The study was conducted in the PICU of Children’s Hospital Béchir Hamza of Tunis. The PICU is in a university-affiliated children’s hospital and provides intensive care services to a national pediatric population of 850 000 children less than 15 years old. The hospital has 360 beds, and the PICU has 16 beds (500 admissions/year).

Pertussis is an acute respiratory illness caused by Bordetella pertussis (B. pertussis). Critical pertussis (CP) is defined as pertussis disease that results in pediatric intensive care unit (PICU) admission or death. It is characterized by severe respiratory failure, important leukocytosis, pulmonary hypertension, septic shock and encephalopathy. Despite intensive care management, it causes substantial morbidity and mortality for children especially among young infants. Resurgence of pertussis in the last 20 years is evident from the Centers for Disease Control (CDC).1 Several reasons for this resurgence have been proposed, including genetic changes in Bordetella pertussis, lessened potency of pertussis vaccines, waning of vaccine-induced immunity, greater awareness of pertussis, and the general availability of better laboratory tests.2 A new resurgence was seen in 2013 in Tunisia even in the presence on a high (98%) coverage of childhood vaccination.3 The purpose of this study was to describe the institutional experience in the management of infants with CP admitted in year 2013 at Children’s hospital Bechir Hamza of Tunis, reporting the relationship between method of presentation, therapies and outcome in order to identify factors associated with death.

Acute respiratory infections (ARIs) remain one of the most common major public health threats, accounting for millions of episodes of severe acute lower respiratory infections that result in hospital admissions of otherwise healthy infants and young children worldwide. One-third of the annual deaths occurring in the world are thought to be due to infectious diseases, and respiratory tract infections are responsible for 4 million deaths worldwide each year. According to estimates made by the World Health Organization (WHO), pneumonia kills more children worldwide than any other disease, even more than acquired immune deficiency syndrome (AIDS), malaria and measles combined.

In healthy children, nasopharyngeal colonization with respiratory bacteria is a prerequisite for the development of respiratory or invasive (i.e., sepsis, meningitis) diseases. Asymptomatic transient nasopharyngeal colonization with bacteria, such as Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus, is common and decreases with age and the maturation of the immune system. Geographic region, ethnicity, season, day-care attendance, environmental factors and previous vaccinations are important determinants of bacterial colonization.

Respiratory viruses including influenza viruses, respiratory syncytial virus (RSV), human rhinoviruses (HRV), human metapneumovirus (HMPV), parainfluenza viruses, adenovirus (ADV) and human bocavirus (BoV) are responsible for approximately 35–87% of ARIs in children. Viral co-infections occur in 4–33% of children hospitalized with ARIs. Bacterial infections caused by S. pneumoniae and H. influenzae may commonly be observed in the later stages of respiratory diseases. The incidence of respiratory viral/bacterial co-infection in young children ranges from 1% to 44%, and studies on influenza pandemics over the last 100 years have strengthened the association of bacterial super-infections and influenza infections. In addition, pertussis and measles still represent serious medical issues with lower respiratory tract involvement in several countries.

There has recently been an increase in the number of available vaccines against respiratory pathogens recommended for children and adolescents by the health authorities, and many studies have been performed to evaluate their efficacy, safety and tolerability. The aim of this review is to report current issues about vaccines against some respiratory pathogens to highlight the available strategies to reduce the burden of paediatric respiratory disease.

Among HAdV pneumonias, severe pneumonia was observed in five patients. Severe pneumonia patients and others did not differ significantly with respect to demographic characteristics and most symptoms (S3 Table). However, high fever, dyspnea, and chest discomfort were more frequent and febrile periods were significantly longer among patients with severe HAdV pneumonia, compared to others (8.6 ± 1.9 vs. 6.3 ± 1.6 days; p = 0.002). The time from fever onset to the greatest radiologic aggravation (increased opacity on follow-up chest X-ray) was also longer in the severe group (9.0 ± 2.7 vs. 6.3 ± 1.6, p = 0.001). Severe HAdV pneumonia was associated with a lower white blood cell count (WBC) and platelet count on admission day (p <0.001 and p = 0.042, respectively). Although the mean CRP value was higher in the severe group (p = 0.002), the mean serum procalcitonin concentration did not differ significantly between patients with severe pneumonia and others (p = 0.102; S4 Table).

Pertussis (whooping cough) is a highly contagious, respiratory disease caused by Bordetella pertussis (B. pertussis). The clinical symptoms of pertussis change with age, previous exposure to B. pertussis and immunization status. In newborns clinical manifestations may be severe. Most infants have a typical paroxysmal cough which can last more than two months.

Pertussis is a major cause of morbidity worldwide and of mortality in infants in developing countries. Pertussis continues as a public health concern threat given its re-emergence despite high vaccination coverage. Epidemic cycles reoccur every 2 to 5 years and 2015 has witnessed the worst outbreak in the past 70 years.

Although ample evidence confirms coinfections between B. pertussis and other pathogens, especially viruses, the role of coinfections remains debated [4–6]. Most mixed infections probably arise accidentally and whether they cause more severe disease than B. pertussis alone remains unclear [7–14]. Extending current knowledge on virus coinfections would make it easier to care for infants with pertussis.

We designed this study to compare clinical disease severity in infants with B. pertussis infection alone and those with B. pertussis and viral coinfections hospitalized in two Italian centers over two years. We also analyzed how respiratory infections and pertussis cases were distributed during the two years study. As primary outcome measures we assigned each infant a clinical severity score and assessed length of hospitalization. As an experimental approach to provide reliable data on lower respiratory virus infections we used an extended respiratory virus panel that can detect 14 respiratory viral targets with real-time reverse-transcriptase-polymerase chain reaction (RT-PCR) assay.

There were some complications among HAdV pneumonia patients. Acute heart failure occurred in two patients. Delirium occurred in one patient. One patient developed upper-extremity deep vein thrombosis, possibly resulting from a central line catheter. Two patients required mechanical ventilation. Of these latter patients, one expired from respiratory and heart failure (Table 4).

Pertussis, also known as whooping cough, is an acute respiratory tract infection caused by Bordetella pertussis. Although the incidence rate of pertussis has significantly decreased following the wide use of pertussis vaccine, B. pertussis infection is continuously occurring as a small outbreak even in several developed countries with high vaccination coverage (1-4). There has been the resurgence of reported pertussis cases primarily in infants younger than 1 yr old, especially less than 3 months of age, in adolescents and young adults worldwide (5, 6). The possible causes of increased incidence in adolescents and adults include waning of vaccine immunity, adaptation of circulating B. pertussis strains, development of diagnostic methods, and active surveillance due to increased awareness of pertussis (7-9). Household contact with infected adolescents and adults also becomes the major source of pertussis infection in infants who are not fully immunized, and this problematic circulation may consequently threaten overall public health (10, 11).

The epidemiological characteristics of pertussis can vary depending on the definition of case, diagnostic method of confirmed case, national reporting system, network organization for epidemiological investigation, and the local vaccination schedule. National immunization program (NIP) of Korea consists of three primary series of diphtheria-tetanus-acellular pertussis vaccine (DTaP) at 2, 4, and 6 months, followed by a first booster at 15-18 months and a second booster between 4 and 6 yr of age. Recently, a tetanus toxoid, reduced diphtheria and acellular pertussis (Tdap) booster vaccine in adolescents aged 11-12 yr is added to Korean NIP in 2012. The vaccination rate of primary DTaP continues to be approximately 94% (12, 13), and there is a mandatory notification system in Korea. An annual average of about 11.5 cases of pertussis has been reported to the Korea Center for Disease Control and Prevention (KCDC), however, the reported cases of pertussis have increased since the 2000s. In addition, the KCDC reported that the incidence of pertussis was markedly increased (more than about 5.5 times) in 2009, compared to the previous (14). Also, the incidence of pertussis in 2011 was more than two times compared with the incidence in 2009 (15). We may predict the substantial outbreak in the future in our country.

Given the importance of accurately determining the epidemiological features of infant pertussis and the lack of reliable existing data in Korea, this study was conducted to describe the clinical characteristics of laboratory confirmed cases less than 1 yr of age and to evaluate the relative importance of family members on infants who are vulnerable to B. pertussis transmission.

Acute respiratory infections (ARIs) are the leading cause of mortality in children worldwide, particularly in developing countries. It represents an important public health problem in early development, with high mortality and morbidity among children under five years of age.1 ARIs are classified as upper respiratory tract infections or lower respiratory tract infections (LRTIs) depending on the airways predominately involved.2

Although ARIs can be caused by bacteria or fungi, viral infections are responsible for most of them. Several viruses have been consistently identified during ARIs: influenza virus, human parainfluenza virus (HPIV), human rhinovirus (HRV), adenovirus (ADV), coronavirus (HCoV), enterovirus, human metapneumovirus (HMPV), and respiratory syncytial virus (RSV).3

Moreover, viral infections are one of the many risk factors associated with wheezing illnesses and exacerbation of respiratory diseases in children of all ages.4 HRV has been associated with these exacerbations, including cough, wheezing, shortness of breath, oxygen use, and length of hospital stay.5,6 In addition, asthma inception and exacerbation had been associated with HRV7–9 and HMPV infection,10 with some reports estimating that approximately 60% of cases are associated with HRV infection.11

Human rhinovirus have been classified into two genetic species: HRV-A (including 76 serotypes) and HRV-B (including 25 serotypes). However, recently, HRV-C has been included. HRV-A and HRV-B are associated with the common cold, whereas the role of HRV-C is relatively unknown, but recent reports suggest that HRV-Cs may be more pathogenic than other HRVs.12–14

Virus identification and molecular characterization is fundamental for epidemiological surveillance and control, but also for diagnostic purposes that may lead to specific therapy and an adequate response to treatment because clinical manifestations of virus and bacteria associated with ARI overlap considerably except in epidemic situations.15

The aim of this study was to determine the association of each type of respiratory viruses with acute hypoxemic respiratory disease mainly asthma acute exacerbation or pneumonia in children admitted to a reference respiratory center in Mexico City during three different seasons.

This prospective study was conducted from December 1, 2016, to May 31, 2018, at the National Reference Center for Neonatology and Nutrition and Medical Research Laboratory at Children's Hospital of Rabat. We included in this study 86 infants admitted with respiratory distress isolated or associated with systemic signs.

Acute bronchitis is an inflammation of the large airways that is characterized by cough and/or sputum that usually lasts one to three weeks. It is one of the most common illnesses among outpatients, and many patients receive antibiotic therapy [1–3].

Traditionally, viruses have been considered the main causative agent of acute bronchitis, possibly explaining the limited benefits of antibiotics [3–5]. However, data regarding the causative microorganisms are still limited. In previous studies, viruses were isolated in 8–23% of community-based cases, not frequently enough to conclude that viruses are the main causal agents for acute bronchitis. Macfarlane et al. identified viruses in only 19% of patients, while typical and atypical bacteria were identified in 25.9% and 23.7% of patients, respectively. In other studies, bacteria were detected in sputum samples in 45% of acute bronchitis patients [8, 9]. In addition, several authors suggested that some patients with acute bronchitis had mixed infections involving both viruses and bacteria. However, the exact prevalence and clinical characteristics of mixed infections have not been well studied. Moreover, it is not clear which subgroup of patients with acute bronchitis could benefit from antibiotic treatments. Recent big data from the UK show that antibiotics substantially reduce the risk of pneumonia after acute bronchitis, particularly in elderly people in whom the risk is highest.

Therefore, in the present study, we aimed to investigate the frequencies and characteristics of viral, bacterial, and mixed infections in acute bronchitis in the community. We also hypothesized that the frequencies of these etiologies would vary with underlying lung co-morbidities and age.

According to the World Health Organization (WHO), pneumonia is defined as acute respiratory tract infections (RTIs) which affect the lungs tissue (bronchi, bronchioles, and alveolar tissue). In Morocco, pediatric pneumonia remains a serious public health problem and constitutes the first cause of mortality due to infectious diseases. Pneumonia is a major cause of childhood morbidity and mortality worldwide. The WHO estimates that the 1.4 million children who die annually are under 5 years of age, where the greatest risk of death is in the neonatal period.

The epidemiology and etiology of pneumonia vary from country to country and from region to region. In developing countries, the incidence of pneumonia among children under 5 years of age is 0.29 episodes per child/year, compared to 0.05 episodes per child/year in developed countries [4, 5].

Pneumonia is caused by a variety of microorganisms (viruses, bacteria, or fungi). Viruses are the most common causative agents for children under 5 years of age, especially respiratory syncytial virus (RSV), rhinovirus (RV), influenza (IV), parainfluenza viruses (PIV), and adenovirus (ADV) [6, 7]. At least 26 viruses have now been associated with pneumonia. Their distribution varies by season, geographic region, and age group (4). Considering the frequency of viral infection, antibacterial therapy is often employed inadequately and unnecessarily.

The etiological diagnosis of pneumonia is difficult, due to the similarity in clinical presentation and also due to the overlap of the symptoms between viruses and bacteria, or between different viruses. For this reason, the use of Multiplex real-time polymerase chain reaction (PCR) assays tests in a routine setting for exact and fast identification appears to be necessary. They detect a wide range of viral and bacterial pathogens simultaneously in a single reaction, with higher sensitivity and specificity in hours.

The aim of this study is to present the clinical results of pediatric pneumonia and describing their epidemiology and etiology among infants who live in Morocco and admitted to a neonatology unit.

Viral pneumonia and lower respiratory tract infections are increasingly being recognized in adult patients including the critically ill.1,2 It appears that most viral lower respiratory tract infections are community-acquired and account for a significant etiology in mechanically ventilated patients with severe community-acquired pneumonia.3,4 Bacterial-viral co-infections are best described with influenza. The long history of bacterial infections occurring concurrently or shortly after influenza illness dates back to the 1918 influenza pandemic in which most of the fatal cases were found to be due to co-infection based on autopsy findings.5 More recently the 2009 H1N1 influenza pandemic was complicated by bacterial pneumonia in 4% to 33% of hospitalized or critically ill patients.6–11 Most commonly isolated co-infecting bacterial organisms with influenza are Streptococcus pneumoniae, Staphylococcus aureus, S. pyogenes, and Haemophilus influenzae. Influenza seasons are not equal as some are associated with lower mortality potentially related to differences in virulence factors or other unknown reasons.12–15

Bacterial co-infection is not limited to influenza and has been described with numerous other respiratory viruses, including respiratory syncytial virus (RSV), parainfluenza virus (PIV), rhinovirus, adenovirus, and human metapneumovirus (hMPV).16–25Advanced technologies have allowed for increased recognition of viral pathogens and diagnoses of viral respiratory infections including pneumonia.26 Several mechanisms by which viral respiratory infections may predispose patients to bacterial co-infections have been investigated including virus-induced alterations in epithelial cells, impaired immune response, and enhanced bacterial colonization.27 Utilizing new diagnostic technologies, it may be possible to better describe the clinical aspects of viral pneumonia and interactions with other infecting organisms. The purpose of this study was to describe hospitalized adult patients with viral pneumonia including possible co-infections and clinical outcomes.

Laryngectomees run a high risk of developing severe respiratory tract infections. Following laryngectomy the tracheal epithelium becomes directly exposed to the relatively cold and dry ambient air entering the tracheostoma [1, 2]. This can cause: drying of the mucus, which makes it more viscous; reduction of ciliary activity that causes impaired mucociliary clearance [2–4]; and tracheal epithelium damage (loss of ciliated cells, goblet cell hyperplasia, and excessive mucus production and metaplasia).

Severe pulmonary infections (tracheobronchitis and pneumonia) in laryngectomees are more frequent in the wintertime and the accompanying tracheal crusting often requires antibiotic treatment or even hospitalization. Tracheobronchitis in laryngectomees was described as a “suffocating” respiratory infection because of the difficulties in maintaining a patent airway in these patients [6, 7].

A case of severe tracheobronchitis in a laryngectomee is presented that illustrates the risks and difficulties encountered in managing this infection in a neck breather.

We compared individuals with a demonstrated single viral infection in the absence of bacterial infection with those with no viral infection detected by logistic regression models, searching for an association between viral infections and clinical symptoms. As shown in Table3, HRV infections were significantly associated with wheezing (P = 0·00 003; OR: 3·58 [95% CI: 1·9–6·7]), supraesternal retraction (P = 0·019; OR: 1·97 [95% CI: 1·11–3·49]), xiphoid retraction (P = 0·029; OR: 2·87 [95% CI: 1·14–7·2]), and with the absence of fever (P = 0·0001; OR: 0·36 [95% CI: 0·21–0·61]) and crackles (P = 0·036; OR: 0·57 [95% CI: 0·34–0·97]). Other viruses such as RSV were mostly related with the presence of crackles (P = 0·009; OR: 2·27 [95% CI: 1·21–4·25]), hyporexia (P = 0·036; OR: 2·02 [95% CI: 1·04–3·93]), and diarrhea (P = 0·002; OR: 4·63 [95% CI: 1·8–11·7]), while influenza A infection presented more malaise (P = 0·003; OR: 3·22 [95% CI: 1·45–7·15]) and postnasal drip (P = 0·008; OR: 3·38 [95% CI: 1·4–8·07]; Table3).

As shown in Table3, wheezing disorders and asthma were common in those with HRV infection (P = 0·000 003; OR: 3·65 [95% CI: 2·09–6·36]) and less likely in those with RSV (P = 0·005; OR: 0·40 [95% CI: 0·21–0·77]) and HMPV infection (P = 0·018; OR: 0·19 [95% CI: 0·04–0·87]), whereas pneumonia was likely in RSV infection (P = 0·003; OR: 2·64 [95% CI: 1·38–5·05]) and more uncommon in HRV infection (P = 0·000 009; OR: 0·29 [95% CI: 0·17–0·51]).

The 115 samples positive to HRV infection were typified, and 49·4% of the samples were classified as HRV-C. To determine the influence of comorbidities and other factors such as age, bacterial, and viral coinfections, multivariate logistic regression was realized. Remarkably, the relationship between HRV-C and asthma is maintained (P = 0·02; OR=2·53 [95% CI: 1·14–5·59]). The rest of types and subtypes of respiratory viruses and comorbidities such as gastroesophageal reflux were not associated with asthma either in the univariate analysis or in the adjusted analysis (data not shown).

Individuals with HMPV infection had prolonged hospital stays in days [7 (5–16·5); P = 0·015], and those with HRV infection had the shortest hospital stays [5 (4–6); P = 0·006].

Adult patients with acute bronchitis were prospectively recruited at 31 Korean hospital outpatient departments and primary clinics between July 2011 and June 2012 (6 university-affiliated teaching hospitals, 5 non-teaching community hospitals, and 20 primary clinics). Sputum samples for Gram stains, conventional cultures, and polymerase chain reaction (PCR) were collected from each patient before any medications (including antibiotics) were prescribed. Medications were chosen at the physicians’ discretion. The study protocol was approved by the Institutional Review Board of Hallym University Sacred Heart Hospital (the principal institute, 2011-I049) and each participating hospital. All participants provided informed written consent.

Patients were eligible if they were ≥18 years old and visited the outpatient clinic because of cough (duration < 1 month) with sputum production. Acute bronchitis is a clinical diagnosis, and therefore, a wrong diagnosis is possible. Coughing symptom may have almost all respiratory illnesses as a differential diagnosis. However, symptoms such as sputum production, after carefully discriminating from postnasal drip, could also lead to a diagnosis of lower respiratory inflammation. Patients with typical upper respiratory infection (URI) and symptoms of influenza or influenza-like illness (ILI) during the epidemic period were excluded by participating physicians. We tried to rule out URI by conducting detailed medical interviews, throat examination, and by auscultation. Typically, URI was defined as an infection affecting patients presenting with key symptoms such as sore throat, and nasal symptoms (nasal obstruction, runny nose) with cough. ILI was defined as an abrupt onset of fever with non-productive cough or sore throat. The period of the influenza epidemic was determined by means of a national respiratory virus surveillance system which was broadcast weekly. In some cases, chest radiographs were done at the investigating physician’s discretion, in order to rule out pneumonia. Other exclusion criteria were: 1) history of antibiotic treatment < 7 days before the visit, 2) exacerbation of chronic lung disease within 6 months, 3) active lesion on the chest or paranasal sinus radiographs (when available), 4) immunocompromised status, and 5) confirmed alternative cause for the cough (e.g., drugs [newly started on angiotensin-converting enzyme inhibitors], pneumonia, allergic rhinitis, sinusitis, or gastro-esophageal reflux). Stable chronic lung disease patients were not excluded.

Viral respiratory tract infections (VRTIs) are very common in children and their presentations vary from simple colds to life-threatening infections.1–5 The detection of a respiratory virus does not necessarily infer that the child has only a viral infection,6 since outbreaks of VRTIs are being linked to increased incidence of bacterial coinfections.7 The human body is usually capable of eliminating respiratory viral infections with no sequelae; however, in some cases, viruses bypass the immune response of the airways, causing conceivable severe respiratory diseases.8 Robust mechanical and immunosuppressive processes protect the lungs against external infections, but a single respiratory tract infection might change immunity and pathology.9

Health care providers often face a dilemma when encountering a febrile infant or child with respiratory tract infection. The reason expressed by many clinicians is the challenge to confirm whether the fever is caused by a virus or bacterium.10 Acute otitis media (AOM) is a usual bacterial coinfection that occurs in 20%–60% of cases of VRTIs.11–14 In addition, almost 60% of children with VRTI have changes in the maxillary, ethmoidal, and frontal sinuses.11,12 Moreover, in the year 1918, it was estimated that 40–50 million individuals died from the influenza pandemic, many of which were due to secondary bacterial pneumonia with Streptococcus pneumoniae.15

Pertussis is a major public health problem, affecting adolescents and adults as well as children. Despite a widespread vaccination program, over the past fifteen years was seen a return of pertussis worldwide. Pertussis resurgence in Europe has been attributed to an incomplete immunization program or to genetic changes in Bordetella pertussis (B. pertussis). The currently used acellular pertussis vaccine contains the pertactin gene variant prn1 and the pertussis toxin-B S1 subunit. Molecular changes in these two genes over the past years suggest that the antigenic divergence may make pertussis vaccination less effective than before.

In some countries pertussis immunization is not mandatory and in others vaccination schedules suggest the first dose to be given at the age of 3 months. Hence, some infants remain unimmunized or incompletely immunized. In those who are incompletely immunized pertussis may develop in an atypical clinical form and be difficult to diagnose. Pertussis can be especially difficult to diagnose in children under 1 year of age during winter season, when other pathogens, such as respiratory syncytial virus (RSV), circulate. In these difficult cases, pertussis acute respiratory symptoms can overlap with those of bronchiolitis. A study conducted in a group of infants hospitalized for RSV bronchiolitis showed that almost 2% of the patients were co-infected with B. pertussis[7,8]. Since B. pertussis-RSV co-infection is infrequent in young infants, physicians should keep the possibility of co-infections in mind as to diagnose it early and prevent bronchiolitis from becoming more severe.

Although the standard diagnostic criterion for identifying B. pertussis is culture obtained from nasal swabs or nasopharyngeal aspirates, confirmatory information comes nowdays from molecular techniques such as real time-polymerase chain reaction (RT-PCR). Usually, in clinical practice the diagnosis is generally reached without microbiological confirmation. What we conspicuously lack is the clinician’s awareness of the clinical and laboratory data needed to reach a suspected B. pertussis diagnosis in order to start treatment early.

The main purposes in our retrospective, single-center study were to describe and compare clinical and laboratory features in infants with pertussis infection to infants hospitalized for RSV bronchiolitis, and to analyze the genetic characteristics of B. pertussis.

A 76-year-old Caucasian man who underwent laryngectomy 10 years earlier, presented with fever (38.9 °C; 102.0 °F), increased sputum production, and purulent conjunctivitis. These symptoms emerged gradually over a period of 48 hours. He noted increasing difficulty in coughing out his sputum that became brownish and viscous. He had been wearing a heat and moisture exchanger (HME) filter that covered his stoma and spoke through a tracheoesophageal voice prosthesis. The symptoms started a day after a very cold weather spell with temperatures of −7 to −1 °C (19–31 °F). He had to remove his HME on several occasions for extended periods of time to enable him to breathe when he walked outside his home.

His past medical history included hypopharyngeal squamous cell carcinoma which was treated with intensity-modulated radiotherapy (IMRT) 12 years earlier. A recurrence of the cancer 2 years later required laryngectomy. He had no signs of tumor recurrence since then. He also suffered from paroxysmal hypertension, diverticulitis, and migraines.

He was vaccinated with the current Influenza virus vaccine 3 month earlier. He had also received a pneumococcal polysaccharide vaccine (PPSV23) 2 years earlier.

He was in mild respiratory distress especially when coughing. He had coughing spells and expectorated green-brown dry and viscous sputum. A physical examination revealed bilateral purulent conjunctivitis and auscultation of his lungs revealed coarse rhonchi and no crepitations. No lymphadenopathy was noted. The results of the rest of the physical and neurological examinations were within normal limits. A chest X-ray was normal.

Sputum and conjunctival culture grew heavy growth of beta-lactamase-producing nontypeable Haemophilus influenzae (NTHi) that was susceptible to levofloxacin and amoxicillin- clavulanate. A FilmArray® Respiratory Panel 2 (RP2) polymerase chain reaction (PCR) system test did not detect 14 viruses (adenovirus, coronavirus HKU1, coronavirus NL63, coronavirus 229E, coronavirus OC43, human rhinovirus/enterovirus, human metapneumovirus, influenza A, influenza B, parainfluenza virus 1, parainfluenza virus 2, parainfluenza virus 3, parainfluenza virus 4, respiratory syncytial virus) and four bacteria (Bordetella pertussis, Bordetella parapertussis, Chlamydophila pneumoniae, Mycoplasma pneumoniae).

He was treated with orally administered levofloxacin 500 mg/day, ciprofloxacin eye drops, acetaminophen, and guaifenesin. Humidification of his trachea and the airway was maintained by repeated insertions of 3–5 cc respiratory saline into the stoma at least once an hour and by breathing humidified air.

The main challenge was to maintain a patent airway as the mucus was very dry and viscous and tended to stick to the walls of his trachea and the stoma. The mucus had to be repeatedly expectorated by vigorous coughing and by manual removal from the upper part of his trachea and stoma.

He experienced repeated episodes of sustained elevated blood pressure (up to 210/110) and tachycardia (112/minute). This was managed by administration of clonidine 0.1 mg as needed (1–2/day).

His fever started to decline 48 hours after antimicrobial therapy was started. The conjunctivitis improved within 36 hours. The sputum production declined and became less viscous over time, but persisted for 5 days.

Antimicrobial therapy was discontinued after 7 days.

His condition improved and he had a complete recovery in 7 days. He was seen in the clinic every 2 months and showed no recurrence of his infection for the following 8 months. He received vaccination for H. influenzae B and Prevnar 13® (pneumococcal conjugate vaccine; PCV13) 4 weeks after his recovery.

Pertussis is a highly contagious respiratory tract infection, caused mainly by Bordetella pertussis and less frequently by Bordetella parapertussis. In the pre-vaccination era, infants and children contracted pertussis in their first years of life, with a clinical course characterized by uncontrollable coughing attacks, often accompanied by paroxysms, post-tussive vomiting, and inspiratory whooping. Consistently high vaccination coverage has substantially decreased pertussis in the population [2, 3], but newborns too young to be vaccinated remain at high risk for severe complications including apnea, cyanosis, pneumonia, encephalopathy or even death. This risk is increasing due to the worldwide pertussis reemergence in the 1990s, even in areas of high vaccination coverage in all age groups, with transmission of disease from household members to newborns. Today, high pertussis incidences in infants are observed, with incidence peaking every two to three years [3, 5, 6]. Worldwide in 2014, an estimated 24 million cases and 160,000 deaths from pertussis occurred in children younger than 5 years, with the African region contributing the greatest share. In the Netherlands, each year approximately 150–180 children <2y are hospitalized and one infant, in general too young to be vaccinated, dies due to pertussis. For this reason, many countries are discussing prenatal pertussis vaccination of mothers to protect newborns, and a growing number of countries now recommend it. This measure is effective in preventing pertussis in the first months of life and has decreased the pertussis disease burden in young infants [10, 11]. In the Netherlands, the Health Council advised that 3rd trimester maternal pertussis vaccination be offered. This is overall very effective in prevention of pertussis in early infancy, but preterms may benefit less due to a smaller time-window for mother-to-child transfer of antibodies before delivery [12, 13]. However, vaccine effectiveness (VE) is reportedly lower after 2nd trimester pertussis vaccination. Given the introduction of a maternal vaccination strategy against pertussis in The Netherlands, we sought to gain more insight into the current pertussis burden among hospitalized infants, with special attention to preterms.

This was a single-center, observational cohort study of patients with a positive respiratory virus panel (RVP) at Barnes-Jewish Hospital (a 1300-bed urban academic medical center in St. Louis, MO) between 1 March 2013 and 7 November 2014. The study protocol was approved by the Barnes-Jewish Hospital, Washington University and St. Louis College of Pharmacy Institutional Review Boards. Adult patients (≥19 years of age) admitted to the hospital for >24 h were identified through a query of an internal database, which tracks respiratory viruses and evaluated for study inclusion. Patients were excluded if no virus was identified by RVP, rhinovirus or enterovirus was identified by nasopharyngeal (NP) swab only, or if a respiratory virus had been identified within the 90 days before the index RVP.

Acute respiratory infections (ARIs) are a leading cause of morbidity, hospitalization, and mortality among children [1–3]. According to World Health Organization (WHO), acute respiratory infections are responsible for 1.9 million annual deaths in children, mainly affecting patients under 5 years old, with a higher incidence in those from low-income countries [1, 4].

ARIs are mainly caused by a wide range of viruses and bacteria [5, 6]. Viruses are isolated in up to 80% of cases, the most common pathogens are the respiratory syncytial virus (RSV) A and B, influenza (Flu) A, B and C, parainfluenza (PIV) types 1, 2, 3 and 4, coronavirus and rhinovirus [7, 8]. Classically, S. pneumoniae and H. influenzae type b are the most commonly isolated bacteria in both throat and nasopharyngeal specimens from patients with ARIs [9, 10]. However, in resource-limited countries, atypical bacteria such as Mycoplasma pneumoniae, Chlamydia pneumoniae, and Bordetella pertussis can play an important role in ARIs and can be detected in more than 40% of patients [2, 11–14].

Although numerous pathogens are associated with ARIs, their clinical manifestations are very similar, regardless of the causative agent. Thus, laboratory identification of the etiological agent is key in order to give a proper treatment and avoid the overuse of antibiotics. Moreover, ARIs due to atypical bacterial infections have become a global concern especially after their reemergence in low-income countries [11, 16].

Simultaneous infections with virus and bacteria species have become an obstacle for clinicians, their prevalence has significantly increased, with studies discovering co-infections in more than 45% of cases [11, 17–19]. Additionally, these coinfections have been associated with longer hospitalization periods, worse clinical outcomes and increased mortality, again highlighting the importance of molecular etiological confirmation [17, 19, 20].

Bordetella pertussis represents a persistent cause of morbidity and mortality in children. Accounting for an estimated 16 million cases and 195,000 deaths worldwide. In a previous study we conducted on children under 1-year-old with a probable diagnosis of Pertussis from 5 Peruvian hospitals, we reported a prevalence of 39.54% pertussis cases. With more than 60% of cases without an identified pathogen, hence a more comprehensive etiological analysis was required.

The main objective of this study was to detect the presence of 8 respiratory viruses (Influenza-A, Influenza-B, RSV-A, RSV-B, Adenovirus, Parainfluenza-1, Parainfluenza-2 and Parainfluenza-3) and atypical bacteria (Mycoplasma pneumoniae, Chlamydia pneumonia), via Polymerase Chain Reaction in samples from Peruvian children under 5 years-old previously analyzed for B. Pertussis.

The human myxovirus resistance protein 1 (MxA) is an important intermediary of the IFN-induced antiviral response against a variety of viruses. MxA expression is firmly modified by type I and type III IFNs, which also requires signal transducer and activator of transcription 1 signaling. Additionally, MxA has many characteristics similar to the superfamily of large guanosine triphosphatases.78 MxA analysis could be beneficial to differentiate between bacterial and viral infections. Engelmann et al79 conducted a prospective, multicenter cohort study in different pediatric emergency departments in France on the role of MxA in the diagnosis of viral infections. MxA blood values were calculated in infants and children with verified bacterial or viral infections, uninfected controls, and infections of unknown origin. A receiver operating characteristic analysis was used to verify the diagnostic performance of MxA. The study, which included 553 children, showed that MxA was significantly higher in children with viral versus bacterial infections and uninfected controls (P<0.0001). Additionally, MxA levels were significantly higher in children with clinically diagnosed viral infections than in those with clinically diagnosed bacterial infections (P<0.001).79 Other authors have also reported the usefulness of blood MxA testing in patients with viral infections.80,81 The use MxA in diagnosing viral infection is very promising, especially in patients who are at risk of infectious complications. Two separate studies have shown that blood MxA is beneficial in differentiating between viral illness and acute graft-versus-host disease after allogenic stem cell transplantation.82,83

The community-acquired pneumonia (CAP) is the leading cause of morbidity and mortality worldwide. According to WHO estimates, 450 million cases of pneumonia are recorded each year, with about 4 million deaths from this illness [1, 2], with the highest incidence cases in children younger than 5 years old. The mortality rate has declined greatly due to early and accurate detection of the etiological agents, together with the timely initiation of appropriate treatment.

Nowadays, the golden standard for CAP diagnosis is still based on the chest radiography; however, a broad range of chest radiographic changes could be induced by various agents, a single and dual bacterium/virus, or mixed pathogens coinfections. These alterations of chest radiography are only helpful in specific cases to confirm a microbial cause of pneumonia. Current diagnostic methods identify a pathogen in only 30%–40% of CAP patients [5, 6], and the frequent lack of a microbiological diagnosis in CAP impairs pathogen-directed antimicrobial therapy. Polymerase chain reaction (PCR) technique has been shown to be reliable for diagnosing the pathogens, especially for those that are difficult to culture. In addition, PCR method has high sensitivity and specificity in detecting multiple microorganisms and yields results faster than culture and serological methods. Most importantly, the results of PCR are not affected by prior use of antibiotics. The findings indicate that the incidence of viral pneumonia in the past has been underestimated. With multiple PCR assay, detection of multiple RNA or DNA targets in a single tube has the potential for rapid identification of complicated respiratory viral pathogens [9, 10]. The conventional techniques of microbial detection have high accuracy, but they are time- and labor-intensive, with limited range of detection and can be subjective, relying very much on technical expertise for the interpretation of cytopathic effect (CPE) in cell culture. Direct fluorescent antibody assay (DFA) and immunochromatographic antigen testing, although rapid, have poor sensitivity for the detection of most viruses. The serological methods also have low sensitivity. Therefore, an assay that is capable of rapid detection and accurate identification of multiple pathogens is desirable.

FilmArray Respiratory Panel (RP) is a multiplexed nucleic acid test for the simultaneous qualitative detection and identification of multiple respiratory virus, Bordetella pertussis, Chlamydophila pneumoniae, and Mycoplasma pneumoniae. Particularly, the whole process only takes about an hour; compared to multiple PCR, the FilmArray RP has provided fast results. As the FilmArray RP is emerging method, which is rarely employed in clinical specimen's detection, its clinical significance in diagnosing CAP is sparse. Therefore, in this study, we evaluated the capability of FilmArray RP for simultaneous identification of multiple pathogens; its microbial yield and clinical significance in CAP diagnosis were also evaluated.

Nasal washings were centrifuged to remove the mucus present in the sample and an aliquot was used for nucleic acid extraction using a total nucleic acid isolation kit (Roche Diagnostics, Mannheim, Germany) and an RT-PCR panel that sought 14 respiratory viruses: influenza virus A and B (IV-A/B), human coronavirus (hCoV) OC43, 229E, NL-63, HUK1, adenovirus (AV), parainfluenza virus 1–3 (PIV 1–3), human-metapneumovirus (hMPV), human-bocavirus (hBoV), respiratory syncytial virus (RSV) and human rhinovirus (hRV), as previously described.

Respiratory syncytial virus (RSV) is the major infectious cause of lower respiratory tract illness in infants and young children around the world.1, 2 It has also been recognized as an important etiologic agent of pneumonia and other respiratory tract infections in adults and elderly patients.3, 4 The clinical presentation of this infection varies widely, from mild upper respiratory tract disease to bronchiolitis and pneumonia.5 This virus is responsible for the majority of bronchiolitis cases and causes approximately 50% of pneumonia cases during the first years of life.6 In children, host factors such as young age, prematurity, and chronic cardiopulmonary diseases have been associated with severe disease. In addition, other factors such as lower socioeconomic status, exposure to cigarette smoke, air pollution, crowded households, and the lack of breastfeeding have also been associated with severe disease.7 Viral factors associated with virulence leading to severe disease are not sufficiently understood.8

Human RSV is a member of the Paramyxoviridae family. Outbreaks of RSV infections occur between fall and spring in temperate climates and tend to last up to 5 months.9, 10 RSV isolates can be divided into two groups: group A and group B based on antigenic and genetic characteristics.8 These two groups cocirculate in the human population, with group A being more prevalent. Several studies have compared the severity of disease between infants infected with RSV group A and group B with mixed results. Most studies have not found significant clinical differences between both subtypes.8 However, a possible effect of different viral strains on disease severity remains an open question.

Despite the recognized importance of RSV as a cause of respiratory illness, the information regarding the epidemiology of this virus in Latin America, particularly among adults, is limited.11 In the present study, 570 cases of RSV infection identified during four epidemic years in Mexico were evaluated to clarify the epidemiology of this infection and to assess the possible variations in demographic and clinical characteristics according to viral groups.