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      Viral Acute Lower Respiratory Tract Infections (ALRI) in Rural Bangladeshi Children Prior to the COVID‐19 Pandemic

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          ABSTRACT

          Background

          Acute lower respiratory tract infections (ALRIs) remain the leading infectious cause of death among children < 5 years, with viruses contributing to a large proportion of cases. Little is known about the epidemiology and etiology of viral ALRI in rural Bangladesh.

          Methods

          We enrolled 3‐ to 23‐month‐old children with ALRIs attending a subdistrict hospital outpatient clinic in Sylhet district in Bangladesh. Trained study physicians ascertained the cases and obtained nasopharyngeal swabs to detect 19 respiratory viruses by multiplex PCR using the Luminex Integrated System NxTAG Respiratory pathogen panel.

          Results

          Between August 2016 and September 2017, we enrolled 1477 children. Median age was 10 months; 58.1% were male. Forty‐seven percent presented during autumn (mid‐June to mid‐October). About a third had temperature ≥ 101°F, 95.4% had cough in the previous 3 days, 72.0% had fast breathing, and 80.0% had chest indrawing. Alveolar consolidation occurred in 23.9%, and 4.4% were hypoxemic (saturation < 90% on room air). Nineteen percent required hospitalization; 79.1% of them were discharged within 48 h. A respiratory virus was identified in 81.8%, majority (75.8%) with single virus isolation. Rhinoenterovirus was most commonly identified (HRV/HEV, 37.9%), followed by respiratory syncytial virus (RSV, 20.2%) and human metapneumovirus (hMPV, 11.7%). Rhinoenterovirus was detected year‐round; RSV was detected during August–November and hMPV during December–March.

          Conclusions

          Respiratory viruses were identified in a majority (82%) of children under 2 years of age presenting with ALRI in rural hospitals of Bangladesh. These findings have implications for future study and potentially for surveillance, antimicrobial stewardship, vaccine program planning, and policy.

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          Most cited references37

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          Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980–2017: a systematic analysis for the Global Burden of Disease Study 2017

          Summary Background Global development goals increasingly rely on country-specific estimates for benchmarking a nation's progress. To meet this need, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 estimated global, regional, national, and, for selected locations, subnational cause-specific mortality beginning in the year 1980. Here we report an update to that study, making use of newly available data and improved methods. GBD 2017 provides a comprehensive assessment of cause-specific mortality for 282 causes in 195 countries and territories from 1980 to 2017. Methods The causes of death database is composed of vital registration (VR), verbal autopsy (VA), registry, survey, police, and surveillance data. GBD 2017 added ten VA studies, 127 country-years of VR data, 502 cancer-registry country-years, and an additional surveillance country-year. Expansions of the GBD cause of death hierarchy resulted in 18 additional causes estimated for GBD 2017. Newly available data led to subnational estimates for five additional countries—Ethiopia, Iran, New Zealand, Norway, and Russia. Deaths assigned International Classification of Diseases (ICD) codes for non-specific, implausible, or intermediate causes of death were reassigned to underlying causes by redistribution algorithms that were incorporated into uncertainty estimation. We used statistical modelling tools developed for GBD, including the Cause of Death Ensemble model (CODEm), to generate cause fractions and cause-specific death rates for each location, year, age, and sex. Instead of using UN estimates as in previous versions, GBD 2017 independently estimated population size and fertility rate for all locations. Years of life lost (YLLs) were then calculated as the sum of each death multiplied by the standard life expectancy at each age. All rates reported here are age-standardised. Findings At the broadest grouping of causes of death (Level 1), non-communicable diseases (NCDs) comprised the greatest fraction of deaths, contributing to 73·4% (95% uncertainty interval [UI] 72·5–74·1) of total deaths in 2017, while communicable, maternal, neonatal, and nutritional (CMNN) causes accounted for 18·6% (17·9–19·6), and injuries 8·0% (7·7–8·2). Total numbers of deaths from NCD causes increased from 2007 to 2017 by 22·7% (21·5–23·9), representing an additional 7·61 million (7·20–8·01) deaths estimated in 2017 versus 2007. The death rate from NCDs decreased globally by 7·9% (7·0–8·8). The number of deaths for CMNN causes decreased by 22·2% (20·0–24·0) and the death rate by 31·8% (30·1–33·3). Total deaths from injuries increased by 2·3% (0·5–4·0) between 2007 and 2017, and the death rate from injuries decreased by 13·7% (12·2–15·1) to 57·9 deaths (55·9–59·2) per 100 000 in 2017. Deaths from substance use disorders also increased, rising from 284 000 deaths (268 000–289 000) globally in 2007 to 352 000 (334 000–363 000) in 2017. Between 2007 and 2017, total deaths from conflict and terrorism increased by 118·0% (88·8–148·6). A greater reduction in total deaths and death rates was observed for some CMNN causes among children younger than 5 years than for older adults, such as a 36·4% (32·2–40·6) reduction in deaths from lower respiratory infections for children younger than 5 years compared with a 33·6% (31·2–36·1) increase in adults older than 70 years. Globally, the number of deaths was greater for men than for women at most ages in 2017, except at ages older than 85 years. Trends in global YLLs reflect an epidemiological transition, with decreases in total YLLs from enteric infections, respiratory infections and tuberculosis, and maternal and neonatal disorders between 1990 and 2017; these were generally greater in magnitude at the lowest levels of the Socio-demographic Index (SDI). At the same time, there were large increases in YLLs from neoplasms and cardiovascular diseases. YLL rates decreased across the five leading Level 2 causes in all SDI quintiles. The leading causes of YLLs in 1990—neonatal disorders, lower respiratory infections, and diarrhoeal diseases—were ranked second, fourth, and fifth, in 2017. Meanwhile, estimated YLLs increased for ischaemic heart disease (ranked first in 2017) and stroke (ranked third), even though YLL rates decreased. Population growth contributed to increased total deaths across the 20 leading Level 2 causes of mortality between 2007 and 2017. Decreases in the cause-specific mortality rate reduced the effect of population growth for all but three causes: substance use disorders, neurological disorders, and skin and subcutaneous diseases. Interpretation Improvements in global health have been unevenly distributed among populations. Deaths due to injuries, substance use disorders, armed conflict and terrorism, neoplasms, and cardiovascular disease are expanding threats to global health. For causes of death such as lower respiratory and enteric infections, more rapid progress occurred for children than for the oldest adults, and there is continuing disparity in mortality rates by sex across age groups. Reductions in the death rate of some common diseases are themselves slowing or have ceased, primarily for NCDs, and the death rate for selected causes has increased in the past decade. Funding Bill & Melinda Gates Foundation.
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            Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in children younger than 5 years in 2019: a systematic analysis

            Summary Background Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory infection in young children. We previously estimated that in 2015, 33·1 million episodes of RSV-associated acute lower respiratory infection occurred in children aged 0–60 months, resulting in a total of 118 200 deaths worldwide. Since then, several community surveillance studies have been done to obtain a more precise estimation of RSV associated community deaths. We aimed to update RSV-associated acute lower respiratory infection morbidity and mortality at global, regional, and national levels in children aged 0–60 months for 2019, with focus on overall mortality and narrower infant age groups that are targeted by RSV prophylactics in development. Methods In this systematic analysis, we expanded our global RSV disease burden dataset by obtaining new data from an updated search for papers published between Jan 1, 2017, and Dec 31, 2020, from MEDLINE, Embase, Global Health, CINAHL, Web of Science, LILACS, OpenGrey, CNKI, Wanfang, and ChongqingVIP. We also included unpublished data from RSV GEN collaborators. Eligible studies reported data for children aged 0–60 months with RSV as primary infection with acute lower respiratory infection in community settings, or acute lower respiratory infection necessitating hospital admission; reported data for at least 12 consecutive months, except for in-hospital case fatality ratio (CFR) or for where RSV seasonality is well-defined; and reported incidence rate, hospital admission rate, RSV positive proportion in acute lower respiratory infection hospital admission, or in-hospital CFR. Studies were excluded if case definition was not clearly defined or not consistently applied, RSV infection was not laboratory confirmed or based on serology alone, or if the report included fewer than 50 cases of acute lower respiratory infection. We applied a generalised linear mixed-effects model (GLMM) to estimate RSV-associated acute lower respiratory infection incidence, hospital admission, and in-hospital mortality both globally and regionally (by country development status and by World Bank Income Classification) in 2019. We estimated country-level RSV-associated acute lower respiratory infection incidence through a risk-factor based model. We developed new models (through GLMM) that incorporated the latest RSV community mortality data for estimating overall RSV mortality. This review was registered in PROSPERO (CRD42021252400). Findings In addition to 317 studies included in our previous review, we identified and included 113 new eligible studies and unpublished data from 51 studies, for a total of 481 studies. We estimated that globally in 2019, there were 33·0 million RSV-associated acute lower respiratory infection episodes (uncertainty range [UR] 25·4–44·6 million), 3·6 million RSV-associated acute lower respiratory infection hospital admissions (2·9–4·6 million), 26 300 RSV-associated acute lower respiratory infection in-hospital deaths (15 100–49 100), and 101 400 RSV-attributable overall deaths (84 500–125 200) in children aged 0–60 months. In infants aged 0–6 months, we estimated that there were 6·6 million RSV-associated acute lower respiratory infection episodes (4·6–9·7 million), 1·4 million RSV-associated acute lower respiratory infection hospital admissions (1·0–2·0 million), 13 300 RSV-associated acute lower respiratory infection inhospital deaths (6800–28 100), and 45700 RSV-attributable overall deaths (38 400–55 900). 2·0% of deaths in children aged 0–60 months (UR 1·6–2·4) and 3·6% of deaths in children aged 28 days to 6 months (3·0–4·4) were attributable to RSV. More than 95% of RSV-associated acute lower respiratory infection episodes and more than 97% of RSV-attributable deaths across all age bands were in low-income and middle-income countries (LMICs). Interpretation RSV contributes substantially to morbidity and mortality burden globally in children aged 0–60 months, especially during the first 6 months of life and in LMICs. We highlight the striking overall mortality burden of RSV disease worldwide, with one in every 50 deaths in children aged 0–60 months and one in every 28 deaths in children aged 28 days to 6 months attributable to RSV. For every RSV-associated acute lower respiratory infection in-hospital death, we estimate approximately three more deaths attributable to RSV in the community. RSV passive immunisation programmes targeting protection during the first 6 months of life could have a substantial effect on reducing RSV disease burden, although more data are needed to understand the implications of the potential age-shifts in peak RSV burden to older age when these are implemented. Funding EU Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe (RESCEU).
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              Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis

              Summary Background The global burden of disease attributable to respiratory syncytial virus (RSV) remains unknown. We aimed to estimate the global incidence of and mortality from episodes of acute lower respiratory infection (ALRI) due to RSV in children younger than 5 years in 2005. Methods We estimated the incidence of RSV-associated ALRI in children younger than 5 years, stratified by age, using data from a systematic review of studies published between January, 1995, and June, 2009, and ten unpublished population-based studies. We estimated possible boundaries for RSV-associated ALRI mortality by combining case fatality ratios with incidence estimates from hospital-based reports from published and unpublished studies and identifying studies with population-based data for RSV seasonality and monthly ALRI mortality. Findings In 2005, an estimated 33·8 (95% CI 19·3–46·2) million new episodes of RSV-associated ALRI occurred worldwide in children younger than 5 years (22% of ALRI episodes), with at least 3·4 (2·8–4·3) million episodes representing severe RSV-associated ALRI necessitating hospital admission. We estimated that 66 000–199 000 children younger than 5 years died from RSV-associated ALRI in 2005, with 99% of these deaths occurring in developing countries. Incidence and mortality can vary substantially from year to year in any one setting. Interpretation Globally, RSV is the most common cause of childhood ALRI and a major cause of admission to hospital as a result of severe ALRI. Mortality data suggest that RSV is an important cause of death in childhood from ALRI, after pneumococcal pneumonia and Haemophilus influenzae type b. The development of novel prevention and treatment strategies should be accelerated as a priority. Funding WHO; Bill & Melinda Gates Foundation.
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                Author and article information

                Contributors
                kmehta6@jhu.edu
                Journal
                Influenza Other Respir Viruses
                Influenza Other Respir Viruses
                10.1111/(ISSN)1750-2659
                IRV
                Influenza and Other Respiratory Viruses
                John Wiley and Sons Inc. (Hoboken )
                1750-2640
                1750-2659
                19 December 2024
                December 2024
                : 18
                : 12 ( doiID: 10.1111/irv.v18.12 )
                : e70062
                Affiliations
                [ 1 ] Department of Medicine Duke University School of Medicine Durham North Carolina USA
                [ 2 ] Duke Global Health Institute Durham North Carolina USA
                [ 3 ] Durham Veterans Affairs Medical Center Durham North Carolina USA
                [ 4 ] Department of International Health Johns Hopkins Bloomberg School of Public Health Baltimore Maryland USA
                [ 5 ] Global Program in Respiratory Sciences, Department of Pediatrics, Eudowood Division of Pediatric Respiratory Sciences Johns Hopkins University School of Medicine Baltimore Maryland USA
                [ 6 ] Projahnmo Research Foundation Dhaka Bangladesh
                [ 7 ] Child Health Research Foundation Dhaka Bangladesh
                Author notes
                [*] [* ] Correspondence:

                Kayur Mehta ( kmehta6@ 123456jhu.edu )

                Article
                IRV70062 IRV-2024-280.R1
                10.1111/irv.70062
                11658914
                39701824
                a29b7560-82ee-4efc-acb8-045cf6bd8eaf
                © 2024 The Author(s). Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 27 November 2024
                : 12 July 2024
                : 01 December 2024
                Page count
                Figures: 3, Tables: 4, Pages: 12, Words: 7100
                Funding
                Funded by: Bill and Melinda Gates Foundation , doi 10.13039/100000865;
                Award ID: OPP1084286
                Award ID: OPP1117483
                Funded by: Thrasher Research Fund , doi 10.13039/100005627;
                Award ID: 14193
                Categories
                Original Article
                Original Article
                Custom metadata
                2.0
                December 2024
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.5.1 mode:remove_FC converted:19.12.2024

                Infectious disease & Microbiology
                alri,bangladesh,child,infant,viral
                Infectious disease & Microbiology
                alri, bangladesh, child, infant, viral

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