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BMJ Global Health Jul 2021The burden of acute lower respiratory infections (ALRI), and common viral ALRI aetiologies among 5-19 years are less well understood. We conducted a systematic review to...
Global hospital admissions and in-hospital mortality associated with all-cause and virus-specific acute lower respiratory infections in children and adolescents aged 5-19 years between 1995 and 2019: a systematic review and modelling study.
INTRODUCTION
The burden of acute lower respiratory infections (ALRI), and common viral ALRI aetiologies among 5-19 years are less well understood. We conducted a systematic review to estimate global burden of all-cause and virus-specific ALRI in 5-19 years.
METHODS
We searched eight databases and Google for studies published between 1995 and 2019 and reporting data on burden of all-cause ALRI or ALRI associated with influenza virus, respiratory syncytial virus, human metapneumovirus and human parainfluenza virus. We assessed risk of bias using a modified Newcastle-Ottawa Scale. We developed an analytical framework to report burden by age, country and region when there were sufficient data (all-cause and influenza-associated ALRI hospital admissions). We estimated all-cause ALRI in-hospital deaths and hospital admissions for ALRI associated with respiratory syncytial virus, human metapneumovirus and human parainfluenza virus by region.
RESULTS
Globally, an estimated 5.5 million (UR 4.0-7.8) all-cause ALRI hospital admissions occurred annually between 1995 and 2019 in 5-19 year olds, causing 87 900 (UR 40 300-180 600) in-hospital deaths annually. Influenza virus and respiratory syncytial virus were associated with 1 078 600 (UR 4 56 500-2 650 200) and 231 800 (UR 142 700-3 73 200) ALRI hospital admissions in 5-19 years. Human metapneumovirus and human parainfluenza virus were associated with 105 500 (UR 57 200-181 700) and 124 800 (UR 67 300-228 500) ALRI hospital admissions in 5-14 years. About 55% of all-cause ALRI hospital admissions and 63% of influenza-associated ALRI hospital admissions occurred in those 5-9 years globally. All-cause and influenza-associated ALRI hospital admission rates were highest in upper-middle income countries, Asia-Pacific region and the Latin America and Caribbean region.
CONCLUSION
Incidence and mortality data for all-cause and virus-specific ALRI in 5-19 year olds are scarce. The lack of data in low-income countries and Eastern Europe and Central Asia, South Asia, and West and Central Africa warrants efforts to improve the development and access to healthcare services, diagnostic capacity, and data reporting.
Topics: Adolescent; Child; Global Health; Hospital Mortality; Hospitalization; Hospitals; Humans; Respiratory Tract Infections
PubMed: 34261758
DOI: 10.1136/bmjgh-2021-006014 -
The Pediatric Infectious Disease Journal May 2021Human metapneumovirus (hMPV) has been associated with upper and lower respiratory tract infections (LRTI) in children and adults. This systematic review evaluated the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Human metapneumovirus (hMPV) has been associated with upper and lower respiratory tract infections (LRTI) in children and adults. This systematic review evaluated the epidemiology of hMPV-associated LRTI, including severe acute respiratory infection (SARI) hospitalization or clinically diagnosed severe pneumonia, in African children under 5 years of age.
METHODS
We searched Science Direct, PubMed, Cochrane Central, Scopus, and WHO regional databases using the terms "("Human metapneumovirus" AND "Africa") OR ("hMPV" AND "Africa")" up to September 17, 2020. Other sources included ClinicalTrials.gov to obtain unpublished data. Studies were included if children were less than 5 years of age and hospitalized with hMPV-associated LRTI, SARI or if clinically diagnosed with severe pneumonia in the community. The main outcomes were prevalence of hMPV identified among children with hospitalized LRTI or SARI. We further calculated odds ratios for hMPV in cases with LRTI compared with non-LRTI controls. Pooled results were calculated using a random-effects model.
RESULTS
Thirty studies were eligible for inclusion in the review. The prevalence of hMPV-LRTI/SARI among hospitalized and severe pneumonia cases was 4.7% [95% confidence interval (CI): 3.9-5.6, I2 = 95.0]. The case-control studies indicated that hMPV was 2.0-fold (95% CI: 0.9-4.4) more likely to be identified in LRTI cases (10.3%) than controls (6.0%). Three of 5 studies reported hMPV-associated LRTI case fatality risk, with a pooled estimate of 1.3% (95% CI: 0.3-2.9; I2 = 49).
CONCLUSIONS
hMPV was associated with approximately 5% of LRTI/SARI hospitalizations or severe pneumonia cases in Africa.
Topics: Africa; Child, Preschool; Hospitalization; Humans; Infant; Metapneumovirus; Paramyxoviridae Infections; Pneumonia; Prevalence; Respiratory Tract Infections
PubMed: 33480663
DOI: 10.1097/INF.0000000000003041 -
The Lancet. Global Health Jan 2021Human metapneumovirus is a common virus associated with acute lower respiratory infections (ALRIs) in children. No global burden estimates are available for ALRIs...
BACKGROUND
Human metapneumovirus is a common virus associated with acute lower respiratory infections (ALRIs) in children. No global burden estimates are available for ALRIs associated with human metapneumovirus in children, and no licensed vaccines or drugs exist for human metapneumovirus infections. We aimed to estimate the age-stratified human metapneumovirus-associated ALRI global incidence, hospital admissions, and mortality burden in children younger than 5 years.
METHODS
We estimated the global burden of human metapneumovirus-associated ALRIs in children younger than 5 years from a systematic review of 119 studies published between Jan 1, 2001, and Dec 31, 2019, and a further 40 high quality unpublished studies. We assessed risk of bias using a modified Newcastle-Ottawa Scale. We estimated incidence, hospital admission rates, and in-hospital case-fatality ratios (hCFRs) of human metapneumovirus-associated ALRI using a generalised linear mixed model. We applied incidence and hospital admission rates of human metapneumovirus-associated ALRI to population estimates to yield the morbidity burden estimates by age bands and World Bank income levels. We also estimated human metapneumovirus-associated ALRI in-hospital deaths and overall human metapneumovirus-associated ALRI deaths (both in-hospital and non-hospital deaths). Additionally, we estimated human metapneumovirus-attributable ALRI cases, hospital admissions, and deaths by combining human metapneumovirus-associated burden estimates and attributable fractions of human metapneumovirus in laboratory-confirmed human metapneumovirus cases and deaths.
FINDINGS
In 2018, among children younger than 5 years globally, there were an estimated 14·2 million human metapneumovirus-associated ALRI cases (uncertainty range [UR] 10·2 million to 20·1 million), 643 000 human metapneumovirus-associated hospital admissions (UR 425 000 to 977 000), 7700 human metapneumovirus-associated in-hospital deaths (2600 to 48 800), and 16 100 overall (hospital and community) human metapneumovirus-associated ALRI deaths (5700 to 88 000). An estimated 11·1 million ALRI cases (UR 8·0 million to 15·7 million), 502 000 ALRI hospital admissions (UR 332 000 to 762 000), and 11 300 ALRI deaths (4000 to 61 600) could be causally attributed to human metapneumovirus in 2018. Around 58% of the hospital admissions were in infants under 12 months, and 64% of in-hospital deaths occurred in infants younger than 6 months, of which 79% occurred in low-income and lower-middle-income countries.
INTERPRETATION
Infants younger than 1 year have disproportionately high risks of severe human metapneumovirus infections across all World Bank income regions and all child mortality settings, similar to respiratory syncytial virus and influenza virus. Infants younger than 6 months in low-income and lower-middle-income countries are at greater risk of death from human metapneumovirus-associated ALRI than older children and those in upper-middle-income and high-income countries. Our mortality estimates demonstrate the importance of intervention strategies for infants across all settings, and warrant continued efforts to improve the outcome of human metapneumovirus-associated ALRI among young infants in low-income and lower-middle-income countries.
FUNDING
Bill & Melinda Gates Foundation.
Topics: Acute Disease; Child, Preschool; Cost of Illness; Female; Global Health; Humans; Infant; Infant, Newborn; Linear Models; Male; Metapneumovirus; Paramyxoviridae Infections; Respiratory Tract Infections
PubMed: 33248481
DOI: 10.1016/S2214-109X(20)30393-4 -
PloS One 2020The advent of genome amplification assays has allowed description of new respiratory viruses and to reconsider the role played by certain respiratory viruses in... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The advent of genome amplification assays has allowed description of new respiratory viruses and to reconsider the role played by certain respiratory viruses in bronchiolitis. This systematic review and meta-analysis was initiated to clarify the prevalence of respiratory viruses in children with bronchiolitis in the pre-COVID-19 pandemic era.
METHODS
We performed an electronic search through Pubmed and Global Index Medicus databases. We included observational studies reporting the detection rate of common respiratory viruses in children with bronchiolitis using molecular assays. Data was extracted and the quality of the included articles was assessed. We conducted sensitivity, subgroups, publication bias, and heterogeneity analyses using a random effect model.
RESULTS
The final meta-analysis included 51 studies. Human respiratory syncytial virus (HRSV) was largely the most commonly detected virus 59.2%; 95% CI [54.7; 63.6]). The second predominant virus was Rhinovirus (RV) 19.3%; 95% CI [16.7; 22.0]) followed by Human bocavirus (HBoV) 8.2%; 95% CI [5.7; 11.2]). Other reported viruses included Human Adenovirus (HAdV) 6.1%; 95% CI [4.4; 8.0]), Human Metapneumovirus (HMPV) 5.4%; 95% CI [4.4; 6.4]), Human Parainfluenzavirus (HPIV) 5.4%; 95% CI [3.8; 7.3]), Influenza 3.2%; 95% CI [2.2; 4.3], Human Coronavirus (HCoV) 2.9%; 95% CI [2.0; 4.0]), and Enterovirus (EV) 2.9%; 95% CI [1.6; 4.5]). HRSV was the predominant virus involved in multiple detection and most codetections were HRSV + RV 7.1%, 95% CI [4.6; 9.9]) and HRSV + HBoV 4.5%, 95% CI [2.4; 7.3]).
CONCLUSIONS
The present study has shown that HRSV is the main cause of bronchiolitis in children, we also have Rhinovirus, and Bocavirus which also play a significant role. Data on the role played by SARS-CoV-2 in children with acute bronchiolitis is needed.
REVIEW REGISTRATION
PROSPERO, CRD42018116067.
Topics: Bronchiolitis, Viral; Female; Human bocavirus; Humans; Infant; Male; Prevalence; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Rhinovirus
PubMed: 33180855
DOI: 10.1371/journal.pone.0242302 -
Journal of Global Health Jun 2020Respiratory syncytial virus (RSV) is the predominant viral cause of childhood pneumonia. Little is known about the role of viral-coinfections in the clinical severity in... (Meta-Analysis)
Meta-Analysis
The role of viral co-infections in the severity of acute respiratory infections among children infected with respiratory syncytial virus (RSV): A systematic review and meta-analysis.
BACKGROUND
Respiratory syncytial virus (RSV) is the predominant viral cause of childhood pneumonia. Little is known about the role of viral-coinfections in the clinical severity in children infected with RSV.
METHODS
We conducted a systematic literature review of publications comparing the clinical severity between RSV mono-infection and RSV co-infection with other viruses in children under five years (<5y). Clinical severity was measured using the following six clinical outcomes: hospitalisation, length of hospital stay, use of supplemental oxygen, intensive care unit (ICU) admission, mechanical ventilation and deaths. We summarised the findings by clinical outcome and conducted random-effect meta-analyses, where applicable, to quantitatively synthesize the association between RSV mono-infection/RSV co-infection and the clinical severity.
RESULTS
Overall, no differences in the clinical severity were found between RSV mono-infection and RSV co-infection with any viruses, except for the RSV-human metapneumovirus (hMPV) co-infection. RSV-hMPV coinfection was found to be associated with a higher risk of ICU admission (odds ratio (OR) = 7.2, 95% confidence interval (CI) = 2.1-25.1; OR after removal of the most influential study was 3.7, 95% CI = 1.1-12.3). We also observed a trend from three studies that RSV-hMPV coinfections were likely to be associated with longer hospital stay.
CONCLUSION
Our findings suggest that RSV-hMPV coinfections might be associated with increased risk for ICU admission in children <5y compared with RSV mono-infection but such association does not imply causation. Our findings do not support the association between RSV coinfections with other viruses and clinical severity but further large-scale investigations are needed to confirm the findings.
PROTOCOL REGISTRATION
PROSPERO CRD42019154761.
Topics: Child, Preschool; Coinfection; Hospitalization; Humans; Infant; Intensive Care Units; Length of Stay; Respiratory Syncytial Virus Infections; Severity of Illness Index
PubMed: 32566164
DOI: 10.7189/jogh.10.010426 -
Fetal and Pediatric Pathology Dec 2021We sought to systematically review the literature and perform a meta-analysis by assessing the prevalence of human metapneumovirus (hMPV) infections from a number of... (Meta-Analysis)
Meta-Analysis
We sought to systematically review the literature and perform a meta-analysis by assessing the prevalence of human metapneumovirus (hMPV) infections from a number of studies conducted in Iran. Entire studies addressing epidemiology of hMPV in Iran using data from PubMed, Scopus, Science Direct, Web of science, Google Scholar, Embase, and national Persian databases up to June 2019 were included. The estimated prevalence of hMPV was 8.9% (95% CI 5.4-14.2) in different regions in Iran. Compared to the global rate, in Iran hMPV infection presented an intermediate prevalence rate. The majority of hMPV positive patients were pediatric populations with pooled prevalence of 7.6% ( = 95%, 95% CI 3.5-15.6). This first comprehensive review covering researches over the last 11 years expanded our knowledge about hMPV circulating in Iran. Future large epidemiological studies are needed for the evaluation of hMPV prevalence and genotype distribution in different unanalyzed regions in Iran.
Topics: Child; Genotype; Humans; Iran; Metapneumovirus; Paramyxoviridae Infections; Prevalence
PubMed: 32081050
DOI: 10.1080/15513815.2020.1725939 -
The Lancet. Global Health Aug 2019Influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus are the most common viruses associated with acute lower respiratory infections in...
BACKGROUND
Influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus are the most common viruses associated with acute lower respiratory infections in young children (<5 years) and older people (≥65 years). A global report of the monthly activity of these viruses is needed to inform public health strategies and programmes for their control.
METHODS
In this systematic analysis, we compiled data from a systematic literature review of studies published between Jan 1, 2000, and Dec 31, 2017; online datasets; and unpublished research data. Studies were eligible for inclusion if they reported laboratory-confirmed incidence data of human infection of influenza virus, respiratory syncytial virus, parainfluenza virus, or metapneumovirus, or a combination of these, for at least 12 consecutive months (or 52 weeks equivalent); stable testing practice throughout all years reported; virus results among residents in well-defined geographical locations; and aggregated virus results at least on a monthly basis. Data were extracted through a three-stage process, from which we calculated monthly annual average percentage (AAP) as the relative strength of virus activity. We defined duration of epidemics as the minimum number of months to account for 75% of annual positive samples, with each component month defined as an epidemic month. Furthermore, we modelled monthly AAP of influenza virus and respiratory syncytial virus using site-specific temperature and relative humidity for the prediction of local average epidemic months. We also predicted global epidemic months of influenza virus and respiratory syncytial virus on a 5° by 5° grid. The systematic review in this study is registered with PROSPERO, number CRD42018091628.
FINDINGS
We initally identified 37 335 eligible studies. Of 21 065 studies remaining after exclusion of duplicates, 1081 full-text articles were assessed for eligibility, of which 185 were identified as eligible. We included 246 sites for influenza virus, 183 sites for respiratory syncytial virus, 83 sites for parainfluenza virus, and 65 sites for metapneumovirus. Influenza virus had clear seasonal epidemics in winter months in most temperate sites but timing of epidemics was more variable and less seasonal with decreasing distance from the equator. Unlike influenza virus, respiratory syncytial virus had clear seasonal epidemics in both temperate and tropical regions, starting in late summer months in the tropics of each hemisphere, reaching most temperate sites in winter months. In most temperate sites, influenza virus epidemics occurred later than respiratory syncytial virus (by 0·3 months [95% CI -0·3 to 0·9]) while no clear temporal order was observed in the tropics. Parainfluenza virus epidemics were found mostly in spring and early summer months in each hemisphere. Metapneumovirus epidemics occurred in late winter and spring in most temperate sites but the timing of epidemics was more diverse in the tropics. Influenza virus epidemics had shorter duration (3·8 months [3·6 to 4·0]) in temperate sites and longer duration (5·2 months [4·9 to 5·5]) in the tropics. Duration of epidemics was similar across all sites for respiratory syncytial virus (4·6 months [4·3 to 4·8]), as it was for metapneumovirus (4·8 months [4·4 to 5·1]). By comparison, parainfluenza virus had longer duration of epidemics (6·3 months [6·0 to 6·7]). Our model had good predictability in the average epidemic months of influenza virus in temperate regions and respiratory syncytial virus in both temperate and tropical regions. Through leave-one-out cross validation, the overall prediction error in the onset of epidemics was within 1 month (influenza virus -0·2 months [-0·6 to 0·1]; respiratory syncytial virus 0·1 months [-0·2 to 0·4]).
INTERPRETATION
This study is the first to provide global representations of month-by-month activity of influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus. Our model is helpful in predicting the local onset month of influenza virus and respiratory syncytial virus epidemics. The seasonality information has important implications for health services planning, the timing of respiratory syncytial virus passive prophylaxis, and the strategy of influenza virus and future respiratory syncytial virus vaccination.
FUNDING
European Union Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe (RESCEU).
Topics: Female; Global Health; Humans; Influenza A virus; Influenza, Human; Male; Metapneumovirus; Paramyxoviridae Infections; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human
PubMed: 31303294
DOI: 10.1016/S2214-109X(19)30264-5 -
Journal of Clinical Virology : the... Aug 2019To set priorities for efficient control of acute respiratory tract infection (ARTI) in Africa, it is necessary to have accurate estimate of its burden, especially among... (Comparative Study)
Comparative Study Meta-Analysis
Case fatality rate and viral aetiologies of acute respiratory tract infections in HIV positive and negative people in Africa: The VARIAFRICA-HIV systematic review and meta-analysis.
BACKGROUND
To set priorities for efficient control of acute respiratory tract infection (ARTI) in Africa, it is necessary to have accurate estimate of its burden, especially among HIV-infected populations.
OBJECTIVES
To compare case fatality rate (CFR) and viral aetiologies of ARTI between HIV-positive and HIV-negative populations in Africa.
STUDY DESIGN
We searched PubMed, EMBASE, Web of Knowledge, Africa Journal Online, and Global Index Medicus to identify studies published from January 2000 to April 2018. Random-effect meta-analysis method was used to assess association (pooled weighted odds ratios (OR) with 95% confidence interval (CI)).
RESULTS
A total of 36 studies (126,526 participants) were included. CFR was significantly higher in patients with HIV than in HIV-negative controls (OR 4.10, 95%CI: 2.63-6.27, I²: 93.7%). The risk was significantly higher among children ≤5 years (OR 5.51, 95%CI 2.83-10.74) compared to people aged >5 years (OR 1.48, 95%CI 1.17-1.89); p = 0.0002. There was no difference between children (15 years) and adults and between regions of Africa. There was no difference for viral respiratory aetiologies (Enterovirus, Adenovirus, Bocavirus, Coronavirus, Metapneumovirus, Parainfluenza, Influenza, and Respiratory Syncytial Virus) of ARTI between HIV-positive and HIV-negative people, except for Rhinovirus where being HIV-negative was associated with Rhinovirus (OR 0.70; 95%CI 0.51-0.97, I²: 63.4%).
CONCLUSIONS
This study shows an increased risk of deaths among HIV-infected individuals with ARTI, however with no difference in viral aetiologies compared to HIV-negative individuals in Africa. ARTI deserves more attention from HIV health-care providers for efficient control. Specific strategies are needed for HIV-positive children under 5.
Topics: Africa; Age Factors; Child; Child, Preschool; Coinfection; HIV Infections; Humans; Infant; Mortality; Respiratory Tract Infections
PubMed: 31272038
DOI: 10.1016/j.jcv.2019.06.006 -
The Journal of Infectious Diseases Oct 2020Acute respiratory tract infections (ARI) constitute a substantial disease burden in adults and elderly individuals. We aimed to identify all case-control studies... (Meta-Analysis)
Meta-Analysis
Acute respiratory tract infections (ARI) constitute a substantial disease burden in adults and elderly individuals. We aimed to identify all case-control studies investigating the potential role of respiratory viruses in the etiology of ARI in older adults aged ≥65 years. We conducted a systematic literature review (across 7 databases) of case-control studies published from 1996 to 2017 that investigated the viral profile of older adults with and those without ARI. We then computed a pooled odds ratio (OR) with a 95% confidence interval and virus-specific attributable fraction among the exposed (AFE) for 8 common viruses: respiratory syncytial virus (RSV), influenza virus (Flu), parainfluenza virus (PIV), human metapneumovirus (HMPV), adenovirus (AdV), rhinovirus (RV), bocavirus (BoV), and coronavirus (CoV). From the 16 studies included, there was strong evidence of possible causal attribution for RSV (OR, 8.5 [95% CI, 3.9-18.5]; AFE, 88%), Flu (OR, 8.3 [95% CI, 4.4-15.9]; AFE, 88%), PIV (OR, not available; AFE, approximately 100%), HMPV (OR, 9.8 [95% CI, 2.3-41.0]; AFE, 90%), AdV (OR, not available; AFE, approximately 100%), RV (OR, 7.1 [95% CI, 3.7-13.6]; AFE, 86%) and CoV (OR, 2.8 [95% CI, 2.0-4.1]; AFE, 65%) in older adults presenting with ARI, compared with those without respiratory symptoms (ie, asymptomatic individuals) or healthy older adults. However, there was no significant difference in the detection of BoV in cases and controls. This review supports RSV, Flu, PIV, HMPV, AdV, RV, and CoV as important causes of ARI in older adults and provides quantitative estimates of the absolute proportion of virus-associated ARI cases to which a viral cause can be attributed. Disease burden estimates should take into account the appropriate AFE estimates (for older adults) that we report.
Topics: Acute Disease; Age Factors; Aged; Humans; Pneumonia, Viral; Respiratory Tract Infections
PubMed: 30849176
DOI: 10.1093/infdis/jiy662