Perin, J. et al. Global, regional, and National causes of under-5 mortality in 2000-19: an updated systematic analysis with implications for the sustainable development goals. Lancet Child. Adolesc. Health. 6, 106–115 (2022).
von Mollendorf, C. et al. Aetiology of childhood pneumonia in low- and middle-income countries in the era of vaccination: a systematic review. J. Glob Health. 12, 10009 (2022).
Weiser, J. N., Ferreira, D. M. & Paton, J. C. Streptococcus pneumoniae: transmission, colonization and invasion. Nat. Rev. Microbiol. 16, 355–367 (2018).
Fan, R. R. et al. Nasopharyngeal Pneumococcal density and evolution of acute respiratory illnesses in young children, Peru, 2009–2011. Emerg. Infect. Dis. 22, 1996–1999 (2016).
Carr, O. J. J. et al. Nasopharyngeal Pneumococcal colonization density is associated with severe pneumonia in young children in the Lao PDR. J. Infect. Dis. jiab239. (2021).
Baggett, H. C. et al. Density of upper respiratory colonization with Streptococcus pneumoniae and its role in the diagnosis of Pneumococcal pneumonia among children aged < 5 years in the PERCH study. Clin. Infect. Dis. Off Publ Infect. Dis. Soc. Am. 64, S317–S327 (2017).
Wolter, N. et al. High nasopharyngeal Pneumococcal density, increased by viral coinfection, is associated with invasive Pneumococcal pneumonia. J. Infect. Dis. 210, 1649–1657 (2014).
Dunne, E. M. et al. Factors associated with Pneumococcal carriage and density in infants and young children in Laos PDR. PloS One. 14, e0224392 (2019).
Chochua, S. et al. Increased nasopharyngeal density and concurrent carriage of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis are associated with pneumonia in febrile children. PloS One. 11, e0167725 (2016).
Danino, D. et al. Decline in Pneumococcal disease in young children during the COVID-19 pandemic in Israel associated with suppression of seasonal respiratory viruses, despite persistent Pneumococcal carriage: A prospective cohort study. Clin. Infect. Dis. Off Publ Infect. Dis. Soc. Am. ciab1014. (2021).
Rybak, A. et al. Association of nonpharmaceutical interventions during the COVID-19 pandemic with invasive Pneumococcal disease, Pneumococcal carriage, and respiratory viral infections among children in France. JAMA Netw. Open. 5, e2218959 (2022).
Dagan, R. et al. The COVID-19 pandemic as an opportunity for unravelling the causative association between respiratory viruses and pneumococcus-associated disease in young children: a prospective study. EBioMedicine 90, 104493 (2023).
Bakaletz, L. O. Viral-bacterial co-infections in the respiratory tract. Curr. Opin. Microbiol. 35, 30–35 (2017).
Hanada, S. et al. Respiratory viral Infection-Induced Microbiome alterations and secondary bacterial pneumonia. Front. Immunol. 9, 2640 (2018).
Walter, N. D. et al. Influenza circulation and the burden of invasive Pneumococcal pneumonia during a Non-pandemic period in the united States. Clin. Infect. Dis. 50, 175–183 (2010).
Talbot, T. R. et al. Seasonality of invasive Pneumococcal disease: Temporal relation to documented influenza and respiratory syncytial viral circulation. Am. J. Med. 118, 285–291 (2005).
Besteman, S. B. et al. Interactions between respiratory syncytial virus and Streptococcus pneumoniae in the pathogenesis of childhood respiratory infections: a systematic review. Lancet Respir Med. S2213-2600 (24), 00148–00146 (2024).
O’Brien, K. L. et al. Causes of severe pneumonia requiring hospital admission in children without HIV infection from Africa and Asia: the PERCH multi-country case-control study. Lancet 394, 757–779 (2019).
Pneumonia Etiology Research for Child Health (PERCH) Study Group. Causes of severe pneumonia requiring hospital admission in children without HIV infection from Africa and Asia: the PERCH multi-country case-control study. Lancet Lond. Engl. 394, 757–779 (2019).
Phommasone, K. et al. A case-control study of the causes of acute respiratory infection among hospitalized patients in Northeastern Laos. Sci. Rep. 12, 939 (2022).
Snoeck, C. J. et al. Etiology of viral respiratory infections in Northern Lao People’s Democratic Republic. J. Med. Virol. 90, 1553–1558 (2018).
Snoeck, C. J. et al. Epidemiology of acute respiratory viral infections in children in Vientiane, Lao People’s Democratic Republic. J. Med. Virol. 93, 4748–4755 (2021).
Vongphrachanh, P. et al. An early report from newly established laboratory-based influenza surveillance in Lao PDR. Influenza Other Respir Viruses. 4, 47–52 (2010).
Sentilhes, A-C. et al. Respiratory virus infections in hospitalized children and adults in Lao PDR. Influenza Other Respir Viruses. 7, 1070–1078 (2013).
Weaver, R. et al. The effectiveness of the 13-valent Pneumococcal conjugate vaccine against hypoxic pneumonia in children in Lao People’s Democratic Republic: an observational hospital-based test-negative study. Lancet Reg. Health West. Pac. 2, 100014 (2020).
WHO. Pocket book of hospital care for children: Guidelines for the management of common childhood illnesses.
O’Brien, K. L. et al. Evaluation of a medium (STGG) for transport and optimal recovery of Streptococcus pneumoniae from nasopharyngeal secretions collected during field studies. J. Clin. Microbiol. 39, 1021–1024 (2001).
Satzke, C. et al. Standard method for detecting upper respiratory carriage of Streptococcus pneumoniae: updated recommendations from the world health organization Pneumococcal carriage working group. Vaccine 32, 165–179 (2013).
Satzke, C. et al. Pneumococcal carriage in vaccine-eligible children and unvaccinated infants in Lao PDR two years following the introduction of the 13-valent Pneumococcal conjugate vaccine. Vaccine 37, 296–305 (2019).
Carvalho, M., Tondella, G. S. & McCaustland, M. L. Evaluation and improvement of real-time PCR assays targeting LytA, ply, and PsaA genes for detection of Pneumococcal DNA. J. Clin. Microbiol. 45, 2460–2466 (2007).
Kim, C. et al. Comparison of nasopharyngeal and oropharyngeal swabs for the diagnosis of eight respiratory viruses by real-time reverse transcription-PCR assays. PloS One. 6, e21610 (2011).
van Elden, L. J. et al. Simultaneous detection of influenza viruses A and B using real-time quantitative PCR. J. Clin. Microbiol. 39, 196–200 (2001).
Fry, A. M. et al. The burden of hospitalized lower respiratory tract infection due to respiratory syncytial virus in rural Thailand. PLoS ONE. 5, e15098 (2010).
Meyler, K. L. et al. Development of a diagnostic real-time polymerase chain reaction assay for the detection of invasive Haemophilus influenzae in clinical samples. Diagn. Microbiol. Infect. Dis. 74, 356–362 (2012).
Thirion, L. et al. Lyophilized matrix containing Ready-to-Use primers and probe solution for standardization of Real-Time PCR and RT-qPCR diagnostics in virology. Viruses 12, 159 (2020).
Siegel, S. J., Roche, A. M. & Weiser, J. N. Influenza promotes Pneumococcal growth during coinfection by providing host sialylated substrates as a nutrient source. Cell. Host Microbe. 16, 55–67 (2014).
Nakamura, S., Davis, K. M. & Weiser, J. N. Synergistic stimulation of type I interferons during influenza virus coinfection promotes Streptococcus pneumoniae colonization in mice. J. Clin. Invest. 121, 3657–3665 (2011).
Short, K. R. et al. Increased nasopharyngeal bacterial titers and local inflammation facilitate transmission of Streptococcus pneumoniae. mBio 3, e00255–e00212 (2012).
McCullers, J. A. et al. Influenza enhances susceptibility to natural acquisition of and disease due to Streptococcus pneumoniae in ferrets. J. Infect. Dis. 202, 1287–1295 (2010).
Vu, H. T. T. et al. Association between nasopharyngeal load of Streptococcus pneumoniae, viral coinfection, and radiologically confirmed pneumonia in Vietnamese children. Pediatr. Infect. Dis. J. 30, 11–18 (2011).
Mitsi, E. et al. RSV and rhinovirus increase Pneumococcal carriage acquisition and density, whereas nasal inflammation is associated with bacterial shedding. Cell. Host Microbe. 32, 1608–1620e4 (2024).
Manna, S. et al. Synergism and antagonism of Bacterial-Viral coinfection in the upper respiratory tract. mSphere 7, e0098421 (2022).
Greenberg, D. et al. Nasopharyngeal Pneumococcal carriage during childhood Community-Acquired alveolar pneumonia: relationship between specific serotypes and coinfecting viruses. J. Infect. Dis. 215, 1111–1116 (2017).
Esposito, S. et al. Pneumococcal bacterial load colonization as a marker of mixed infection in children with alveolar community-acquired pneumonia and respiratory syncytial virus or rhinovirus infection. Pediatr. Infect. Dis. J. 32, 1199–1204 (2013).
Vissers, M. et al. High Pneumococcal density correlates with more mucosal inflammation and reduced respiratory syncytial virus disease severity in infants. BMC Infect. Dis. 16, 129 (2016).
Nation, M. L. et al. Impact of COVID-19 nonpharmaceutical interventions on Pneumococcal carriage prevalence and density in Vietnam. Microbiol. Spectr. 11, e0361522 (2023).
Baker, R. E. et al. The impact of COVID-19 nonpharmaceutical interventions on the future dynamics of endemic infections. Proc. Natl. Acad. Sci. U S A. 117, 30547–30553 (2020).
Li, Z. J. et al. Broad impacts of coronavirus disease 2019 (COVID-19) pandemic on acute respiratory infections in China: an observational study. Clin. Infect. Dis. Off Publ Infect. Dis. Soc. Am. 75, e1054–e1062 (2022).
Heiskanen, A. et al. Seasonal respiratory virus circulation was diminished during the COVID-19 pandemic. Influenza Other Respir Viruses. 17, e13065 (2023).
Oh, D-Y. et al. Trends in respiratory virus circulation following COVID-19-targeted nonpharmaceutical interventions in Germany, January – September 2020: analysis of National surveillance data. Lancet Reg. Health – Eur. 6, 100112 (2021).
Ngocho, J. S. et al. Viral-bacterial (co-)occurrence in the upper airways and the risk of childhood pneumonia in resource-limited settings. J. Infect. 81, 213–220 (2020).
Diaz-Diaz, A. et al. Nasopharyngeal codetection of Haemophilus influenzae and Streptococcus pneumoniae shapes respiratory syncytial virus disease outcomes in children. J. Infect. Dis. 225, 912–923 (2022).
Brealey, J. C. et al. Viral bacterial co-infection of the respiratory tract during early childhood. FEMS Microbiol. Lett. 362, fnv062 (2015).
Nathan, A. M. et al. Bacterial pneumonia and its associated factors in children from a developing country: A prospective cohort study. PloS One. 15, e0228056 (2020).