Effects of the Optional Protocols to the Convention on the Rights of the Child on the causes of child death: a statistical study on a global scale

The Convention on the Rights of the Child (CRC) and the Optional Protocol to the Convention on the Rights of the Child on a Communications Procedure (OPCP) make commitments and guarantees in relation to child health. The aim of the study is to verify the effects of these commitments on the causes of child death. To analyze these effects, we apply the one-way analysis of variance. For each group, we calculated the averages of child deaths in their respective countries for the years 2002, 2007, 2012, and 2017. The p-value resulting indicated whether there was a difference between the means of child deaths in those years that were compared. We also observed the time series for each cause of death over the years 2000 to 2017. The CRC has an expressive adhesion. OPCP has a smaller number of acceptors in all regions compared to CRC. The acceptance of OPCP did not significantly alter the results of the number of deaths in the accepting countries in any of the 13 causes of child death observed. In the non- accepting group, significant differences were found concerning five causes of child death: HIV/AIDS, diarrhoeal diseases, measles, meningitis/encephalitis, and acute lower respiratory infections (p-values 0.01, 0.01, 0.003, 0.002, and 0.003, respectively). Our results suggest that the group of countries that have accepted the OPCP are more committed to issues of child deaths causes studied. In all of them the annual death numbers were considerably lower in this group.

Alveolar-like Macrophages Attenuate Respiratory Syncytial Virus Infection

Respiratory Syncytial Virus (RSV) is the leading cause of acute lower respiratory infections in young children and infection has been linked to the development of persistent lung disease in the form of wheezing and asthma. Despite substantial research efforts, there are no RSV vaccines currently available and an effective monoclonal antibody targeting the RSV fusion protein (palivizumab) is of limited general use given the associated expense. Therefore, the development of novel approaches to prevent RSV infection is highly desirable to improve pediatric health globally. We have developed a method to generate alveolar-like macrophages (ALMs) from pluripotent stem cells. These ALMs have shown potential to promote airway innate immunity and tissue repair and so we hypothesized that ALMs could be used as a strategy to prevent RSV infection. Here, we demonstrate that ALMs are not productively infected by RSV and prevent the infection of epithelial cells. Prevention of epithelial infection was mediated by two different mechanisms: phagocytosis of RSV particles and release of an antiviral soluble factor different from type I interferon. Furthermore, intratracheal administration of ALMs protected mice from subsequent virus-induced weight loss and decreased lung viral titres and inflammation, indicating that ALMs can impair the pathogenesis of RSV infection. Our results support a prophylactic role for ALMs in the setting of RSV infection and warrant further studies on stem cell-derived ALMs as a novel cell-based therapy for pulmonary viral infections.

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

IntroductionThe 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.MethodsWe 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.ResultsGlobally, 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.ConclusionIncidence 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.

Vitamin D Modulation of the Innate Immune Response to Paediatric Respiratory Pathogens Associated with Acute Lower Respiratory Infections

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 Streptococcus pneumoniae, 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 “Streptococcus pneumoniae” 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.