Sunshine, rainfall, humidity and child pneumonia in the tropics : time-series analyses

Few studies have formally examined the relationship between meteorological factors and the incidence of child pneumonia in the tropics, despite the fact that most child pneumonia deaths occur there. We examined the association between four meteorological exposures (rainy days, sunshine, relative humidity, temperature) and the incidence of clinical pneumonia in young children in the Philippines using three time-series methods: correlation of seasonal patterns, distributed lag regression, and case-crossover. Lack of sunshine was most strongly associated with pneumonia in both lagged regression [overall relative risk over the following 60 days for a 1-h increase in sunshine per day was 0·67 (95% confidence interval (CI) 0·51–0·87)] and case-crossover analysis [odds ratio for a 1-h increase in mean daily sunshine 8–14 days earlier was 0·95 (95% CI 0·91–1·00)]. This association is well known in temperate settings but has not been noted previously in the tropics. Further research to assess causality is needed.

Rates of radiologically confirmed pneumonia as defined by the World Health Organization in Northern Territory Indigenous children

Objective To determine the burden of hospitalised, radiologically confirmed pneumonia (World Health Organization protocol) in Northern Territory Indigenous children. Design, setting and participants Historical, observational study of all hospital admissions for any diagnosis of NT resident Indigenous children, aged between >= 29 days and < 5 years, 1 April 1997 to 31 March 2005. Intervention All chest radiographs taken during these admissions, regardless of diagnosis, were assessed for pneumonia in accordance with the WHO protocol. Main outcome measure The primary outcome was endpoint consolidation (dense fluffy consolidation [alveolar infiltrate] of a portion of a lobe or the entire lung) present on a chest radiograph within 3 days of hospitalisation. Results We analysed data on 24 115 hospitalised episodes of care for 9492 children and 13 683 chest radiographs. The average annual cumulative incidence of endpoint consolidation was 26.6 per 1000 population per year (95% Cl, 25.3-27.9); 57.5 per 1000 per year in infants aged 1-11 months, 38.3 per 1000 per year in those aged 12-23 months, and 13.3 per 1000 per year in those aged 24-59 months. In all age groups, rates of endpoint consolidation in children in the arid southern region of NT were about twice that of children in the tropical northern region. Conclusion The rates of severe pneumonia in hospitalised NT Indigenous children are among the highest reported in the world. Reducing this unacceptable burden of disease should be a national health priority.

Identification of radiological alveolar pneumonia in children with high rates of hospitalized respiratory infections : Comparison of WHO-defined and pediatric pulmonologist diagnosis in the clinical context

Background A reliable standardized diagnosis of pneumonia in children has long been difficult to achieve. Clinical and radiological criteria have been developed by the World Health Organization (WHO), however, their generalizability to different populations is uncertain. We evaluated WHO defined chest radiograph (CXRs) confirmed alveolar pneumonia in the clinical context in Central Australian Aboriginal children, a high risk population, hospitalized with acute lower respiratory illness (ALRI). Methods CXRs in children (aged 1-60 months) hospitalized and treated with intravenous antibiotics for ALRI and enrolled in a randomized controlled trial (RCT) of Vitamin A/Zinc supplementation were matched with data collected during a population-based study of WHO-defined primary endpoint pneumonia (WHO-EPC). These CXRs were reread by a pediatric pulmonologist (PP) and classified as pneumonia-PP when alveolar changes were present. Sensitivities, specificities, positive and negative predictive values (PPV, NPV) for clinical presentations were compared between WHO-EPC and pneumonia-PP. Results Of the 147 episodes of hospitalized ALRI, WHO-EPC was significantly less commonly diagnosed in 40 (27.2%) compared to pneumonia-PP (difference 20.4%, 95% CI 9.6-31.2, P < 0.001). Clinical signs on admission were poor predictors for both pneumonia-PP and WHO-EPC; the sensitivities of clinical signs ranged from a high of 45% for tachypnea to 5% for fever + tachypnea + chest-indrawing. The PPV range was 40-20%, respectively. Higher PPVs were observed against the pediatric pulmonologist's diagnosis compared to WHO-EPC. Conclusions WHO-EPC underestimates alveolar consolidation in a clinical context. Its use in clinical practice or in research designed to inform clinical management in this population should be avoided. Pediatr Pulmonol. 2012; 47:386-392. (C) 2011 Wiley Periodicals, Inc.

Effectiveness of 7-valent pneumococcal conjugate vaccine against radiologically diagnosed pneumonia in indigenous infants in Australia

Objective To evaluate the effectiveness of the 7-valent pneumococcal conjugate vaccine (PCV7) in preventing pneumonia, diagnosed radiologically according to World Health Organization (WHO) criteria, among indigenous infants in the Northern Territory of Australia. Methods We conducted a historical cohort study of consecutive indigenous birth cohorts between 1 April 1998 and 28 February 2005. Children were followed up to 18 months of age. The PCV7 programme commenced on 1 June 2001. All chest X-rays taken within 3 days of any hospitalization were assessed. The primary endpoint was a first episode of WHO-defined pneumonia requiring hospitalization. Cox proportional hazards models were used to compare disease incidence. Findings There were 526 pneumonia events among 10 600 children - an incidence of 3.3 per 1000 child-months; 183 episodes (34.8%) occurred before 5 months of age and 247 (47.0%) by 7 months. Of the children studied, 27% had received 3 doses of vaccine by 7 months of age. Hazard ratios for endpoint pneumonia were 1.01 for 1 versus 0 doses; 1.03 for 2 versus 0 doses; and 0.84 for 3 versus 0 doses. Conclusion There was limited evidence that PCV7 reduced the incidence of radiologically confirmed pneumonia among Northern Territory indigenous infants, although there was a non-significant trend towards an effect after receipt of the third dose. These findings might be explained by lack of timely vaccination and/or occurrence of disease at an early age. Additionally, the relative contribution of vaccine-type pneumococcus to severe pneumonia in a setting where multiple other pathogens are prevalent may differ with respect to other settings where vaccine efficacy has been clearly established.

Impact of temperature on childhood pneumonia estimated from satellite remote sensing

The effect of temperature on childhood pneumonia in subtropical regions is largely unknown so far. This study examined the impact of temperature on childhood pneumonia in Brisbane, Australia. A quasi-Poisson generalized linear model combined with a distributed lag non linear model was used to quantify the main effect of temperature on emergency department visits (EDVs) for childhood pneumonia in Brisbane from 2001 to 2010. The model residuals were checked to identify added effects due to heat waves or cold spells. Both high and low temperatures were associated with an increase in EDVs for childhood pneumonia. Children aged 2–5 years, and female children were particularly vulnerable to the impacts of heat and cold, and Indigenous children were sensitive to heat. Heat waves and cold spells had significant added effects on childhood pneumonia, and the magnitude of these effects increased with intensity and duration. There were changes over time in both the main and added effects of temperature on childhood pneumonia. Children, especially those female and Indigenous, should be particularly protected from extreme temperatures. Future development of early warning systems should take the change over time in the impact of temperature on children’s health into account.

Temperature variability and childhood pneumonia : an ecological study

Background Few data on the relationship between temperature variability and childhood pneumonia are available. This study attempted to fill this knowledge gap. Methods A quasi-Poisson generalized linear regression model combined with a distributed lag nonlinear model was used to quantify the impacts of diurnal temperature range (DTR) and temperature change between two neighbouring days (TCN) on emergency department visits (EDVs) for childhood pneumonia in Brisbane, from 2001 to 2010, after controlling for possible confounders. Results An adverse impact of TCN on EDVs for childhood pneumonia was observed, and the magnitude of this impact increased from the first five years (2001–2005) to the second five years (2006–2010). Children aged 5–14 years, female children and Indigenous children were particularly vulnerable to TCN impact. However, there was no significant association between DTR and EDVs for childhood pneumonia. Conclusions As climate change progresses, the days with unstable weather pattern are likely to increase. Parents and caregivers of children should be aware of the high risk of pneumonia posed by big TCN and take precautionary measures to protect children, especially those with a history of respiratory diseases, from climate impacts.

The geographical co-distribution and socio-ecological drivers of childhood pneumonia and diarrhoea in Queensland, Australia

This study aimed to explore the spatiotemporal patterns, geographic co-distribution, and socio-ecological drivers of childhood pneumonia and diarrhea in Queensland. A Bayesian conditional autoregressive model was used to quantify the impacts of socio-ecological factors on both childhood pneumonia and diarrhea at a postal area level. A distinct seasonality of childhood pneumonia and diarrhea was found. Childhood pneumonia and diarrhea mainly distributed in northwest of Queensland. Mount Isa was the high-risk cluster where childhood pneumonia and diarrhea co-distributed. Emergency department visits (EDVs) for pneumonia increased by 3% per 10-mm increase in monthly average rainfall, in wet seasons. In comparison, a 10-mm increase in monthly average rainfall may increase 4% of EDVs for diarrhea. Monthly average temperature was negatively associated with EDVs for childhood diarrhea, in wet seasons. Low socioeconomic index for areas (SEIFA) was associated with high EDVs for childhood pneumonia. Future pneumonia and diarrhea prevention and control measures in Queensland should focus more on Mount Isa.

The radiological diagnosis of pneumonia in children

Despite the importance of paediatric pneumonia as a cause of short and long-term morbidity and mortality worldwide, a reliable gold standard for its diagnosis remains elusive. The utility of clinical, microbiological and radiological diagnostic approaches varies widely within and between populations and is heavily dependent on the expertise and resources available in various settings. Here we review the role of radiology in the diagnosis of paediatric pneumonia. Chest radiographs (CXRs) are the most widely employed test, however, they are not indicated in ambulatory settings, cannot distinguish between viral and bacterial infections and have a limited role in the ongoing management of disease. A standardised definition of alveolar pneumonia on a CXR exists for epidemiological studies targeting bacterial pneumonias but it should not be extrapolated to clinical settings. Radiography, computed tomography and to a lesser extent ultrasonography and magnetic resonance imaging play an important role in complicated pneumonias but there are limitations that preclude their use as routine diagnostic tools. Large population-based studies are needed in different populations to address many of the knowledge gaps in the radiological diagnosis of pneumonia in children, however, the feasibility of such studies is an important barrier.

Assessment of temperature effects on childhood pneumonia and diarrhoea

This thesis has identified the high risk areas of childhood pneumonia and diarrhoea in Queensland and quantified the effects of temperature on emergency department visits for childhood pneumonia and diarrhoea. It adds to the increasing evidence about the impacts of climate variability and change on children's health and may have significant implications for developing climate change adaptation strategies and paediatric care policies.

Modelling staphylococcal pneumonia in a human 3D lung tissue model system delineates toxin-mediated pathology

Staphylococcus aureus necrotizing pneumonia is recognized as a toxin-mediated disease, yet the tissue-destructive events remain elusive, partly as a result of lack of mechanistic studies in human lung tissue. In this study, a three-dimensional (3D) tissue model composed of human lung epithelial cells and fibroblasts was used to delineate the role of specific staphylococcal exotoxins in tissue pathology associated with severe pneumonia. To this end, the models were exposed to the mixture of exotoxins produced by S. aureus strains isolated from patients with varying severity of lung infection, namely necrotizing pneumonia or lung empyema, or to purified toxins. The necrotizing pneumonia strains secreted high levels of alpha-toxin and Panton-Valentine leukocidin (PVL), and triggered high cytotoxicity, inflammation, necrosis and loss of E-cadherin from the lung epithelium. In contrast, the lung empyema strain produced moderate levels of PVL, but negligible amounts of alpha-toxin, and triggered limited tissue damage. alpha-toxin had a direct damaging effect on the epithelium, as verified using toxin-deficient mutants and pure alpha-toxin. Moreover, PVL contributed to pathology through the lysis of neutrophils. A combination of alpha-toxin and PVL resulted in the most severe epithelial injury. In addition, toxin-induced release of pro-inflammatory mediators from lung tissue models resulted in enhanced neutrophil migration. Using a collection of 31 strains from patients with staphylococcal pneumonia revealed that strains producing high levels of alpha-toxin and PVL were cytotoxic and associated with fatal outcome. Also, the strains that produced the highest toxin levels induced significantly greater epithelial disruption. Of importance, toxin-mediated lung epithelium destruction could be inhibited by polyspecific intravenous immunoglobulin containing antibodies against alpha-toxin and PVL. This study introduces a novel model system for study of staphylococcal pneumonia in a human setting. The results reveal that the combination and levels of alpha-toxin and PVL correlate with tissue pathology and clinical outcome associated with pneumonia.

Streptococcus pyogenes Pneumonia in Adults: Clinical Presentation and Molecular Characterization of Isolates 2006-2015

Introduction In the preantibiotic era Streptococcus pyogenes was a common cause of severe pneumonia but currently, except for postinfluenza complications, it is not considered a common cause of community-acquired pneumonia in adults. Aim and Material and Methods This study aimed to identify current clinical episodes of S. pyogenes pneumonia, its relationship with influenza virus circulation and the genotypes of the involved isolates during a decade in a Southern European region (Gipuzkoa, northern Spain). Molecular analysis of isolates included emm, multilocus-sequence typing, and superantigen profile determination. Results Forty episodes were detected (annual incidence 1.1 x 100,000 inhabitants, range 0.29-2.29). Thirty-seven episodes were community-acquired, 21 involved an invasive infection and 10 developed STSS. The associated mortality rate was 20%, with half of the patients dying within 24 hours after admission. Influenza coinfection was confirmed in four patients and suspected in another. The 52.5% of episodes occurred outside the influenza seasonal epidemic. The 67.5% of affected persons were elderly individuals and adults with severe comorbidities, although 13 patients had no comorbidities, 2 of them had a fatal outcome. Eleven clones were identified, the most prevalent being emm1/ST28 (43.6%) causing the most severe cases. Conclusions S. pyogenes pneumonia had a continuous presence frequently unrelated to influenza infection, being rapidly fatal even in previously healthy individuals.

Efeito do Sistema de Secreção do Tipo VI de Pseudomonas aeruginosa em modelo murino de pneumonia aguda

O Sistema de Secreção do Tipo VI (SST6), o mais recente maquinário de secreção descrito em bactérias Gram-negativas, é amplamente distribuído entre as diversas espécies deste grupo de microrganismos. Esse aparato de secreção é capaz de injetar efetores proteicos em células alvo, eucarióticas e procarióticas. Estudos sobre o papel do SST6 na virulência microbiana revelaram que este sistema secretório participa ativamente do estabelecimento de infecções, contribuindo para a sobrevivência das bactérias no interior de fagócitos. O genoma da cepa PAO1 de Pseudomonas aeruginosa apresenta três loci que codificam aparatos de SST6, denominados de H1-SST6, H2-SST6 e H3-SST6, Porém, pouco se sabe sobre a participação do SST6 na patogênese de infecções por P. aeruginosa. Assim, o presente estudo investigou o papel de H1-SST6, H2-SST6 e H3-SST6 durante a infecção pulmonar aguda de camundongos. Para isso, camundongos C57/BL6 foram infectados com diferentes doses de bactérias da cepa selvagem PAO1 ou das cepas mutantes PAO1∆H1, PAO1∆H2, PAO1∆H3 ou PAO1∆H1∆H2∆H3. Após 24 horas, os lavados broncoalveolares (LBAs) de animais controle e infectados foram recuperados para a contagem de leucócitos totais e polimorfonucleares e para a quantificação, por ELISA, da quimiocina para neutrófilos, KC, e das citocinas pró-inflamatórias IL-1β e TNF-α. Em outros experimentos, os pulmões, fígados, baços e rins dos animais foram macerados para a pesquisa da carga bacteriana e da disseminação sistêmica das bactérias. A citotoxicidade do SST6 foi determinada, in vitro, em neutrófilos humanos, pela marcação com iodeto de propídeo (PI) e anexina-V seguida da análise em citometria de fluxo. Os resultados mostraram que a inativação dos três SST6 reduziu significativamente a concentração de neutrófilos nos LBAs quando os animais foram infectados com 10⁷ Unidades Formadoras de Colônias de P. aeruginosa. Nesta dose, foi observado que as medianas do número de bactérias detectadas nos animais infectados com as mutantes no SST6 foram menores do que as detectadas nos animais infectados com a cepa parental PAO1. As mutações no SST6 não afetaram a disseminação sistêmica da bactéria. A pesquisa da secreção de citocinas pró-inflamatórias mostrou que, embora tenha sido observada uma redução nas medianas das concentrações de TNF-α nos LBAs de camundongos infectados com a cepa PAO1∆H1∆H2∆H3, em relação aos LBAs de camundongos infectados com a cepa parental, essa diferença não foi significativa. Como a pesquisa de IL-1β e KC não contribuiu para a elucidação dos mecanismos envolvidos na redução da concentração de neutrófilos nos LBAs dos camundongos infectados pela cepa tripla mutante, foi pesquisado o possível efeito do SST6 na morte de neutrófilos humanos. Os resultados mostraram que não houve diferenças significativas quando as diferentes amostras de células infectadas foram comparedas entre si. Em conclusão, os resultados do presente estudo mostraram que o SST6 pode interferir na resposta de neutrófilos durante a pneumonia aguda, mas estudos adicionais são necessários para determinar o papel deste mecanismo de secreção na patogênese de P. aeruginosa.