https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(13)60222-6.pdf

Global burden of childhood pneumonia and diarrhoea

https://www.pure.ed.ac.uk/ws/files/39859314/1_s2.0_S0140673617309388_main_1.pdf

Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic review and modelling study

Burden of Streptococcus pneumoniae and Haemophilus influenzae type b disease in children in the era of conjugate vaccines: global, regional, and national estimates for 2000–15

Objective Pneumonia accounts for more deaths than any other infectious disease worldwide. The intestinal microbiota supports local mucosal immunity and is increasingly recognised as an important modulator of the systemic immune system. The precise role of the gut microbiota in bacterial pneumonia, however, is unknown. Here, we investigate the function of the gut microbiota in the host defence against Streptococcus pneumoniae infections. Design We depleted the gut microbiota in C57BL/6 mice and subsequently infected them intranasally with S. pneumoniae . We then performed survival and faecal microbiota transplantation (FMT) experiments and measured parameters of inflammation and alveolar macrophage whole-genome responses. Results We found that the gut microbiota protects the host during pneumococcal pneumonia, as reflected by increased bacterial dissemination, inflammation, organ damage and mortality in microbiota-depleted mice compared with controls. FMT in gut microbiota-depleted mice led to a normalisation of pulmonary bacterial counts and tumour necrosis factor-α and interleukin-10 levels 6 h after pneumococcal infection. Whole-genome mapping of alveolar macrophages showed upregulation of metabolic pathways in the absence of a healthy gut microbiota. This upregulation correlated with an altered cellular responsiveness, reflected by a reduced responsiveness to lipopolysaccharide and lipoteichoic acid. Compared with controls, alveolar macrophages derived from gut microbiota-depleted mice showed a diminished capacity to phagocytose S. pneumoniae . Conclusions This study identifies the intestinal microbiota as a protective mediator during pneumococcal pneumonia. The gut microbiota enhances primary alveolar macrophage function. Novel therapeutic strategies could exploit the gut–lung axis in bacterial infections.

https://gut.bmj.com/content/gutjnl/65/4/575.full.pdf

The gut microbiota plays a protective role in the host defence against pneumococcal pneumonia

Background The recent series of reviews conducted within the Global Action Plan for Pneumonia and Diarrhoea (GAPPD) addressed epidemiology of the two deadly diseases at the global and regional level; it also estimated the effectiveness of interventions, barriers to achieving high coverage and the main implications for health policy. The aim of this paper is to provide the estimates of childhood pneumonia at the country level. This should allow national policy–makers and stakeholders to implement proposed policies in the World Health Organization (WHO) and UNICEF member countries. Methods We conducted a series of systematic reviews to update previous estimates of the global, regional and national burden of childhood pneumonia incidence, severe morbidity, mortality, risk factors and specific contributions of the most common pathogens: Streptococcus pneumoniae (SP), Haemophilus influenzae type B (Hib), respiratory syncytial virus (RSV) and influenza virus (flu). We distributed the global and re gional–level estimates of the number of cases, severe cases and deaths from childhood pneumonia in 2010–2011 by specific countries using an epidemiological model. The model was based on the prevalence of the five main risk factors for childhood pneumonia within countries (mal nutrition, low birth weight, non–exclusive breastfeeding in the first four months, solid fuel use and crowding) and risk effect sizes estimated using meta–analysis. Findings The incidence of community–acquired childhood pneumonia in low– and middle–income countries (LMIC) in the year 2010, using World Health Organization's definition, was about 0.22 (interquartile range (IQR) 0.11–0.51) episodes per child–year (e/cy), with 11.5% (IQR 8.0–33.0%) of cases progressing to severe episodes. This is a reduction of nearly 25% over the past decade, which is consistent with observed reductions in the prevalence of risk factors for pneumonia throughout LMIC. At the level of pneumonia incidence, RSV is the most common pathogen, present in about 29% of all episodes, followed by influenza (17%). The contribution of different pathogens varies by pneumonia severity strata, with viral etiologies becoming relatively less important and most deaths in 2010 caused by the main bacterial agents – SP (33%) and Hib (16%), accounting for vaccine use against these two pathogens. Conclusions In comparison to 2000, the primary epidemiological evidence contributing to the models of childhood pneumonia burden has improved only slightly; all estimates have wide uncertainty bounds. Still,

/pdf/epidemiology-and-etiology-of-childhood-pneumonia-in-2010-4hfdzjr05x.pdf

Epidemiology and etiology of childhood pneumonia in 2010: estimates of incidence, severe morbidity, mortality, underlying risk factors and causative pathogens for 192 countries.

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(12)61901-1.pdf

Jennifer C Moiïsi

Papers

Global and regional burden of hospital admissions for severe acute lower respiratory infections in young children in 2010: a systematic analysis