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PloS One 2021Viral outbreaks present a particular challenge in countries in Africa where there is already a high incidence of other infectious diseases, including malaria which can... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Viral outbreaks present a particular challenge in countries in Africa where there is already a high incidence of other infectious diseases, including malaria which can alter immune responses to secondary infection. Ebola virus disease (EVD) is one such problem; understanding how Plasmodium spp. and Ebolavirus (EBOV) interact is important for future outbreaks.
METHODS
We conducted a systematic review in PubMed and Web of Science to find peer-reviewed papers with primary data literature to determine 1) prevalence of EBOV/Plasmodium spp. coinfection, 2) effect of EBOV/Plasmodium spp. coinfection on EVD pathology and the immune response, 3) impact of EBOV/Plasmodium spp. coinfection on the outcome of EVD-related mortality. Random effects meta-analyses were conducted with the R package meta to produce overall proportion and effect estimates as well as measure between-study heterogeneity.
RESULTS
From 322 peer-reviewed papers, 17 were included in the qualitative review and nine were included in a meta-analysis. Prevalence of coinfection was between 19% and 72%. One study reported significantly lower coagulatory response biomarkers in coinfected cases but no difference in inflammatory markers. Case fatality rates were similar between EBOV(+)/Pl(+) and EBOV(+)/Pl(-) cases (62.8%, 95% CI 49.3-74.6 and 56.7%, 95% CI 53.2-60.1, respectively), and there was no significant difference in risk of mortality (RR 1.09, 95% CI 0.90-1.31) although heterogeneity between studies was high. One in vivo mouse model laboratory study found no difference in mortality by infection status, but another found prior acute Plasmodium yoeli infection was protective against morbidity and mortality via the IFN-γ signalling pathway.
CONCLUSION
The literature was inconclusive; studies varied widely and there was little attempt to adjust for confounding variables. Laboratory studies may present the best option to answer how pathogens interact within the body but improvement in data collection and analysis and in diagnostic methods would aid patient studies in the future.
Topics: Animals; Coinfection; Disease Outbreaks; Ebolavirus; Hemorrhagic Fever, Ebola; Humans; Malaria; Prevalence
PubMed: 34029352
DOI: 10.1371/journal.pone.0251101 -
Vaccine May 2021In North America, the first dose of a measles-containing vaccine (MCV1) is administered at ≥12 months of age. However, MCV1 may be given to infants <12 months living... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In North America, the first dose of a measles-containing vaccine (MCV1) is administered at ≥12 months of age. However, MCV1 may be given to infants <12 months living in highly endemic areas or traveling to these areas. Although an early dose of MCV1 leads to immediate protection, it remains unclear how this impacts long-term immunity.
METHODS
This systematic review and meta-analysis evaluates the impact of MCV1 given at <12 months vs. ≥12 months of age on long-term immunogenicity and vaccine effectiveness, with long-term defined as at least one-year post-vaccination. PubMed, EMBASE, Global Health, Web of Science and Scopus were searched on October 31st, 2019. Studies were included if they included a cohort of infants vaccinated <12 months of age and evaluated long-term immunogenicity, vaccine efficacy, or effectiveness.
RESULTS
A total of 51 texts were identified: 23 reported outcomes related to vaccine effectiveness and 30 to immunogenicity. Infants vaccinated with MCV1 < 12 months of age showed an overall higher risk of measles compared to ≥12 months of age (RR = 3.16, 95% CI: 2.00, 5.01; OR = 2.46, 95% CI: 1.40, 4.32). Risk of measles decreased with increasing age at first vaccination, with those vaccinated with one dose ≥15 months at a lesser risk compared to 12-14 months or <12 months. Measles seroconversion and seropositivity was not affected by age at first vaccination, but antibody levels were significantly lower in the MCV1 < 12-month group (MD = -0.40, 95% CI: -0.71, -0.09).
CONCLUSION
Long-term measles seroconversion and seropositivity did not appear to be affected by age at MCV1, while vaccine effectiveness decreased with younger age. There was not enough evidence to look at the effect of age at MCV1 on immune blunting.
Topics: Antibodies, Viral; Humans; Immunization Schedule; Infant; Measles; Measles Vaccine; Measles virus; North America; Vaccination
PubMed: 33926750
DOI: 10.1016/j.vaccine.2021.04.012 -
Influenza and Other Respiratory Viruses Jul 2021Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory infection globally. There are vaccine candidates in development, but a systematic review... (Review)
Review
BACKGROUND
Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory infection globally. There are vaccine candidates in development, but a systematic review on immunogenicity and safety of vaccine is lacking.
METHODS
This systematic review of RSV vaccine clinical trials was undertaken using four databases. Searches were conducted using both controlled vocabulary terms such as "Respiratory Syncytial Virus, Human," "Respiratory Syncytial Virus Infections," "Respiratory Syncytial Virus Vaccines," "Immunization," "Immunization Programs" and "Vaccines" and corresponding text word terms. The included studies were limited to clinical trials published from January 2000 to 31 December 2020. RSV infection case was defined as RSV-associated medically attended acute respiratory illness (MAARI) or RSV infection by serologically confirmed test (Western blot) during the RSV surveillance period. We calculated the relative risk of each vaccine trial with RSV infection case.
RESULTS
Of 6306 publications, 38 were included and data were extracted covering four major types of RSV vaccine candidates, these being live-attenuated/chimeric (n = 14), recombinant-vector (n = 6), subunit (n = 12) and nanoparticle vaccines (n = 6). For RSV infection cases, nine trials were involved and none of them showed a vaccine-related increased MAARI during RSV surveillance season.
CONCLUSION
LID ∆M2-2, MEDI M2-2, RSVcps2 and LID/∆M2-2 /1030s (live-attenuated) were considered the most promising vaccine candidates in infant and children. In the elderly, a nanoparticle F vaccine candidate and Ad26.RSV.preF were considered as two potential effective vaccines. A promising maternal vaccine candidate is still lacking.
Topics: Aged; Antibodies, Neutralizing; Antibodies, Viral; Child; Humans; Infant; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus, Human; Vaccines, Attenuated
PubMed: 33764693
DOI: 10.1111/irv.12850 -
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 -
Nutrients Jan 2021Vitamin D is an essential component of immune function and childhood deficiency is associated with an increased risk of acute lower respiratory infections (ALRIs)....
Vitamin D is an essential component of immune function and childhood deficiency is associated with an increased risk of acute lower respiratory infections (ALRIs). Globally, the leading childhood respiratory pathogens are , respiratory syncytial virus and the influenza virus. There is a growing body of evidence describing the innate immunomodulatory properties of vitamin D during challenge with respiratory pathogens, but recent systematic and unbiased synthesis of data is lacking, and future research directions are unclear. We therefore conducted a systematic PubMed literature search using the terms "vitamin D" and "" or "Respiratory Syncytial Virus" or "Influenza". A priori inclusion criteria restricted the review to in vitro studies investigating the effect of vitamin D metabolites on human innate immune cells (primary, differentiated or immortalised) in response to stimulation with the specified respiratory pathogens. Eleven studies met our criteria. Despite some heterogeneity across pathogens and innate cell types, vitamin D modulated pathogen recognition receptor (PRRs: Toll-like receptor 2 (TLR2), TLR4, TLR7 and nucleotide-binding oligomerisation domain-containing protein 2 (NOD2)) expression; increased antimicrobial peptide expression (LL-37, human neutrophil peptide (HNP) 1-3 and β-defensin); modulated autophagosome production reducing apoptosis; and modulated production of inflammatory cytokines (Interleukin (IL) -1β, tumour necrosis factor-α (TNF-α), interferon-ɣ (IFN-ɣ), IL-12p70, IFN-β, Regulated on Activation, Normal T cell Expressed (RANTES), IL-10) and chemokines (IL-8 and C-X-C motif chemokine ligand 10 (CXCL10)). Differential modulation of PRRs and IL-1β was reported across immune cell types; however, this may be due to the experimental design. None of the studies specifically focused on immune responses in cells derived from children. In summary, vitamin D promotes a balanced immune response, potentially enhancing pathogen sensing and clearance and restricting pathogen induced inflammatory dysregulation. This is likely to be important in controlling both ALRIs and the immunopathology associated with poorer outcomes and progression to chronic lung diseases. Many unknowns remain and further investigation is required to clarify the nuances in vitamin D mediated immune responses by pathogen and immune cell type and to determine whether these in vitro findings translate into enhanced immunity and reduced ALRI in the paediatric clinical setting.
Topics: Child; Child, Preschool; Cytokines; Humans; Immunity, Innate; Immunomodulation; Infant; Influenza A virus; Influenza, Human; Pneumonia, Pneumococcal; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Respiratory Tract Infections; Streptococcus pneumoniae; Vitamin D
PubMed: 33478006
DOI: 10.3390/nu13010276 -
PharmacoEconomics Mar 2021Several vaccine and antibody candidates are currently in development for the prevention of lower respiratory tract infections caused by the respiratory syncytial virus...
Assessment of the Effects of Active Immunisation against Respiratory Syncytial Virus (RSV) using Decision-Analytic Models: A Systematic Review with a Focus on Vaccination Strategies, Modelling Methods and Input Data.
BACKGROUND
Several vaccine and antibody candidates are currently in development for the prevention of lower respiratory tract infections caused by the respiratory syncytial virus (RSV).
METHODS
We searched MEDLINE, Embase, and SCOPUS and included model-based evaluations of RSV vaccinations. Two reviewers performed the selection, data extraction, and quality evaluation with EVIDEM. Cost-effectiveness (CE) estimates were converted to $US purchasing power parity (PPP), year 2018 values. Potential economic and epidemiological outcomes were summarised for maternal, infant, children, and elderly vaccinations. The PROSPERO identifier is CRD42019122570.
RESULTS
In total, 22 model-based studies were reviewed. On average, a potential 27% reduction in RSV hospitalisations in infants was projected for maternal vaccination and 50% for direct infant immunisation. The CE of maternal vaccination was $US1766-5857 PPP 2018/disability-adjusted life-years (DALYs) for Global Alliance for Vaccines and Immunisation (Gavi)-eligible countries. For England, the maximum cost-effective price of maternal vaccination was estimated at $US81.5 PPP 2018. Infant vaccination was associated with higher CE ratios in low- and high-income settings. Vaccination of neonates born before the RSV season was the most cost effective in high-income settings. Higher values for vaccine effectiveness, duration of protection, and vaccine uptake increased the benefits. Due to indirect effects, the vaccination of school-age children and a cocooning strategy were effective alternatives to protect infants, and the vaccination of children aged < 5 years had a beneficial impact on the elderly.
CONCLUSION
RSV vaccines with anticipated characteristics may reduce a sizeable proportion of the RSV burden. The results are subject to uncertainty because of the limited epidemiological and clinical data. Data on RSV incidence and hospitalisation risk for granular age strata should be prioritised to facilitate the evaluation of RSV interventions and decision making.
Topics: Aged; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Pregnancy; Quality-Adjusted Life Years; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus, Human; Vaccination
PubMed: 33462760
DOI: 10.1007/s40273-020-00991-7 -
The Journal of Infectious Diseases Mar 2022Although global reviews of infant respiratory syncytial virus (RSV) burden exist, none have summarized data from the United States or evaluated how RSV burden estimates... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Although global reviews of infant respiratory syncytial virus (RSV) burden exist, none have summarized data from the United States or evaluated how RSV burden estimates are influenced by variations in study design.
METHODS
We performed a systematic literature review and meta-analysis of studies describing RSV-associated hospitalization rates among US infants and examined the impact of key study characteristics on these estimates.
RESULTS
We reviewed 3328 articles through 14 August 2020 and identified 25 studies with 31 unique estimates of RSV-associated hospitalization rates. Among US infants <1 year of age, annual rates ranged from 8.4 to 40.8 per 1000 with a pooled rate of 19.4 (95% confidence interval [CI], 17.9-20.9). Study type influenced RSV-associated hospitalization rates (P = .003), with active surveillance studies having pooled rates (11.0; 95% CI, 9.8-12.2) that were half that of studies based on administrative claims (21.4; 19.5-23.3) or modeling approaches (23.2; 20.2-26.2).
CONCLUSIONS
Applying our pooled rates to the 2020 US birth cohort suggests that 79 850 (95% CI, 73 680-86 020) RSV-associated infant hospitalizations occur each year. The full range of RSV-associated hospitalization rates identified in our review can better inform future evaluations of RSV prevention strategies. More research is needed to better understand differences in estimated RSV burden across study design.
Topics: Hospitalization; Humans; Infant; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; United States
PubMed: 33346360
DOI: 10.1093/infdis/jiaa752 -
PloS One 2020Wheezing is a major problem in children, and respiratory viruses are often believed to be the causative agent. While molecular detection tools enable identification of... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Wheezing is a major problem in children, and respiratory viruses are often believed to be the causative agent. While molecular detection tools enable identification of respiratory viruses in wheezing children, it remains unclear if and how these viruses are associated with wheezing. The objective of this systematic review is to clarify the prevalence of different respiratory viruses in children with wheezing.
METHODS
We performed an electronic in Pubmed and Global Index Medicus on 01 July 2019 and manual search. We performed search of studies that have detected common respiratory viruses in children ≤18 years with wheezing. We included only studies using polymerase chain reaction (PCR) assays. Study data were extracted and the quality of articles assessed. We conducted sensitivity, subgroup, publication bias, and heterogeneity analyses using a random effects model.
RESULTS
The systematic review included 33 studies. Rhinovirus, with a prevalence of 35.6% (95% CI 24.6-47.3, I2 98.4%), and respiratory syncytial virus, at 31.0% (95% CI 19.9-43.3, I2 96.4%), were the most common viruses detected. The prevalence of other respiratory viruses was as follows: human bocavirus 8.1% (95% CI 5.3-11.3, I2 84.6%), human adenovirus 7.7% (95% CI 2.6-15.0, I2 91.0%), influenza virus6.5% (95% CI 2.2-12.6, I2 92.4%), human metapneumovirus5.8% (95% CI 3.4-8.8, I2 89.0%), enterovirus 4.3% (95% CI 0.1-12.9, I2 96.2%), human parainfluenza virus 3.8% (95% CI 1.5-6.9, I2 79.1%), and human coronavirus 2.2% (95% CI 0.6-4.4, I2 79.4%).
CONCLUSIONS
Our results suggest that rhinovirus and respiratory syncytial virus may contribute to the etiology of wheezing in children. While the clinical implications of molecular detection of respiratory viruses remains an interesting question, this study helps to illuminate the potential of role respiratory viruses in pediatric wheezing.
REVIEW REGISTRATION
PROSPERO, CRD42018115128.
Topics: Bocavirus; Child; Child, Preschool; Coronavirus; Humans; Orthomyxoviridae; Parainfluenza Virus 1, Human; Polymerase Chain Reaction; Respiratory Sounds; Respiratory System; Respiratory Tract Infections
PubMed: 33315873
DOI: 10.1371/journal.pone.0243735 -
Microbiology and Immunology Jan 2021Human parainfluenza virus (HPIV) infection is associated with every kind of respiratory tract illnesses, including the common cold, laryngotracheobronchitis (i.e.... (Review)
Review
Human parainfluenza virus (HPIV) infection is associated with every kind of respiratory tract illnesses, including the common cold, laryngotracheobronchitis (i.e. croup), tracheobronchitis, bronchiolitis, and pneumonia, in both children and adults. Although HPIVs are common respiratory pathogens, there are increasing reports about extrapulmonary manifestations of HPIVs infection. Each of the HPIVs could produce infection of other organs (central nervous system, heart, myocardium, etc.) in all age groups who are either immunocompetent or immunocompromised. This review aimed at summarizing the available data on clinical manifestations of HPIV infection outside the respiratory tract from 1961 to 2020. The findings support the possibility of extrapulmonary infections that were thought to be due to rare host genetic or immunologic defects in infected patients. These findings highlight the fact that extrapulmonary dissemination of HPIV can occur, but the association is not clearly demonstrated. Our data support the hypothesis that HPIV infection is one of the possible causes of these alterations and may even be the direct cause in some cases.
Topics: Adult; Central Nervous System; Child; Heart; Humans; Parainfluenza Virus 1, Human; Parainfluenza Virus 2, Human; Parainfluenza Virus 3, Human; Paramyxoviridae Infections; Pneumonia; Respiratory Tract Infections
PubMed: 33270253
DOI: 10.1111/1348-0421.12865 -
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