persons per year. In 2022, TB incidence in the United States was 2.5 TB cases per 100,000 persons. CDC's TB program developed a set of national TB indicators to evaluate progress toward TB elimination through monitoring performance of state and city TB program activities. Examining TB indicator data enables state- and city-level TB programs to identify areas for program evaluation and improvement activities. These data also help CDC identify states and cities that might benefit from technical assistance. Period Covered: The 5-year period for which the most recent data were available for each of five indicators: 1) overall TB incidence (2018-2022), 2) TB incidence among non-U.S.-born persons (2018-2022), 3) percentage of persons with drug susceptibility results reported (2018-2022), 4) percentage of contacts to sputum acid-fast bacillus (AFB) smear-positive TB patients with newly diagnosed latent TB infection (LTBI) who completed treatment (2017-2021), and 5) percentage of patients with completion of TB therapy within 12 months (2016-2020). Description of System: The National TB Indicators Project (NTIP) is a web-based performance monitoring tool that uses national TB surveillance data reported through the National TB Surveillance System and the Aggregate Reports for TB Program Evaluation. NTIP was developed to facilitate the use of existing data to help TB program staff members prioritize activities, monitor progress, and focus program improvement efforts. The following five indicators were selected for this report because of their importance in Federal TB funding allocation and in accelerating the decline in TB cases: 1) overall TB incidence in the United States, 2) TB incidence among non-U.S.-born persons, 3) percentage of persons with drug susceptibility results reported, 4) percentage of contacts to sputum AFB smear-positive TB cases who completed treatment for LTBI, and 5) percentage of patients with completion of TB therapy within 12 months. For this report, 52 TB programs (50 states, the District of Columbia, and New York City) were categorized into terciles based on the 5-year average number of TB cases reported to National TB Surveillance System. This grouping allows comparison of TB programs that have similar numbers of TB cases and allocates a similar number of TB programs to each category. The following formula was used to calculate the relative change by TB program for each indicator: [(% from year 5 - % from year 1 ÷ % from year 1) × 100]. Results: During the 5-year period for which the most recent data were available, most TB programs had improvements in reducing overall TB incidence (71.2%) and increasing the percentage of contacts receiving a diagnosis of LTBI who completed LTBI treatment (55.8%); the majority of programs (51.0%) also had improvements in reducing incidence among non-U.S.-born persons. The average percentage of persons with drug susceptibility results reported in most jurisdictions (28 of 52, [53.9%]) met or exceeded the 5-year national average of 97% (2018-2022). The percentage of contacts to sputum acid-fast bacillus (AFB) smear-positive TB patients with newly diagnosed latent TB infection (LTBI) who completed treatment increased in 29 of 52 (55.8%) jurisdictions from 2017 to 2021, signifying that, for most jurisdictions, steps have been taken to enhance performance in this area. The average percentage of patients with completion of TB therapy within 12 months was at or above the national average of 89.7% in approximately two-thirds (32 of 52 [61.5%]) of jurisdictions. Interpretation: This report is the first to describe a 5-year relative change for TB program performance. These results suggest that TB programs are making improvements in activities that help identify persons with TB and LTBI and ensure patients complete treatment in a timely manner. Public Health Action: Use of NTIP data from individual TB programs enables a more detailed examination of trends in program performance and identification of areas for program improvement. Assessing indicator trends by TB program provides an opportunity to gain a better understanding of program performance in comparison to other programs. It can also facilitate communication between programs regarding successes and challenges in program improvement. This information is valuable for TB programs to allocate resources effectively and provide additional context on TB control for public health policymakers.

Exploring the potential of Oxford Nanopore Technologies sequencing for Mycobacterium tuberculosis sequencing: An assessment of R10 flowcells and V14 chemistry.

Oxford Nanopore Technologies (ONT) sequencing is a promising technology. We assessed the performance of the new ONT R10 flowcells and V14 rapid sequencing chemistry for Mtb whole genome sequencing of Mycobacterium tuberculosis (Mtb) DNA extracted from clinical primary liquid cultures (CPLCs). Using the recommended protocols for MinION Mk1C, R10.4.1 MinION flowcells, and the ONT Rapid Sequencing Kit V14 on six CPLC samples, we obtained a pooled library yield of 10.9 ng/µl, generated 1.94 Gb of sequenced bases and 214k reads after 48h in a first sequencing run. Only half (49%) of all generated reads met the Phred Quality score threshold (>8). To assess if the low data output and sequence quality were due to impurities present in DNA extracted directly from CPLCs, we added a pre-library preparation bead-clean-up step and included purified DNA obtained from an Mtb subculture as a control sample in a second sequencing run. The library yield for DNA extracted from four CPLCs and one Mtb subculture (control) was similar (10.0 ng/µl), 2.38 Gb of bases and 822k reads were produced. The quality was slightly better with 66% of the produced reads having a Phred Quality >8. A third run of DNA from six CPLCs with bead clean-up pre-processing produced a low library yield (±1 Gb of bases, 166k reads) of low quality (51% of reads with a Phred Quality score >8). A median depth of coverage above 10× was only achieved for five of 17 (29%) sequenced libraries. Compared to Illumina WGS of the same samples, accurate lineage predictions and full drug resistance profiles from the generated ONT data could not be determined by TBProfiler. Further optimization of the V14 ONT rapid sequencing chemistry and library preparation protocol is needed for clinical Mtb WGS applications.

Current landscape of exosomes in tuberculosis development, diagnosis, and treatment applications.

Tuberculosis (TB), caused by the bacterial pathogen Mycobacterium tuberculosis (MTB), remains one of the most prevalent and deadly infectious diseases worldwide. Currently, there are complex interactions between host cells and pathogens in TB. The onset, progression, and regression of TB are correlated not only with the virulence of MTB but also with the immunity of TB patients. Exosomes are cell-secreted membrane-bound nanovesicles with lipid bilayers that contain a variety of biomolecules, such as metabolites, lipids, proteins, and nucleic acids. Exosome-mediated cell-cell communication and interactions with the microenvironment represent crucial mechanisms through which exosomes exert their functional effects. Exosomes harbor a wide range of regulatory roles in physiological and pathological conditions, including MTB infection. Exosomes can regulate the immune response, metabolism, and cellular death to remodel the progression of MTB infection. During MTB infection, exosomes display distinctive profiles and quantities that may act as diagnostic biomarkers, suggesting that exosomes provide a revealing glimpse into the evolving landscape of MTB infections. Furthermore, exosomes derived from MTB and mesenchymal stem cells can be harnessed as vaccine platforms and drug delivery vehicles for the precise targeting and treatment of TB. In this review, we highlight the functions and mechanisms through which exosomes influence the progression of TB. Additionally, we unravel the critical significance of exosomal constituents in the diagnosis and therapeutic applications of TB, aiming to offer novel perspectives and strategies for combating TB.

Testing novel strategies for patients hospitalised with HIV-associated disseminated tuberculosis (NewStrat-TB): protocol for a randomised controlled trial.

BACKGROUND: HIV-associated tuberculosis (TB) contributes disproportionately to global tuberculosis mortality. Patients hospitalised at the time of the diagnosis of HIV-associated disseminated TB are typically severely ill and have a high mortality risk despite initiation of tuberculosis treatment. The objective of the study is to assess the safety and efficacy of both intensified TB treatment (high dose rifampicin plus levofloxacin) and immunomodulation with corticosteroids as interventions to reduce early mortality in hospitalised patients with HIV-associated disseminated TB. METHODS: This is a phase III randomised controlled superiority trial, evaluating two interventions in a 2 × 2 factorial design: (1) high dose rifampicin (35 mg/kg/day) plus levofloxacin added to standard TB treatment for the first 14 days versus standard tuberculosis treatment and (2) adjunctive corticosteroids (prednisone 1.5 mg/kg/day) versus identical placebo for the first 14 days of TB treatment. The study population is HIV-positive patients diagnosed with disseminated TB (defined as being positive by at least one of the following assays: urine Alere LAM, urine Xpert MTB/RIF Ultra or blood Xpert MTB/RIF Ultra) during a hospital admission. The primary endpoint is all-cause mortality at 12 weeks comparing, first, patients receiving intensified TB treatment to standard of care and, second, patients receiving corticosteroids to those receiving placebo. Analysis of the primary endpoint will be by intention to treat. Secondary endpoints include all-cause mortality at 2 and 24 weeks. Safety and tolerability endpoints include hepatoxicity evaluations and corticosteroid-related adverse events. DISCUSSION: Disseminated TB is characterised by a high mycobacterial load and patients are often critically ill at presentation, with features of sepsis, which carries a high mortality risk. Interventions that reduce this high mycobacterial load or modulate associated immune activation could potentially reduce mortality. If found to be safe and effective, the interventions being evaluated in this trial could be easily implemented in clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov NCT04951986. Registered on 7 July 2021 https://clinicaltrials.gov/study/NCT04951986.

[Progress in lipoarabinomannan antigen detection for tuberculosis diagnosis in people living with HIV/AIDS].

Tuberculosis (TB) is the leading cause of death among people living with HIV/AIDS (PLWHA), posing a significant disease burden. Early TB screening in PLWHA is a key intervention to reduce transmission and control disease progression. ​Lipoarabinomannan (LAM) is a glycolipid of Mycobacterium tuberculosis (MTB) that can be detected in the urine of tuberculosis patients. LAM is useful for the rapid and accurate diagnosis of tuberculosis. This article reviews LAM and its application and limitations in the diagnosis of PLWHA, hoping to provide a reference for the diagnosis of tuberculosis in PLWHA.

[Retrospective analysis of diagnosis and treatment of tuberculosis in designated medical institutions in China from 2017 to 2022].

Objective: To understand the status of tuberculosis diagnosis and treatment capacity and the development and changes of tuberculosis diagnosis and treatment in provincial and municipal designated medical institutions in China from 2017 to 2022, so as to provide a basis for the formulation of relevant policies for the improvement and development of designated medical institutions for tuberculosis and the tuberculosis prevention and treatment service system, and to provide reasonable support for further strengthening the capacity of designated medical institutions for tuberculosis. Methods: This study was initiated and carried out by Beijing Chest Hospital affiliated to Capital Medical University/Clinical Center for Tuberculosis Prevention and Control of China CDC (hereinafter referred to as "Clinical Center") by means of questionnaire survey, and the investigation was carried out from March to November 2023. During this period, the clinical center distributed questionnaires to the hospital member units of "Beijing Tuberculosis Diagnosis and Treatment Technology Innovation Alliance", retrospectively collected their tuberculosis-related diagnosis and treatment data from 2017 to 2022, and used descriptive statistical methods to analyze the number of tuberculosis beds, outpatients and hospitalizations in medical institutions. The results were expressed in absolute numbers (percentages), and three-line tables, bar charts and line charts were drawn to describe the analysis results and changing trends. Results: The 54 medical institutions surveyed in this survey included 21 provincial-level designated medical institutions and 33 prefecture-level designated medical institutions. Most medical institutions have set up clinical departments, auxiliary departments and functional departments to undertake public health tasks of infectious diseases. The tuberculosis laboratory in the hospital has a comprehensive ability and has the detection technology needed for most tuberculosis diagnosis; The number of tuberculosis beds, children's tuberculosis beds and ICU beds all showed an increasing trend from 2017 to 2022. The proportion of tuberculosis beds in the hospital decreased slightly, from 39.31% in 2017 to 34.76% in 2022, showing a slight downward trend. Compared with the hospital surveyed, the number of tuberculosis outpatients in 2019 was 562 029, and the number of outpatients in 2020-2022 was 462 328, 519 630 and 424 069 respectively, which was significantly lower than that in 2019. The number of tuberculosis outpatients in medical institutions decreased significantly from 2020 to 2022. By analyzing the proportion of patients with different types of tuberculosis, the proportion of sensitive tuberculosis outpatients in 2017-2022 decreased from 84.49% in 2017 to 78.05% in 2022, showing a downward trend year by year. The proportion of patients with multidrug-resistant/ rifampin-resistant tuberculosis increased from 2.03% in 2017 to 7.18% in 2022. From 2017 to 2019, the total number of inpatients with tuberculosis showed an upward trend. Compared with 2019, the number of inpatients in 2020, 2021 and 2022 showed a downward trend, and the decline in 2020 was large (down 14.94% compared with 2019). Among the inpatients, the absolute number and proportion of patients with sensitive pulmonary tuberculosis remained relatively stable, and the number and proportion of inpatients with multidrug-resistant/rifampin-resistant pulmonary tuberculosis increased year by year. Conclusions: Most medical institutions have the capacity to carry out routine diagnosis and treatment of tuberculosis, but the public health function needs to be strengthened. The transformation of medical institutions requires proper guidance and adequate support. During 2019-2022, most medical institutions were affected by the COVID-19 epidemic, and their tuberculosis diagnosis and treatment work also changed to varying degrees. During this period, hospitals took various measures to overcome difficulties and tried their best to maintain the normal development of tuberculosis diagnosis and treatment, and the tuberculosis diagnosis and treatment work of various institutions gradually resumed in 2022.

Granulomatous meningoencephalitis and blindness associated with Mycobacterium tuberculosis complex infection in a senile female chimpanzee (Pan troglodytes).

A 40-year old female chimpanzee (Pan troglodytes) developed hyporexia, weight loss, followed by progressive and complete blindness. Tomography demonstrated an intracranial mass in the rostroventral brain involving the optic chiasm, with a presumptive diagnosis of neoplasm. However, histopathology revealed a granulomatous meningoencephalitis, and tissue samples tested positive for Mycobacterium tuberculosis.

Tuberculosis in southern Morocco: Retrospective analysis from 2006 to 2012.

INTRODUCTION: Tuberculosis, a global major concern, causes millions of deaths annually despite WHO strategies. A persistent gap in detection and treatment facilitates rapid spread in high-burden countries. AIMS: Analyze the clinical-epidemiological profile of tuberculosis patients in Laayoune and Tarfaya, Morocco, emphasizing risk factors and evolution of the tuberculosis Methods: Retrospective analysis of 1332 tuberculosis cases at the Respiratory Diseases Diagnosis and Treatment Center in Laayoune (2006-2012). Variables with P < 0.10 in univariate analysis were included in multivariate analysis using multiple logistic regression to define the risk factors for tuberculosis, expressed as odds ratios (OR) with a 95% confidence interval (CI). RESULTS: The analysis revealed a pulmonary predominance (≈61%), with pleural (41.3%) and lymph node (31.5%) tuberculosis prevalent among extrapulmonary cases. Among 515 extrapulmonary tuberculosis cases, intestinal tuberculosis (14 cases) showed the highest mortality rate at 14.29%. The 15 to 64 age groups had a significantly higher risk of contracting pulmonary tuberculosis to children, and the 65 and over age group also had the highest risk of developing pulmonary tuberculosis (aOR=5.83 [2.43, 14.00]). Other risk factors included rural origin, personal history of tuberculosis, and smoking, all significantly associated with pulmonary tuberculosis (aOR=2.40 [1.001, 5.76]; aOR=2.00 [1.11, 3.61]; aOR=2.38 [1.40, 4.06]). Conversely, female gender was a protective factor (aOR=0.53 [0.40, 0.70]). Regarding recovery and loss to follow-up rates, they were higher in those with pulmonary tuberculosis (39.0% vs 2.1%; aOR=33.41 [17, 66.52]; 16.9% vs 10.3%; aOR=1.57 [1.02, 2.41], respectively). CONCLUSION: Holistic initiatives across various sectors will be essential to eliminate tuberculosis by 2030.

Whole-course quality of tuberculosis (TB) care in rural China: a retrospective study based on chart abstraction.

OBJECTIVES: The aim of this study was to assess the quality of tuberculosis (TB) care for the whole course and assess factors that affect completing treatment. DESIGN: This is an observational retrospective study using chart abstraction for the whole course of TB care conducted at two underserved provinces in China. SETTING: The study was conducted from June 2021 to July 2021. All medical records (outpatient and inpatient) for the whole course (6-8 months) of patients with TB newly registered from July 2020 to December 2020 were reviewed and abstracted using predetermined checklists. PARTICIPANTS: A total of 268 outpatient medical records and 126 inpatient records were included. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome included diagnostic quality, treatment quality and management quality. The secondary outcome was completing treatment. RESULTS: For diagnostic quality, 94.2% of the diagnosis were based on adequate evidence. For treatment quality, 240 (91.6%) outpatients and 100 (85.5%) inpatients took the standard chemotherapy regimens. 234 (87.3%) patients completed treatment. 85.1% of the inpatients prescribed with second-line drugs were inappropriate. For management quality, 128 (47.9%) patients received midterm assessments, but only 47 (19.7%) received sufficient services for the whole course. Patients with TB symptoms were 1.8 times more likely to complete treatment (p=0.011). CONCLUSION: Patients with TB received high-quality diagnosis and treatment services, but low-quality whole-course management. Integration of medical and public health services should be strengthened to improve whole-course quality.

Prediction of tuberculosis clusters in the riverine municipalities of the Brazilian Amazon with machine learning.

OBJECTIVE: Tuberculosis (TB) is the second most deadly infectious disease globally, posing a significant burden in Brazil and its Amazonian region. This study focused on the "riverine municipalities" and hypothesizes the presence of TB clusters in the area. We also aimed to train a machine learning model to differentiate municipalities classified as hot spots vs. non-hot spots using disease surveillance variables as predictors. METHODS: Data regarding the incidence of TB from 2019 to 2022 in the riverine town was collected from the Brazilian Health Ministry Informatics Department. Moran's I was used to assess global spatial autocorrelation, while the Getis-Ord GI* method was employed to detect high and low-incidence clusters. A Random Forest machine-learning model was trained using surveillance variables related to TB cases to predict hot spots among non-hot spot municipalities. RESULTS: Our analysis revealed distinct geographical clusters with high and low TB incidence following a west-to-east distribution pattern. The Random Forest Classification model utilizes six surveillance variables to predict hot vs. non-hot spots. The machine learning model achieved an Area Under the Receiver Operator Curve (AUC-ROC) of 0.81. CONCLUSION: Municipalities with higher percentages of recurrent cases, deaths due to TB, antibiotic regimen changes, percentage of new cases, and cases with smoking history were the best predictors of hot spots. This prediction method can be leveraged to identify the municipalities at the highest risk of being hot spots for the disease, aiding policymakers with an evidenced-based tool to direct resource allocation for disease control in the riverine municipalities.

Tuberculosis Immunoreactivity Surveillance in Malawi (Timasamala)-A protocol for a cross-sectional Mycobacterium tuberculosis immunoreactivity survey in Blantyre, Malawi.

Tuberculosis (TB) transmission and prevalence are dynamic over time, and heterogeneous within populations. Public health programmes therefore require up-to-date, accurate epidemiological data to appropriately allocate resources, target interventions, and track progress towards End TB goals. Current methods of TB surveillance often rely on case notifications, which are biased by access to healthcare, and TB disease prevalence surveys, which are highly resource-intensive, requiring many tens of thousands of people to be tested to identify high-risk groups or capture trends. Surveys of "latent TB infection", or immunoreactivity to Mycobacterium tuberculosis (Mtb), using tests such as interferon-gamma release assays (IGRAs) could provide a way to identify TB transmission hotspots, supplementing information from disease notifications, and with greater spatial and temporal resolution than is possible to achieve in disease prevalence surveys. This cross-sectional survey will investigate the prevalence of Mtb immunoreactivity amongst young children, adolescents and adults in Blantyre, Malawi, a high HIV-prevalence city in southern Africa. Through this study we will estimate the annual risk of TB infection (ARTI) in Blantyre and explore individual- and area-level risk factors for infection, as well as investigating geospatial heterogeneity of Mtb infection (and its determinants), and comparing these to the distribution of TB disease case-notifications. We will also evaluate novel diagnostics for Mtb infection (QIAreach QFT) and sampling methodologies (convenience sampling in healthcare settings and community sampling based on satellite imagery), which may increase the feasibility of measuring Mtb infection at large scale. The overall aim is to provide high-resolution epidemiological data and provide new insights into methodologies which may be used by TB programmes globally.

Primary Health Care and Tuberculosis Detection during the COVID-19 Pandemic: Crucial Actions for Intensifying Efforts.

BACKGROUND: Tuberculosis has been considered a global emergency since 1993, and controlling it has become even more challenging since 2020 due to the health and social crisis resulting from the COVID-19 pandemic. This study aimed to identify the impact of the COVID-19 pandemic on tuberculosis case detection activities within primary health Care in the largest city in Brazil. METHODS: This is a cross-sectional and analytical study on the provision of tuberculosis detection actions in primary healthcare units during the pandemic period. A descriptive analysis was performed for characterization, and Generalized Mixed Models were used for evaluating associations, with a Bonferroni post hoc test applied. RESULTS: The study sample comprised 80 health units in the municipality. There was a moderate alteration level in the provision of consultations for individuals with signs and symptoms of tuberculosis in 2020 (13.8%) and in 2021 (15.1%). Statistical significance (p < 0.05) was found between the pandemic period and detection actions, with a lower alteration level in 2022. CONCLUSIONS: Tuberculosis detection activities underwent changes due to the COVID-19 pandemic, mainly in 2020, which was associated with alterations in consultation and case notification provision.

miR-29 as diagnostic biomarkers for tuberculosis: a systematic review and meta-analysis.

Background: The timely diagnosis of tuberculosis through innovative biomarkers that do not rely on sputum samples is a primary focus for strategies aimed at eradicating tuberculosis. miR-29 is an important regulator of tuberculosis pathogenesis. Its differential expression pattern in healthy, latent, and active people who develop tuberculosis has revealed its potential as a biomarker in recent studies. Therefore, a systematic review and meta-analysis were performed for the role of miR-29 in the diagnosis of tuberculosis. Methods: EMBASE, PubMed, CNKI, Web of Science, and Cochrane Library databases were searched utilizing predefined keywords for literature published from 2000 to February 2024.Included in the analysis were studies reporting on the accuracy of miR-29 in the diagnosis of tuberculosis, while articles assessing other small RNAs were not considered. All types of study designs, including case-control, cross-sectional, and cohort studies, were included, whether prospectively or retrospectively sampled, and the quality of included studies was determined utilizing the QUADAS-2 tool. Publication bias was analyzed via the construction of funnel plots. Heterogeneity among studies and summary results for specificity, sensitivity, and diagnostic odds ratio (DOR) are depicted in forest plots. Results: A total of 227 studies were acquired from the various databases, and 18 articles were selected for quantitative analysis. These articles encompassed a total of 2,825 subjects, primarily sourced from the Asian region. Patient specimens, including sputum, peripheral blood mononuclear cells, cerebrospinal fluid and serum/plasma samples, were collected upon admission and during hospitalization for tuberculosis testing. miR-29a had an overall sensitivity of 82% (95% CI 77, 85%) and an overall specificity of 82% (95% CI 78, 86%) for detecting tuberculosis. DOR was 21 (95% CI 16-28), and the area under the curve was 0.89 (95% CI 0.86, 0.91). miR-29a had slightly different diagnostic efficacy in different specimens. miR-29a showed good performance in both the diagnosis of pulmonary tuberculosis and extrapulmonary tuberculosis. miR-29b and miR-29c also had a good performance in diagnosis of tuberculosis. Conclusion: As can be seen from the diagnostic performance of miR-29, miR-29 can be used as a potential biomarker for the rapid detection of tuberculosis. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=461107.

Evaluation of serological assays for the diagnosis of childhood tuberculosis disease: a study protocol.

BACKGROUND: Tuberculosis (TB) poses a major public health challenge, particularly in children. A substantial proportion of children with TB disease remain undetected and unconfirmed. Therefore, there is an urgent need for a highly sensitive point-of-care test. This study aims to assess the performance of serological assays based on various antigen targets and antibody properties in distinguishing children (0-18 years) with TB disease (1) from healthy TB-exposed children, (2) children with non-TB lower respiratory tract infections, and (3) from children with TB infection. METHODS: The study will use biobanked plasma samples collected from three prospective multicentric diagnostic observational studies: the Childhood TB in Switzerland (CITRUS) study, the Pediatric TB Research Network in Spain (pTBred), and the Procalcitonin guidance to reduce antibiotic treatment of lower respiratory tract infections in children and adolescents (ProPAED) study. Included are children diagnosed with TB disease or infection, healthy TB-exposed children, and sick children with non-TB lower respiratory tract infection. Serological multiplex assays will be performed to identify M. tuberculosis antigen-specific antibody features, including isotypes, subclasses, Fc receptor (FcR) binding, and IgG glycosylation. DISCUSSION: The findings from this study will help to design serological assays for diagnosing TB disease in children. Importantly, those assays could easily be developed as low-cost point-of-care tests, thereby offering a potential solution for resource-constrained settings. GOV IDENTIFIER: NCT03044509.

Chest Radiograph Screening for Detecting Subclinical Tuberculosis in Asymptomatic Household Contacts, Peru.

The World Health Organization's end TB strategy promotes the use of symptom and chest radiograph screening for tuberculosis (TB) disease. However, asymptomatic early states of TB beyond latent TB infection and active disease can go unrecognized using current screening criteria. We conducted a longitudinal cohort study enrolling household contacts initially free of TB disease and followed them for the occurrence of incident TB over 1 year. Among 1,747 screened contacts, 27 (52%) of the 52 persons in whom TB subsequently developed during follow-up had a baseline abnormal radiograph. Of contacts without TB symptoms, persons with an abnormal radiograph were at higher risk for subsequent TB than persons with an unremarkable radiograph (adjusted hazard ratio 15.62 [95% CI 7.74-31.54]). In young adults, we found a strong linear relationship between radiograph severity and time to TB diagnosis. Our findings suggest chest radiograph screening can extend to detecting early TB states, thereby enabling timely intervention.