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Pathogen landscape and synergistic interactions in pediatric ARIs: implications for broad-spectrum surveillance via
Jingjiao Zhou1, Ting Li1, Shenzhen Yuan1
1Department of Biology and Genetics, The College of Life Sciences and Health, Wuhan University of Science and Technology, Hubei, China.
Insights
This study reveals complex co-infections in pediatric acute respiratory infections (ARIs), showing specific pathogen combinations significantly impact disease severity. Advanced sequencing aids in understanding these dynamics for better treatment.
Area of Science:
- Pediatric Infectious Diseases
- Microbiology
- Genomics
Background:
- Acute respiratory infections (ARIs) in children cause significant morbidity and mortality.
- Understanding the complex interplay between respiratory pathogens and the host is crucial for effective treatment.
Purpose of the Study:
- To delineate the pathogen spectrum and co-infection patterns in pediatric ARIs.
- To identify biomarkers associated with disease severity and co-infections.
- To analyze the epidemiological landscape of ARIs in children.
Main Methods:
- Targeted next-generation sequencing (tNGS) was used to test 2,044 pediatric in-patient samples for 198 pathogens.
- Analysis included pathogen spectrum, co-infection patterns, blood test results, and clinical data.
- Epidemiological data from 2022-2023 were analyzed.
Main Results:
- Viral infections predominated in children under 3 years.
- Specific viral-bacterial co-infections (e.g., HMPV-S. pneumoniae) were linked to increased disease severity.
- Mycoplasma pneumoniae (MP) emerged as a dominant pathogen in older children, with high loads associated with inflammation and airway hyperreactivity.
- Subnormal prealbumin and creatinine levels indicated homeostasis disruption in viral-bacterial co-infections.
- Co-infections with MP and other pathogens like HHV or H. influenzae were associated with severe cases.
Conclusions:
- Pediatric ARIs involve complex pathogen interactions, including viral-bacterial and MP-bacterial co-infections.
- Detecting pathogen-pathogen and host-pathogen dynamics is essential for precision diagnostics.
- tNGS monitoring aids in targeted treatment and improved clinical outcomes for pediatric ARIs.
Abstract:
Acute respiratory infections (ARIs) in children present complex interactions between respiratory pathogens and host, contributing to high morbidity, hospitalization, and mortality. In this cross-sectional study, 2,044 pediatric in-patient samples were tested for 198 pathogens using targeted next-generation sequencing (tNGS). Pathogen spectrum and co-infection pattern were analyzed alongside blood-test results and clinical data. Pediatric ARIs presented staggered viral epidemics and age-specific infection patterns from 2022 to 2023. Viral infections were predominant in children under 3 years (67.5%). Specific viral-bacterial co-infections were associated with disease severity, including human metapneumovirus (HMPV)-Streptococcus pneumoniae (OR = 3.172, 95% CI: 1.257-8.009), human parainfluenza virus (HPIV)-Fusobacterium nucleatum (3.016, 1.051-8.653), and HPIV-S. pneumoniae (2.825, 1.007-7.927). Subnormal levels of prealbumin and creatinine served as biomarkers for homeostasis disruption in viral-bacterial co-infections. From June to December 2023, Mycoplasma pneumoniae (MP) became the dominant pathogen in preschool (31.3%) and school-age (45.3%) children. High MP loads were correlated with elevated eosinophil, IL-4, and IL-6 and decreased IgG and IL-2, linking to airway hyperreactivity and inflammation. At low MP loads, patients co-detected with human herpesvirus (HHV) (50.0%), or Haemophilus influenzae (40.0%) had a high proportion of severe cases. This study delineated the complex pathogen landscape of pediatric ARIs and highlighted the major role of viral-bacterial and MP-bacterial co-infections. Monitoring these pathogens through tNGS can aid in precise diagnosis and targeted treatment to improve clinical outcomes in children.IMPORTANCEMoving beyond the outdated "one germ, one disease" model, this study characterizes the etiological and epidemiological landscape and highlights co-infection patterns of virus-bacterium or MP-bacterium in 2044 pediatric respiratory in-patient children across three epidemic phases. Specific pathogen combinations are associated with clinical severity, as well as host immune and metabolic profiles. Our findings underscore the necessity of detecting pathogen-pathogen and host-pathogen dynamics, rather than individual pathogens, thereby informing precision diagnostics and targeted intervention strategies.
