Viral Lower Respiratory Infections Research Articles

Feasibility of Training Clinical Officers in Point-of-Care Ultrasound for Pediatric Respiratory Diseases in Aweil, South Sudan

.Lower respiratory tract infections (LRTIs) are the leading cause of deaths in children < 5 years old worldwide, particularly affecting low-resource settings such as Aweil, South Sudan. In these settings, diagnosis can be difficult because of either lack of access to radiography or clinical algorithms that overtreat children with antibiotics who only have viral LRTIs. Point-of-care ultrasound (POCUS) has been applied to LRTIs, but not by nonphysician clinicians, and with limited data from low-resource settings. Our goal was to examine the feasibility of training the mid-level provider cadre clinical officers (COs) in a Médecins Sans Frontières project in South Sudan to perform a POCUS algorithm to differentiate among causes of LRTI. Six COs underwent POCUS training, and each subsequently performed 60 lung POCUS studies on hospitalized pediatric patients < 5 years old with criteria for pneumonia. Two blinded experts, with a tiebreaker expert adjudicating discordant results, served as a reference standard to calculate test performance characteristics, assessed image quality and CO interpretation. The COs performed 360 studies. Reviewers rated 99.1% of the images acceptable and 86.0% CO interpretations appropriate. The inter-rater agreement (κ) between COs and experts for lung consolidation with air bronchograms was 0.73 (0.63–0.82) and for viral LRTI/bronchiolitis was 0.81 (0.74–0.87). It is feasible to train COs in South Sudan to use a POCUS algorithm to diagnose pneumonia and other pulmonary diseases in children < 5 years old.

Refinement of estimates of mortality risk using the Radiologic Severity Index in hematologic malignancy patients with respiratory syncytial virus infection.

Immunocompromised hematologic malignancy (HM) patients experience high mortality after respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI). We measured radiologic severity to determine whether it could improve the performance of 60-day mortality models based only upon immunodeficiency severity. We studied 155 HM patients, including 84 hematopoietic cell transplant recipients, who developed RSV LRTI from 2001 to 2013. We measured immunodeficiency using lymphopenia (lymphocyte count <200cells/mm3 ), Immunodeficiency Severity Index (ISI), and Severe Immunodeficiency (SID) criteria. Radiologic severity was measured by the Radiologic Severity Index (RSI, range 0-72) at time of LRTI (baseline-RSI) and peak severity (peak-RSI). Delta-RSI was defined as the difference between baseline-RSI and peak-RSI. We used logistic regression models to measure the association of immunodeficiency and RSI with 60-day all-cause mortality, and measured model discrimination using areas under the receiver-operating characteristics curves, calibration using Brier scores, and explained variance using pseudo-R2 values. Forty-one patients died within 60days of RSV LRTI. Severe immunodeficiency was associated with higher mortality. Peak-RSI (odds ratio [OR] 1.06/point, 95% confidence interval [CI] 1.04-1.08), and delta-RSI (OR 1.07/point, 95% CI 1.05-1.10) were associated with 60-day mortality after RSV LRTI, but not baseline-RSI. Addition of peak-RSI or delta-RSI to baseline immunodeficiency improved the discrimination, calibration, and explained variance (P<0.001) of 60-day mortality models. Although baseline immunodeficiency in HM patients helps predict 60-day mortality after RSV LRTI, mortality risk estimates can be further refined by also measuring LRTI progression using RSI. RSI is well-suited as a marker of LRTI severity in RSV infection.

The Etiology of Viral Lower Respiratory Tract Infections at a Tertiary Hospital in Jordan over Five Years

Background&#x0D; Lower respiratory tract infection (LRTI) is the most common condition treated in primary care and is considered the third leading cause of death worldwide. The objective of our study is to determine the etiological agents that cause viral LRTI in Jordan, aiming to help physicians to choose the appropriate treatment strategy.&#x0D; Materials and Methods &#x0D; We conducted a retrospective study on patients who were admitted with the diagnosis of LRTI between January, 2011 and January, 2016. We used Fast-track Diagnostics (FTD)® Respiratory 21 Kit (Fast-track Diagnostics, Luxembourg) real-time PCR to determine the viral etiology of LRTI, and we investigated pandemic H1N1 2009 swine flu virus using rapid test PCR.&#x0D; Results &#x0D; This study involved 495 patients with a mean age of 57.79 ± 18.43 years. The causative agents were identified in 157 patients out of 495 patients (31.7%). FTD real-time PCR was done for 170 patients, and the test was positive for seasonal Influenza A virus in 7.1% of patients, influenza B in 4.1%, RSV in 4.7%, metapneumovirus in 4.1%, adenovirus in 4.1%, corona 229E/NL63 in 4.1%, parainfluenza virus in 7.6%, and rhinovirus in 3.5%. The percent of cases who were positive for pandemic H1N1 2009 swine flu virus was 4.2%. The rate of ICU admission was 16.8%, and the mortality rate of LRTI was as low as 3.64%.&#x0D; Conclusions&#x0D; Viral LRTI is more common in winter season in Jordan, especially in January. Remarkably, Influenza A and Parainfluenza viruses were the main viral causative agents for LRTI in our study.

The Use of Aerosolized Ribavirin in Respiratory Syncytial Virus Lower Respiratory Tract Infections in Adult Immunocompromised Patients: A Systematic Review.

Introduction: Respiratory syncytial virus (RSV)-associated lower respiratory tract infection (LRTI) is a concern in immunocompromised patients. Aerosolized ribavirin (RBV AER) is used for treatment of RSV LRTI; however, adverse events and rising drug costs remain a challenge for patient management. The purpose of this systematic review is to summarize the efficacy and adverse event profile of RBV AER for the treatment of hospitalized RSV LRTI in immunocompromised adult patients. Methods: A Medline/PubMed, Embase, Google Scholar, Clinicaltrials.gov, and Cochrane Library database search was conducted from 1966 to January 2019 for the use of RBV AER. Search strategy: [(ribavirin OR ICN1229) AND ("administration, oral" OR "oral" OR "administration, inhalation" OR "inhalation)] AND ("respiratory tract infection" OR "pneumonia"). Studies were reviewed if adult patients were hospitalized, immunocompromised, had RSV LRTI, received RBV AER, and included the outcome of mortality and/or adverse reactions. Methodological quality was assessed using the Cochrane Collaboration GRADE approach. Results: A total of 1787 records were identified and 15 articles met inclusion criteria: hematopoietic stem cell transplant (HSCT)/bone marrow transplant (n = 8), other malignancy/neutropenic (n = 2), solid organ transplant (n = 5). All of the trials are observational with a low quality rating; therefore, a meta-analysis was not performed. The 30-day mortality in studies that contain >10 patients with HSCT, malignancy, and transplant range from 0 to 15.4%, 6.3%, and 0 to 27%, respectively. Improved mortality was cited in 4 studies when RBV AER started before mechanical ventilation or within 2 weeks of symptom onset. Only 3 studies had comparative mortality data with RBV AER and RBV PO. Adverse reactions were reported in 5 studies and included psychiatric manifestations (anxiety, depression, feeling of isolation; n = 14), wheezing/bronchospasm (n = 6), snowflakes/hail blowing in face (n = 6), and precipitation in ventilator tubing (n = 5). Conclusion: There is a lack of high quality, comparative trials on the use of RBV AER for the treatment of RSV LRTI in adult hospitalized immunocompromised patients. There may be a mortality benefit when RBV AER is initiated early after diagnosis or prior to mechanical ventilation, but requires further study. Patient isolation and psychological effects must be weighed against the benefit of therapy.

Evaluation of a New Molecular Point-of-Care-Testing (POCT) System to Shorten Antibiotic Treatment Duration in Hospitalized Patients with Lower Respiratory Tract Infections: A Randomized Clinical Trial

Background: Many unnecessary antibiotics are prescribed to patients with viral lower respiratory tract infections (LRTIs). The FilmArray® Respiratory Panel is a new molecular point-of-care testing (POCT) procedure, which provides faster and comprehensive identification of viruses and atypical pathogens. But whether POCT could potentially help optimize antibiotics use for LRTIs remains a controversial topic. Methods: In this single-center, open-label, randomized controlled study, hospitalized adult patients diagnosed with community-acquired pneumonia, acute exacerbation of chronic obstructive pulmonary disease, or acute exacerbation of bronchiectasis were enrolled in the study. Patients were randomly assigned to the POCT group or the routine real-time PCR assays (control) group. The primary outcome was the duration of intravenous antibiotics used during hospitalization. The secondary outcomes included the length of hospital stay and the total cost of hospitalization. We also evaluated the effects of a combination of viral testing with serum procalcitonin (PCT) levels on the duration of antibiotic use. Findings: Between October 2017 and July 2018, 761 eligible patients were enrolled (383 in the POCT group and 378 in the control group). The positive rates of virus and atypical pathogens in the POCT group was 31·7% (121/383) compared with 17·2% (32/378) in the control group (difference 14·5%, 95% CI 7·3% to 21·6%; P = 0·0003). The median duration of intravenous antibiotics in the POCT group was significantly shorter than that in the control group (7·0 days [IQR, 5·0, 9·0] in the POCT group vs 8·0 [IQR, 6·0, 11·0] days in the control group; mean difference -1·6 days, 95% CI -2·2 to -1·0 days; P < 0·0001). The median length of hospital stay of patients in the POCT group was significantly shorter than that in the control group (8·0 days [IQR, 6·0, 10·0] in the POCT group vs 9·0 days [IQR, 7·0, 12·0] in the control group; mean difference -1·1 days, 95% CI -1·7 to -0·5 days; P < 0·0001). The median cost of hospitalization was significantly lower in the POCT group ($1,761·1 [IQR, 1,261·1, 2581·3] in the POCT group vs $2,017·3 [IQR, 1,442·9, 2,894·3] in the control group). Furthermore, the median duration of intravenous antibiotic treatment was significantly shorter and the median cost of hospitalization was significantly lower in patients with a positive FilmArray Respiratory Panel test result and PCT < 0·25 ng/mL compared with a negative FilmArray test result and PCT ≥ 0·25 ng/mL (6·0 days [IQR, 4·5, 7·5] vs 7·0 days [IQR, 6·0, 10·5]; mean difference 2·3 days, 95% CI 0·6 to 4·0 days; P = 0·0079 and $1,374·6 [IQR, 1,034·2, 1991·7] vs $1,939·6 [IQR, 1,307·6, 2,955·7]). Interpretation: The use of POCT testing for respiratory viruses and atypical pathogens could help to optimize antibiotic use and improve clinical outcomes in hospitalized LRTI patients. Clinical Trial Number: clinicaltrials.gov Identifier: NCT03391076. Funding Statement: National Science Grant for Distinguished Young Scholars (81425001/H0104) Declaration of Interests: We declare that we have no competing interests. Ethics Approval Statement: The study was approved by the Ethics Committee of CJFH. Written informed consent was obtained from each participant before data collection.

A Post-Hoc Analysis of the Randomized, Double-Blind, Placebo-Controlled Multicenter Phase 2 Trial to Examine the Effects of DAS181 in Hematopoeitic Cell Transplant (HCT) Recipients with Parainfluenza Virus (PIV) Lower Respiratory Tract Infection (LRTI) on Supplemental Oxygen (SO)

Background PIV infections are an important cause of morbidity and mortality in HCT recipients. DAS181, a sialidase fusion protein, has demonstrated activity in pre-clinical and clinical studies. Methods Adult immunocompromised patients (IC), including HCT recipients, diagnosed with PIV LRTI on chest imaging and required SO ≥ 2L/min were randomized 2:1 (stratified by mechanical ventilation [MV] at baseline) to nebulized DAS181 (4.5 mg in 3.5mL/day) or matching placebo for up to 10 consecutive days. The primary endpoint was the proportion of patients reaching clinical stability survival (CSS, defined as alive, resolution of SO requirement, and normalization of vital signs) by Day 45. An exploratory end point of proportion to return to room air (RTRA) was analyzed. Results Out of the 110 patients randomized, 64 HCT recipients received study drug (43 DAS181 and 21 placebo). Median age was 53 years (range, 19-77), half were male (50%), white (84%), and had received an allogeneic HCT (86%). A post-hoc analysis of the HCT recipients on SO showed that day 45 CSS was achieved by 46.5% of DAS181-treated patients compared to 33.3% of placebo (p = 0.23). In addition, when compared to placebo, HCT recipients on SO who received DAS181 within 1 year from transplant were more likely to achieve CSS at day 45 (48.4% vs. 12.5%; p = 0.071), were more likely to RTRA at day 28 and day 45 (53.3% vs. 12.5%; p = 0.04 and 60% vs. 25%; p = 0.086, respectively), more likely to be discharged from the hospital by day 45 (64.5% vs. 12.5%; p = 0.011), and had a trend for lower mortality at day 45 (25.8% vs. 62.5%, p = 0.064). The rate of adverse events was similar in both treatment groups. Conclusion DAS181 was well tolerated and a post-hoc analysis in HCT recipients with PIV LRTI on SO within 1 year of transplant, DAS181 was effective (RTRA) and showed a trend towards lower mortality by day 45. DAS181 was granted Breakthrough Therapy Designation for the treatment of PIV LRTI in IC patients and a phase 3 trial is being planned.

Estimating seasonal onsets and peaks of bronchiolitis with spatially and temporally uncertain data.

RSV bronchiolitis (an acute lower respiratory tract viral infection in infants) is the most common cause of infant hospitalizations in the United States (US). The only preventive intervention currently available is monthly injections of immunoprophylaxis. However, this treatment is expensive and needs to be administered simultaneously with seasonal bronchiolitis cycles in order to be effective. To increase our understanding of bronchiolitis timing, this research focuses on identifying seasonal bronchiolitis cycles (start times, peaks, and declinations) throughout the continental US using data on infant bronchiolitis cases from the US Military Health System Data Repository. Because this data involved highly personal information, the bronchiolitis dates in the dataset were "jittered" in the sense that the recorded dates were randomized within a time window of the true date. Hence, we develop a statistical change point model that estimates spatially varying seasonal bronchiolitis cycles while accounting for the purposefully introduced jittering in the data. Additionally, by including temperature and humidity data as regressors, we identify a relationship between bronchiolitis seasonality and climate. We found that, in general, bronchiolitis seasons begin earlier and are longer in the southeastern states compared to the western states with peak times lasting approximately 1 month nationwide.

871. Symptomatic Respiratory Syncytial Virus and Adenovirus Upper Respiratory Tract Infections Increase the Risk of Invasive Aspergillosis After Allogeneic Hematopoietic Cell Transplantation

BackgroundInvasive aspergillosis (IA) is a serious infectious complication following hematopoietic cell transplantation (HCT). Few studies have reported respiratory viral infections (RVIs) as a risk factor for developing IA, and data regarding specific viruses is sparse. We examined whether specific respiratory viruses were associated with increased risk of developing IA post-HCT.MethodsIn a longitudinal surveillance study of RVIs among allogeneic HCT recipients conducted 2005–2010, weekly post-HCT nasal washes were collected through day 100, then every 3 months, and whenever respiratory symptoms occurred through 1 year post-HCT. Nasal and bronchoalveolar lavage (BAL) samples were tested by multiplex PCR for respiratory syncytial virus (RSV), parainfluenza viruses (PIV)1–4, influenza A/B, human metapneumovirus, adenovirus (ADV), and human rhinoviruses, and coronaviruses. Only respiratory virus detections with symptoms were counted as RVI. Separate Cox proportional hazards models were used to examine adjusted associations between each RVI and the development of first proven/probable IA by 1-year post-HCT.ResultsAmong 437 patients who survived >28 days following HCT, 39 patients developed IA by 1-year post-HCT (median 87 days, range 5–283). After adjusting for age at HCT, neutropenia, high-grade CMV viremia, and HLA status (matched related vs. others) or severe acute graft-versus-host disease (GVHD Grade 0–2 vs. 3–4), RSV and ADV upper respiratory tract infections (URTI) were associated with increased risk of developing IA (figure). Detection of any respiratory virus in the BAL was associated with IA (P < 0.001).ConclusionRSV and ADV URTI are significant risk factors for development of IA post-HCT; the association between PIV URTI and development of IA approached statistical significance. Viral lower respiratory tract infection was associated with IA. Our data provide a rationale to assess IA as an endpoint in preventive studies of novel agents for respiratory viruses and further emphasize the importance of effective infection prevention practices for RVIs after HCT. Disclosures J. Chien, Gilead Sciences, Inc.: Employee and Shareholder, Salary and stocks. A. Waghmare, Ablynx: Investigator, Research support. J. Englund, Gilead: Consultant and Investigator, Consulting fee and Research support. Novavax: Investigator, Research support. GlaxoSmithKline: Investigator, Research support. Alios: Investigator, Research support. MedImmune: Investigator, Research support. M. Boeckh, Asun Biopharma: Consultant and Investigator, Consulting fee and Research support. Gilead Sciences: Consultant and Investigator, Consulting fee and Research support. Chimerix Inc.: Consultant and Investigator, Consulting fee and Research support. Humabs: Consultant, Consulting fee. GSK: Investigator, Research support.

1715. A Randomized, Double-Blind, Placebo-Controlled Multicenter Phase 2 Trial to Examine the Effects of DAS181 in Immunocompromised (IC) Patients With Parainfluenza Virus (PIV) Lower Respiratory Tract Infection (LRTI) on Supplemental Oxygen (SO)

BackgroundPIV infections are an important cause of morbidity and mortality in IC patients. DAS181, a sialidase fusion protein, has demonstrated activity in preclinical and clinical studies.MethodsAdult IC patients diagnosed with PIV LRTI on chest imaging and required SO ≥ 2 L/minute were randomized 2:1 (stratified by mechanical ventilation [MV] at baseline) to nebulized DAS181 (4.5 mg in 3.5 mL/day) or matching placebo for up to 10 days. The primary endpoint was the proportion of patients reaching clinical stability survival (CSS, defined as alive, resolution of SO requirement, and normalization of vital signs) by Day 45.ResultsFrom 2014 to 2016, 110 patients were randomized and received study drug (74 DAS181 and 36 placebo). Median age was 57 years (range, 18–85). The majority were hematopoietic cell transplant (HCT) recipients (74), followed by hematological malignancy/solid tumor patients on chemotherapy (29), and lung transplant recipients (7). Day 45 CSS was achieved by 39.2% of DAS181-treated patients compared with 31.4% of placebo (P = 0.29), while the proportion among non-MV patients was 45.0% vs. 31.0% (difference −14.0%, P = 0.15), respectively. Time to CSS in the non-MV stratum was shorter in DAS181-treated patients (figure). Median change in nasopharyngeal PIV viral load by Day 10 and median hospitalization days were −1.44 vs. −0.68 log10 (P = 0.51) and 13.5 vs. 21 days (P = 0.10) for DAS181 and placebo, respectively. Mean absolute increase from baseline FEV1% predicted was 16.82 for DAS181 vs. 2.02 for placebo (P = 0.001). Post-hoc analysis on the probability to return to room air (RTRA) suggested that DAS181 reduced SO need in the non-MV stratum after Day 21 (P = 0.09). HCT recipients within 360 days from transplant had a 40.8% treatment effect on RTRA at Day 28 (P = 0.04) and 36.7% on mortality at Day 45 when compared with placebo (P = 0.06). The rate of adverse events was similar in both treatment groups. Day 45 all-cause mortality was comparable in both groups (32.4% DAS181 vs. 31.4% placebo).ConclusionDAS181 was well tolerated and showed a signal for clinical efficacy in IC patients with PIV LRTI. DAS181 was granted Breakthrough Therapy Designation for the treatment of PIV LRTI in IC patients and a phase 3 trial is being planned. Disclosures R. F. Chemaly, Ansun Biopharma: Consultant and Investigator, Consulting fee and Research grant. R. Moss, Ansun Biopharma: Employee, Salary. F. M. Marty, Ansun Biopharma: Investigator, Research grant. C. R. Wolfe, Ansun Biopharma: Investigator, Research grant. S. J. Lawrence, Ansun Biopharma: Investigator, Research grant. S. Dadwal, Ansun Biopharma: Investigator, Research grant. R. Soave, Ansun Biopharma: Investigator, Research grant. J. Hwang, Ansun Biopharma: Employee, Salary. S. Hawley, Ansun Biopharma: Employee, Salary. R. Routh, Ansun Biopharma: Employee, Salary. J. Ho, Ansun Biopharma: Employee, Salary. G. Wang, Ansun Biopharma: Employee, Salary. N. Chang, Ansun Biopharma: Employee, Salary. M. Boeckh, Ansun Biopharma: Consultant and Investigator, Consulting fee and Research support.

Comparative Efficacy of Nebulized 7% Hypertonic Saline versus 3% Hypertonic Saline in Children with Acute Bronchiolitis

Background: Acute bronchiolitis is an acute viral lower respiratory tract infection in early childhood and is the leading cause of hospitalization in infants below 2 years of age. Being a viral disease, there is no effective treatment of this problem other than supportive care. To provide this care, both 3% hypertonic saline and 7% hypertonic saline has been used and found effective. However, which option is more effective to reduce clinical severity and length of hospital stay, still remain unsettled.Objective: To determined the efficacy of 7% hypertonic saline in children with acute bronchiolitis.Methodology: The study was a randomized controlled trial and carried out in the Department of Paediatrics, Dhaka Medical College Hospital (DMCH), Dhaka between January 2015 to December 2016. A total of 135 children from 1 month to 2 years of age irrespective of sex with clinical presentation of acute bronchiolitis admitted in the paediatrics ward of DMCH were included in the study and were randomly assigned to either 7% nebulized hypertonic saline (Group-I = 45) or to 3% nebulized hypertonic saline (Group-II = 90) in ratio (1:2). The main outcome variables were clinical severity score and length of hospital stay. The outcome was evaluated at 12 hourly and 24 hourly intervals till discharge (up to 120 hours)Result: In this study both groups were almost similar with respect to their demographic characteristics like age and sex and baseline clinical characteristics. The study demonstrated that respiratory rate score, wheezing score, retraction score, general condition score and clinical severity score of both treatment modalities were reduced. Children of group-I(7% HS) 40(88.9%) recovered at the end of 72 hours where as 67(74.4%) of the children of group-II(3% HS) recovered from the disease during the same period. Length of hospital stay was shorter in 7% hypertonic saline group compared to 3% hypertonic saline group (56.36±16.33 hours vs63.07±21.48 hours, p=.067). The patients of 7% hypertonic saline group required a shorter duration of oxygen therapy compared to 3% hypertonic saline group (16.53±3.98) hours vs (20.25± 4.15) hours, (p=0.109) respectively.Conclusion: Nebulized 7% hypertonic saline as well as 3% hypertonic saline both were effective in acute bronchiolitis and found no significant difference in efficacy between these options in terms of reducing clinical severity, length of hospital stay and duration of oxygen therapy. No side effect were observed in either group.J Dhaka Medical College, Vol. 26, No.2, October, 2017, Page 153-156

Association of Procalcitonin Value and Bacterial Coinfections in Pediatric Patients With Viral Lower Respiratory Tract Infections Admitted to the Pediatric Intensive Care Unit.

Our primary objective was to determine the utility of procalcitonin (PCT) in detection of bacterial coinfection in children < 5 years admitted to the pediatric intensive care unit with viral lower respiratory tract infection (LRTI). Electronic medical record review of children < 5 years admitted to the pediatric intensive care unit with a viral LRTI who also had at least 1 PCT concentration measurement. Seventy-five patients were admitted to the intensive care unit and met the inclusion criteria for this investigation. The PCT threshold concentrations of 0.9, 1, 1.4, and 2 ng/mL were found to be statistically significant in determining the presence of a bacterial coinfection. The PCT concentration with the most utility was 1.4 ng/mL with sensitivity, specificity, positive and negative predictive values of 46%, 83%, 68%, and 76%, respectively. For patients with serial PCTs, the second PCT correctly influenced treatment decisions for 11 of 25 patients (44%). A PCT value of 1.4 ng/mL determined the presence of a bacterial coinfection primarily owing to the high specificity and negative predictive value. Our data add evidence to the relatively high negative predictive value of PCT concentrations in identifying patients with bacterial coinfection, specifically in the case of viral LRTI. In addition, our preliminary data indicate serial PCT measurements may help further influence correct treatment decisions. Prospective, controlled studies are warranted to validate an appropriate PCT threshold concentration to help in identifying bacterial coinfection as well as to further explore the role of serial PCT values in determining the absence or presence of a bacterial coinfection.

Antibiotic Overuse in Children with Respiratory Syncytial Virus Lower Respiratory Tract Infection

Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infections (LRTI) during the first year of life. Antibiotic treatment is recommended in cases suspected of bacterial coinfection. The aim of this prospective study was to estimate the incidence of bacterial coinfections and the amount of antibiotic overuse in children infected with RSV using expert panel diagnosis. Children 1 month of age and over with LRTI or fever without source were prospectively recruited in hospitals in the Netherlands and Israel. Children with confirmed RSV infection by Polymerase Chain Reaction (PCR) on nasal swabs were evaluated by an expert panel as reference standard diagnosis. Three experienced pediatricians distinguished bacterial coinfection from simple viral infection using all available clinical information, including all microbiologic evaluations and a 28-day follow-up evaluation. A total of 188 children (24% of all 784 recruited patients) were positive for RSV. From these, 92 (49%) were treated with antibiotics. All 27 children (29%) with bacterial coinfection were treated with antibiotics. Fifty-seven patients (62%) were treated with antibiotics without a diagnosis of bacterial coinfection. In 8 of the 92 (9%), the expert panel could not distinguish simple viral infection from bacterial coinfection. This is the first prospective international multicenter RSV study using an expert panel as reference standard to identify children with and without bacterial coinfection. All cases of bacterial coinfections are treated, whereas as many as one-third of all children with RSV LRTI are treated unnecessarily with antibiotics.

Lower Respiratory Tract Infection in Pediatrics, Treatment Approaches: Review Article

This article outlines the etiology and epidemiology of childhood acute lower respiratory tract infections (ALRI), preventative measures, and management of the most common and important cause of ALRI, pneumonia. Method: We conducted a review to determine the proper treatment of Lower respiratory tract infection in pediatrics. In May 2018 we searched PubMed, Medline, and EMBASE databases Conclusion: Viral lower respiratory system infections in newborns and children are important clinical and socioeconomic problems worldwide. Viral lower respiratory system infections are mild and self-restricting in many cases. Specific patient groups are at risk of a severe program of illness, although formerly healthy infants with a viral lower respiratory tract infection may additionally develop extreme illness.

Distal respiratory tract viral infections in young children trigger a marked increase in alveolar mast cells.

Viral infections predispose to the development of childhood asthma, a disease associated with increased lung mast cells (MCs). This study investigated whether viral lower respiratory tract infections (LRTIs) can already evoke a MC response during childhood.Lung tissue from young children who died following LRTIs were processed for immunohistochemical identification of MCs. Children who died from nonrespiratory causes served as controls. MCs were examined in relation to sensitisation in infant mice exposed to allergen during influenza A infection.Increased numbers of MCs were observed in the alveolar parenchyma of children infected with LRTIs (median (range) 12.5 (0–78) MCs per mm2) compared to controls (0.63 (0–4) MCs per mm2, p=0.0005). The alveolar MC expansion was associated with a higher proportion of CD34+ tryptase+ progenitors (controls: 0% (0–1%); LRTIs: 0.9% (0–3%) CD34+ MCs (p=0.01)) and an increased expression of the vascular cell adhesion molecule (VCAM)-1 (controls: 0.2 (0.07–0.3); LRTIs: 0.3 (0.02–2) VCAM-1 per mm2 (p=0.04)). Similarly, infant mice infected with H1N1 alone or together with house dust mite (HDM) developed an increase in alveolar MCs (saline: 0.4 (0.3–0.5); HDM: 0.6 (0.4–0.9); H1N1: 1.4 (0.4–2.0); HDM+H1N1: 2.2 (1.2–4.4) MCs per mm2 (p<0.0001)). Alveolar MCs continued to increase and remained significantly higher into adulthood when exposed to H1N1+HDM (day 36: 2.2 (1.2–4.4); day 57: 4.6 (1.6–15) MCs per mm2 (p=0.01)) but not when infected with H1N1 alone.Our data demonstrate that distal viral infections in young children evoke a rapid accumulation of alveolar MCs. Apart from revealing a novel immune response to distal infections, our data may have important implications for the link between viral infections during early childhood and subsequent asthma development.

DETECTION OF RESPIRATORY SYNCYTIAL VIRUS IN INFANTS AND YOUNG CHILDREN WITH CHEST INFECTION: A COMPARISON OF REVERSE TRANSCRIPTION-PCR TECHNIQUE TO CHROMATOGRAPHIC IMMUNOASSAY AND ENZYME LINKED IMMUNOSORBENT ASSAY

Background: Human respiratory syncytial virus (hRSV) is a major cause of viral lower respiratory tract infection among infants and young children less than 2 years old. Multiple methods are used for the laboratory diagnosis of hRSV infections, including chromatographic immunoassay, enzyme linked immunosorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT-PCR) technique for detection hRSV-antigens, hRSV-antibodies and hRSV-RNA, respectively. Objective: To compare the efficiency of three diagnostic methods in detection of hRSV in infants and young children with chest infection. Methods: This study included 100 hospitalized infants and young children (39 females and 61 males) aged from (1) month to (24) months, their mean age (6.87 ± 6.03) months, who required hospital admission at the Pediatric Department in Al-Imamein AL-Kadhimein Medical City Hospital, Central Teaching Pediatric Hospital, and Al-Kadhimiya Pediatric Hospital in Baghdad-Iraq. Samples were collected over a three-month winter period from January 2017 to April 2017. Fresh nasal swab specimens were collected and testes for hRSV antigens by using chromatographic immunoassay as a rapid test, in addition, nasopharyngeal/throat swabs specimens were processed for detection of hRSV-RNA by RT-PCR, both for direct detection. Also, ELISA was done to measure anti-hRSV IgM antibodies in serum for indirect detection of RSV infection. Results: hRSV was found to be positive in (27%), (56%) and (44%) of specimens by rapid chromatographic immunoassay, ELISA and RT-PCR technique, respectively. Comparing with RT-PCR, the sensitivity of rapid test was (59.09%) ranged from (44.41) to (72.31) and the specificity was (98.21%) ranged from (90.55) to (99.91) with likelihood ratio equal to (33.09), while the sensitivity of ELISA test was (75.61%) ranged from (60.66) to (86.17) and specificity was (59.62%) ranged from (46.07) to (71.84) with likelihood ratio equals to (1.87). Conclusion: The RT-PCR technique was more sensitive than antigen or antibody detection methods for the diagnosis of hRSV Keywords: hRSV, rapid chromatographic immunoassay, ELISA, RT-PCR Citation: Al-Shuwaikh AMA, Ali SH, Arif HS. Detection of respiratory syncytial virus in infants and young children with chest infection: a comparison of reverse transcription-PCR technique to chromatographic immunoassay and enzyme linked immunosorbent assay. Iraqi JMS. 2018; 16(3): 319-326. doi: 10.22578/IJMS.16.3.11

Risk factors for mortality after respiratory syncytial virus lower respiratory tract infection in adults with hematologic malignancies.

BackgroundRespiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) is associated with high mortality in patients with hematologic malignancies (HM). We sought to determine whether allogeneic hematopoietic cell transplant (allo‐HCT) recipients would be at higher risk for 60‐day mortality.MethodsWe examined a retrospective cohort of adults with HM with or without HCT treated for RSV LRTI (n = 154) at our institution from 1996‐2013. We defined possible RSV LRTI as RSV detected only in the upper respiratory tract with new radiologic infiltrates and proven RSV LRTI as RSV detected in BAL fluid with new radiologic infiltrates. Immunodeficiency Scoring Index (ISI) and Severe Immunodeficiency (SID) criteria were calculated for HCT recipients. Multivariable logistic regression analyses were performed to identify independent risk factors associated with 60‐day all‐cause mortality.ResultsMortality was high in HM patients (25%), but there was no difference between those without HCT, autologous or allo‐HCT recipients in logistic regression models. Separate multivariate models showed that at RSV diagnosis, neutropenia (OR 8.3, 95% CI 2.8‐24.2, P = 0.005) and lymphopenia (OR 3.7, 95% CI 1.7‐8.2, P = 0.001) were associated with 60‐day mortality. Proven LRTI was associated with higher 60‐day mortality (neutropenia model: OR 4.7, 95%CI 1.7‐13.5; lymphopenia model: OR 3.3, 95% CI 1.2‐8.8), and higher ICU admission. In HCT recipients, high ISI and very severe immunodeficiency by SID criteria were associated with higher 60‐day all‐cause mortality.ConclusionsMortality is similarly high among HM patients without HCT and HCT recipients. High‐grade immunodeficiency and detection of RSV from BAL fluid are associated with higher 60‐day mortality.

An Initiative to Reduce Routine Viral Diagnostic Testing in Pediatric Patients Admitted with Bronchiolitis

Bronchiolitis is a viral lower respiratory tract infection that causes significant morbidity and mortality in the pediatric population. Viral diagnostic testing (VDT) has been used to identify specific viral pathogens. However, current guidelines suggest that routine use of this testing is not advisable. For children admitted to a children's hospital from the pediatric emergency department (PED), the rate of VDT was 63%, which was higher than the national rate. A quality improvement project was conducted to reduce the use of routine VDT. Key drivers of VDT were identified, and interventions, which included staff education about the cost and use of VDT and dissemination of a simplified cohorting policy aimed to eliminate VDT without medical necessity, were implemented through the PED and inpatient unit settings. Between January 2017 and April 2017, VDT use in all non-ICU patients admitted from the PED with bronchiolitis decreased from 63% to 12%. In the same time period, patients with VDT sent from the PED fell from 53% to 14%. A reduction in VDT for patients admitted with asthma exacerbation was also observed-from 24% to 0%-demonstrating early spread of these effects. Cost savings of approximately $8,584 per year in direct supply costs alone was documented. Using simple, low-cost interventions, including education and guideline refinement, the rate of VDT use for bronchiolitis was significantly reduced. Further directions for this project include the reduction of routine testing for patients with bronchiolitis who are admitted to the ICU or discharged for outpatient care.

Procalcitonin-Guided Therapy for Reduction of Antibiotic Use in Patients with Bronchiolitis

Objective Procalcitonin (PCT)-guided treatment could reduce antibiotic use in viral lower respiratory tract infections. We evaluated the impact of PCT-guided treatment on antibiotic use in patients hospitalized with bronchiolitis. Study Design A total of 100 patients aged 1 to 24 months old who were hospitalized with bronchiolitis were included in the study. Patients were randomized into two groups: PCT-guided group received an antibiotic treatment based on PCT levels and control group received an antibiotic treatment according to the physician decision. Results Antibiotic use on first day in the PCT-guided group (12%) was found to be statistically significantly lower than in the control group (80%) (p = 0.001; p &lt; 0.05; relative risk [RR]: 29.33; 95% confidence interval [CI]: 9.77–88.03). On the third day, antibiotic use was statistically significantly lower in the PCT-guided group (16%) than in the control group (40%) (p = 0.014; p &lt; 0.05; RR: 3.5; 95% CI: 1.36–9). Conclusion We suggested that PCT guidance will have important contributions to reduce antibiotic use in children with bronchiolitis. Particularly in countries with higher antibiotic prescription rates, this strategy may have implication for reducing the development of antibiotic resistance and side effects due to disturbance of microbiota.

Predicting healthcare outcomes in prematurely born infants using cluster analysis.

Prematurely born infants are at high risk of respiratory morbidity following neonatal unit discharge, though prediction of outcomes is challenging. We have tested the hypothesis that cluster analysis would identify discrete groups of prematurely born infants with differing respiratory outcomes during infancy. A total of 168 infants (median (IQR) gestational age 33 (31-34) weeks) were recruited in the neonatal period from consecutive births in a tertiary neonatal unit. The baseline characteristics of the infants were used to classify them into hierarchical agglomerative clusters. Rates of viral lower respiratory tract infections (LRTIs) were recorded for 151 infants in the first year after birth. Infants could be classified according to birth weight and duration of neonatal invasive mechanical ventilation (MV) into three clusters. Cluster one (MV ≤5 days) had few LRTIs. Clusters two and three (both MV ≥6 days, but BW ≥or <882 g respectively), had significantly higher LRTI rates. Cluster two had a higher proportion of infants experiencing respiratory syncytial virus LRTIs (P = 0.01) and cluster three a higher proportion of rhinovirus LRTIs (P < 0.001) CONCLUSIONS: Readily available clinical data allowed classification of prematurely born infants into one of three distinct groups with differing subsequent respiratory morbidity in infancy.

ANTIBIOTIC USE FOR INPATIENT BRONCHIOLITIS: DID NATIONAL GUIDELINES CHANGE PRACTICE?

Abstract BACKGROUND Millions of infants and young children are affected by bronchiolitis annually around the globe. This viral lower respiratory tract infection often results in hospital admissions, thus impacting the cost of the healthcare system. Because of its heterogeneous clinical presentation, inpatient management practices amongst paediatricians varies widely. The publication of national guidelines by the Canadian Paediatric Society (CPS) in 2014 was aimed at decreasing the use of unnecessary investigations and therapies for inpatient management of bronchiolitis. OBJECTIVES To evaluate the levels of antibiotic prescriptions and supportive investigations for inpatient management of bronchiolitis before and after the publication of national guidelines. DESIGN/METHODS This study is a single-centre retrospective chart review of inpatients with confirmed cases of bronchiolitis. We included children with no other relevant co-morbidities, aged 1- 24 months, who were admitted from November 2011 – October 2016. We excluded those who were born less than 35 weeks gestational age and patients with chronic complex medical problems. Our inclusion and exclusion criteria mirrored those used in the CPS guidelines. Those admitted prior to December 2014 were analysed in the pre-guidelines cohort and the remaining were placed in the post-guidelines cohort. The main outcome was antibiotic prescription during the hospital stay. Secondary outcomes included the frequency of chest x-rays, nasopharyngeal swabs, and blood cultures. RESULTS 131 patients were included in the first (pre-guideline) cohort and 71 in the second (post- guideline) cohort. The overall initiation of antibiotics was almost equal in both cohorts, regardless of whether a chest x-ray was ordered (p=1.000). There was no significant difference in the number of chest x-rays ordered between cohorts (p=0.099). The percentage of patients discharged on antibiotics were significantly lower in the second cohort (p=0.018). More antibiotics were discontinued after a viral cause was isolated in the second cohort (p=0.001). The gender distribution, mean age and mean length of stay were almost equivalent between the cohorts. CONCLUSION Our study did not show a significant change in antibiotic prescription despite the release of national guidelines. We found that isolating a viral aetiology often leads to the discontinuation of antibiotics. This study emphasizes the need for local antimicrobial stewardship initiatives to reduce the use of unnecessary antibiotics.