Global human parainfluenza virus estimates for action on childhood pneumonia
Authors: Carina King, Tim Colbourn
Journal: The Lancet Global Health (2021)

In The Lancet Global Health, Xin Wang and colleagues1Wang X Li Y Deloria-Knoll M et al.Global burden of acute lower respiratory infection associated with human parainfluenza virus in children younger than 5 years for 2018: a systematic review and meta-analysis.Lancet Glob Health. 2021; (published online June 21.)https://doi.org/10.1016/S2214-109X(21)00218-7Summary Full Text Full Text PDF Scopus (5) Google Scholar provide important estimates of the global paediatric burden of acute lower respiratory infections (ALRI) associated with human parainfluenza virus (hPIV). Their efforts to collate data from 162 published and 41 unpublished studies are commendable. However, it is apparent that more data are needed to refine some estimates, notably the incidence (13 studies), and burden in low-income (eight studies) and lower-middle-income countries (37 studies). More accurately establishing the proportion of infections that result in severe disease and hypoxaemia (13 studies) is also needed to quantify the associated need for oxygen therapy and intensive care. Such granular data need not be pathogen-specific, but would be especially useful in settings where such care is absent. The importance of the detailed epidemiological data for pathogen-specific ALRI provided in this Article lies more in establishing antiviral drug and vaccine development priorities, and assessing temporal changes. The authors report hPIV as causing 13% of all ALRI cases in children and 4–14% of paediatric ALRI hospital admissions,1Wang X Li Y Deloria-Knoll M et al.Global burden of acute lower respiratory infection associated with human parainfluenza virus in children younger than 5 years for 2018: a systematic review and meta-analysis.Lancet Glob Health. 2021; (published online June 21.)https://doi.org/10.1016/S2214-109X(21)00218-7Summary Full Text Full Text PDF Scopus (5) Google Scholar representing a substantial, though considerably uncertain, health system burden. The directly attributed mortality burden was lower, at an estimated 4% of all ALRI deaths in children. Given that the authors account for co-infections—via applying attributable fractions for hPIV-associated ALRI cases (72%) and deaths (65%) from the multi-country PERCH2O'Brien KL Baggett HC Brooks WA 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. 2019; 394: 757-779Summary Full Text Full Text PDF PubMed Scopus (218) Google Scholar and GABRIEL3Bénet T Sánchez Picot V Messaoudi M et al.Microorganisms associated with pneumonia in children <5 years of age in developing and emerging countries: the GABRIEL pneumonia multicenter, prospective, case-control study.Clin Infect Dis. 2017; 65: 604-612PubMed Google Scholar studies—these data suggest that hPIV could be less lethal than other childhood ALRI pathogens. The authors cite papers on early parainfluenza vaccine trials published between 2011 and 2015 that indicate—given that there are no hPIV vaccines available yet—a modest speed of vaccine development. Given that the burdens of mortality (an estimated 34 400 [UR 16 400–73 800] deaths globally) and admission to hospital (725 000 [UR 433 000–1 260 000])1Wang X Li Y Deloria-Knoll M et al.Global burden of acute lower respiratory infection associated with human parainfluenza virus in children younger than 5 years for 2018: a systematic review and meta-analysis.Lancet Glob Health. 2021; (published online June 21.)https://doi.org/10.1016/S2214-109X(21)00218-7Summary Full Text Full Text PDF Scopus (5) Google Scholar are still considerable, and given what has been possible during the COVID-19 pandemic,4Mathieu E Ritchie H Ortiz-Ospina E et al.A global database of COVID-19 vaccinations.Nat Hum Behav. 2021; (published online May 10.)https://doi.org/10.1038/s41562-021-01122-8PubMed Google Scholar the development and licensing of vaccines for hPIV and other respiratory pathogens affecting children should and could be accelerated. The hPIV burdens reported by Wang and colleagues1Wang X Li Y Deloria-Knoll M et al.Global burden of acute lower respiratory infection associated with human parainfluenza virus in children younger than 5 years for 2018: a systematic review and meta-analysis.Lancet Glob Health. 2021; (published online June 21.)https://doi.org/10.1016/S2214-109X(21)00218-7Summary Full Text Full Text PDF Scopus (5) Google Scholar could make the introduction of hPIV vaccines cost-effective in most settings, although vaccine effectiveness, price, and the possibility of serotype or pathogen replacement are important unknowns.5Saokaew S Rayanakorn A Wu DB Chaiyakunapruk N Cost effectiveness of pneumococcal vaccination in children in low- and middle-income countries: a systematic review.PharmacoEconomics. 2016; 34: 1211-1225Crossref PubMed Scopus (29) Google Scholar A strength of Wang and colleagues' Article1Wang X Li Y Deloria-Knoll M et al.Global burden of acute lower respiratory infection associated with human parainfluenza virus in children younger than 5 years for 2018: a systematic review and meta-analysis.Lancet Glob Health. 2021; (published online June 21.)https://doi.org/10.1016/S2214-109X(21)00218-7Summary Full Text Full Text PDF Scopus (5) Google Scholar is their ability to include a large amount of unpublished data. However, this also raises an interesting discussion on who has access to causal data, and when. COVID-19 has shown the ability for many country and regional level public health agencies to publish near real-time RT-PCR testing data. The further collation onto open-access, easy to use, interactive platforms (eg, Our World in Data) has made these data both accessible and to some extent comparable between countries. Single respiratory pathogen data platforms exist (eg, RSV Gold or WHO's sentinel Global Influenza Surveillance and Response System). However, the potential to exploit the data architecture being used for COVID-19 provides an exciting opportunity for more comprehensive monitoring of ALRI causes. A key piece of this puzzle will be strengthening country-level laboratory and reporting capacities. In some high-burden countries, surveillance infrastructure needs to be developed. There are already promising new initiatives, such as Africa's Pathogen Genomics Initiative,6Makoni M Africa's $100-million pathogen genomics initiative.Lancet Microbe. 2020; 1: e318Summary Full Text Full Text PDF Google Scholar and ensuring that such infrastructure has sustained national focus and commitment is crucial. The estimates generated by Wang and colleagues1Wang X Li Y Deloria-Knoll M et al.Global burden of acute lower respiratory infection associated with human parainfluenza virus in children younger than 5 years for 2018: a systematic review and meta-analysis.Lancet Glob Health. 2021; (published online June 21.)https://doi.org/10.1016/S2214-109X(21)00218-7Summary Full Text Full Text PDF Scopus (5) Google Scholar provide a timely pre-COVID-19 snapshot of paediatric hPIV epidemiology. Moving forward, it will be important to understand the effect of non-pharmaceutical interventions related to COVID-19 on other respiratory viruses. There have been several reports of major shifts in paediatric ALRI hospital admissions,7Kuitunen I Artama M Mäkelä L Backman K Heiskanen-Kosma T Renko M Effect of social distancing due to the COVID-19 pandemic on the incidence of viral respiratory tract infections in children in Finland during early 2020.Pediatr Infect Dis J. 2020; 39: e423-e427Crossref PubMed Scopus (71) Google Scholar, 8Huh K Jung J Hong J et al.Impact of nonpharmaceutical interventions on the incidence of respiratory infections during the coronavirus disease 2019 (COVID-19) outbreak in Korea: a nationwide surveillance study.Clin Infect Dis. 2021; 72: e184-e191Crossref PubMed Scopus (19) Google Scholar and the near disappearance of flu seasons in 2020 and 2021.9Adlhoch C Mook P Lamb F et al.Very little influenza in the WHO European Region during the 2020/21 season, weeks 40 2020 to 8 2021.Euro Surveill. 2021; 26Crossref Scopus (15) Google Scholar, 10Olsen SJ Azziz-Baumgartner E Budd AP et al.Decreased influenza activity during the COVID-19 pandemic - United States, Australia, Chile, and South Africa, 2020.MMWR Morb Mortal Wkly Rep. 2020; 69: 1305-1309Crossref PubMed Scopus (133) Google Scholar It is crucial that efforts are made to closely monitor the subsequent epidemiology of important respiratory pathogens, such as hPIV. Interruptions to the normal seasonal circulation of this virus might have left cohorts of children more susceptible to outbreaks as non-pharmaceutical interventions are lifted and global movement increases. There is hope that increased investments in oxygen during COVID-19 will reduce one key bottleneck to effective paediatric ALRI management.11Every Breath CountsEvery Breath Counts Coalition Work Plan 2021.https://stoppneumonia.org/wp-content/uploads/2021/05/Every-Breath-Counts-Coalition-Work-Plan-2021.pdfDate: 2021Date accessed: May 13, 2021Google Scholar The focus on an improved capacity for localised laboratory diagnostics and a clear precedent for rapid vaccine pipelines and novel vaccine platforms give two more reasons for hope. The work done by Wang and colleagues1Wang X Li Y Deloria-Knoll M et al.Global burden of acute lower respiratory infection associated with human parainfluenza virus in children younger than 5 years for 2018: a systematic review and meta-analysis.Lancet Glob Health. 2021; (published online June 21.)https://doi.org/10.1016/S2214-109X(21)00218-7Summary Full Text Full Text PDF Scopus (5) Google Scholar provides a starting to point to move forward with a more focused and sustainable prevention, detection, and treatment agenda for hPIV. We declare no competing interests. Global burden of acute lower respiratory infection associated with human parainfluenza virus in children younger than 5 years for 2018: a systematic review and meta-analysisWe report the first global burden estimates of hPIV-associated and hPIV-attributable ALRI in young children. Globally, approximately 13% of ALRI cases, 4–14% of ALRI hospital admissions, and 4% of childhood ALRI mortality were attributable to hPIV. These numbers indicate a potentially notable burden of hPIV in ALRI morbidity and mortality in young children. These estimates should encourage and inform investment to accelerate the development of targeted interventions. Full-Text PDF Open Access