Challenges in the diagnosis of paediatric pneumonia in intervention field trials: recommendations from a pneumonia field trial working group

By Dina Goodman, Mary E Crocker, Farhan Pervaiz, Eric D McCollum,  Kyle Steenland, Suzanne M Simkovich, et al.

 

The Lancet Respiratory Medicine, December 1, 2019

 

Pneumonia is a leading killer of children younger than 5 years despite high vaccination coverage, improved nutrition, and widespread implementation of the Integrated Management of Childhood Illnesses algorithm. Assessing the effect of interventions on childhood pneumonia is challenging because the choice of case definition and surveillance approach can affect the identification of pneumonia substantially. In anticipation of an intervention trial aimed to reduce childhood pneumonia by lowering household air pollution, we created a working group to provide recommendations regarding study design and implementation. We suggest to, first, select a standard case definition that combines acute (≤14 days) respiratory symptoms and signs and general danger signs with ancillary tests (such as chest imaging and pulse oximetry) to improve pneumonia identification; second, to prioritise active hospital-based pneumonia surveillance over passive case finding or home-based surveillance to reduce the risk of non-differential misclassification of pneumonia and, as a result, a reduced effect size in a randomised trial; and, lastly, to consider longitudinal follow-up of children younger than 1 year, as this age group has the highest incidence of severe pneumonia.

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Assessment and Validation of Syndromic Case Definitions for Respiratory Syncytial Virus Infections in Young Infants A Latent Class Analysis

By Lalani, Karim MD; Yildirim, Inci, Phadke, Varun K. MD; Bednarczyk, Robert A.; Omer, Saad B.

The Pediatric Infectious Disease Journal, December 2019

 

Respiratory syncytial virus (RSV) is a major cause of pediatric morbidity and mortality worldwide. Standardized case definitions that are applicable to variety of populations are critical for robust surveillance systems to guide decision-making regarding RSV control strategies including vaccine evaluation. Limited data exist on performance of RSV syndromic case definitions among young infants or in high-resource settings.

The purpose of this study was to evaluate existing and potential syndromic case definitions for RSV among young infants in an urban, high-income setting using latent class analyses (LCA).

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Chest ultrasound compared to chest X‐ray for pediatric pulmonary tuberculosis

By Heuvelings CC, Bélard S, Andronikou S, Lederman H, Moodley H, Grobusch MP, Zar HJ.

Pediatric Pulmonology, December 2019

 

Chest ultrasound is increasingly used to radiologically diagnose childhood pneumonia, but there are limited data on its use for pulmonary tuberculosis (PTB).

 Children (up to 13 years) with suspected PTB were enrolled. Bedside chest ultrasound findings were compared to CXR. The analysis was stratified by PTB category: confirmed PTB (microbiologically confirmed), unconfirmed PTB (clinical diagnosis with negative microbiological tests), or unlikely PTB (other respiratory diseases with improvement without tuberculosis treatment).

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Safety and Efficacy of C-reactive Protein–guided Antibiotic Use to Treat Acute Respiratory Infections in Tanzanian Children: A Planned Subgroup Analysis of a Randomized Controlled Noninferiority Trial Evaluating a Novel Electronic Clinical Decision Algorithm (ePOCT)

By Kristina Keitel, Josephine Samaka, John Masimba, Hosiana Temba, Zamzam Said, Frank Kagoro, Tarsis Mlaganile, Willy Sangu, Blaise Genton, Valerie D’Acremont

Clinical Infectious Diseases, December 2019

This was a randomized (1:1) controlled noninferiority trial in 9 primary care centers in Tanzania (substudy of the ePOCT trial evaluating a novel electronic decision algorithm). Children aged 2–59 months with fever and cough and without life-threatening conditions received an antibiotic based on a CRP-informed strategy (combination of CRP ≥80 mg/L plus age/temperature-corrected tachypnea and/or chest indrawing) or current World Health Organization standard (respiratory rate ≥50 breaths/minute). The primary outcome was clinical failure by day (D) 7; the secondary outcomes were antibiotic prescription at D0, secondary hospitalization, or death by D30.

A total of 1726 children were included (intervention: 868, control: 858; 0.7% lost to follow-up). The proportion of clinical failure by D7 was 2.9% (25/865) in the intervention arm vs 4.8% (41/854) in the control arm (risk difference, –1.9% [95% confidence interval {CI}, –3.7% to –.1%]; risk ratio [RR], 0.60 [95% CI, .37–.98]). Twenty of 865 (2.3%) children in the intervention arm vs 345 of 854 (40.4%) in the control arm received antibiotics at D0 (RR, 0.06 [95% CI, .04–.09]). There were fewer secondary hospitalizations and deaths in the CRP arm: 0.5% (4/865) vs 1.5% (13/854) (RR, 0.30 [95% CI, .10–.93])..

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Rapid detection of respiratory organisms with FilmArray respiratory panel and its impact on clinical decisions in Shanghai, China, 2016‐2018

By Yiyi Qian, Jingwen Ai, Jing Wu, Shenglei Yu, Peng Cui, Yan Gao, Jialin Jin, Xinhua Weng, Wenhong Zhang

Influenza and Other Respiratory Viruses., December 1,  2019

In this study, we evaluated the diagnostic potential and clinical impact of an automated multiplex PCR platform (the FilmArray Respiratory Panel; FA-RP), specially designed for pathogen detection in respiratory tract infections in adults with unexplained pneumonia (UP).

Between October 2016 and March 2018, the positive rate obtained using FA-RP for UP was 76.8%. The primary pathogens in adults with UP were Influenza A/B (47.3%, 53/112). Compared with the patients before FA-RP was available, patients who underwent FA-RP testing had higher rates of antiviral drug use and antibiotic de-escalation during clinical treatment. FA-RP significantly decreased the total DDDs of antibiotic or antifungal drugs DDDs by 7 days after admission (10.6 ± 2.5 vs 14.1 ± 8.8, P < .01).

The FA-RP is a rapid and sensitive nucleic acid amplification test method for UP diagnosis in adults. The application of FA-RP may lead to a more accurately targeted antimicrobial treatment and reduced use of antibiotic/antifungal drugs.

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Prevalence and clinical impact of VIral Respiratory tract infections in patients hospitalized for Community-Acquired Pneumonia: the VIRCAP study

By Tatarelli P, Magnasco L, Borghesi ML, Russo C, Marra A, Mirabella M, Sarteschi G, Ungaro R, Arcuri C, Murialdo G, Viscoli C, Del Bono V, Nicolini LA

Internal and Emergency Medicine, November 30,  2019

Prevalence and clinical impact of viral respiratory tract infections (VRTIs) on community-acquired pneumonia (CAP) has not been well defined so far. The aims of this study were to investigate the prevalence and the clinical impact of VRTIs in patients with CAP. Prospective study involving adult patients consecutively admitted at medical wards for CAP and tested for VRTIs by real-time PCR on pharyngeal swab. Patients' features were evaluated with regard to the presence of VRTI and aetiology of CAP. Clinical failure was a composite endpoint defined by worsening of signs and symptoms requiring escalation of antibiotic treatment or ICU admission or death within 30 days. 91 patients were enrolled, mean age 65.7 ± 10.6 years, 50.5% female. 62 patients (68.2%) had no viral co-infection while in 29 patients (31.8%) a VRTI was detected; influenza virus was the most frequently identified (41.9%). The two groups were similar in terms of baseline features. In presence of a VRTI, pneumonia severity index (PSI) was more frequently higher than 91 and patients had received less frequently pre-admission antibiotic therapy (adjusted OR 2.689, 95% CI 1.017-7.111, p = 0.046; adjusted OR 0.143, 95% CI 0.030-0.670, p = 0.014). Clinical failure and antibiotic therapy duration were similar with regards to the presence of VRTI and the aetiology of CAP. VRTIs can be detected in almost a third of adults with CAP; influenza virus is the most relevant one. VRTI was associated with higher PSI at admission, but it does not affect patients' outcome.

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The Usefulness of Lung Ultrasound for the Aetiological Diagnosis of Community-Acquired Pneumonia in Children

By Vojko Berce, Maja Tomazin, Mario Gorenjak, Tadej Berce & Barbara Lovrenčič

Nature, November 29,  2019

The aetiology of community-acquired pneumonia (CAP) is not easy to establish. As lung ultrasound (LUS) has already proved to be an excellent diagnostic tool for CAP, we analysed its usefulness for discriminating between the aetiologically different types of CAP in children. We included 147 children hospitalized because of CAP. LUS was performed in all patients at admission, and follow-up LUS was performed in most patients. LUS-detected consolidations in viral CAP were significantly smaller, with a median diameter of 15 mm, compared to 20 mm in atypical bacterial CAP (p = 0.05) and 30 mm in bacterial CAP (p < 0.001). Multiple consolidations were detected in 65.4% of patients with viral CAP and in 17.3% of patients with bacterial CAP (p < 0.001). Bilateral consolidations were also more common in viral CAP than in bacterial CAP (51.9% vs. 8.0%, p < 0.001). At follow-up, a regression of consolidations was observed in 96.6% of patients with bacterial CAP and in 33.3% of patients with viral CAP (p < 0.001). We found LUS to be especially suitable for differentiating bacterial CAP from CAP due to other aetiologies. However, LUS must be interpreted in light of clinical and laboratory findings.

 

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Pneumonia mortality, comorbidities matter?

By Venceslau Pinto Hespanhola, Cristina Bárbarab

Pulmonology, November 29,  2019

Pneumonia remains one of the most important causes of mortality. In Portugal, it is the first cause of respiratory death, excluding lung cancer. This is a retrospective cohort study designed to seek for explanations, identifying the characteristics of patients and measure the impact of each one of them on the risk of dying from pneumonia. We analyzed demographic and clinical data of all patients (pts) with 18 years or older with pneumonia requiring hospitalization registered on the national health service registry of mainland Portugal over 2015. A total of 36366 patients corresponding to 40696 pneumonia hospital admissions in 2015 were analyzed. Most of the patients were very old (median age 80 years). Hospital mortality for pneumonia was higher among older (30,3% pts > 75 years). Pneumococcus is the more frequent bacterial isolate, reaching 41.2% of the isolates of total pneumonia cases. The frequency of pneumococcus decreases with aging; conversely, gram-negative bacteria and staphylococcus increase.

Pneumococcus is more frequently identified in the winter, closely related to influenza outbreaks. Gram-negative bacteria are more prevalent during the summer months. Diabetes, obesity, COPD, and tobacco smoking are not associated with an increased risk of dying from pneumonia. Patients older than 75 years; living in a senior house; or with chronic renal disease, lung cancer, metastatic disease, mobility impairment, cachexia, dementia, cerebrovascular disease, and ischemic heart disease are at greater risk of dying from pneumonia. Comorbidities contribute decisively to the risk of dying from pneumonia in the hospital, regardless of their type or origin.

 

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Whole-genome Sequencing Provides Data for Stratifying Infection Prevention and Control Management of Nosocomial Influenza A

By Sunando Roy, John Hartley, Helen Dunn, Rachel Williams, Charlotte A Williams, Judith Breuer

 

Clinical Infectious Diseases. November 15, 2019

 

We obtained all clinical samples from influenza (H1N1)-positive patients at the Great Ormond Street Hospital between January and March 2016. Samples were sequenced using targeted enrichment on an Illumina MiSeq sequencer. Maximum likelihood trees were computed for both whole genomes and concatenated HA/NA sequences. Epidemiological data was taken from routine IPC team activity during the period.

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Decreased plasma phospholipid concentrations and increased acid sphingomyelinase activity are accurate biomarkers for community-acquired pneumonia

By Haroon Arshad, Juan Carlos, López Alfonso, Raimo Franke, Katina Michaelis, Leonardo Araujo,  Aamna Habib, Yuliya Zboromyrska, Eva Lücke, Emilia Strungaru, Manas K. Akmatov, Haralampos Hatzikirou, Michael Meyer-Hermann, Astrid Petersmann, Matthias Nauck, Mark Brönstrup, Ursula Bilitewski, Laurent Abel, Jorg Sievers, Jordi Vila, Thomas Illig, Jens Schreiber, and Frank Pessler

 

Journal of Translational Medicine. November 11, 2019

 

We measured concentrations of 105 phospholipids, 40 acylcarnitines, and 4 ceramides, as well as acid sphingomyelinase activity, in plasma from patients with CAP (n = 29, sampled on admission and 4 subsequent time points), chronic obstructive pulmonary disease exacerbation with infection (COPD, n = 13) as a clinically important disease control, and 33 age- and sex-matched controls.

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Blood cultures versus respiratory cultures: Two different views of pneumonia

By Sarah Haessler, Peter K Lindenauer,  Marya D Zilberberg, Peter B Imrey, Pei-Chun Yu, Tom Higgins, Abhishek Deshpande, Michael B Rothberg

 

Clinical Infectious Diseases, October 26,2019

 

We studied adult patients discharged from 177 US hospitals from July 2010-June 2015, with principal diagnoses of pneumonia, or principal diagnoses of respiratory failure, ARDS, respiratory arrest, or sepsis with a secondary diagnosis of pneumonia, and who had blood or respiratory cultures performed. Demographics, treatment, microbiologic results and outcomes were examined.

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Improved diagnostics help to identify clinical features and biomarkers that predict Mycoplasma pneumoniae community-acquired pneumonia in children

By Patrick M Meyer Sauteur, Selina Krautter, Lilliam Ambroggio, Michelle Seiler, Paolo Paioni, Christa Relly, Riccarda Capaul, , Christian Kellenberger, Thorsten Haas, Claudine Gysin, et al.

 

Clinical Infectious Diseases, October 26,2019

 

This is a prospective cohort study of children, 3–18 years, with CAP from 2016–2017. Clinical features and biomarkers were compared between Mp-positive and -negative groups by Mann-Whitney U test or Fisher’s exact test, as appropriate. Area under the receiver operating characteristics curves (AUC) differences and optimal thresholds were determined by using the DeLong’s test and Youden’s J statistic, respectively.

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Rate and Predictors of Bacteremia in Afebrile Community-Acquired Pneumonia

By Sunando Roy, John Hartley, Helen Dunn, Rachel Williams, Charlotte A Williams, Judith Breuer

 

Chest. October 26, 2019

 

Although blood cultures (BCs) are the criterion standard for detecting bacteremia, the utility of BCs in patients with community-acquired pneumonia (CAP) is controversial. This study describes the proportion of patients with CAP and afebrile bacteremia and identifies the clinical characteristics predicting the necessity for BCs in patients who are afebrile.

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Detection of Pneumonia Pathogens from Plasma Cell-Free DNA

By Charles Langelier, Monica Fung, Saharai Caldera, Thomas Deiss, Amy Lyden, Brian C Prince, Paula Hayakawa Serpa, Farzad Moazed, Peter Chin-Hong, Joseph L DeRisi, and Carolyn S Calfee

 

American Journal of Respiratory and Critical Care Medicine, October 24,2019

 

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Usability and acceptability of an automated respiratory rate counter to assess children for symptoms of pneumonia: A cross‐sectional study in Ethiopia

By Charlotte Ward, Kevin Baker, Helen Smith, Alice Maurel, Dawit Getachew,  Tedila Habte, Cindy McWhorter, Paul LaBarre, Jonas Karlstrom, Jim Black,  Quique Bassat, Agazi Ameha, Abraham Tariku, Max Petzold, Karin Källander

 

Acta Pædiatrica. October 22, 2019

Manually counting respiratory rate (RR) is commonly practiced by community health workers to detect fast breathing, an important sign of childhood pneumonia. Correctly counting and classifying breaths manually is challenging, often leading to inappropriate treatment. This study aimed to determine the usability of a new automated RR counter (ChARM) by health extension workers (HEWs), and its acceptability to HEWs, first‐level health facility workers (FLHFWs) and caregivers in Ethiopia.

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Usability and acceptability of two automated pneumonia diagnostic aids: Findings from Ethiopia and Nepal

By Malaria Consortium. Published October 2019.

 

The Acute Respiratory Infection Diagnostic Aid (ARIDA) project introduced two automated respiratory rate counting aids in Ethiopia and Nepal to support frontline health workers to classify fast breathing: a symptom of pneumonia. This research brief discusses the usability of the devices, as well as their acceptability to frontline health workers and caregivers.

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Potential of Minimally Invasive Tissue Sampling for Attributing Specific Causes of Childhood Deaths in South Africa: A Pilot, Epidemiological Study

By Richard Chawana, Vicky Baillie, Alane Izu, Fatima Solomon, Quique Bassat, Dianna M Blau, Robert F Breiman, Martin Hale, Eric R Houpt, Sanjay G Lala, et al.

Clinical Infectious Diseases, October 15, 2019

 

An underlying CoD was determined for 99% of 127 cases, leading causes being congenital malformations (18.9%), complications of prematurity (14.2%), human immunodeficiency virus/AIDS (12.6%), diarrheal disease (8.7%), acute respiratory infections (7.9%), injuries (7.9%), and malignancies (7.1%). The main immediate CoD was pneumonia, sepsis, and diarrhea in 33.9%, 19.7%, and 10.2% of cases, respectively. Infection-related deaths were either an underlying or immediate CoD in 78.0% of cases. Community-acquired pneumonia deaths (n = 32) were attributed to respiratory syncytial virus (21.9%), Pneumocystis jirovecii (18.8%), cytomegalovirus (15.6%), Klebsiella pneumoniae (15.6%), and Streptococcus pneumoniae (12.5%). Seventy-one percent of 24 sepsis deaths were hospital-acquired, mainly due to Acinetobacter baumannii (47.1%) and K. pneumoniae (35.3%). Sixty-two percent of cases were malnourished.

 

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Multiplex Polymerase Chain Reaction Panel for Suspected Pertussis What About a Positive Mycoplasma pneumoniae Result?

By Michaël  Desjardins, Paméla Doyon-Plourde, Sarah Mousseau, Daniela Iachimov, Fabien Rallu, Caroline Quach. Published in The Journal of Pediatric Infectious Diseases. Published October 1, 2019.  

 

The use of bacterial multiplex polymerase chain reaction (PCR) in children with suspected pertussis sometimes yields unexpected positive results for Mycoplasma pneumoniae. We aimed to evaluate the clinical significance of positive M. pneumoniae results in this population. Retrospective cohort of consecutive patients with suspected pertussis tested with a bacterial multiplex PCR (including Bordetella pertussis and M. pneumoniae) between June 2015 and March 2017. Medical records were reviewed to compare demographics, clinical presentations and outcomes of patients positive for M. pneumoniae with those positive for B. pertussis and those with negative results, using multivariable logistic regression. A total of 1244 patients were included as follows: 56 (4.5%) with M. pneumoniae, 116 (9.3%) with B. pertussis and 1029 (82.7%) with negative results. Mean age was respectively 4.8 years, 6.5 years and 2.8 years (P < 0.05). Children with M. pneumoniae were less likely to present with cardinal symptoms of pertussis such as paroxysmal cough [adjusted odds ratio (OR): 0.19, 95% confidence interval (CI): 0.08–0.40) but were more likely to have fever (adjusted OR: 10.53, 95% CI: 3.54–39.49) and other nonspecific respiratory symptoms compared with children with B. pertussis. Children with M. pneumoniae had very similar clinical presentations to those with a negative PCR, but were more likely to have radiologically confirmed pneumonia (adjusted OR: 5.48, 95% CI: 2.96–9.99) and were less likely to be diagnosed with a concomitant viral infection (adjusted OR: 0.32, 95% CI: 0.07–0.99). In children with suspected pertussis, the detection of M. pneumoniae is clinically relevant. However, the impact of this finding on patients’ outcome is still unclear.

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Lung ultrasound in children: What does it give us?

By Sara Bobillo-Perez, Monica Girona-Alarcon, Javier Rodriguez-Fanjul, Iolanda Jordan, Monica Balaguer Gargallo

 

Paediatric Respiratory Reviews. September 30, 2019

 

Lung ultrasound (LUS), a non-invasive non-ionizing radiation tool, has become essential at the bedside in both adults and children, particularly in the critically ill. This manuscript reviews normal LUS patterns and the most important pathologies that LUS allows to diagnose. Normal LUS is represented by the pleural line, the lung-sliding and the A-lines and B-lines. These two last findings are artifacts derived from the pleural line. Pleural effusion appears as an anechoic collection. Pneumothorax is suspected when only A-lines are present, without lung-sliding and B-lines. Alveolo-interstitial syndrome is characterized by different degrees of confluent B-lines and can be present in different pathologies such as pulmonary edema and acute respiratory distress syndrome. The distribution of B-lines helps to differentiate between them. LUS is useful to evaluate the response to lung recruitment in pathologies such as acute respiratory distress syndrome or acute chest syndrome. The distribution of B-lines also appears to be useful to monitor the response to antibiotics in pneumonia. However, further studies are needed to further ascertain this evidence. LUS is also useful to guide thoracocentesis.

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Evolution of cytokines/chemokines in cases with community-acquired pneumonia and distinct etiologies

By Eduardo C. Nascimento‐Carvalho, Ângela G. Vasconcellos, Jorge Clarêncio, Daniela Andrade, Aldina Barra, et al.

 

Pediatric Pulmonology, September 25, 2019

 

Children less than 5‐years‐old hospitalized with CAP were prospectively investigated in Salvador, Brazil. Clinical data and biological samples were collected to investigate 20 etiological agents and to determine serum cytokines/chemokines levels on admission and 2 to 4 weeks later. Cases with pneumococcal infection received this diagnosis irrespective of also having other etiologies.

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