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. 2023 Nov 16;10(12):ofad580.
doi: 10.1093/ofid/ofad580. eCollection 2023 Dec.

Etiology of Acute Lower Respiratory Illness Hospitalizations Among Infants in 4 Countries

John Kubale  1 , Stephanie Kujawski  2   3 , Irena Chen  4 , Zhenke Wu  4 , Ilham Abu Khader  5 , Iris Hasibra  6 , Brett Whitaker  3 , Lionel Gresh  7 , Artan Simaku  6 , Eric A F Simões  8   9 , Mahmoud Al-Gazo  5 , Shannon Rogers  3 , Susan I Gerber  3 , Angel Balmaseda  7   10 , Veronica L Tallo  11 , Tareq M Al-Sanouri  5 , Rachael Porter  3 , Silvia Bino  6 , Eduardo Azziz-Baumgartner  3 , Meredith McMorrow  3 , Danielle Hunt  12 , Mark Thompson  3 , Holly M Biggs  3 , Aubree Gordon  13
Affiliations

Etiology of Acute Lower Respiratory Illness Hospitalizations Among Infants in 4 Countries

John Kubale et al. Open Forum Infect Dis. .

Abstract

Background: Recent studies explored which pathogens drive the global burden of pneumonia hospitalizations among young children. However, the etiology of broader acute lower respiratory tract infections (ALRIs) remains unclear.

Methods: Using a multicountry study (Albania, Jordan, Nicaragua, and the Philippines) of hospitalized infants and non-ill community controls between 2015 and 2017, we assessed the prevalence and severity of viral infections and coinfections. We also estimated the proportion of ALRI hospitalizations caused by 21 respiratory pathogens identified via multiplex real-time reverse transcription polymerase chain reaction with bayesian nested partially latent class models.

Results: An overall 3632 hospitalized infants and 1068 non-ill community controls participated in the study and had specimens tested. Among hospitalized infants, 1743 (48.0%) met the ALRI case definition for the etiology analysis. After accounting for the prevalence in non-ill controls, respiratory syncytial virus (RSV) was responsible for the largest proportion of ALRI hospitalizations, although the magnitude varied across sites-ranging from 65.2% (95% credible interval, 46.3%-79.6%) in Albania to 34.9% (95% credible interval, 20.0%-49.0%) in the Philippines. While the fraction of ALRI hospitalizations caused by RSV decreased as age increased, it remained the greatest driver. After RSV, rhinovirus/enterovirus (range, 13.4%-27.1%) and human metapneumovirus (range, 6.3%-12.0%) were the next-highest contributors to ALRI hospitalizations.

Conclusions: We observed substantial numbers of ALRI hospitalizations, with RSV as the largest source, particularly in infants aged <3 months. This underscores the potential for vaccines and long-lasting monoclonal antibodies on the horizon to reduce the burden of ALRI in infants worldwide.

Keywords: RSV; etiology; global health; influenza virus; respiratory infections.

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Conflict of interest statement

Potential conflicts of interest. A. G. serves on a scientific advisory board for Janssen. E. A. F. S. reports grants and consulting fees to the institution from Merck & Co and Pfizer Inc; grants to the institution from Astra Zeneca Inc, Roche Pharmaceuticals, and Johnson & Johnson; consulting fees to the institution from Sanofi Pasteur, Cidara Therapeutics, Adiago Therapeutics, and Nuance Pharmaceuticals; manuscript writing support from Pfizer Inc and Astra Zeneca Inc; support for attending a meeting Astra Zeneca Inc; and participation on a data and safety monitoring board from AbbVie Inc, GlaxoSmithKline plc, and the Bill and Melinda Gates Foundation. None of these are directly related to this manuscript. All other authors report no potential conflicts.

Figures

Figure 1.
Figure 1.
Hospitalized and non-ill participant enrollment (by number of samples per week) over time by study site. The dark blue bars reflect the number of enrollment samples from hospitalized infants at each site, while the brown bars show the number taken from non-ill community controls.
Figure 2.
Figure 2.
Viral prevalence by site and cohort. Left, The prevalence of all pathogens by site among hospitalized participants: number positive for each pathogen/number tested, stratified by study site and cohort (hospitalized or non-ill). Right, The prevalence of all pathogens by site among non-ill community controls. Cor229, coronavirus 229E; Cor43, coronavirus OC43; Cor63, coronavirus NL63; CorHKU1, coronavirus HKU1; HMPV, human metapneumovirus; HPIV1-HPIV4, human parainfluenza virus 1–4; RSV, respiratory syncytial virus; RV/EV, rhinovirus/enterovirus.
Figure 3.
Figure 3.
Population etiologic fraction for each pathogen by study site (marginalized over sex and age). The points represent the mean population etiologic fraction for a given pathogen from the posterior distribution, while the bar corresponds to the 95% credible interval. A pathogen's population attributable fraction can be interpreted as the proportion of ALRI hospitalizations at a site that were attributable to specific ALRI. For example, in Albania 65.2% (95% CrI, 46.3–79.6) of ALRI hospitalizations among infants were attributable to RSV. ALRI, acute lower respiratory tract infection; Cor229, coronavirus 229E; Cor43, coronavirus OC43; Cor63, coronavirus NL63; CorHKU1, coronavirus HKU1; HMPV, human metapneumovirus; HPIV1-HPIV4, human parainfluenza virus 1–4; RSV, respiratory syncytial virus; RV/EV, rhinovirus/enterovirus.
Figure 4.
Figure 4.
Top 5 etiologies of acute lower respiratory tract infection hospitalizations by study site. Points represent the posterior mean of the population etiologic fraction of each pathogen by site. Lines reflect the 95% credible intervals. HAdV, human adenovirus; HMPV, human metapneumovirus; HPIV3, human parainfluenza virus; RSV, respiratory syncytial virus; RV/EV, rhinovirus/enterovirus.
Figure 5.
Figure 5.
Top 5 etiologies of acute lower respiratory tract infection hospitalizations by age group. Points represent the posterior mean of the population etiologic fraction of each pathogen by site. Lines reflect the 95% credible intervals. HMPV, human metapneumovirus; HPIV3, human parainfluenza virus; RSV, respiratory syncytial virus; RV/EV, rhinovirus/enterovirus.
See this image and copyright information in PMC

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