ToolCAP: Novel Tools to Improve Management of Paediatric Community-Acquired Pneumonia

In 2019, lower respiratory tract infections (LRTI) caused 2.6 million deaths worldwide, making them the fourth leading cause of death overall. While the statistic is global the effect is concentrated in low-resource settings and among children, with pneumonia being the single largest infectious cause of death in children worldwide.

LRTI (including pneumonia) are the most common reason for sick children to present for acute outpatient care and current best practice pneumonia management guidelines advocate for all cases to receive a course of antibiotics. This relies on the World Health Organization's (WHO) Integrated Management of Childhood Infections (IMCI) guidelines, first developed in the 1990s - a time when providing access to antibiotics was a major goal for public health programs. Today, antibiotics are readily available in most countries in sub-Saharan Africa (SSA) and antibiotic over-prescription has become a public health crisis. The IMCI guidelines were re-iterated in 2014 but still rely on presumptive treatment based on clinical signs alone (cough, respiratory rate, and lower costal indrawing), as evidence to include additional diagnostic tests into the IMCI approach has been lacking. However clinical features inadequately distinguish bacterial infections and complications from common, self-limiting viral infections. Furthermore, recent evidence estimates the incidence of bacterial respiratory infections in SSA, using a combination of microbiology, chest x-ray (CXR), and clinical outcomes as reference standards, is as low as 2-4% in primary, and 23.3-31.6% in secondary, care. Therefore, approximately 9 out of 10 courses of antibiotics recommended by current guidelines for children with LRTI are estimated to be unnecessary.

Bacterial antimicrobial resistance (AMR), responsible for 1.27 million deaths in 2019 and with the highest burden in SSA, is thus of increasing concern; with nearly as many deaths as malaria and HIV combined. Inappropriately and excessively prescribing antibiotics represents one primary contributor of bacterial AMR. In SSA, more than 50% of children who are sick receive antibiotics when visiting health facilities with 80-90% of such antibiotics prescribed at the outpatient level and most deemed inappropriate. Most inappropriate antibiotic use occurs with respiratory infections due to systematic overprescription as outlined above. Antibiotic use and AMR are projected to increase over the next years, indicating urgent action. Accordingly, WHO declared AMR as "one of the biggest threats to global health, food security and development today.". Effective solutions to improve antibiotic stewardship for childhood infections in SSA primary care settings remain lacking, though its well recognized improved diagnostic and management processes are essential.

Lacking more effective tools to safely identify the minority of children requiring antibiotics, frontline clinicians in low resource settings therefore prescribe antibiotics to nearly every child, driving the above-described overuse and fuelling local AMR, whilst significantly overtreating cases of viral pneumonia. Besides the risk of AMR at the population level, reducing antibiotic prescriptions is also important for each individual patient. Antibiotic exposure early in life has been associated with an increased risk of health conditions, including asthma, allergic rhinitis, atopic dermatitis, autoimmune disease, obesity, and neurodevelopmental disorders. Improving IMCI diagnostic criteria to better identify children with pneumonia that would benefit from antibiotic therapy is therefore a WHO research priority.

Several tools have since been proposed (currently at different stages of diagnostic development) to both improve diagnostic pathways and improve appropriateness of antimicrobial prescriptions in low and middle income countries. These include the use of point of care C-reactive Protein (CRP), Procalcitonin (PCT), comprehensive electronic decision support algorithms, and more novel applications of established technologies. Two such technologies are Lung Ultrasound (LUS) and Lung Auscultation (LAusc). LUS is a well-established, near consumable-free, and non-invasive point-of-care respiratory exam. While LUS is less ubiquitous than the stethoscope, it's new portable and affordable ultrasound-on-a-chip design, pluggable into a mobile device, has the potential to be integrated into the standard clinical exam without incurring extra costs, time, radiation, or specialist consultation. These portable ultrasound devices have reached regulatory approval and are used in medical care across SSA. This together with increasing evidence showing its ability to effectively detect lung consolidation in pneumonia have made it an increasingly attractive tool for frontline clinicians; already becoming an established practice in the outpatient case management of children with respiratory infections in many high-resource settings as well as growing steadily in popularity in SSA.