Pharmacokinetics and Optimal Dosing of Levofloxacin in Children for Drug-Resistant Tuberculosis: An Individual Patient Data Meta-Analysis.

Background: Each year 25 000-32 000 children develop rifampicin- or multidrug-resistant tuberculosis (RR/MDR-TB), and many more require preventive treatment. Levofloxacin is a key component of RR/MDR-TB treatment and prevention, but the existing pharmacokinetic data in children have not yet been comprehensively summarized. We aimed to characterize levofloxacin pharmacokinetics through an individual patient data meta-analysis of available studies and to determine optimal dosing in children.

Uptake and Completion of Tuberculosis Preventive Treatment Using 12-Dose, Weekly Isoniazid-Rifapentine Regimen in Bangladesh: A Community-Based Implementation Study.

Background: The United Nations high-level meeting (UNHLM) pledged to enroll 30 million in tuberculosis preventive treatment (TPT) by 2022, necessitating TPT expansion to all at tuberculosis (TB) risk. We assessed the uptake and completion of a 12-dose, weekly isoniazid-rifapentine (3HP) TPT regimen.

Methods: Between February 2018 and March 2019 in Dhaka, community-based TPT using 3HP targeted household contacts of 883 confirmed drug-sensitive pulmonary TB patients.

Two Clinical Prediction Tools to Inform Rapid Tuberculosis Treatment Decision-making in Children.

Background: In the absence of bacteriologic confirmation to diagnose tuberculosis (TB) in children, it is suggested that treatment should be initiated when sufficient clinical evidence of disease is available. However, it is unclear what clinical evidence is sufficient to make this decision. To identify children who would benefit from rapid initiation of TB treatment, we developed 2 clinical prediction tools.

Scale-Up of Rifapentine and Isoniazid for Tuberculosis Prevention Among Household Contacts in 2 Urban Centers: An Effectiveness Assessment.

Background: Scaling up a shorter preventive regimen such as weekly isoniazid and rifapentine (3HP) for 3 months is a priority for tuberculosis (TB) preventive treatment (TPT). However, there are limited data on 3HP acceptability and completion from high-burden-TB countries.

Methods: We scaled up 3HP from 2018 to 2021 in 2 cities in Pakistan.

Economic analysis of different throughput scenarios and implementation strategies of computer-aided detection software as a screening and triage test for pulmonary TB.

Background: Artificial Intelligence (AI) systems have demonstrated potential in detecting tuberculosis (TB) associated abnormalities from chest X-ray (CXR) images. Thus, they might provide a solution to radiologist shortages in high TB burden countries. However, the cost of implementing computer-aided detection (CAD) software has thus far been understudied.

Drug-Resistant Tuberculosis Treatment Outcomes among Children and Adolescents in Karachi, Pakistan.

Background: Significant data gaps exist for children and adolescents with drug-resistant (DR) TB, particularly from high TB incidence settings. This report provides a descriptive analysis of programmatic outcomes among children and adolescents treated for DR-TB in Pakistan.

Methods: We extracted programmatic data from January 2014 to December 2019 from a tertiary care hospital with specialised child and adolescent DR-TB services.

Tuberculosis care models for children and adolescents: a scoping review.

Objective: To map which tuberculosis care models are best suited for children and adolescents.

Methods: We conducted a scoping review to assess the impact of decentralized, integrated and family-centred care on child and adolescent tuberculosis-related outcomes, describe approaches for these care models and identify key knowledge gaps. We searched seven literature databases on 5 February 2021 (updated 16 February 2022), searched the references of 18 published reviews and requested data from ongoing studies.

Correction: Malik et al. Integrated Tuberculosis and COVID-19 Activities in Karachi and Tuberculosis Case Notifications. 2022, , 12.

The authors wish to revise the second citation of reference [26] to [27] in the original article main text [...

Age-specific Clinical Presentation and Risk Factors for Extrapulmonary Tuberculosis Disease in Children.

Background: Clinical presentation for extrapulmonary tuberculosis (EPTB) in children can be variable and nonspecific, leading to delayed diagnosis, disease and death. We describe the age-specific clinical presentation and identify risk factors for EPTB among children in Pakistan.

Methods: In 2015-2016 in 4 facilities in Sindh, Pakistan, children were diagnosed with TB either through bacteriologic confirmation or clinical-radiologic criteria.

Re-evaluating the merits of decentralization as a core strategy for effective delivery of drug-resistant tuberculosis care in Pakistan.

Decentralized, person-centred models of care delivery for drug-resistant tuberculosis (DR-TB) continue to be under-resourced in high-burden TB countries. The implementation of such models-made increasingly urgent by the COVID-19 pandemic-are key to addressing gaps in DR-TB care. We abstracted data of rifampicin-resistant (RR)/multidrug-resistant tuberculosis (MDR-TB) patients initiated on treatment at 11 facilities between 2010 and 2017 in Sindh and Balochistan provinces of Pakistan.

Sub-district level correlation between tuberculosis notifications and socio-demographic factors in Dhaka City corporation, Bangladesh.

We developed a novel method to align two data sources (TB notifications and the Demographic Health Survey, DHS) captured at different geographic scales. We used this method to identify sociodemographic indicators - specifically population density - that were ecologically correlated with elevated TB notification rates across wards (~100 000 people) in Dhaka, Bangladesh. We found population density was the variable most closely correlated with ward-level TB notification rates (Spearman's rank correlation 0.

Age-specific effectiveness of a tuberculosis screening intervention in children.

Objective: To apply a cascade-of-care framework to evaluate the effectiveness-by age of the child-of an intensified tuberculosis patient-finding intervention.

Design: From a prospective screening program at four hospitals in Pakistan (2014-2016) we constructed a care cascade comprising six steps: screened, positive screen, evaluated, diagnosed, started treatment, and successful outcome. We evaluated the cascade by each year of age from 0 to 14 and report the age-specific mean proportion and standard deviation.

Integrated Tuberculosis and COVID-19 Activities in Karachi and Tuberculosis Case Notifications.

As the COVID-19 pandemic surged, lockdowns led to the cancellation of essential health services. As part of our Zero TB activities in Karachi, we adapted our approach to integrate activities for TB and COVID-19 to decrease the impact on diagnosis and linkage to care for TB treatment. We implemented the following: (1) integrated COVID-19 screening and testing within existing TB program activities, along with the use of an artificial intelligence (AI) software reader on digital chest X-rays; (2) home delivery of medication; (3) use of telehealth and mental health counseling; (4) provision of PPE; (5) burnout monitoring of health workers; and (6) patient safety and disinfectant protocol.

Provision of Decentralized TB Care Services: A Detect-Treat-Prevent Strategy for Children and Adolescents Affected by TB.

In this review, we discuss considerations and successful models for providing decentralized diagnosis, treatment, and prevention services for children and adolescents. Key approaches to building decentralized capacity for childhood TB diagnosis in primary care facilities include provider training and increased access to child-focused diagnostic tools and techniques. Treatment of TB disease should be managed close to where patients live; pediatric formulations of both first- and second-line drugs should be widely available; and any hospitalization should be for as brief a period as medically indicated.

Triage of Persons With Tuberculosis Symptoms Using Artificial Intelligence-Based Chest Radiograph Interpretation: A Cost-Effectiveness Analysis.

Background: In settings without access to rapid expert radiographic interpretation, artificial intelligence (AI)-based chest radiograph (CXR) analysis can triage persons presenting with possible tuberculosis (TB) symptoms, to identify those who require additional microbiological testing. However, there is limited evidence of the cost-effectiveness of this technology as a triage tool.

Methods: A decision analysis model was developed to evaluate the cost-effectiveness of triage strategies with AI-based CXR analysis for patients presenting with symptoms suggestive of pulmonary TB in Karachi, Pakistan.

Isoniazid or rifampicin preventive therapy with and without screening for subclinical TB: a modeling analysis.

Background: Short-course, rifamycin-based regimens could facilitate scale-up of tuberculosis preventive therapy (TPT), but it is unclear how stringently tuberculosis (TB) disease should be ruled out before TPT use.

Methods: We developed a state-transition model of a TPT intervention among two TPT-eligible cohorts: adults newly diagnosed with HIV in South Africa (PWH) and TB household contacts in Pakistan (HHCs). We modeled two TPT regimens-4 months of rifampicin [4R] or 6 months of isoniazid [6H]-comparing each to a reference of no intervention.

Cost-effectiveness of household contact investigation for detection of tuberculosis in Pakistan.

Objectives: Despite WHO guidelines recommending household contact investigation, and studies showing the impact of active screening, most tuberculosis (TB) programmes in resource-limited settings only carry out passive contact investigation. The cost of such strategies is often cited as barriers to their implementation. However, little data are available for the additional costs required to implement this strategy.

One year of COVID-19 and its impact on private provider engagement for TB: A rapid assessment of intermediary NGOs in seven high TB burden countries.

The COVID-19 pandemic has impacted health systems and health programs across the world. For tuberculosis (TB), it is predicted to set back progress by at least twelve years. Public private mix (PPM)has made a vital contribution to reach End TB targets with a ten-fold rise in TB notifications from private providers between 2012 and 2019.

Special Issue "Innovation and Evidence for Achieving TB Elimination in the Asia-Pacific Region".

The World Health Organization's (WHO) END-TB strategy has set the world on course to climb the highest of medical mountains by 2035, with a targeted peak of reductions in TB deaths by 95%, TB cases by 90%, and no burden of catastrophic expenses on families due to TB [...

Integrating tuberculosis screening into antenatal visits to improve tuberculosis diagnosis and care: Results from a pilot project in Pakistan.

Background: Active tuberculosis (TB) during pregnancy has an adverse effect on maternal and neonatal outcomes. This study analysed the results of a pilot project integrating TB screening into antenatal care (ANC) visits in a high-TB-burden, low-resource setting.

Methods: Data were extracted from the TB screening pilot in obstetrician-gynaecologist clinics of six tertiary care facilities in Karachi, Pakistan from April to December 2017.

Quantifying geographic heterogeneity in TB incidence and the potential impact of geographically targeted interventions in South and North City Corporations of Dhaka, Bangladesh: a model-based study.

In rapidly growing and high-burden urban centres, identifying tuberculosis (TB) transmission hotspots and understanding the potential impact of interventions can inform future control and prevention strategies. Using data on local demography, TB reports and patient reporting patterns in Dhaka South City Corporation (DSCC) and Dhaka North City Corporation (DNCC), Bangladesh, between 2010 and 2017, we developed maps of TB reporting rates across wards in DSCC and DNCC and identified wards with high rates of reported TB (i.e.

Quantified TB Exposure Can Predict Prevalent TB Disease in Child Contacts.

In a matched case-control study in Pakistan, we found that quantified tuberculosis (TB) exposure using a 10-point score is associated with prevalent TB disease in pediatric household contacts. A 1 unit increase in TB exposure score increased the odds of TB disease by 44% (conditional odds ratio: 1.44, 95% confidence interval: 1.

Safety and feasibility of 1 month of daily rifapentine plus isoniazid to prevent tuberculosis in children and adolescents: a prospective cohort study.

Background: Shorter regimens for tuberculosis prevention can improve completion rates and protection against developing active tuberculosis disease after tuberculosis exposure. We aimed to assess the safety and feasibility of 1 month of daily isoniazid and rifapentine (1HP) in children and adolescents in a low-resource setting in south Asia with low prevalence of HIV.

Methods: This prospective cohort study was done in eight tuberculosis facilities in Karachi, Pakistan.