Epidemiological and health economic implications of symptom propagation in respiratory pathogens: A mathematical modelling investigation.

BACKGROUND: Respiratory pathogens inflict a substantial burden on public health and the economy. Although the severity of symptoms caused by these pathogens can vary from asymptomatic to fatal, the factors that determine symptom severity are not fully understood. Correlations in symptoms between infector-infectee pairs, for which evidence is accumulating, can generate large-scale clusters of severe infections that could be devastating to those most at risk, whilst also conceivably leading to chains of mild or asymptomatic infections that generate widespread immunity with minimal cost to public health. Although this effect could be harnessed to amplify the impact of interventions that reduce symptom severity, the mechanistic representation of symptom propagation within mathematical and health economic modelling of respiratory diseases is understudied. METHODS AND FINDINGS: We propose a novel framework for incorporating different levels of symptom propagation into models of infectious disease transmission via a single parameter, α. Varying α tunes the model from having no symptom propagation (α = 0, as typically assumed) to one where symptoms always propagate (α = 1). For parameters corresponding to three respiratory pathogens-seasonal influenza, pandemic influenza and SARS-CoV-2-we explored how symptom propagation impacted the relative epidemiological and health-economic performance of three interventions, conceptualised as vaccines with different actions: symptom-attenuating (labelled SA), infection-blocking (IB) and infection-blocking admitting only mild breakthrough infections (IB_MB). In the absence of interventions, with fixed underlying epidemiological parameters, stronger symptom propagation increased the proportion of cases that were severe. For SA and IB_MB, interventions were more effective at reducing prevalence (all infections and severe cases) for higher strengths of symptom propagation. For IB, symptom propagation had no impact on effectiveness, and for seasonal influenza this intervention type was more effective than SA at reducing severe infections for all strengths of symptom propagation. For pandemic influenza and SARS-CoV-2, at low intervention uptake, SA was more effective than IB for all levels of symptom propagation; for high uptake, SA only became more effective under strong symptom propagation. Health economic assessments found that, for SA-type interventions, the amount one could spend on control whilst maintaining a cost-effective intervention (termed threshold unit intervention cost) was very sensitive to the strength of symptom propagation. CONCLUSIONS: Overall, the preferred intervention type depended on the combination of the strength of symptom propagation and uptake. Given the importance of determining robust public health responses, we highlight the need to gather further data on symptom propagation, with our modelling framework acting as a template for future analysis.

Assessment of Illness Severity in Adults Hospitalized With Acute Respiratory Tract Infection due to Influenza, Respiratory Syncytial Virus, or Human Metapneumovirus.

BACKGROUND: Influenza, respiratory syncytial virus (RSV), and human metapneumovirus (hMPV) are common respiratory viruses causing similar symptoms. Optimal tools to assess illness severity for these viruses have not been defined. Using the Hospitalized Acute Respiratory Tract Infection (HARTI) study data, we report symptom severity by clinician-rated clinical severity scores (CSS) in adults with influenza, RSV, or hMPV and correlations between CSS and patient-reported outcomes (PROs). METHODS: HARTI was a global epidemiologic study in adults hospitalized with acute respiratory tract infections. Patients were assessed at enrollment within 24 h of admission with CSS and twice during hospitalization with CSS, Respiratory Infection Intensity and Impact Questionnaire™ (RiiQ™), and EQ-5D-5L. Data were summarized descriptively, stratified by pathogen and baseline and hospitalization characteristics. Domain (general, upper respiratory, and lower respiratory) and sign/symptom subscores are presented for CSS; sign/symptom subscores are presented for RiiQ™ results. RESULTS: Data from 635 patients with influenza, 248 with RSV, and 107 with hMPV were included. At enrollment, total CSS and general and lower respiratory signs/symptoms (LRS) scores were higher for RSV and hMPV than influenza. Between-pathogen differences were greatest for LRS scores. Dyspnea, rales/rhonchi, wheezing, and shortness of breath scores trended higher for RSV and hMPV than influenza. RiiQ™ scores for cough, fatigue, and short of breath were strongly correlated with corresponding clinician-rated symptoms. CONCLUSIONS: These findings support the use of PROs (e.g., the RiiQ™) correlating with clinician assessments to gauge patient well-being and aid patient management by accurately assessing respiratory illness severity due to RSV, hMPV, or influenza.

Applications of Quantitative Microbial Risk Assessment to Respiratory Pathogens and Implications for Uptake in Policy: A State-of-the-Science Review.

BACKGROUND: Respiratory tract infections are major contributors to the global disease burden. Quantitative microbial risk assessment (QMRA) holds potential as a rapidly deployable framework to understand respiratory pathogen transmission and inform policy on infection control. OBJECTIVES: The goal of this paper was to evaluate, motivate, and inform further development of the use of QMRA as a rapid tool to understand the transmission of respiratory pathogens and improve the evidence base for infection control policies. METHODS: We conducted a literature review to identify peer-reviewed studies of complete QMRA frameworks on aerosol inhalation or contact transmission of respiratory pathogens. From each of the identified studies, we extracted and summarized information on the applied exposure model approaches, dose-response models, and parameter values, including risk characterization. Finally, we reviewed linkages between model outcomes and policy. RESULTS: We identified 93 studies conducted in 16 different countries with complete QMRA frameworks for diverse respiratory pathogens, including SARS-CoV-2, Legionella spp., Staphylococcus aureus, influenza, and Bacillus anthracis. Six distinct exposure models were identified across diverse and complex transmission pathways. In 57 studies, exposure model frameworks were informed by their ability to model the efficacy of potential interventions. Among interventions, masking, ventilation, social distancing, and other environmental source controls were commonly assessed. Pathogen concentration, aerosol concentration, and partitioning coefficient were influential exposure parameters as identified by sensitivity analysis. Most (84%, n=78) studies presented policy-relevant content including a) determining disease burden to call for policy intervention, b) determining risk-based threshold values for regulations, c) informing intervention and control strategies, and d) making recommendations and suggestions for QMRA application in policy. CONCLUSIONS: We identified needs to further the development of QMRA frameworks for respiratory pathogens that prioritize appropriate aerosol exposure modeling approaches, consider trade-offs between model validity and complexity, and incorporate research that strengthens confidence in QMRA results. https://doi.org/10.1289/EHP12695.

Value-based comparison of ambulatory children with respiratory diseases in an emergency department and a walk-in clinic: a retrospective cohort study in Québec, Canada.

OBJECTIVE: To compare health outcomes and costs given in the emergency department (ED) and walk-in clinics for ambulatory children presenting with acute respiratory diseases. DESIGN: A retrospective cohort study. SETTING: This study was conducted from April 2016 to March 2017 in one ED and one walk-in clinic. The ED is a paediatric tertiary care centre, and the clinic has access to lab tests and X-rays. PARTICIPANTS: Inclusion criteria were children: (1) aged from 2 to 17 years old and (2) discharged home with a diagnosis of upper respiratory tract infection (URTI), pneumonia or acute asthma. MAIN OUTCOME MEASURES: The primary outcome measure was the proportion of patients returning to any ED or clinic within 3 and 7 days of the index visit. The secondary outcome measures were the mean cost of care estimated using time-driven activity-based costing and the incidence of antibiotic prescription for URTI patients. RESULTS: We included 532 children seen in the ED and 201 seen in the walk-in clinic. The incidence of return visits at 3 and 7 days was 20.7% and 27.3% in the ED vs 6.5% and 11.4% in the clinic (adjusted relative risk at 3 days (aRR) (95% CI) 3.17 (1.77 to 5.66) and aRR at 7 days 2.24 (1.46 to 3.44)). The mean cost (95% CI) of care (CAD) at the index visit was $C96.68 (92.62 to 100.74) in the ED vs $C48.82 (45.47 to 52.16) in the clinic (mean difference (95% CI): 46.15 (41.29 to 51.02)). Antibiotic prescription for URTI was less common in the ED than in the clinic (1.5% vs 16.4%; aRR 0.10 (95% CI 0.03 to 0.32)). CONCLUSIONS: The incidence of return visits and cost of care were significantly higher in the ED, while antibiotic use for URTI was more frequent in the walk-in clinic. These data may help determine which setting offers the highest value to ambulatory children with acute respiratory conditions.

Global disease burden of and risk factors for acute lower respiratory infections caused by respiratory syncytial virus in preterm infants and young children in 2019: a systematic review and meta-analysis of aggregated and individual participant data.

BACKGROUND: Infants and young children born prematurely are at high risk of severe acute lower respiratory infection (ALRI) caused by respiratory syncytial virus (RSV). In this study, we aimed to assess the global disease burden of and risk factors for RSV-associated ALRI in infants and young children born before 37 weeks of gestation. METHODS: We conducted a systematic review and meta-analysis of aggregated data from studies published between Jan 1, 1995, and Dec 31, 2021, identified from MEDLINE, Embase, and Global Health, and individual participant data shared by the Respiratory Virus Global Epidemiology Network on respiratory infectious diseases. We estimated RSV-associated ALRI incidence in community, hospital admission, in-hospital mortality, and overall mortality among children younger than 2 years born prematurely. We conducted two-stage random-effects meta-regression analyses accounting for chronological age groups, gestational age bands (early preterm, <32 weeks gestational age [wGA], and late preterm, 32 to <37 wGA), and changes over 5-year intervals from 2000 to 2019. Using individual participant data, we assessed perinatal, sociodemographic, and household factors, and underlying medical conditions for RSV-associated ALRI incidence, hospital admission, and three severity outcome groups (longer hospital stay [>4 days], use of supplemental oxygen and mechanical ventilation, or intensive care unit admission) by estimating pooled odds ratios (ORs) through a two-stage meta-analysis (multivariate logistic regression and random-effects meta-analysis). This study is registered with PROSPERO, CRD42021269742. FINDINGS: We included 47 studies from the literature and 17 studies with individual participant-level data contributed by the participating investigators. We estimated that, in 2019, 1 650 000 (95% uncertainty range [UR] 1 350 000-1 990 000) RSV-associated ALRI episodes, 533 000 (385 000-730 000) RSV-associated hospital admissions, 3050 (1080-8620) RSV-associated in-hospital deaths, and 26 760 (11 190-46 240) RSV-attributable deaths occurred in preterm infants worldwide. Among early preterm infants, the RSV-associated ALRI incidence rate and hospitalisation rate were significantly higher (rate ratio [RR] ranging from 1·69 to 3·87 across different age groups and outcomes) than for all infants born at any gestational age. In the second year of life, early preterm infants and young children had a similar incidence rate but still a significantly higher hospitalisation rate (RR 2·26 [95% UR 1·27-3·98]) compared with all infants and young children. Although late preterm infants had RSV-associated ALRI incidence rates similar to that of all infants younger than 1 year, they had higher RSV-associated ALRI hospitalisation rate in the first 6 months (RR 1·93 [1·11-3·26]). Overall, preterm infants accounted for 25% (95% UR 16-37) of RSV-associated ALRI hospitalisations in all infants of any gestational age. RSV-associated ALRI in-hospital case fatality ratio in preterm infants was similar to all infants. The factors identified to be associated with RSV-associated ALRI incidence were mainly perinatal and sociodemographic characteristics, and factors associated with severe outcomes from infection were mainly underlying medical conditions including congenital heart disease, tracheostomy, bronchopulmonary dysplasia, chronic lung disease, or Down syndrome (with ORs ranging from 1·40 to 4·23). INTERPRETATION: Preterm infants face a disproportionately high burden of RSV-associated disease, accounting for 25% of RSV hospitalisation burden. Early preterm infants have a substantial RSV hospitalisation burden persisting into the second year of life. Preventive products for RSV can have a substantial public health impact by preventing RSV-associated ALRI and severe outcomes from infection in preterm infants. FUNDING: EU Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe.

Cost of illness due to respiratory syncytial virus acute lower respiratory tract infection among infants hospitalized in Argentina.

BACKGROUND: Information is scarce regarding the economic burden of respiratory syncytial virus (RSV) disease in low-resource settings. This study aimed to estimate the cost per episode of hospital admissions due to RSV severe disease in Argentina. METHODS: This is a prospective cohort study that collected information regarding 256 infants under 12 months of age with acute lower respiratory tract infection (ALRTI) due to RSV in two public hospitals of Buenos Aires between 2014 and 2016. Information on healthcare resource use was collected from the patient's report and its associated costs were estimated based on the financial database and account records of the hospitals. We estimated the total cost per hospitalization due to RSV using the health system perspective. The costs were estimated in US dollars as of December 2022 (1 US dollar = 170 Argentine pesos). RESULTS: The mean costs per RSV hospitalization in infants was US$587.79 (95% confidence interval [CI] $535.24 - $640.33). The mean costs associated with pediatric intensive care unit (PICU) admission more than doubled from those at regular pediatric wards ($1,556.81 [95% CI $512.21 - $2,601.40] versus $556.53 [95% CI $514.59 - $598.48]). CONCLUSIONS: This study shows the direct economic impact of acute severe RSV infection on the public health system in Argentina. The estimates obtained from this study could be used to inform cost-effectiveness analyses of new preventive RSV interventions being developed.

Assessment and comparison of the ILI case definition in clinical and school-based community settings: ORCHARDS/IISP.

Context: Influenza-like illness (ILI) is commonly used in clinical and public health settings to identify influenza cases. CDC defines ILI as fever and either cough or sore throat, with symptom onset within 7 days. Objective: Assess performance of ILI criteria in two settings (clinical and community), comparing symptom profiles and laboratory detection of influenza in children. Study Design and Analysis: Retrospective analyses of data from medically attended influenza (MAI) surveillance and a communitybased study. Datasets were analyzed separately to assess predictors of influenza cases. Analyses were limited to specimens collected within 7 days of symptom onset. Relationships between influenza and each categorical variable were described by the confusion matrix, sensitivity, and specificity. Associations were tested using chi-square tests. Unadjusted and adjusted logistic regression models were used for all variables with RT-PCR result as the outcome. Setting or Dataset: The ORegon CHild Absenteeism due to Respiratory Disease Study (ORCHARDS) is a respiratory infection study based in the Oregon School District (Dane County, WI). The Wisconsin Influenza Incidence Surveillance Project (IISP) is a MAI surveillance system operating in five family medicine clinics in Dane County. Population Studied: Children aged 4-18 years with acute respiratory infections. Intervention/Instrument: Oropharyngeal specimens, collected by research staff (ORCHARDS) or clinicians (IISP), were tested for influenza via RT-PCR and for multiple respiratory viruses at the Wisconsin State Laboratory of Hygiene. Extensive demographic and symptoms data were collected from all participants. Outcome Measures: Influenza(+)PCR. Results: From 9/7/2010-3/12/2020, 1,338 and 2,359 specimens meeting inclusion criteria were collected for IISP and ORCHARDS, respectively. Cough, fever, and ILI classification were significantly associated with influenza (sensitivity ≥92.8%, ≥85.9%, and ≥84.5%, respectively). Receiver operator curve analysis confirmed ILI had high predictive ability in both settings, improved by the inclusion of seasonality and influenza vaccination status (IISP: 0.61 vs 0.76, ORCHARDS: 0.68 vs 0.78). Conclusions: ILI performed well in both clinical and community contexts. Factors most highly associated with increased odds of RT-PCR(+) results were cough, fever, and ILI. Inclusion of seasonality and influenza vaccination status improved the predictive value of ILI in both datasets.

The global burden of lower respiratory infections attributable to respiratory syncytial virus in 204 countries and territories, 1990-2019: findings from the Global Burden of Disease Study 2019.

AIMS: The purpose of this study is to investigate the global epidemiological characteristics of lower respiratory infections (LRI) burden attributable to respiratory syncytial virus (RSV) from 1990 to 2019. MATERIALS AND METHODS: We used the recent Global Burden of Disease Study (GBD) 2019 to systematically evaluate the current burden and temporal trend of LRI burden attributable to RSV by global, age, sex, geographic location, and socio-economic status. RESULTS: Globally, the disability-adjusted life years (DALYs) cases of LRI attributable to RSV dropped from an estimated 39,964,488 [95% uncertainty interval (UI): 16,825, 572 to 68,800,553] in 1990 to 14,956,514 (95%UI: 6,271,751 to 25,910,753) in 2019 and estimated death cases droped from 541,172 (95%UI:226,614 to 958,596) to 338,495 (95%UI:126,555 to 667,109) from1990 to 2019. Similarly, age-standardized DALYs rate of LRI attributable to RSV decreased from an estimated 646.2 (95%UI: 276.9 to 1121.5) in 1990 to 218.3 (95%UI:92.1 to 376.8) in 2019 and estimated age-standardized deaths rate decreased from 10.3 (95%UI:4.1 to 18.5) to 4.8 (95%UI:1.8 to 9.3) between 1990 and 2019. In 2019, the highest age-standardized DALYs and death rates of LRI attributable to RSV were seen in the lower SDI regions, children and old people. From 1990 to 2019, age-standardized DALYs and death rates of LRI attributable to RSV decreased with increasing SDI. CONCLUSIONS: In this study, we found that the LRI burden attributable to RSV decreased significantly from 1990 to 2019. However, the lower SDI regions, children and old people urgently require cost-effective interventions to prevent and reduce the LRI burden attributable to RSV.

Frequency and burden of disease for SARS-CoV-2 and other viral respiratory tract infections in children under the age of 2 months.

OBJECTIVE: To evaluate the frequency and burden of disease of SARS-CoV-2 and other respiratory viruses in children under the age of 2 months. METHODS: A retrospective, cross-sectional, single-center study was conducted between March 2021 and February 2022. All children under the age of 2 months and tested for SARS-CoV-2 were included. The frequency of SARS-CoV-2, of other respiratory viruses and the burden of disease caused by SARS-CoV-2 and other respiratory viruses were evaluated. RESULTS: Seven hundred and twenty-seven children with an RT-PCR test for SARS-CoV-2 were included (mean age: 0.9 months (±0.6); boys: 57%); 514 (71%) in the emergency room and 213 (29%) in hospital. Among them, 62 (8.5%) had a positive RT-PCR test for SARS-CoV-2, more often in the Omicron period (23%) than in the Alpha period (4%). Of the 565 (78%) with a multiplex RT-PCR test for other viruses, 325 (58%) were positive. Children with a positive SARS-CoV-2 were less likely to have required respiratory support (p = 0.001), enteral nutrition (p = 0.03), or intensive care admission (p = 0.01) and had a shorter hospital stay than children with other respiratory viruses (5 days vs. 7 days, p = 0.007). CONCLUSION: In this young population of children, SARS-CoV-2 infection was less frequent and less severe than other viral respiratory infections.

Impact of Nonpharmacological Interventions on Severe Acute Respiratory Infections in Children: From the National Surveillance Database.

BACKGROUND: Nonpharmacological interventions (NPIs) reduce the incidence of respiratory infections. After NPIs imposed during the coronavirus disease 2019 pandemic ceased, respiratory infections gradually increased worldwide. However, few studies have been conducted on severe respiratory infections requiring hospitalization in pediatric patients. This study compares epidemiological changes in severe respiratory infections during pre-NPI, NPI, and post-NPI periods in order to evaluate the effect of that NPI on severe respiratory infections in children. METHODS: We retrospectively studied data collected at 13 Korean sentinel sites from January 2018 to October 2022 that were lodged in the national Severe Acute Respiratory Infections (SARIs) surveillance database. RESULTS: A total of 9,631 pediatric patients were admitted with SARIs during the pre-NPI period, 579 during the NPI period, and 1,580 during the post-NPI period. During the NPI period, the number of pediatric patients hospitalized with severe respiratory infections decreased dramatically, thus from 72.1 per 1,000 to 6.6 per 1,000. However, after NPIs ceased, the number increased to 22.8 per 1,000. During the post-NPI period, the positive test rate increased to the level noted before the pandemic. CONCLUSION: Strict NPIs including school and daycare center closures effectively reduced severe respiratory infections requiring hospitalization of children. However, childcare was severely compromised. To prepare for future respiratory infections, there is a need to develop a social consensus on NPIs that are appropriate for children.

Global burden of lower respiratory infections attributable to secondhand smoke among children under 5 years of age, 2010-2019: a systematic analysis of the global burden of disease study 2019.

BACKGROUND: Epidemiological trends of lower respiratory infections (LRIs) attributable to secondhand smoke (SHS) among children under 5 years since smoking bans have been increasingly applied globally remain unclear. Here, we aimed to estimate the spatiotemporal trends of the global, regional, and national burden of LRIs attributable to SHS among children under 5 years old between 2010 and 2019. METHODS: Data on the deaths, and disability adjusted life years (DALYs) of the disease burden was retrieved from the Global Burden of Disease (GBD) 2019 for 204 countries and territories between 2010 and 2019. The rates per 100,000 population, along with 95% uncertainty intervals, as well as population-attributable fraction (PAF) was presented for each estimate. RESULTS: In 2019, an estimated 6.94% (3.80-10.12%) of under-5 LRIs deaths were attributable to SHS globally, with an under-5 mortality rate of 7.02 per 100,000, a decrease of 5.77% since 2010. Similarly, 6.95% (3.81-10.13%) of LRIs DALYs were due to SHS among children under 5 years, with a rate in under-5s of 619.36 DALYs per 100,000, and also a 5.77% decrease since 2010. Azerbaijan, Turkmenistan, and Papua New Guinea showed the highest under-5 mortality and DALYs burden rates of LRIs attributable to SHS in 2019. In contrast, the PAF was stagnant over the past ten years and there is even a year-on-year upward trend in South Asia. Nationally, in 2019, Bosnia and Herzegovina, Armenia, and Montenegro showed the highest PAFSHS of LRIs burden among children under 5 years of age. In addition, the burden was heavier in children under 1 year of age and was significantly negatively associated with sociodemographic index. CONCLUSIONS: SHS remains a risk factor that cannot be ignored for LRIs burden worldwide. Hence, governments and health systems should continue to take steps to reduce SHS pollution among young children to mitigate this burden.

Burden of lower respiratory infections and associated risk factors across regions in Ethiopia: a subnational analysis of the Global Burden of Diseases 2019 study.

OBJECTIVE: This analysis is to present the burden and trends of morbidity and mortality due to lower respiratory infections (LRIs), their contributing risk factors, and the disparity across administrative regions and cities from 1990 to 2019. DESIGN: This analysis used Global Burden of Disease 2019 framework to estimate morbidity and mortality outcomes of LRI and its contributing risk factors. The Global Burden of Disease study uses all available data sources and Cause of Death Ensemble model to estimate deaths from LRI and a meta-regression disease modelling technique to estimate LRI non-fatal outcomes with 95% uncertainty intervals (UI). STUDY SETTING: The study includes nine region states and two chartered cities of Ethiopia. OUTCOME MEASURES: We calculated incidence, death and years of life lost (YLLs) due to LRIs and contributing risk factors using all accessible data sources. We calculated 95% UIs for the point estimates. RESULTS: In 2019, LRIs incidence, death and YLLs among all age groups were 8313.7 (95% UI 7757.6-8918), 59.4 (95% UI 49.8-71.4) and 2404.5 (95% UI 2059.4-2833.3) per 100 000 people, respectively. From 1990, the corresponding decline rates were 39%, 61% and 76%, respectively. Children under the age of 5 years account for 20% of episodes, 42% of mortalities and 70% of the YLL of the total burden of LRIs in 2019. The mortality rate was significantly higher in predominantly pastoralist regions-Benishangul-Gumuz 101.8 (95% UI 84.0-121.7) and Afar 103.7 (95% UI 86.6-122.6). The Somali region showed the least decline in mortality rates. More than three-fourths of under-5 child deaths due to LRIs were attributed to malnutrition. Household air pollution from solid fuel attributed to nearly half of the risk factors for all age mortalities due to LRIs in the country. CONCLUSION: In Ethiopia, LRIs have reduced significantly across the regions over the years (except in elders), however, are still the third-leading cause of mortality, disproportionately affecting children younger than 5 years old and predominantly pastoralist regions. Interventions need to consider leading risk factors, targeted age groups and pastoralist and cross-border communities.

Disease burden among refugees in camps on mainland Greece, 2016-2017: a retrospective cross-sectional study.

BACKGROUND: Despite the importance of baseline health data for evidence-informed decision-making, these data are rarely available for displaced populations. At the height of the European refugee crisis, most of those seeking asylum in Europe were from regions with high prevalences of communicable and non-communicable diseases. To create an epidemiologic profile for refugees in camps on mainland Greece, this study assessed the prevalence of 11 communicable and non-communicable diseases among refugees utilizing Médecins du Monde (MdM) in-camp clinics. METHODS: The proportional morbidity of selected diseases among individuals utilizing MdM services were determined from data collected at refugee camp clinics on mainland Greece from April 2016 - July 2017. Overall and age-specific proportional morbidities were reported. Differences in disease burden among refugees from the largest sending countries - Afghanistan and Syria - were compared using proportional morbidity ratios and 95% confidence intervals. Patterns in results were compared with disease burden estimates in sending countries and with findings from comparable settings. RESULTS: Respiratory tract infections (RTIs) were the most prevalent outcome. Among RTIs, upper RTIs were most common, with a proportional morbidity of nearly 40%; throughout the study period, over 46% of children under 18 years had at least one upper RTI consultation. Musculoskeletal conditions (3.64%), were the most prevalent non-communicable outcome, followed by hypertension (2.21%) and asthma (1.28%). Afghans were 31.68% more likely than Syrians to have a consultation for at least one condition (PR: 1.32; 95% CI: 1.25, 1.39). The proportional morbidity of RTIs was comparable to sending countries, but there was a comparatively lower burden of other conditions among refugees than literature estimates from sending countries. CONCLUSION: Refugees utilizing MdM clinics in camps had higher burdens of communicable diseases - predominantly RTIs - relative to non-communicable diseases. Non-communicable disease burdens were comparatively lower than reported prevalences from in-country populations. These findings can be attributed to a range of considerations including differences in demographic profiles between sending countries and refugee populations and missed opportunities for utilizing clinical care. Further investment is needed to capture the health profiles of displaced populations to support evidence-informed decision-making processes in humanitarian emergency responses.

Effect of PM2.5 air pollution on the global burden of lower respiratory infections, 1990-2019: A systematic analysis from the Global Burden of Disease Study 2019.

Particulate matter (PM) air pollution is closely related to lower respiratory infections (LRIs). However, the global LRI burden attributable to PM remains unclear. Here, we provide a comprehensive assessment of the PM2.5-attributable LRI burden using data from the Global Burden and Disease Study (GBD) 2019. We found that PM2.5 air pollution contributed to approximately 0.7 million deaths and 37.6 million disability-adjusted life years (DALYs) of LRIs in 2019. The LRI burden attributable to PM2.5 has decreased from 1990 to 2019, with a more pronounced decrease in household PM2.5 than in ambient PM2.5. Unlike the decreasing trend in LRI burden due to household PM2.5 worldwide, nearly one fifth of countries experienced an increase of LRI burden due to ambient PM2.5. The burden was unevenly distributed to less developed countries, mainly in Sub-Saharan Africa. All age groups experienced a decrease in the PM2.5-attributable burden, with the most significant decrease in children younger than 10 years. Notably, individuals aged 20-84 years experienced an increase in the LRI burden attributable to ambient PM2.5. Males had higher burden than females in the elder age and higher SDI regions. This study provided an evidence-based guidance for the prevention of LRIs and control of PM2.5 air pollution.

Cost and health-related quality of life for children hospitalized with respiratory syncytial virus in Central China.

BACKGROUND: The economic burden of respiratory syncytial virus (RSV) infection and its impact on health-related quality of life (HRQoL) are not well-understood in China. This study assessed total cost and HRQoL for children hospitalized with RSV in Central China. METHODS: Based on a prospective case series study in Henan Province in 2020-2021, inpatients aged 0-59 months with RSV-related acute respiratory infections (ARIs) were included into analysis. Total cost included direct medical cost (sum of medical cost before and during hospitalization), direct non-medical cost, and indirect cost. Direct medical cost during hospitalization data were extracted from the hospital information system. Other costs and HRQoL status were obtained from a telephone survey conducted in the caregivers of the enrolled patients. RESULTS: Among 261 RSV-infected inpatients, caregivers of 170 non-severe cases (65.1%, 170/261) were successfully interviewed. Direct medical cost per episode was 1055.3 US dollars (US$) (95% CI: 998.2-1112.5 US$). Direct non-medical cost and indirect cost per episode were 83.6 US$ (95% CI: 77.5-89.7 US$) and 162.4 US$ (95% CI: 127.9-197.0 US$), respectively. Quality adjusted life years (QALY) loss for non-severe RSV hospitalization was 8.9 × 10-3 (95% CI: 7.9 × 10-3 -9.9 × 10-3 ). The majority of inpatients were <1 year of age comprising significantly higher cost and more QALY loss than older children. CONCLUSIONS: RSV-associated hospitalization poses high economic and health burden in Central China particularly for children <1 year old. Our findings are crucial for determining the priority of interventions and allocation of health resources.

Seasonal influence on respiratory tract infection severity including COVID-19 quantified through Markov Chain modeling.

Respiratory tract infections (RTIs) are a burden to global health, but their characterization is complicated by the influence of seasonality on incidence and severity. The Re-BCG-CoV-19 trial (NCT04379336) assessed BCG (re)vaccination for protection from coronavirus disease 2019 (COVID-19) and recorded 958 RTIs in 574 individuals followed over 1 year. We characterized the probability of RTI occurrence and severity using a Markov model with health scores (HSs) for four states of symptom severity. Covariate analysis on the transition probability between HSs explored the influence of demographics, medical history, severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), or influenza vaccinations, which became available during the trial, SARS-CoV-2 serology, and epidemiology-informed seasonal influence of infection pressure represented as regional COVID-19 pandemic waves, as well as BCG (re)vaccination. The infection pressure reflecting the pandemic waves increased the risk of RTI symptom development, whereas the presence of SARS-CoV-2 antibodies protected against RTI symptom development and increased the probability of symptom relief. Higher probability of symptom relief was also found in participants with African ethnicity and with male biological gender. SARS-CoV-2 or influenza vaccination reduced the probability of transitioning from mild to healthy symptoms. Model diagnostics over calendar-time indicated that COVID-19 cases were under-reported during the first wave by an estimated 2.76-fold. This trial was performed during the initial phase of the COVID-19 pandemic in South Africa and the results reflect that situation. Using this unique clinical dataset of prospectively studied RTIs over the course of 1 year, our Markov Chain model was able to capture risk factors for RTI development and severity, including epidemiology-informed infection pressure.

The unfinished agenda of communicable diseases among children and adolescents before the COVID-19 pandemic, 1990-2019: a systematic analysis of the Global Burden of Disease Study 2019.

BACKGROUND: Communicable disease control has long been a focus of global health policy. There have been substantial reductions in the burden and mortality of communicable diseases among children younger than 5 years, but we know less about this burden in older children and adolescents, and it is unclear whether current programmes and policies remain aligned with targets for intervention. This knowledge is especially important for policy and programmes in the context of the COVID-19 pandemic. We aimed to use the Global Burden of Disease (GBD) Study 2019 to systematically characterise the burden of communicable diseases across childhood and adolescence. METHODS: In this systematic analysis of the GBD study from 1990 to 2019, all communicable diseases and their manifestations as modelled within GBD 2019 were included, categorised as 16 subgroups of common diseases or presentations. Data were reported for absolute count, prevalence, and incidence across measures of cause-specific mortality (deaths and years of life lost), disability (years lived with disability [YLDs]), and disease burden (disability-adjusted life-years [DALYs]) for children and adolescents aged 0-24 years. Data were reported across the Socio-demographic Index (SDI) and across time (1990-2019), and for 204 countries and territories. For HIV, we reported the mortality-to-incidence ratio (MIR) as a measure of health system performance. FINDINGS: In 2019, there were 3·0 million deaths and 30·0 million years of healthy life lost to disability (as measured by YLDs), corresponding to 288·4 million DALYs from communicable diseases among children and adolescents globally (57·3% of total communicable disease burden across all ages). Over time, there has been a shift in communicable disease burden from young children to older children and adolescents (largely driven by the considerable reductions in children younger than 5 years and slower progress elsewhere), although children younger than 5 years still accounted for most of the communicable disease burden in 2019. Disease burden and mortality were predominantly in low-SDI settings, with high and high-middle SDI settings also having an appreciable burden of communicable disease morbidity (4·0 million YLDs in 2019 alone). Three cause groups (enteric infections, lower-respiratory-tract infections, and malaria) accounted for 59·8% of the global communicable disease burden in children and adolescents, with tuberculosis and HIV both emerging as important causes during adolescence. HIV was the only cause for which disease burden increased over time, particularly in children and adolescents older than 5 years, and especially in females. Excess MIRs for HIV were observed for males aged 15-19 years in low-SDI settings. INTERPRETATION: Our analysis supports continued policy focus on enteric infections and lower-respiratory-tract infections, with orientation to children younger than 5 years in settings of low socioeconomic development. However, efforts should also be targeted to other conditions, particularly HIV, given its increased burden in older children and adolescents. Older children and adolescents also experience a large burden of communicable disease, further highlighting the need for efforts to extend beyond the first 5 years of life. Our analysis also identified substantial morbidity caused by communicable diseases affecting child and adolescent health across the world. FUNDING: The Australian National Health and Medical Research Council Centre for Research Excellence for Driving Investment in Global Adolescent Health and the Bill & Melinda Gates Foundation.

Association of greenness with the disease burden of lower respiratory infections and mediation effects of air pollution and heat: a global ecological study.

Exposure to greenness is increasingly linked to beneficial health outcomes, but the associations between greenness and the disease burden of lower respiratory infections (LRIs) are unclear. We used the normalized difference vegetation index (NDVI) and the leaf area index (LAI) to measure greenness and incidence, death, and disability-adjusted life years (DALYs) due to LRIs to represent the disease burden of LRIs. We applied a generalized linear mixed model to evaluate the association between greenness and LRI disease burden and performed a stratified analysis, after adjusting for covariates. Additionally, we assessed the potential mediating effects of fine particulate matter (PM2.5), ozone (O3), nitrogen dioxide (NO2), and heat on the association between greenness and the disease burden of LRIs. In the adjusted model, one 0.1 unit increase of NDVI and 0.5 increase in LAI were significantly inversely associated with incidence, death, and DALYs due to LRIs, respectively. Greenness was negatively correlated with the disease burden of LRIs across 15-65 age group, both sexes, and low SDI groups. PM2.5, O3, and heat mediated the effects of greenness on the disease burden of LRIs. Greenness was significantly negatively associated with the disease burden of LRIs, possibly by reducing exposure to air pollution and heat.

Burden of disease attributable to unsafe drinking water, sanitation, and hygiene in domestic settings: a global analysis for selected adverse health outcomes.

BACKGROUND: Assessments of disease burden are important to inform national, regional, and global strategies and to guide investment. We aimed to estimate the drinking water, sanitation, and hygiene (WASH)-attributable burden of disease for diarrhoea, acute respiratory infections, undernutrition, and soil-transmitted helminthiasis, using the WASH service levels used to monitor the UN Sustainable Development Goals (SDGs) as counterfactual minimum risk-exposure levels. METHODS: We assessed the WASH-attributable disease burden of the four health outcomes overall and disaggregated by region, age, and sex for the year 2019. We calculated WASH-attributable fractions of diarrhoea and acute respiratory infections by country using modelled WASH exposures and exposure-response relationships from two updated meta-analyses. We used the WHO and UNICEF Joint Monitoring Programme for Water Supply, Sanitation and Hygiene public database to estimate population exposure to different WASH service levels. WASH-attributable undernutrition was estimated by combining the population attributable fractions (PAF) of diarrhoea caused by unsafe WASH and the PAF of undernutrition caused by diarrhoea. Soil-transmitted helminthiasis was fully attributed to unsafe WASH. FINDINGS: We estimate that 1·4 (95% CI 1·3-1·5) million deaths and 74 (68-80) million disability-adjusted life-years (DALYs) could have been prevented by safe WASH in 2019 across the four designated outcomes, representing 2·5% of global deaths and 2·9% of global DALYs from all causes. The proportion of diarrhoea that is attributable to unsafe WASH is 0·69 (0·65-0·72), 0·14 (0·13-0·17) for acute respiratory infections, and 0·10 (0·09-0·10) for undernutrition, and we assume that the entire disease burden from soil-transmitted helminthiasis was attributable to unsafe WASH. INTERPRETATION: WASH-attributable burden of disease estimates based on the levels of service established under the SDG framework show that progress towards the internationally agreed goal of safely managed WASH services for all would yield major public-health returns. FUNDING: WHO and Foreign, Commonwealth & Development Office.

Clinical epidemiology and disease burden of bronchiolitis in hospitalized children in China: a national cross-sectional study.

BACKGROUND: Bronchiolitis is a common acute lower respiratory tract infection (ALRTI) and the most frequent cause of hospitalization of infants and young children with ALRTI. Respiratory syncytial virus is the main pathogen that leads to severe bronchiolitis. The disease burden is relatively high. To date, few descriptions of the clinical epidemiology and disease burden of children hospitalized for bronchiolitis are available. This study reports the general clinical epidemiological characteristics and disease burden of bronchiolitis in hospitalized children in China. METHODS: This study included the face sheet of discharge medical records collected from 27 tertiary children's hospitals from January 2016 to December 2020 that were aggregated into the FUTang Update medical REcords (FUTURE) database. The sociodemographic variables, length of stay (LOS) and disease burden of children with bronchiolitis were analyzed and compared using appropriate statistical tests. RESULTS: In total, 42,928 children aged 0-3 years were hospitalized due to bronchiolitis from January 2016 to December 2020, accounting for 1.5% of the total number of hospitalized children of the same age in the database during the period and 5.31% of the hospitalizations for ALRTI. The male to female ratio was 2.01:1. Meanwhile, more boys than girls were observed in different regions, age groups, years, and residences. The 1-2 year age group had the greatest number of hospitalizations for bronchiolitis, while the 29 days-6 months group had the largest proportion of the total inpatients and inpatients with ALRTI in the same age group. In terms of region, the hospitalization rate of bronchiolitis was the highest in East China. Overall, the number of hospitalizations from 2017 to 2020 showed a decreasing trend from that in 2016. Seasonally, the peak hospitalizations for bronchiolitis occurred in winter. Hospitalization rates in North China in autumn and winter were higher than those in South China, while hospitalization rates in South China were higher in spring and summer. Approximately, half of the patients with bronchiolitis had no complications. Among the complications, myocardial injury, abnormal liver function and diarrhea were more common. The median LOS was 6 days [interquartile range (IQR) = 5-8], and the median hospitalization cost was 758 United States dollars (IQR = 601.96-1029.53). CONCLUSIONS: Bronchiolitis is a common respiratory disease in infants and young children in China, and it accounts for a higher proportion of both total hospitalizations and hospitalizations due to ALRTI in children. Among them, children aged 29 days-2 years are the main hospitalized population, and the hospitalization rate of boys is significantly higher than that of girls. The peak season for bronchiolitis is winter. Bronchiolitis causes few complications and has a low mortality rate, but the burden of this disease is heavy.