Evaluation of Multiplex Real-time PCR and WHO Criteria for Diagnosing Childhood Bacterial Meningitis in a Tertiary Referral Hospital in Iran

Background: Childhood bacterial meningitis (BM) requires prompt and precise diagnosis to provide proper treatment and decline mortality and morbidity. Objectives: We aimed to evaluate the World Health Organization (WHO) criteria and polymerase chain reaction (PCR) for diagnosing BM in children admitted to a tertiary referral hospital in Shiraz, southern Iran. Materials: We included all 492 children aged one month to 17 years suspected of meningitis who had cerebrospinal fluid (CSF) leukocytosis admitted to Nemazi Hospital from August 2016 to September 2017. The CSF specimens were examined for routine analysis, Gram staining, and culture. A multiplex real-time PCR was used to identify Streptococcus pneumoniae, Haemophilus influenzae type b (Hib), and Neisseria meningitidis in the CSF samples. Seven viruses were also investigated using real-time PCR. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated using the WHO criteria and the multiplex real-time PCR results. Results: Seventy-four CSF samples had leukocytosis. Nineteen (22.9%) patients had BM caused by S. pneumoniae (n = 14), Hib (n = 2), Salmonella enterica (n = 2), and N. meningitidis (n = 1). The PCR test detected all cases, except for two with Salmonella meningitis (sensitivity 89.4%, specificity 100%, PPV 100%, and NPV 96%). The WHO criteria detected all cases, except three who received antibiotics at least four days before performing lumbar puncture (sensitivity 84.2%, specificity 98.2%, PPV 94.1%, and NPV 94.7%). Enterovirus was the most common viral etiology (6.75%). Conclusions: The WHO criteria and the multiplex real-time PCR had high accuracy in our setting, and their use could decrease the antibiotic over-prescription in febrile children suspected of meningitis.

Prevalence of Human Bocavirus in Children Under 5 Years with Upper and Lower Respiratory Infections in Southeastern Iran

Background: Human Bocavirus (HBoV) is a parvovirus associated with mild to severe upper and lower respiratory tract infections in children. Objectives: This study aimed to detect the virus in the nasopharynx of children under 5-year-old with respiratory infection by polymerase chain reaction (PCR). Methods: Two hundred samples were taken from children referred to pediatric clinics in Kerman, southeastern Iran, with respiratory infections and were positive for virus by PCR. Next, the positive samples were genotyped by real-time PCR. Results: Out of 200 samples, 13 (6.5%) were positive for the Bocavirus gene, and all positive samples were infected by HBoV-1. We observed that 116 patients were male, and there was no difference in the prevalence of the virus based on gender (P = 0.345). The prevalence was significantly higher in infants under 10 months old (P = 0.049). Infection by Bucavirus virus was significantly correlated with symptoms, such as fever (P = 0.035, r = 0.7), otitis media (P = 0.013, r = 0.8), diarrhea, nausea, and vomiting (P = 0.001, r = 0.4). Conclusions: According to our findings, HBoV could be one of the causes of infections in the respiratory system of children, and the only type in the studied region is HBoV-1.

Low Frequency of Adenovirus, Rotavirus, and Norovirus in Pediatric Diarrheal Samples from Central Iran

Background: Acute viral gastroenteritis is a disorder that affects children globally but mostly in developing countries. Adenoviruses, rotaviruses, and noroviruses are the leading viral causes of childhood gastroenteritis. Objectives: This study is the first to investigate the frequency of these viruses in diarrheal samples from pediatric patients living in central Iran. Methods: A total of 173 samples of pediatric diarrhea, from May 2015 to May 2016, were included in this descriptive cross-sectional study. The samples were analyzed using in-house developed PCR and reverse transcription (RT)-PCR methods to investigate the frequency of adenoviruses, rotaviruses, and noroviruses. Results: Out of 173 samples of pediatric diarrhea, eight were shown to contain enteric viruses (4.6%): (1) four with adenoviruses (2.3%); (2) three with rotaviruses (1.7%); and (3) one with a genogroup II norovirus (0.6%). Most of the positive samples were obtained from children under the age of seven. The most common additional clinical symptoms in pediatric patients with viral agents were fever, vomiting, and abdominal pain. Conclusions: In central Iran, adenoviruses and rotaviruses were rarely found as agents responsible for gastroenteritis. Although viral gastroenteritis in this area had less frequency than bacterial gastroenteritis, we need to monitor all enteropathogenic agents for longer periods to understand better real endemicity and the possibility of unexpected viral enteritis outbreaks.

Microbiology of Post-Cardiac Surgery Infections in Children with Congenital Heart Diseases, A Single-Center Experience, Mashhad, Iran

Background: Children who have undergone cardiac surgeries due to congenital heart disease are prone to various kinds of infections. Objectives: This study was done to investigate the prevalence of nosocomial infections and microbiology of post-cardiac surgery infections in pediatric patients with congenital heart disease (CHD). Methods: In this cross-sectional study, the epidemiology and microbiology of post-cardiac surgery for pediatric patients with CHD at Imam Reza Hospital of Mashhad University of Medical Sciences between 2014 and 2017 were investigated. Demographic and clinical information was recorded, and the findings were analyzed using SPSS 16. Results: Out of 1128 patients with open heart surgery during the four years of the study, 135 patients, including 80 males (60.1%) and 55 females (39.9%) with a mean age of 8.06 ± 3.86 months, were enrolled in the study. The prevalence of infection was 11.96%. The most common isolated bacteria were Acinetobacter (19/135, 14.1%), Pseudomonas spp. (13/135, 9.6%), and Enterobacter (13/135, 9.6%) as Gram-negative ones and Corynebacterium diphtheria (10/135, 7.4%) and Staphylococcus epidermidis (10/135, 7.4%) as Gram-positive types. Candida albicans (14/135, 10.4%) were also the most frequent fungi. The frequency of infection-causing masses did not differ significantly between different cardiac abnormalities (P = 0.831), sex (P = 0.621), age (P = 0.571), and weight (P = 0.786) groups. Also, the duration of hospitalization, intubation, bypass time, and urinary catheterization in positive culture cases were significantly longer than in negative cases. Conclusions: In our study, the most common infections in children who underwent heart surgery were Acinetobacter, C. albicans, Pseudomonas, and Enterobacter. It is suggested to reduce the hospitalization, intubation, bypass, and urinary catheterization time to reduce nosocomial infections in these patients and decrease treatment costs.

Factors Associated with Severe Acute Respiratory Infections Due to Rhinovirus/Enterovirus Complex in Children and Their Comparison with Those of Respiratory Syncytial Virus

Background: Acute respiratory tract infections (ARTIs) are one of the main causes of morbidity and mortality in children under the age of five worldwide. Objectives: The objective of this research was to describe the main characteristics of hospitalized patients with ARTI caused by the rhinovirus/enterovirus (RV/EV) complex and the risk factors associated with severe infection. Methods: This was a retrospective descriptive study in patients from one month to 18-years-old who had been hospitalized for ARTI between October 2015 and December 2019 at Fundación Cardioinfantil in Bogotá, Colombia, and had had an RT-PCR viral panel during their hospitalization. Rhinovirus/enterovirus infection was characterized to identify factors associated with disease severity as compared to respiratory syncytial virus (RSV). A multivariate analysis was performed, controlling for confounding factors, to identify groups at risk of developing associated acute respiratory distress syndrome (ARDS). Results: During the study period, 645 RT-PCRs were performed, with the two main etiological agents identified being RV/EV (n = 224) and RSV (n = 68). The median age of patients with the RV/EV complex was 27 months (IQR: 8 - 70), and seven months for those with RSV (IQR: 2 - 11). Severe RV/EV complex infections required more transfers to intensive care (47% vs. 11%), showed more viral coinfection (OR: 2.13, 95% CI: 1.42 - 4.64), and had less bacterial coinfection (OR: 0.55, 95% CI: 0.31 - 0.98) than RSV infections. The RV/EV group had a higher risk of developing ARDS (OR: 3.6, 95% CI: 1.07 - 12:18), especially in premature infants (P: 0.05; exp(B), 2.99; 95% CI = 1.01 - 8.82), those with heart disease (P: 0.047; exp(B), 2.99; 95% CI = 1.01 - 8.82), and those with inborn errors of metabolism (P: 0.032; exp(B), 5 - 01; 95% CI = 1.15 - 21.81). A total of 13 patients from both study groups died (4.5%), with no differences found between the groups (RV/EV 54% vs. RSV 46%; P = 0.3). Conclusions: Respiratory infection due to RV/EV in children can frequently be severe, requiring management with intensive care therapy. When compared to RSV, this complex is more frequently associated with the development of ARDS, especially in risk groups such as those with prematurity, heart disease, or inborn errors of metabolism.

Implementing the Protocol of Perioperative Narrow-spectrum Antibiotic Prophylaxis in the Surgical Wards of Mofid Children’s Hospital in 2019 - 2020, A Comparative Study

Background: Surgical procedures may be complicated by post-surgical infections. This study investigates the role of administering perioperative narrow-spectrum antibiotic prophylaxis in preventing post-surgical infections as compared to routine broad-spectrum antibiotic usage in the surgical ward. Methods: Narrow-spectrum perioperative antibiotic prophylaxis, in accordance with CDC guidelines, was implemented in our hospital in October 2019. In this quasi-experimental study, all the children (one month to fifteen years old) who underwent surgery from April to September 2019 and had received broad-spectrum antibiotics for various durations, as well as those operated after the implementation of the perioperative narrow-spectrum antibiotic prophylaxis plan (October 2019 to March 2020) were enrolled. Surgical wound type (clean, clean/contaminated, contaminated, and dirty), type and site of the infection, and the patient’s age and sex were recorded. Cases with postoperative infections were followed up in the two groups during hospitalization and for 30 days (or 90 days if a prosthetic material was implanted) after discharge. The rate of post-surgical infections was compared between the two groups by the Mann-Whitney and Chi-squared tests. Results: In total, 4308 cases were enrolled in the first six months and 3650 in the second six months of the study. The rate of post-surgical infections in the first group was 31/4380 (23.7%) as compared to 22/3650 (20%) in the second group (P-value = 0.3365) Conclusions: There was no increase in the frequency of post-surgical infections after the implementation of the perioperative narrow-spectrum antibiotic prophylaxis protocol. Reducing the use of antibiotics before surgery shrinks costs and antibiotic resistance without any effect on the post-surgical infection rate.

Spontaneous Pneumothorax in a Child with COVID-19

Introduction: SARS-CoV2 (COVID-19) is a serious and global infection that has spread to numerous countries, including Iran. Pneumothorax may occur in cases of COVID-19 as a consequence of lung parenchymal damage, which can disrupt the healing process and increase mortality. Case Presentation: This manuscript describes the case of a 2-year-old boy with hyper IgM syndrome and COVID-19 infection. The patient developed spontaneous pneumothorax and recovered without chest tube by supportive care and was discharged in good general condition after the completion of the antibiotic course and cessation of fever. Conclusions: The severity, prognosis, and best treatment for spontaneous pneumothorax in COVID-19 infection, especially in children, remain nebulous. It is recommended that conservative treatment be performed if the patient has stable vital signs and no severe respiratory failure. However, this requires more detailed clinical evaluations.

Human Cell Receptors and Downstream Cascades: A Review of Molecular Aspects and Potential Therapeutic Targets against COVID-19

Context: There have been two coronavirus-related pandemics during the past 18 years, including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV in 2002 and 2012, respectively. Seven years after the emergence of MERS, a new coronavirus (i.e., SARS-CoV-2) was detected in several patients in 2019. SARS-CoV-2 spread widely, and its high prevalence enabled the virus to start a new pandemic in 2020. It is believed that the higher infectivity of the virus in comparison to that of SARS-CoV is related to its molecular interaction affinity of transmembrane spike glycoprotein and human angiotensin-converting enzyme 2 (ACE-2) cell receptors. Moreover, the primary reason for the high case fatality rate (CFR) is the cytokine storm and acute respiratory distress syndrome (ARDS) because of the immune system response to the invaders. Hence, a solid understanding of the components involved in the mechanism of viral entry and immune system response is crucial for finding approaches to disrupt the virus interplay and neutralizing its impacts on the host immune system. In this review, we investigated the molecular aspect and potential therapeutic targets associated with cell receptors and downstream signaling cascades. Evidence Acquisition: In this review, we presented the available information regarding the coronavirus disease 2019 (COVID-19). A systematic search was implemented on several online databases, including Google Scholar, PubMed, and Scopus during 2019-2021 using the following keywords: "SARS-CoV-2", "COVID-19", "ACE-2", "Therapeutic Targets", "Acute respiratory distress syndrome", and "Cytokine Storm". Results: Various internal or external agents are responsible for the virus infectivity and stimulating acute immune system response. Since currently there is no cure for the treatment of COVID-19, several repurposed drugs can be employed to disrupt the process of viral entry and mitigate the symptoms raised by the cytokine storm. Inhibition of several agents, including signal transduction mediators and TMPRSS2 may be momentous. Conclusions: Despite the increase in the CFR, no drugs were developed with significant efficacy. Understanding the virus entry mechanism and the immune system’s role could help us surmount the problems in developing a promising drug or employing the repurposed ones.

Successful Treatment of Severely Hypotensive Pediatric Patients with Multisystem Inflammatory Syndrome in Children (MIS-C) with the Guidance of Invasive Hemodynamic Monitoring: A Report of Three Cases

Introduction: Since the beginning of the coronavirus disease 2019 (COVID-19) outbreak, it was assumed that infection rate in pediatric patients is lower than in adults and that infection is less severe in children than adult patients. Recently, there have been several reports and case series presenting critically-ill children with COVID-19, but still, severe hypotension is rare in pediatric patients with COVID-19. Case Presentation: We describe three pediatric cases with COVID-19 who presented with multi-system organ failure and severe hypotension treated with the guidance of the parameters of an invasive continuous hemodynamic monitoring device. We also compare their parameters with few articles on pediatric sepsis parameters. Conclusions: Although we usually start the treatment of hypotensive pediatric patients with hydration and epinephrine as an inotrope, in our cases, we required a different treatment plan according to the hemodynamic monitoring parameters, which indicates the value of the utilization of these devices in pediatric intensive care units

Serotype Distribution of Streptococcus pneumoniae Carriage ‎in Six-Month-Old Infants: A Cross-sectional Study During 2017-18, Tehran, ‎Iran

Background: Streptococcus pneumoniae is recognized as one of the main pathogens inducing several invasive and non-invasive infections in children. Objective: The present study aimed to evaluate the serotype distribution of S. pneumoniae in six–month–old carriers. Methods: This study encompassed 600 six-month-old healthy infants whose pharyngeal swap samples were collected and then cultured to isolate S. pneumoniae. Twenty- five different serotypes were defined on positive culture samples by multiplex PCR. Results: In this study, 13 cases (2.2%) were positive S. pneumonia. The most common isolated serotypes of S. pneumoniae were serotypes 23F (n = 6, 1%) and 3 (n = 3, 0.5%), respectively. Notably, the most frequent serotype in formula-fed infants (n = 300) was Serotype 23F (n = 5, 1.7%); however, Serotype 3 (n = 3, 1%) was the most frequent one in breastfed participants (n = 300). According to the findings, the overall coverage of PCV10, PCV13, and PPSV23 on the S. pneumoniae serotypes at the age of six months was 50%, 73%, and 85%, respectively. Conclusions: At this age, the type of feeding could not significantly affect the frequency rate of S. pneumoniae colonization, while the serotype distributions in the two breastfed and formula-fed groups were different.