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Epidemics Jun 2021Due to high burden of respiratory syncytial virus (RSV) in low- and middle-income countries (LMIC), international funding organizations have prioritized the development...
BACKGROUND
Due to high burden of respiratory syncytial virus (RSV) in low- and middle-income countries (LMIC), international funding organizations have prioritized the development of RSV vaccines. Mathematical models of RSV will play an important role in assessing the relative value of these interventions. Our objectives were to provide an overview of the existing RSV modelling literature in LMIC and summarize available results on population-level effectiveness and cost-effectiveness.
METHODS
We searched MEDLINE from 2000 to 2020 for English language publications that employed a mathematical model of RSV calibrated to LMIC. Qualitative data were extracted on study and model characteristics. Quantitative data were collected on key model input assumptions and base case effectiveness and cost-effectiveness estimates for various immunization strategies.
FINDINGS
Of the 283 articles reviewed, 15 met inclusion criteria. Ten studies used modelling techniques to explore RSV transmission and/or natural history, while eight studies evaluated RSV vaccines and/or monoclonal antibodies, three of which included cost-effectiveness analyses. Six studies employed deterministic compartmental models, five studies employed individual transmission models, and four studies used different types of cohort models. Nearly every model was calibrated to at least one middle-income country, while four were calibrated to low-income countries.
INTERPRETATION
The mathematical modelling literature in LMIC has demonstrated the potential effectiveness of RSV vaccines and monoclonal antibodies. This review has demonstrated the importance of accounting for seasonality, social contact rates, immunity from prior infection and maternal antibody transfer. Future models should consider incorporating individual-level risk factors, subtype-specific effects, long-term sequelae of RSV infections, and out-of-hospital mortality.
Topics: Developing Countries; Humans; Models, Theoretical; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus, Human
PubMed: 33662812
DOI: 10.1016/j.epidem.2021.100444 -
BMC Infectious Diseases Oct 2022Respiratory syncytial virus (RSV) and influenza viruses are important global causes of morbidity and mortality. We evaluated the diagnostic accuracy of the Luminex NxTAG... (Meta-Analysis)
Meta-Analysis
Respiratory syncytial virus (RSV) and influenza viruses are important global causes of morbidity and mortality. We evaluated the diagnostic accuracy of the Luminex NxTAG respiratory pathogen panels (RPPs)™ (index) against other RPPs (comparator) for detection of RSV and influenza viruses. Studies comparing human clinical respiratory samples tested with the index and at least one comparator test were included. A random-effect latent class meta-analysis was performed to assess the specificity and sensitivity of the index test for RSV and influenza. Risk of bias was assessed using the QUADAS-2 tool and certainty of evidence using GRADE. Ten studies were included. For RSV, predicted sensitivity was 99% (95% credible interval [CrI] 96-100%) and specificity 100% (95% CrI 98-100%). For influenza A and B, predicted sensitivity was 97% (95% CrI 89-100) and 98% (95% CrI 88-100) respectively; specificity 100% (95% CrI 99-100) and 100% (95% CrI 99-100), respectively. Evidence was low certainty. Although index sensitivity and specificity were excellent, comparators' performance varied. Further research with clear patient recruitment strategies could ascertain performance across different populations.Protocol Registration: Prospero CRD42021272062.
Topics: Humans; Influenza A virus; Influenza B virus; Influenza, Human; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Sensitivity and Specificity
PubMed: 36229786
DOI: 10.1186/s12879-022-07766-9 -
The Lancet. Global Health Aug 2021Human parainfluenza virus (hPIV) is a common virus in childhood acute lower respiratory infections (ALRI). However, no estimates have been made to quantify the global... (Meta-Analysis)
Meta-Analysis
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.
BACKGROUND
Human parainfluenza virus (hPIV) is a common virus in childhood acute lower respiratory infections (ALRI). However, no estimates have been made to quantify the global burden of hPIV in childhood ALRI. We aimed to estimate the global and regional hPIV-associated and hPIV-attributable ALRI incidence, hospital admissions, and mortality for children younger than 5 years and stratified by 0-5 months, 6-11 months, and 12-59 months of age.
METHODS
We did a systematic review of hPIV-associated ALRI burden studies published between Jan 1, 1995, and Dec 31, 2020, found in MEDLINE, Embase, Global Health, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Global Health Library, three Chinese databases, and Google search, and also identified a further 41 high-quality unpublished studies through an international research network. We included studies reporting community incidence of ALRI with laboratory-confirmed hPIV; hospital admission rates of ALRI or ALRI with hypoxaemia in children with laboratory-confirmed hPIV; proportions of patients with ALRI admitted to hospital with laboratory-confirmed hPIV; or in-hospital case-fatality ratios (hCFRs) of ALRI with laboratory-confirmed hPIV. We used a modified Newcastle-Ottawa Scale to assess risk of bias. We analysed incidence, hospital admission rates, and hCFRs of hPIV-associated ALRI using a generalised linear mixed model. Adjustment was made to account for the non-detection of hPIV-4. We estimated hPIV-associated ALRI cases, hospital admissions, and in-hospital deaths using adjusted incidence, hospital admission rates, and hCFRs. We estimated the overall hPIV-associated ALRI mortality (both in-hospital and out-hospital mortality) on the basis of the number of in-hospital deaths and care-seeking for child pneumonia. We estimated hPIV-attributable ALRI burden by accounting for attributable fractions for hPIV in laboratory-confirmed hPIV cases and deaths. Sensitivity analyses were done to validate the estimates of overall hPIV-associated ALRI mortality and hPIV-attributable ALRI mortality. The systematic review protocol was registered on PROSPERO (CRD42019148570).
FINDINGS
203 studies were identified, including 162 hPIV-associated ALRI burden studies and a further 41 high-quality unpublished studies. Globally in 2018, an estimated 18·8 million (uncertainty range 12·8-28·9) ALRI cases, 725 000 (433 000-1 260 000) ALRI hospital admissions, and 34 400 (16 400-73 800) ALRI deaths were attributable to hPIVs among children younger than 5 years. The age-stratified and region-stratified analyses suggested that about 61% (35% for infants aged 0-5 months and 26% for 6-11 months) of the hospital admissions and 66% (42% for infants aged 0-5 months and 24% for 6-11 months) of the in-hospital deaths were in infants, and 70% of the in-hospital deaths were in low-income and lower-middle-income countries. Between 73% and 100% (varying by outcome) of the data had a low risk in study design; the proportion was 46-65% for the adjustment for health-care use, 59-77% for patient groups excluded, 54-93% for case definition, 42-93% for sampling strategy, and 67-77% for test methods. Heterogeneity in estimates was found between studies for each outcome.
INTERPRETATION
We 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.
FUNDING
Bill & Melinda Gates Foundation.
Topics: Child, Preschool; Global Health; Humans; Infant; Infant, Newborn; Paramyxoviridae Infections; Paramyxovirinae; Respiratory Tract Infections
PubMed: 34166626
DOI: 10.1016/S2214-109X(21)00218-7 -
Expert Review of Clinical Immunology Oct 2020The tripartite motif (TRIM) plays various roles in pathological and physiological functions, including neurological diseases, genetic disorders, carcinogenesis, innate...
INTRODUCTION
The tripartite motif (TRIM) plays various roles in pathological and physiological functions, including neurological diseases, genetic disorders, carcinogenesis, innate immune signaling, and antiviral activity. TRIM56 is a cytoplasmic protein whose expression is stimulated by type I interferon and may function as an antiviral agent. Here, the authors conducted a systematic search on papers that reported antiviral effects of TRIM56.
AREAS COVERED
The authors conducted a comprehensive search of the PubMed database without time or language limitation, after using the Medical Subject Headings (MeSH) Database terms. Initially, a structured search and full article review yielded 31 papers. Relevant original and review articles on TRIM56 were included. The reference lists were then reviewed, and the cited articles were added. : TRIM56 has been shown to have direct antiviral actions against positive-sense single-stranded RNA viruses from the families , and . Moreover, it may be effective against negative-sense single-strand RNA viruses from the families and , as well as a DNA virus, Herpes simplex virus 1 (HSV-1). These studies could suggest the potential of a TRIM56-based antiviral against COVID-19 from the family , containing single-stranded positive-sense RNA genome. However, its efficacy and antiviral mechanisms need to be further examined.
Topics: Animals; Antiviral Agents; COVID-19; Humans; RNA Viruses; SARS-CoV-2; Tripartite Motif Proteins; Ubiquitin-Protein Ligases
PubMed: 32903131
DOI: 10.1080/1744666X.2020.1822168 -
BMC Public Health Dec 2023A significant proportion of the global respiratory syncytial virus (RSV) associated morbidity is accounted for by infants aged 0 to 6 months, who are particularly...
BACKGROUND
A significant proportion of the global respiratory syncytial virus (RSV) associated morbidity is accounted for by infants aged 0 to 6 months, who are particularly vulnerable to severe disease. In 2015, 44% of global hospitalisations in infants in this age group were secondary to RSV. The objective of this systematic review is to appraise and synthesise the local evidence of RSV infection morbidity among Australian infants aged 0 to 6 months and to assess the implications for future immunisation strategies.
METHODS
Electronic databases (Medline, Embase, Pubmed and Global Health) were searched for full-text articles published between 2000 and 2023 in English language. Studies that examined markers of RSV disease morbidity in infants aged 0 to 6 months in Australia who had laboratory confirmed RSV infection were eligible for inclusion. The outcomes of interest were incidence, prevalence, testing rate, positivity rate, mortality, emergency department visits, community health visits, hospitalisation, intensive care unit admission, supplementary oxygen use, mechanical ventilation, risk factors for disease severity and monoclonal antibody use.
RESULTS
The database search identified 469 studies. After removal of duplicates and full-text review, 17 articles were eligible for inclusion. This review was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Synthesis without meta-analysis guidelines.
CONCLUSIONS
Qualitative analysis of the included studies showed that Australian infants aged 0 to 6 months have higher rates of RSV testing, positivity and incidence; and more likely to develop severe disease that requires hospitalisation, intensive care unit admission or respiratory support, compared to children and adults of all ages. Aboriginal and Torres Strait Islander infants aged 0 to 6 months demonstrated higher rates of RSV infection and hospitalisation, compared to non-Indigenous infants. Age-related trends persisted in geographic areas with varying seasonal transmission of RSV, and during the SARS-CoV-2 pandemic. Passive immunisation strategies targeting infants in their first 6 months of life, either via vaccination of pregnant women or administration of long-acting monoclonal antibody during infancy, could effectively reduce RSV disease burden in Australia.
Topics: Pregnancy; Infant; Child; Adult; Humans; Female; Respiratory Syncytial Virus Infections; Australia; Communicable Diseases; Antibodies, Monoclonal; Respiratory Syncytial Virus, Human; Hospitalization; Prevalence
PubMed: 38129854
DOI: 10.1186/s12889-023-17474-x -
Journal of Global Health Jul 2022This systematic review aimed to describe common aetiologies of severe and non-severe community acquired pneumonia among children aged 1 month to 9 years in low- and...
BACKGROUND
This systematic review aimed to describe common aetiologies of severe and non-severe community acquired pneumonia among children aged 1 month to 9 years in low- and middle-income countries.
METHODS
We searched the MEDLINE, EMBASE, and PubMed online databases for studies published from January 2010 to August 30, 2020. We included studies on acute community-acquired pneumonia or acute lower respiratory tract infection with ≥1 year of continuous data collection; clear consistent case definition for pneumonia; >1 specimen type (except empyema studies where only pleural fluid was required); testing for >1 pathogen including both viruses and bacteria. Two researchers reviewed the studies independently. Results were presented as a narrative summary. Quality of evidence was assessed with the Quality Assessment Tool for Quantitative Studies. The study was registered on PROSPERO [CRD42020206830].
RESULTS
We screened 5184 records; 1305 duplicates were removed. The remaining 3879 titles and abstracts were screened. Of these, 557 articles were identified for full-text review, and 55 met the inclusion criteria - 10 case-control studies, three post-mortem studies, 11 surveillance studies, eight cohort studies, five cross-sectional studies, 12 studies with another design and six studies that included patients with pleural effusions or empyema. Studies which described disease by severity showed higher bacterial detection (Streptococcus pneumoniae, Staphylococcus aureus) in severe vs non-severe cases. The most common virus causing severe disease was respiratory syncytial virus (RSV). Pathogens varied by age, with RSV and adenovirus more common in younger children. Influenza and atypical bacteria were more common in children 5-14 years than younger children. Malnourished and HIV-infected children had higher rates of pneumonia due to bacteria or tuberculosis.
CONCLUSIONS
Several viral and bacterial pathogens were identified as important targets for prevention and treatment. Bacterial pathogens remain an important cause of moderate to severe disease, particularly in children with comorbidities despite widespread PCV and Hib vaccination.
Topics: Child; Community-Acquired Infections; Cross-Sectional Studies; Developing Countries; Humans; Infant; Pneumonia; Respiratory Syncytial Viruses; Vaccination
PubMed: 35866332
DOI: 10.7189/jogh.12.10009 -
The Journal of Pediatrics Dec 2021To describe the features and frequency of respiratory syncytial virus (RSV)-associated severe acute neurologic disease in children.
OBJECTIVES
To describe the features and frequency of respiratory syncytial virus (RSV)-associated severe acute neurologic disease in children.
STUDY DESIGN
We performed a systematic review of the literature to identify reports of severe acute neurologic complications associated with acute RSV infection in children aged <15 years (PROSPERO Registration CRD42019125722). Main outcomes included neurologic, clinical, and demographic features of cases and the frequency of disease. We aggregated available case data from the published literature and from the Australian Acute Childhood Encephalitis (ACE) study.
RESULTS
We identified 87 unique studies from 26 countries describing a spectrum of RSV-associated severe acute neurologic syndromes including proven encephalitis, acute encephalopathy, complex seizures, hyponatremic seizures, and immune-mediated disorders. The frequency of RSV infection in acute childhood encephalitis/encephalopathy was 1.2%-6.5%. We aggregated data from 155 individual cases with RSV-associated severe acute neurologic complications; median age was 11.0 months (IQR 2.0-21.5), most were previously healthy (71/104, 68%). Seizure was the most frequently reported neurologic feature (127/150, 85%). RSV was detected in the central nervous system of 12 cases. Most children recovered (81/122, 66%); however, some reports described partial recovery (33/122, 27%) and death (8/122, 7%).
CONCLUSIONS
RSV-associated neurologic complications have been widely reported, but there is substantial heterogeneity in the design and quality of existing studies. The findings from our study have implications for the investigation, management, and prevention of RSV-associated neurologic complications. Further, this systematic review can inform the design of future studies aiming to quantify the burden of childhood RSV-associated neurologic disease.
Topics: Adolescent; Child; Child, Preschool; Diagnostic Tests, Routine; Female; Humans; Incidence; Infant; Male; Nervous System Diseases; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human
PubMed: 34181989
DOI: 10.1016/j.jpeds.2021.06.045 -
International Journal of Infectious... Jan 2020The present study provides a comprehensive review of the recently published data on RSV epidemiology in adults and the elderly in Latin America. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The present study provides a comprehensive review of the recently published data on RSV epidemiology in adults and the elderly in Latin America.
METHODS
A systematic literature search was carried out in Medline, Scielo, Lilacs, and Cochrane Library. The search strategy aimed at retrieving studies focusing on RSV prevalence, burden, risk factors, and the routine clinical practice in the prevention and management of RSV infections in Latin American countries. Only articles published between January 2011 and December 2017 were considered.
RESULTS
Eighteen studies were included. Percentages of RSV detection varied highly across included studies for adult subjects with respiratory infections (0% to 77.9%), influenza-like illness (1.0% to 16.4%) and community-acquired pneumonia (1.3% to 13.5%). Considerable percentages of hospitalization were reported for RSV-infected adults with influenza-like illness (40.9% and 69.9%) and community-acquired pneumonia (91.7%).
CONCLUSIONS
Recent RSV data regarding adult populations in Latin America are scarce. RSV was documented as a cause of illness in adults and the elderly, being identified in patients with acute respiratory infections, influenza-like illness and community-acquired pneumonia. The studies suggest that RSV infections may be a significant cause of hospitalization in adult populations in Latin America, including younger adults.
Topics: Adult; Aged; Aged, 80 and over; Community-Acquired Infections; Female; Hospitalization; Humans; Latin America; Male; Middle Aged; Prevalence; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Risk Factors; Young Adult
PubMed: 31669592
DOI: 10.1016/j.ijid.2019.10.025 -
Planta Medica Oct 2020Viruses have a high mutation rate, and, thus, there is a continual emergence of new antiviral-resistant strains. Therefore, it becomes imperative to explore and develop...
Viruses have a high mutation rate, and, thus, there is a continual emergence of new antiviral-resistant strains. Therefore, it becomes imperative to explore and develop new antiviral compounds continually. The search for pharmacological substances of plant origin that are effective against animal viruses, which have a high mortality rate or cause large economic losses, has garnered interest in the last few decades. This systematic review compiles 130 plant species that exhibit antiviral activity on 37 different virus species causing serious diseases in animals. The kind of extract, fraction, or compound exhibiting the antiviral activity and the design of the trial were particularly considered for review. The literature revealed details regarding plant species exhibiting antiviral activities against pathogenic animal virus species of the following families-, and that cause infections, among others, in poultry, cattle, pigs, horses, shrimps, and fish. Overall, 30 plant species exhibited activity against various influenza viruses, most of them causing avian influenza. Furthermore, 30 plant species were noted to be active against Newcastle disease virus. In addition, regarding the pathogens most frequently investigated, this review provides a compilation of 20 plant species active against bovine herpesvirus, 16 against fowlpox virus, 12 against white spot syndrome virus in marine shrimps, and 10 against suide herpesvirus. Nevertheless, some plant extracts, particularly their compounds, are promising candidates for the development of new antiviral remedies, which are urgently required.
Topics: Animal Diseases; Animals; Antiviral Agents; Cattle; Horses; Orthomyxoviridae; Plant Extracts; Plants, Medicinal; Swine; Veterinary Medicine
PubMed: 32777833
DOI: 10.1055/a-1224-6115 -
Current Molecular Pharmacology 2020Nipah virus (NiV) and Hendra virus (HeV) of genus Henipavirus are the deadliest zoonotic viruses, which cause severe respiratory ailments and fatal encephalitis in...
BACKGROUND
Nipah virus (NiV) and Hendra virus (HeV) of genus Henipavirus are the deadliest zoonotic viruses, which cause severe respiratory ailments and fatal encephalitis in humans and other susceptible animals. The fatality rate for these infections had been alarmingly high with no approved treatment available to date. Viral attachment and fusion with host cell membrane is essential for viral entry and is the most essential event of viral infection. Viral attachment is mediated by interaction of Henipavirus attachment glycoprotein (G) with the host cell receptor: Ephrin B2/B3, while viral fusion and endocytosis are mediated by the combined action of both viral glycoprotein (G) and fusion protein (F).
CONCLUSION
This review highlights the mechanism of viral attachment, fusion and also explains the basic mechanism and pathobiology of this infection in humans. The drugs and therapeutics used either experimentally or clinically against NiV and HeV infection have been documented and classified in detail. Some amino acid residues essential for the functionality of G and F proteins were also emphasized. Therapeutic designing to target and block these residues can serve as a promising approach in future drug development against NiV and HeV.
Topics: Animals; Antiviral Agents; Drug Design; Hendra Virus; Henipavirus Infections; Humans; Nipah Virus; Virus Internalization
PubMed: 31657692
DOI: 10.2174/1874467212666191023123732