Trial of Respiratory Infections in Children for Enhanced Diagnostics

Background: Respiratory viral and bacterial infections are hard to distinguish clinically, and many children with viral infections receive unnecessary treatment with antibiotics, which contributes to development and spread of antibiotic resistance. Therefore, there is a need for new point-of-care diagnostic tests that better distinguish viral from antibiotic-requiring bacterial infections, particularly in children presenting with suspected clinical community-acquired pneumonia (CAP), and thus assist health-care workers decision making and improve rational use of antibiotics.

Myxovirus resistance protein A (MxA) is a promising biomarker for viral infection, but no studies have investigated MxA in children with CAP. Procalcitonin (PCT) is used as a biomarker for severe bacterial infection as the protein rapidly increases in plasma levels in response to stress and systemic infection. PCT has been reported to be more specific for bacterial infection as compared to CRP, but there are conflicting data on the clinical utility of PCT in children with CAP.

The role of viruses and atypical bacteria in childhood CAP Is increasingly recognized. Recent studies have reported an increasing incidence of B. pertussis and there have been several deaths in previously healthy infants associated with whooping cough in Sweden over the last ten years. Consequently, there is a need for new etiologic studies in childhood CAP.

Real-time PCR is currently considered gold-standard for detection of respiratory viruses in children with respiratory tract infection. Nevertheless, the turn-around time is usually long and the test results can rarely be used for decision making regarding treatment. There are currently several new antigen-based point-of-care tests of respiratory infections on the market, one is Multianalyte Point-of-care Antigen Detection Test System (MariPOC®) Respi. The sensitivity for respiratory syncytial virus (RSV) and influenza virus is as high as 90% as compared to PCR, the current gold-standard PCR, but, the sensitivity for less common respiratory viruses such as metapneumovirus (hMPV), parainfluenza virus (PIV), coronavirus and bocavirus have been insufficiently investigated.

Recombinase polymerase amplification (RPA) is a nucleic acid amplification method that doesn't require thermal cycling. As the test reaction can be carried out at room temperature it is a particularly interesting method for resource-limited settings where the need for new diagnostic tests is high.