In childhood tuberculosis (TB), with an estimated 69% of missed cases in children under 5 years of age, the case detection gap is larger than in other age groups, mainly due to its paucibacillary nature and children’s difficulties in delivering sputum specimens. Accurate and accessible point-of-care tests (POCTs) are needed to detect TB disease in children and, in turn, reduce TB-related morbidity and mortality in this vulnerable population. In recent years, several POCTs for TB have been developed. These include new tools to improve the detection of TB in respiratory and gastric samples, such as molecular detection of Mycobacterium tuberculosis using loop-mediated isothermal amplification (LAMP) and portable polymerase chain reaction (PCR)-based GeneXpert. In addition, the urine-based detection of lipoarabinomannan (LAM), as well as imaging modalities through point-of-care ultrasonography (POCUS), are currently the POCTs in use. Further to this, artificial intelligence-based interpretation of ultrasound imaging and radiography is now integrated into computer-aided detection products. In the future, portable radiography may become more widely available, and robotics-supported ultrasound imaging is currently being trialed. Finally, novel blood-based tests evaluating the immune response using “omic-“techniques are underway. This approach, including transcriptomics, metabolomic, proteomics, lipidomics and genomics, is still distant from being translated into POCT formats, but the digital development may rapidly enhance innovation in this field. Despite these significant advances, TB-POCT development and implementation remains challenged by the lack of standard ways to access non-sputum-based samples, the need to differentiate TB infection from disease and to gain acceptance for novel testing strategies specific to the conditions and settings of use.

Electronic clinical decision support algorithms (CDSAs) have been developed to address high childhood mortality and inappropriate antibiotic prescription by helping clinicians adhere to guidelines. Previously identified challenges of CDSAs include their limited scope, usability, and outdated clinical content. To address these challenges we developed ePOCT+, a CDSA for the care of pediatric outpatients in low- and middle-income settings, and the medical algorithm suite (medAL-suite), a software for the creation and execution of CDSAs. Following the principles of digital development, we aim to describe the process and lessons learnt from the development of ePOCT+ and the medAL-suite. In particular, this work outlines the systematic integrative development process in the design and implementation of these tools required to meet the needs of clinicians to improve uptake and quality of care. We considered the feasibility, acceptability and reliability of clinical signs and symptoms, as well as the diagnostic and prognostic performance of predictors. To assure clinical validity, and appropriateness for the country of implementation the algorithm underwent numerous reviews by clinical experts and health authorities from the implementing countries. The digitalization process involved the creation of medAL-creator, a digital platform which allows clinicians without IT programming skills to easily create the algorithms, and medAL-reader the mobile health (mHealth) application used by clinicians during the consultation. Extensive feasibility tests were done with feedback from end-users of multiple countries to improve the clinical algorithm and medAL-reader software. We hope that the development framework used for developing ePOCT+ will help support the development of other CDSAs, and that the open-source medAL-suite will enable others to easily and independently implement them. Further clinical validation studies are underway in Tanzania, Rwanda, Kenya, Senegal, and India.

Background: Complicated urinary tract infections (cUTI) present a challenge to the clinician because of the variety in clinical syndromes included and consequent difficulties in synthesizing evidence. A harmonized definition of cUTI does not exist. In national guidelines, management recommendations for cUTI are often neglected. We aimed to define the four most important controversies and formulate management recommendations for cUTI in children and adolescents. Methods: The European Society of Pediatric Infectious Diseases Guideline Committee convened a working group of experts from microbiology, pediatric nephrology and infectious diseases with expertise in managing children with UTI. A comprehensive literature review was done using PubMed, Embase and the Cochrane library to find studies in children under 18 years published until December 2024. Four controversies were defined from experience and available evidence. Children with cUTI were categorized into 5 subgroups: anatomical/functional urological abnormalities, multiple UTI recurrences, severe clinical presentation, nonurological underlying conditions and neonates. Respective management guidelines were formulated through the evidence and by consensus of working group members. Recommendations were made using GRADE criteria. Results: The term cUTI is generally used to define children with UTI with an increased likelihood of failing conventional management. The included 5 subgroups are the most likely to need additional investigations at diagnosis and during the course of infection, initial intravenous antibiotics, longer treatment duration, antibiotic prophylaxis, follow-up imaging and surgical referral. These are detailed for each subgroup. Conclusions: These comprehensive guidelines offer evidence-graded recommendations specifically for pediatric cUTI, addressing gaps that exist in current guidelines.

Rifampicin is an antimicrobial drug used in the treatment of mycobacterial and gram-positive bacterial infections. In vitro studies suggest additional rifampicin-associated reduction of neurotoxicity. The aim of this study was to review the evidence for neuroprotective effects of rifampicin in infectious and non-infectious diseases in human studies. A systematic literature search was done in MEDLINE and Embase including studies from 1 Jan 1946/47-20 Jan 2024, in accordance with the preferred reporting items for systematic reviews and meta-analysis (PRISMA) (PROSPERO ID: CRD42022349852). Original articles investigating the effect of rifampicin on infections of the central nervous system (CNS) or on neurodegenerating diseases, were included. Screening, data extraction and risk of bias assessment were done using the Covidence software. Two authors assessed and extracted articles independently and blinded to each other. 1438 articles were identified of which eight were included in the final analysis: Four studies included patients with infectious diseases and four studies with neurodegenerative diseases. A neuroprotective effect of rifampicin was shown in five studies. The studies found reduced inflammatory parameters in the cerebrospinal fluid, improved neurological outcome, less cognitive decline, less brain atrophy or less metabolic decline on imaging as an effect of rifampicin. One RCT showed worsening of cognitive assessment scales in neurodegenerative patients. Current evidence suggests a neuroprotective effect of rifampicin in humans. As evaluation of neuroprotection is not standardized, a consensus definition for evaluation of clinical, radiological, and neuropsychological follow-up after pharmacological intervention would be helpful for future studies assessing neuroprotection.

During the current episode, an MRI was performed, suggesting a diagnosis of an acute focal bacterial nephritis (AFBN). A 2-week course of intravenous ceftriaxone was given followed by oral prophylactic treatment. Nonetheless, clinical relapse and new renal lesions on the follow-up MRI 6 weeks later were seen and prompted the team to treat her condition with a prolonged course of intravenous ceftriaxone over 4 weeks.