Hypoxic Pneumonia Research Articles

Clinical predictors of hypoxic pneumonia in children from the Eastern Highlands Province, Papua New Guinea: secondary analysis of two prospective observational studies

BackgroundPneumonia is the leading cause of death in young children globally and is prevalent in the Papua New Guinea highlands. We investigated clinical predictors of hypoxic pneumonia to inform local treatment guidelines in this resource-limited setting. MethodsBetween 2013 and 2020, two consecutive prospective observational studies were undertaken enrolling children 0-4 years presenting with pneumonia to health-care facilities in Goroka Town, Eastern Highlands Province. Logistic regression models were developed to identify clinical predictors of hypoxic pneumonia (oxygen saturation <90% on presentation). Model performance was compared against established criteria to identify severe pneumonia. FindingsThere were 2067 cases of pneumonia; hypoxaemia was detected in 36·1%. The strongest independent predictors of hypoxic pneumonia were central cyanosis on examination (adjusted odds ratio [aOR] 5·14; 95%CI 3·47-7·60), reduced breath sounds (aOR 2·92; 95%CI 2·30-3·71), and nasal flaring or grunting (aOR 2·34; 95%CI 1·62-3·38). While the model developed to predict hypoxic pneumonia outperformed established pneumonia severity criteria, it was not sensitive enough to be clinically useful at this time. InterpretationGiven signs and symptoms are unable to accurately detect hypoxia, all health care facilities should be equipped with pulse oximeters. However, for the health care worker without access to pulse oximetry, consideration of central cyanosis, reduced breath sounds, nasal flaring or grunting, age-specific tachycardia, wheezing, parent-reported drowsiness, or bronchial breathing as suggestive of hypoxaemic pneumonia, and thus severe disease, may prove useful in guiding management, hospital referral and use of oxygen therapy.

Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation in Vexas Syndrome: A Systematic Review and Meta-Analysis

Introduction: Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic (VEXAS) syndrome presents as an auto-inflammatory disorder with overlapping hematological and rheumatological features. It is caused by mutation in UBA1 and is often refractory to treatment. Corticosteroids and Janus Kinase (JAK) inhibitors are being used for symptomatic treatment. Here, we review the literature for the outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with VEXAS Syndrome. Methods: Following the preferred reporting items for systemic reviews and meta-analysis (PRISMA) guidelines, a comprehensive literature search was performed on three databases (PubMed, Cochrane Register of Controlled Trials, and Clinicaltrials.gov) using MeSH terms and keywords for “VEXAS Syndrome” AND “treatment” from the date of inception to May 31, 2023. Our search produced 100 results, and duplicates were removed. After excluding irrelevant and review articles during primary and secondary screening, six studies were included which mentioned the outcomes of allogeneic hematopoietic stem cell transplantation in adult VEXAS syndrome patients. Inter-study variance was calculated using the Der Simonian-Laird Estimator. Proportions along with 95% confidence Interval (CI) were extracted to compute pooled analysis using the ‘meta’ package by Schwarzer et al. in the R programming language (version 4.16-2). Results: A total of 18 patients from six studies reporting the outcomes of allogeneic HSCT in VEXAS syndrome patients were included for this systematic review and meta-analysis. (Table 1) The median age of the participants was 59.5 years (43-69) and all the patients were male. The median follow-up time was 11.6 months (0.4-67). Manifestations of the disease included myelodysplastic syndrome (MDS) 38.9% (n=7), refractory inflammatory symptoms 16.7% (n=3), transfusion dependent disease 16.7% (n=3), myelofibrosis (MF) 5.6% (n=1), MDS plus MF 5.6% (n=1), systematic lupus erythematosus 5.6% (n=1), multiple myeloma 5.6% (n=1), and IgG4-related disease 5.6% (n=1). Donor type was matched unrelated 50% (n=9), matched related 33.3% (n=6), mismatched unrelated 11% (n=2), and the donor type was unknown for one patient. The source of stem cells was peripheral blood and bone marrow in 83.3% (n=15) and 5.6 % (n=1) of the patients, respectively, while it was not reported for 11% (n=2) of the patients. The pooled overall survival (OS) at a median of 6 (0.4-67) months was 93.3% (95% CI 0.67-0.1, I 2=0%, p=0.64, n=18). The incidence of acute graft versus host disease (GvHD) grade I-II, acute GvHD grade III-IV, and chronic GvHD was 17% (n=3), 11% (n=2), and 11% (n=2), respectively. Among the 3 patients who died, one patient expired due to sepsis, multiorgan failure, and cardiac arrest, second patient due to infection, and the third patient due to severe hypoxic pneumonia. Conclusion: Allogeneic HSCT has shown promising results in treating patients with VEXAS syndrome with good overall survival and acceptable incidence of graft versus host disease. However, considering the small sample size more studies should be done to consolidate these findings.

Right heart echocardiography findings in hypoxic pneumonia patients during the COVID-19 pandemic in a South African population.

The right ventricle is affected by Coronavirus disease 19 (COVID-19) via multiple mechanisms, which can result in right ventricular dysfunction (RVD). This study aimed to provide an assessment of right heart function using conventional echocardiography and advanced strain imaging, in patients with hypoxic pneumonia during the COVID-19 pandemic. This study was an observational, prospective, single-centre study, including adults with hypoxic pneumonia, in two groups: COVID-19 pneumonia; and non-COVID-19 pneumonia. Bedside echocardiography was performed according to a pre-specified protocol and all right heart measurements were done as per standard guidelines. Right ventricular free wall strain (RVFWS) was measured using Philips® QLAB 11.0 speckle tracking software. Descriptive and comparative statistics were used to analyse data. Spearman Rank Order Correlations were used to determine the correlation between right ventricular (RV) parameters and clinical parameters. Univariate and multivariate logistic regression analyses were performed to characterize the predictors of in-hospital mortality. We enrolled 48 patients with COVID-19 pneumonia and 24 with non-COVID-19 pneumonia. COVID-19 patients were significantly older with a higher frequency of hypertension and diabetes and a trend towards a lower severity of illness score. Mean RVFWS yielded the highest estimates for the prevalence of RVD (81%), with no difference between the two pneumonia groups. Median Tricuspid Annular Plane Systolic Excursion (TAPSE) and right ventricular systolic excursion velocity (RVS') were not significantly different between COVID-19 (TAPSE 17.2 and RVS' 12), and non-COVID-19 pneumonia (TAPSE 17.8 and RVS' 12.1) with P values of 0.29 and 0.86, respectively. Non-COVID-19 pneumonia patients with moderate to severe hypoxaemia (PF < 150) were at greater risk of an elevated RV Systolic Pressure >30 mmHg respiratory rate = 3.25 (CI 1.35-7.82) on admission. Troponin levels discriminated between COVID-19 survivors (6 ng/L) and non-survivors (13 ng/L), P = 0.04. The mortality rate for COVID-19 was high (27%) compared to non-COVID-19 pneumonia (12%). Patients with COVID-19 pneumonia had a similar admission prevalence of RVD when compared to patients with non-COVID-19 pneumonia. Despite preserved traditional parameters of RV systolic function, RVFWS was diminished in both groups, and we propose that RVFWS serves as an important marker of the subclinical disease of RV.

Cytomegalovirus viral load as predictor of the clinical course of hypoxic pneumonia in children.

BACKGROUND: Children under 1 year of age with hypoxic pneumonia regularly have concurrent cytomegalovirus (CMV) viremia. In these children, the diagnosis of CMV-associated pneumonia and the prediction of an outcome are difficult. It is unclear whether quantification of blood CMV viral load (CMV-VL) can predict outcomes in these children.METHODS: This was a retrospective study including children (1-12 months of age), with detectable CMV-VL and hypoxic pneumonia admitted to the paediatric intensive care unit of Tygerberg Hospital, Cape Town, South Africa between 1 January 2014 and 31 December 2015. Clinical, radiological and biochemical data were collected.RESULTS: Of the 87 participants included (median age: 3.9 months, IQR 2.2-4.8), 35 were (40%) born prematurely. The median weight-for-age Z-score was -2.68 (IQR -3.0 to -0.83); 37 (43%) were severely underweight for age; 27 (31%) were HIV-positive, 3 were on ART. The median CMV-VL was log 4.0 (IQR 3.3-4.79); CMVhigh was defined as CMV-VL > median; CMV-VL < median was classified as CMVlow. Overall survival was 90%; 12 (15.4%) remained oxygen-dependent at Day 28 post-admission. There was no difference in survival, 24-h post-admission ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO₂:FiO₂), oxygen dependence or ventilation duration between CMVlow and CMVhigh. High-frequency oscillation ventilation duration was longer (P = 0.005) and Pneumocystis jirovecii (PJP) co-infection more frequent (P = 0.018) in CMVhigh.CONCLUSION: CMV-VL is unable to predict the clinical outcome in children with hypoxic pneumonia. Specific treatment for CMV should be considered in all children at risk of CMV-associated pneumonia with detectable CMV-VL.

A Diagnostic Dilemma: Was This Death Not a Case of an Infant with Cytomegalovirus Infection?

A 3-month-old female infant was referred to a teaching hospital with a 3-day history of fever, fast breathing, cough and 19 hours of yellowish discoloration of sclera. She was deeply jaundiced and febrile, had hepatosplenomegaly, was microcephalic and thrombocytopenic. Child was worked out and treated for bacterial pneumonia, atypical pneumonia, pulmonary tuberculosis, fungal opportunist infection, and heart failure. She was oxygen dependent throughout the 2 months of admission and deteriorateddespite all interventions. Considerations for viral infection was made later into her admission but delayed farther due to financialchallenges. Immunoglobins (IgG and IgM) for Cytomegalovirus (CMV) came up positive. Child had hypoxic pneumonia of which CMV is a documented cause in this age group and could have benefitted from empiric ganciclovir cover if clinicians had thought of it.There is the urgent need for clinicians to widen the differential list especially when response to conventional treatment is poor. Valid National Health Insurance card holders should benefit from a wider range of laboratory services if our aim to decrease infant mortality will materialize.

Effectiveness of 13-valent pneumococcal conjugate vaccine against hypoxic pneumonia and hospitalisation in Eastern Highlands Province, Papua New Guinea: An observational cohort study

SummaryBackgroundPneumonia is a leading cause of childhood mortality with Streptococcus pneumoniae a major contributor. Pneumococcal conjugate vaccines (PCVs) have been introduced into immunisation programs in many low- to middle-income countries (LMICs) yet there is a paucity of data evaluating the effectiveness in these settings. We assess the effectiveness of 13-valent PCV (13vPCV) against hypoxic pneumonia, hospitalisation and other clinical endpoints in children <5 years living in Eastern Highlands Province, Papua New Guinea (PNG).MethodsData from two consecutive prospective observational studies (2013–2019) enrolling children <60 months presenting with pneumonia were included. Hypoxic pneumonia was defined as oxygen saturations <90%. Outcomes included hospitalisation, severe clinical pneumonia and death. 13vPCV status was determined using written records. Logistic regression models were used to estimate the odds ratios of key outcomes by 13vPCV vaccination status adjusted for confounders using inverse probability of treatment weighting.FindingsData from 2067 children (median age; 9 months [IQR: 5–11]) were included. 739 children (36.1%) were hypoxic and 623 (30.4%) hospitalised. Twelve children (0.6% of total cohort) died in hospital. 670 children (32.7%) were fully 13vPCV-vaccinated. 13vPCV vaccination was associated with a 28.7% reduction (95% confidence interval [CI]: 9.9; 43.6%) in hypoxic pneumonia and a 57.4% reduction (38.0; 70.7%) in pneumonia hospitalisation.Interpretation13vPCV vaccination is effective against hypoxic pneumonia and pneumonia hospitalisation in PNG children. Strategies to improve access to and coverage of 13vPCV in PNG and other similar LMICs are urgently required.FundingFunded by Pfizer Global and the Bill & Melinda Gates Foundation.

Epidemiology of Hypoxic Community-Acquired Pneumonia in Children Under 5 Years of Age: An Observational Study in Northern India.

BackgroundCommunity-acquired pneumonia (CAP) is the leading cause of under-five mortality in India. An increased risk of mortality has been reported in cases of hypoxic pneumonia.MethodsThe primary objective of this study was to assess the proportion of children aged 2–59 months, hospitalized with hypoxic CAP, as well as socio-demographic, clinical, and radiological features associated with it. The secondary objective was to determine the risk of mortality among hospitalized cases of hypoxic CAP. This prospective, observational study was conducted in four districts of Northern India, between January 2015 and April 2021. A hospital-based surveillance network was established. Inclusion criteria were as follows: (a) child between 2 and 59 months, (b) hospitalization with symptoms of WHO-defined CAP, (c) resident of project district, (d) illness of <14 days, and (e) child had neither been hospitalized for this illness nor recruited previously. Children whose chest x-rays (CXRs) were either unavailable/un-interpretable and those that received any dose of pneumococcal conjugate vaccine-13 were excluded. Hypoxic pneumonia was defined as oxygen saturation <90% on pulse oximetry or requiring oxygen supplementation during hospital stay.ResultsDuring the study period, 71.9% (7,196/10,006) children of severe pneumonia were eligible for inclusion, of whom 35.9% (2,580/7,196) were having hypoxic pneumonia. Female gender and use of biomass fuel for cooking increased the odds of hypoxic CAP. Clinical factors like wheezing, pallor, tachypnea, low pulse volume, presence of comorbidity, general danger signs, severe malnutrition, and radiological finding of primary end-point pneumonia ± other infiltrates (PEP±OI) also increased the odds of hypoxic CAP in a conditional logistic regression model. Adjusted odds ratio for mortality with hypoxia was 2.36 (95% CI: 1.42–3.92).ConclusionAlmost one-third of cases hospitalized with severe CAP had hypoxia, which increased chances of mortality. Besides known danger signs, certain newer clinical signs such as pallor and wheezing as well as PEP+OI were associated with hypoxic CAP. Therefore, objective assessment of oxygen saturation must be done by pulse oximetry in all cases of CAP at the time of diagnosis.

Evaluation strategies for measuring pneumococcal conjugate vaccine impact in low-resource settings

Objectives : Pneumococcal conjugate vaccines (PCVs) are effective in reducing pneumococcal disease. We measured 13-valent PCV (PCV13) effect on different pneumococcal outcomes using diverse studies in Lao People’s Democratic Republic (Laos). Methods : Studies included: pre-PCV13 population-based record review of hospitalized childhood pneumonia cases; acute respiratory infection (ARI) study post-PCV13 to demonstrate effectiveness (VE) against hypoxic pneumonia; invasive pneumococcal disease (IPD) surveillance in all ages (2004-2018); carriage studies in children hospitalized with ARI (2013-2019); community carriage surveys pre- and post-PCV13. Results : Annual pneumonia incidence rate in children 2-59 months pre-PCV13 was 1,530 (95% confidence interval [CI] 1,477-1,584) per 100,000. Adjusted VE against hypoxic pneumonia was 37% (95% CI 6-57%). For IPD, 85% (11/13) of cases were due to vaccine-types prior to PCV13, and 43% (3/7) post-PCV13 in children aged <5 years; for ≥5 years, this was 61% (27/44) and 42% (17/40), respectively. For ARI cases, adjusted VE for vaccine-type carriage was 39% (95% CI 4-60) in <5 year olds; slightly higher than community surveys (23% [95% CI 4-39%] in 12-23 month olds). Conclusions : Despite limited baseline data, we found evidence of PCV13 impact on disease and carriage. Our approach could be used in similar settings to augment existing WHO PCV evaluation guidelines.

383Pneumococcal conjugate vaccine is effective against hypoxic pneumonia in Laos, Mongolia and Papua New Guinea

Abstract Background We describe a novel approach to determine PCV13 effectiveness (VE) against hypoxic pneumonia in children admitted with pneumonia in Lao People’s Democratic Republic (Laos), Mongolia and Papua New Guinea (PNG). Methods A 3-5 year prospective hospital-based observational study of children &amp;lt; =59 months admitted with pneumonia was undertaken. Pneumonia was defined using the 2013 WHO definition. Hypoxia was defined as an oxygen saturation &amp;lt;90% in room air or requiring oxygen supplementation during hospitalisation. PCV13 status was determined by written record. VE was calculated using logistic regression comparing the odds of hypoxia between vaccinated and under-vaccinated pneumonia cases. To handle potential confounding, a propensity score (PS) analysis using inverse probability of treatment weighting (IPW) was used. In Laos, multiple imputation (MI) analysis was undertaken for missing data. Results The VE against hypoxic pneumonia were: in Laos, unadjusted 23% (95% CI: -9, 46%; p = 0·14), IPW adjusted 37% (6, 57%; p = 0.02), MI and IPW adjusted 35% (7, 55%; p = 0.02); in Mongolia, unadjusted 33% (26, 40%; p &amp;lt; 0.001), IPW adjusted 33% (16, 47%; p &amp;lt; 0.001); and in PNG, unadjusted 6% (-15, 24%; p = 0.53), IPW adjusted 36% (17, 51%; p = 0.001). Conclusions Our novel approach shows that PCV13 is effective against hypoxic pneumonia. PCV13 will contribute to reducing child mortality. Key messages We describe a novel, single hospital-based approach for determining VE that can be applied to other similar settings. This is one of the first studies showing PCV13 to be effective against hypoxic pneumonia in children in Asia.

370Measuring pneumococcal conjugate vaccine impact in a low-resource setting with minimal baseline data

Abstract Background We aimed to measure 13-valent pneumococcal conjugate vaccine (PCV13) impact on various pneumococcal endpoints with minimal baseline data. Methods PCV13 was introduced in October 2013 in Lao People’s Democratic Republic. We implemented studies to evaluate PCV13 impact: retrospective record review of pneumonia cases for three years pre-PCV13; prospective study of acute respiratory infection (ARI) for 4.5 years post-PCV to demonstrate effectiveness against hypoxic pneumonia; invasive pneumococcal disease (IPD) surveillance (2004-2019); carriage in children hospitalised with ARI (2013-2019); and community carriage surveys pre- and two years post-PCV13. Results Annual incidence of hospitalized pneumonia pre-PCV13 in children 2-59 months was 1,530 (95% confidence interval [CI] 1,477-1,584) per 100,000. Vaccine effectiveness against hypoxic pneumonia was 37% (95% CI 6-57%). In children &amp;lt;5 years, 85% (11/13) of IPD cases were due to PCV13 serotypes pre-PCV13, and 43% (3/7) post-PCV13; and in individuals ≥5 years, 61% (27/44) and 42% (17/40), respectively. In hospitalised children, vaccine type carriage prevalence reduced from 20.0% (95% CI 15.2-24.9%) in 2013 to 12.8% (95% CI 8.5-17.1%) in 2019 with increasing vaccine coverage. Results were consistent with community carriage studies. Conclusions Despite limited baseline data in Laos, we found evidence of PCV13 impact using a variety of methods. Our approach could be used in similar settings to augment existing WHO guidelines. Key messages A combination of methods may be useful to determine the impact of vaccine introduction in countries with limited surveillance.

Non-invasive respiratory support strategies in COVID-19

Non-invasive respiratory support strategies in COVID-19

Helmet CPAP to treat hypoxic pneumonia outside the ICU: an observational study during the COVID-19 outbreak

BackgroundRespiratory failure due to COVID-19 pneumonia is associated with high mortality and may overwhelm health care systems, due to the surge of patients requiring advanced respiratory support. Shortage of intensive care unit (ICU) beds required many patients to be treated outside the ICU despite severe gas exchange impairment. Helmet is an effective interface to provide continuous positive airway pressure (CPAP) noninvasively. We report data about the usefulness of helmet CPAP during pandemic, either as treatment, a bridge to intubation or a rescue therapy for patients with care limitations (DNI).MethodsIn this observational study we collected data regarding patients failing standard oxygen therapy (i.e., non-rebreathing mask) due to COVID-19 pneumonia treated with a free flow helmet CPAP system. Patients’ data were recorded before, at initiation of CPAP treatment and once a day, thereafter. CPAP failure was defined as a composite outcome of intubation or death.ResultsA total of 306 patients were included; 42% were deemed as DNI. Helmet CPAP treatment was successful in 69% of the full treatment and 28% of the DNI patients (P < 0.001). With helmet CPAP, PaO2/FiO2 ratio doubled from about 100 to 200 mmHg (P < 0.001); respiratory rate decreased from 28 [22–32] to 24 [20–29] breaths per minute, P < 0.001). C-reactive protein, time to oxygen mask failure, age, PaO2/FiO2 during CPAP, number of comorbidities were independently associated with CPAP failure. Helmet CPAP was maintained for 6 [3–9] days, almost continuously during the first two days. None of the full treatment patients died before intubation in the wards.ConclusionsHelmet CPAP treatment is feasible for several days outside the ICU, despite persistent impairment in gas exchange. It was used, without escalating to intubation, in the majority of full treatment patients after standard oxygen therapy failed. DNI patients could benefit from helmet CPAP as rescue therapy to improve survival.Trial Registration: NCT04424992

Effect of ten-valent pneumococcal conjugate vaccine introduction on pneumonia hospital admissions in Fiji: a time-series analysis

In October, 2012, Fiji introduced routine infant immunisation with a ten-valent pneumococcal conjugate vaccine (PCV10) using three primary doses and no booster dose (3 + 0 schedule). Data are scarce for the effect of PCV in the Asia and Pacific region. We aimed to evaluate the effect of PCV10 on pneumonia hospital admissions in children younger than 5 years and adults aged 55 years and older in Fiji, 5 years after vaccine introduction. We did a time-series analysis assessing changes in pneumonia hospital admissions at three public tertiary hospitals in Fiji. Four pneumonia outcomes were evaluated: all-cause pneumonia, severe or very severe pneumonia, hypoxic pneumonia, and radiological pneumonia. Participants aged younger than 2 months, 2-23 months, 24-59 months, and 55 years and older were included. Data were extracted from the national hospital admission database according to International Classification of Diseases-tenth revision codes J10·0-18·9, J21, and J22 for all-cause pneumonia. Medical records and chest radiographs were reviewed for the main tertiary hospital to reclassify hospital admissions in children aged younger than 2 years as severe or very severe, hypoxic, or radiological pneumonia as per WHO definitions. Time-series analyses were done using the synthetic control method and multiple imputation to adjust for changes in hospital usage and missing data. Between Jan 1, 2007, and Dec 31, 2017, the ratio of observed cases to expected cases for all-cause pneumonia was 0·92 (95% CI 0·70-1·36) for children aged younger than 2 months, 0·86 (0·74-1·00) for children aged 2-23 months, 0·74 (0·62-0·87) for children aged 24-59 months, and 1·90 (1·53-2·31) in adults aged 55 years and older, 5 years after PCV10 introduction. These findings indicate a reduction in all-cause pneumonia among children aged 24-59 months and an increase in adults aged 55 years and older, but no change among children aged younger than 2 months. Among children aged 2-23 months, we observed declines of 21% (95% CI 5-35) for severe or very severe pneumonia, 46% (33-56) for hypoxic pneumonia, and 25% (9-38) for radiological pneumonia. Mortality reduced by 39% (95% CI 5-62) for all-cause pneumonia, bronchiolitis, and asthma admissions in children aged 2-23 months. The introduction of PCV10 was associated with a decrease in pneumonia hospital admissions in children aged 2-59 months. This is the first study in a middle-income country in the Asia and Pacific region to show the effect of PCV on pneumonia, filling gaps in the literature on the effects of PCV10 and 3 + 0 schedules. These data support decision making on PCV introduction for other low-income and middle-income countries in the region. Department of Foreign Affairs and Trade of the Australian Government.

The effectiveness of the 13-valent pneumococcal conjugate vaccine against hypoxic pneumonia in children in Lao People's Democratic Republic: An observational hospital-based test-negative study

BackgroundPneumococcal pneumonia is a leading cause of childhood mortality. Pneumococcal conjugate vaccines (PCVs) have been shown to reduce hypoxic pneumonia in children. However, there are no studies from Asia examining the effectiveness of PCVs on hypoxic pneumonia. We describe a novel approach to determine the effectiveness of the 13-valent PCV (PCV13) against hypoxia in children admitted with pneumonia in the Lao People's Democratic Republic. MethodsA prospective hospital-based, test-negative observational study of children aged up to 59 months admitted with pneumonia to a single tertiary hospital in Vientiane was undertaken over 54 months. Pneumonia was defined using the 2013 WHO definition. Hypoxia was defined as oxygen saturation <90% in room air or requiring oxygen supplementation during hospitalisation. Test-negative cases and controls were children with hypoxic and non-hypoxic pneumonia, respectively. PCV13 status was determined by written record. Vaccine effectiveness was calculated using logistic regression. Propensity score and multiple imputation analyses were used to handle confounding and missing data. FindingsThere were 826 children admitted with pneumonia, 285 had hypoxic pneumonia and 377 were PCV13-vaccinated. The unadjusted, propensity-score adjusted and multiple-imputation adjusted estimates of vaccine effectiveness against hypoxic pneumonia were 23% (95% confidence interval: -9, 46%; p=0•14); 37% (6, 57%; p=0•02) and 35% (7, 55%; p=0•02) respectively. InterpretationPCV13 is effective against hypoxic pneumonia in Asia, and should be prioritised for inclusion in national immunisation programs. This single hospital-based, test-negative approach can be used to assess vaccine effectiveness in other similar settings. FundingFunded by the Bill & Melinda Gates Foundation.

The 13-Valent Pneumococcal Conjugate Vaccine Is Effective Against Hypoxic Pneumonia in Children in Lao PDR: A Novel Method Using a Hospital-Based Observational Study

Background: Pneumococcal pneumonia is a leading cause of childhood mortality. Pneumococcal conjugate vaccines (PCVs) have been shown to reduce hypoxic pneumonia in children. However, there are no 13-valent PCV (PCV13) vaccine effectiveness (VE) studies on hypoxic pneumonia from Asia. We describe a novel approach to determine the effectiveness of PCV13 against hypoxic pneumonia in children admitted with pneumonia in the Lao People's Democratic Republic, a low-resource setting. Methods: A prospective hospital-based observational study of children up to 59 months old admitted with pneumonia to a single tertiary hospital in Vientiane was undertaken over 54 months. Pneumonia was defined using the 2013 WHO definition. Hypoxia was defined as an oxygen saturation <90% in room air or requiring oxygen supplementation during hospitalisation. PCV13 status was determined by written record. VE was calculated using logistic regression comparing the odds of hypoxia between vaccinated and undervaccinated pneumonia cases. To handle potential confounders a propensity score (PS) analysis using inverse probability of treatment weighting was used; for missing data, multiple imputation (MI) analysis was undertaken. Findings: There were 826 children admitted with pneumonia, 285 had hypoxic pneumonia and 377 were PCV13-vaccinated. The unadjusted, PS adjusted and MI adjusted VE against hypoxic pneumonia were 23% (95% confidence interval [CI]: -9, 46%; p=0·14); 37% ([CI]: 6, 57%; p=0·02) and 35% ([CI]: 7, 55%; p=0·02) respectively. Interpretation: This is the first apparent study to show PCV13 is effective against hypoxic pneumonia in Asia. This single hospital-based approach will enable other similar settings to test for VE. Funding Statement: This study received funding from the Bill & Melinda Gates Foundation (OPP1115490). Declaration of Interests: KM and CN receive grants from Pfizer, outside the submitted work. The Institute of Research for Development (IRD) and Aix-Marseille University funds both ADP and the HRSV testing. PN receives grants from the Wellcome Trust. JL receives funding from Bill and Melinda Gates foundation. All other authors declare no competing interests. The opinion presented in this paper is that of the authors and does not reflect Pfizer. We have not been paid by a pharmaceutical company to write this article. Ethics Approval Statement: This study was conducted according to the study protocol approved by the Oxford Tropical Research Ethics Committee (OxTREC reference:1050-13), Laos Ministry of Health National Ethics Committee for Health Research (No 061NECHR), the Ethics Review Committee of the WHO Regional Office for the Western Pacific Region (WPRO-ERC) (reference ID:2013.30.LAO.2.EPI) and by The Royal Children’s Hospital Human Resources Ethics Committee (HREC) (reference number:33177B).

Impact of the introduction of pneumococcal conjugate vaccination on pneumonia in The Gambia: population-based surveillance and case-control studies

SummaryBackgroundPneumococcal conjugate vaccines (PCVs) are used in many low-income countries but their impact on the incidence of pneumonia is unclear. The Gambia introduced PCV7 in August, 2009, and PCV13 in May, 2011. We aimed to measure the impact of the introduction of these vaccines on pneumonia incidence.MethodsWe did population-based surveillance and case-control studies. The primary endpoint was WHO-defined radiological pneumonia with pulmonary consolidation. Population-based surveillance was for suspected pneumonia in children aged 2–59 months (minimum age 3 months in the case-control study) between May 12, 2008, and Dec 31, 2015. Surveillance for the impact study was limited to the Basse Health and Demographic Surveillance System (BHDSS), whereas surveillance for the case-control study included both the BHDSS and Fuladu West Health and Demographic Surveillance System. Nurses screened all outpatients and inpatients at all health facilities in the surveillance area using standardised criteria for referral to clinicians in Basse and Bansang. These clinicians recorded clinical findings and applied standardised criteria to identify patients with suspected pneumonia. We compared the incidence of pneumonia during the baseline period (May 12, 2008, to May 11, 2010) and the PCV13 period (Jan 1, 2014, to Dec 31, 2015). We also investigated the effectiveness of PCV13 using case-control methods between Sept 12, 2011, and Sept 31, 2014. Controls were aged 90 days or older, and were eligible to have received at least one dose of PCV13; cases had the same eligibility criteria with the addition of having WHO-defined radiological pneumonia.FindingsWe investigated 18 833 children with clinical pneumonia and identified 2156 cases of radiological pneumonia. Among children aged 2–11 months, the incidence of radiological pneumonia fell from 21·0 cases per 1000 person-years in the baseline period to 16·2 cases per 1000 person-years (23% decline, 95% CI 7–36) in 2014–15. In the 12–23 month age group, radiological pneumonia decreased from 15·3 to 10·9 cases per 1000 person-years (29% decline, 12–42). In children aged 2–4 years, incidence fell from 5·2 to 4·1 cases per 1000 person-years (22% decline, 1–39). Incidence of all clinical pneumonia increased by 4% (–1 to 8), but hospitalised cases declined by 8% (3–13). Pneumococcal pneumonia declined from 2·9 to 1·2 cases per 1000 person-years (58% decline, 22–77) in children aged 2–11 months and from 2·6 to 0·7 cases per 1000 person-years (75% decline, 47–88) in children aged 12–23 months. Hypoxic pneumonia fell from 13·1 to 5·7 cases per 1000 person-years (57% decline, 42–67) in children aged 2–11 months and from 6·8 to 1·9 cases per 1000 person-years (72% decline, 58–82) in children aged 12–23 months. In the case-control study, the best estimate of the effectiveness of three doses of PCV13 against radiological pneumonia was an adjusted odds ratio of 0·57 (0·30–1·08) in children aged 3–11 months and vaccine effectiveness increased with greater numbers of doses (p=0·026). The analysis in children aged 12 months and older was underpowered because there were few unvaccinated cases and controls.InterpretationThe introduction of PCV in The Gambia was associated with a moderate impact on the incidence of radiological pneumonia, a small reduction in cases of hospitalised pneumonia, and substantial reductions of pneumococcal and hypoxic pneumonia in young children. Low-income countries that introduce PCV13 with reasonable coverage can expect modest reductions in hospitalised cases of pneumonia and a marked impact on the incidence of severe childhood pneumonia.FundingGAVI's Pneumococcal vaccines Accelerated Development and Introduction Plan, Bill & Melinda Gates Foundation, and UK Medical Research Council.

Percutaneous Dilatational Tracheostomy via Griggs Technique.

Tracheostomy is considered the airway management of choice for patients who need prolonged mechanical ventilation support. Percutaneous Dilatational Tracheotomy (PDT) is a technique that can be performed easily and rapidly at bedside and is particularly useful in the intensive care setting. The Griggs percutaneous tracheotomy is unique in its utilization of a guide wire dilator forceps. We aimed to describe the early perioperative and late postoperative complications of PDT using the Griggs technique in patients in the intensive care unit (ICU). This cross-sectional study was conducted on all patients who underwent tracheostomy in the ICU of the Imam Reza Hospital of Kermanshah, Iran, from June 2011 to June 2015. PDT was performed in 184 patients with the Griggs technique. Demographic variables, as well as perioperative and late postoperative complications were recorded. The mean age of patients was 57.3 ± 15.37 years. The most common primary causes of tracheostomy were hypoxic brain damage disorders (43.2%) and pneumonia (14.8%). Perioperative and early complications occurred in 16.7 % of procedures, of which 9.3% were bleedings (minor, significant and major). Furthermore, the incidence of late complications was 8.6%, including: stomal infection, difficult replace tracheostomy tube, tracheoesophageal fistula, tracheal stenosis, and tracheomalacia. PDT via Griggs technique is a safe, quick, and effective method. The low incidence of complications indicates that bedside percutaneous tracheostomy can be performed safely as a routine procedure for daily care implemented in the ICU.

Difficulties with interpreting cytokines/chemokines values in disease states

This edition of the journal features an interesting article on cytokine/chemokine profiles in HIV exposed infants with hypoxic pneumonia.

Cytokine profile and clinical correlates in HIV-exposed infants with severe (hypoxic) pneumonia

&lt;p&gt;&lt;strong&gt;Introduction. &lt;/strong&gt;Severe pneumonia in infants who are HIV-infected is a common problem in many parts of the developing world, especially sub-Saharan Africa. What has been missing from previous studies of severe pneumonia in HIV-infected infants, however, is a description of the host inflammatory response and cytokine/chemokine profile that accompanies this disease.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective.&lt;/strong&gt; To describe the cytokine profiles associated with severe hypoxic pneumonia in HIV-infected infants&lt;/p&gt;&lt;p class="Body1"&gt;&lt;strong&gt;Methods. &lt;/strong&gt;In a cohort of HIV-infected children diagnosed clinically with severe hypoxic pneumonia, paired serum and sputum cytokines were tested. A control group of HIV-infected children with bronchiectasis contributed matching controls.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results.&lt;/strong&gt; A total of 100 infants (mean age 2.8 months) with a clinical diagnosis of severe hypoxic pneumonia were included in this study. IP-10 was markedly elevated in both sputum (mean 560.77pg/ml) and serum (mean 9091.14pg/ml), while IP-10 was elevated in serum (mean 39.55 pg/ml), with both these cytokines being significantly higher than in stable children with HIV-related bronchiectasis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion. &lt;/strong&gt;This study of HIV-infected infants with severe hypoxic pneumonia suggests that IL-10 and IP-10 are associated with more severe lung disease. However, further investigation of this association is required.&lt;/p&gt;

Pneumocystis pneumonia in South African children diagnosed by molecular methods

BackgroundPneumocystis pneumonia (PCP) is an important cause of hospitalization and mortality in HIV-infected children. However, the incidence of PCP has been underestimated due to poor sensitivity of diagnostic tests. The use of polymerase chain reaction (PCR) for pneumocystis has enabled more reliable diagnosis. This study describes the incidence, clinical features and outcome of PCP in South African children diagnosed using PCR.MethodsA prospective study of children hospitalised in South Africa with suspected PCP was done from November 2006 to August 2008. Clinical, laboratory and radiological information were collected. Lower respiratory tract specimens were obtained for PCP immunofluorescence (IF), real- time PCR for pneumocystis, bacterial and mycobacterial culture. Nasopharyngeal aspirates were taken for immunofluorescence (IF), real-time PCR for pneumocystis and PCR for respiratory viruses. A blood specimen for bacterial culture and for cytomegalovirus PCR was taken. Children were followed for the duration of their hospitalisation and the outcome was recorded.Results202 children [median (interquartile range, IQR) age 3.2 (2.1– 4.6) months] were enrolled; 124 (61.4%) were HIV infected. PCP was identified in 109 (54%) children using PCR, compared to 43 (21%) using IF and Grocott staining (p < 0.0001). Most PCP cases (88, 81%) occurred in HIV-infected children. All 21 cases (19%) occurring in HIV- negative children had another risk factor for PCP. On logistic regression, predictive factors for PCP were HIV infection, lack of fever, high respiratory rate and low oxygen saturation whilst cotrimoxazole prophylaxis was protective (OR 0.24; 95% CI 0.1 to 0.5; p < 0.002). The case fatality of children with PCP was higher than those without PCP (32.1% versus 17.2%; relative risk 1.87; 95% confidence interval (CI) 1.11 – 3.15). Amongst HIV-infected children, a CD4 less than 15% was the only independent predictor of mortality.ConclusionsThe diagnostic yield for PCP is more than 2.5 times higher on PCR than other detection methods. PCP is a very common cause of severe hypoxic pneumonia and is associated with high mortality in HIV-infected African infants.