Immune system's role in viral encephalitis.

Viral infections can be a major thread for the central nervous system (CNS), therefore, the immune system must be able to mount a highly proportionate immune response, not too weak, which would allow the virus to proliferate, but not too strong either, to avoid collateral damages. Here, we aim at reviewing the immunological mechanisms involved in the host defense in viral CNS infections. First, we review the specificities of the innate as well as the adaptive immune responses in the CNS, using several examples of various viral encephalitis. Then, we focus on three different modes of interactions between viruses and immune responses, namely human Herpes virus-1 encephalitis with the defect in innate immune response which favors this disease; JC virus-caused progressive multifocal leukoencephalopathy and the crucial role of adaptive immune response in this example; and finally, HIV infection with the accompanying low grade chronic inflammation in the CNS in some patients, which may be an explanation for the presence of cognitive disorders, even in some well-treated HIV-infected patients. We also emphasize that, although the immune response is generally associated with viral replication control and limited cellular death, an exaggerated inflammatory reaction can lead to tissue damage and can be detrimental for the host, a feature of the immune reconstitution inflammatory syndrome (IRIS). We will briefly address the indication of steroids in this situation.

New respiratory enterovirus and recombinant rhinoviruses among circulating picornaviruses.

Rhinoviruses and enteroviruses are leading causes of respiratory infections. To evaluate genotypic diversity and identify forces shaping picornavirus evolution, we screened persons with respiratory illnesses by using rhinovirus-specific or generic real-time PCR assays. We then sequenced the 5 untranslated region, capsid protein VP1, and protease precursor 3CD regions of virus-positive samples. Subsequent phylogenetic analysis identified the large genotypic diversity of rhinoviruses circulating in humans. We identified and completed the genome sequence of a new enterovirus genotype associated with respiratory symptoms and acute otitis media, confirming the close relationship between rhinoviruses and enteroviruses and the need to detect both viruses in respiratory specimens. Finally, we identified recombinants among circulating rhinoviruses and mapped their recombination sites, thereby demonstrating that rhinoviruses can recombine in their natural host. This study clarifies the diversity and explains the reasons for evolution of these viruses.

Respiratory viruses in children younger than five years old with acute respiratory disease from 2001 to 2004 in Uberlândia, MG, Brazil

The main viruses involved in acute respiratory diseases among children are: respiratory syncytial virus (RSV), influenzavirus (FLU), parainfluenzavirus (PIV), adenovirus (AdV), human rhinovirus (HRV), and the human metapneumovirus (hMPV). The purpose of the present study was to identify respiratory viruses that affected children younger than five years old in Uberlândia, Midwestern Brazil. Nasopharyngeal aspirates from 379 children attended at Hospital de Clínicas (HC/UFU), from 2001 to 2004, with acute respiratory disease, were collected and tested by immunofluorescence assay (IFA) to detect RSV, FLU A and B, PIV 1, 2, and 3 and AdV, and RT-PCR to detect HRV. RSV was detected in 26.4% (100/379) of samples, FLU A and B in 9.5% (36/379), PIV 1, 2 and 3 in 6.3% (24/379) and AdV in 3.7% (14/379). HRV were detected in 29.6% (112/379) of the negative and indeterminate samples tested by IFI. RSV, particularly among children less than six months of life, and HRV cases showed highest incidence. Negative samples by both IFA and RT-PCR might reflect the presence of other pathogens, such as hMPV, coronavirus, and bacteria. Laboratorial diagnosis constituted an essential instrument to determine the incidence of the most common viruses in respiratory infections among children in this region.

Northern Ireland Point Prevalence Survey of Hospital-acquired Infections and Antimicrobial Use 2012

The PHA�coordinated Northern Ireland's participation in ECDC's National Prevalence Survey on�Hospital-Acquired Infections & on Antimicrobial Use. Hospitals in Northern Ireland participated in data collection between May and June 2012.This report provides a snapshot of the levels of hospital-acquired infections (HAI) and levels of antimicrobial use (AMU) in hospitals in Northern Ireland during 2012.There have been three previous HAI PPS surveys and the last survey was carried out in 2006. It is difficult to compare each survey as the data was collected in a different way. However, after making allowances, there was an overall drop in HAI prevalence of 18% from 2006 to 2012.The PPS data collection was undertaken by hospital teams between May and June 2012 (one hospital deferred data collection until September 2012 because of a move to a new hospital); 16 hospitals surveyed 3,992 eligible patients. The median age of all patients was 66 years. A total of 383 (10 per cent) children under 16 years of age were surveyed.�Key results from this year's survey:The prevalence of HAI was 4.2%. A total of 166 patients were diagnosed with an active HAI with 3 patients having more than one infection.When comparing ward specialties, HAI prevalence was highest for patients in adult intensive care units (ICUs) at 9.1 per cent, followed by care of the elderly wards at 5.7%.The most common types of HCAI were respiratory infections (including pneumonia and infections of the lower respiratory tract) (27.9 per cent of all infections), surgical site infections (18.9 per cent) and urinary tract infections (UTI) (11.8 per cent).Since the last PPS in 2006 there has been a reduction in MRSA infections - from 0.9 per cent �of the hospital population to less than 0.1 per cent in patients; and a five-fold reduction in C. difficile infections (from 1.1 per cent to 0.2 per cent).The prevalence of antimicrobial use was 29.5%.Most antibiotic use (60 per cent) in hospitals was in patients receiving treatment for infections which commenced in the community. Eleven percent of surgical prophylaxis was prescribed for greater than one day.��

Duplex-PCR assay for the detection of adenovirus and respiratory syncytial virus in nasopharyngeal samples

Human adenovirus (HAdV) and human respiratory syncytial virus (HRSV) are important etiologic agents of acute respiratory infections. In this study, a duplex polymerase chain reaction (PCR) assay was developed for the simultaneous detection of HAdV and HRSV in clinical samples. Sixty previously screened nasopharyngeal aspirates were used: 20 HAdV-positive, 20 HRSV-positive and 20 double-negative controls. Eight samples were positive for both viruses. The duplex PCR assay proved to be as sensitive and specific as single-target assays and also detected the mixed infections with certainty. The identification of both viruses in a single reaction offers a reduction in both cost and laboratory diagnostic time.

Impact of human metapneumovirus infection on in and outpatients for the years 2006-2008 in Southern Brazil

The human metapneumovirus (hMPV), member of the Paramyxoviridae family, has been reported as an important agent involved with acute respiratory infections (ARIs). The aim of this study is to identify hMPV as the etiological agent of ARIs on in and outpatients in the city of Curitiba, Southern Brazil, and describe clinical data of hMPV subtyping. A retrospective study was performed in 1,572 respiratory samples over a period of three years. hMPV was detected by reverse transcription-polymerase chain reaction and subtyping was performed by nucleotide sequencing. hMPV was present in 61 (3.9%) samples and subtypes A1, A2a, B1 and B2 were detected. The incidence of hMPV was higher in outpatients (5.9%), whose mean age was 19.7 years (range 6 months-75 years old), than in inpatients (3%), whose mean age was 7.6 months (range 1 month-26 years old). The outpatients had upper respiratory tract infections with flu-like symptoms and all hospitalized children had lower respiratory tract infections. A pediatric patient died from complications associated with hMPV A2a infection. hMPV has been reported as a respiratory pathogen in all age groups. No correlation was observed between viral subtype and disease severity in the samples of this study.

Infections with human coronaviruses NL63 and OC43 among hospitalised and outpatient individuals in São Paulo, Brazil

The incidence and clinical features of human coronaviruses (HCoVs) among Brazilian patients with respiratory illness are not well known. We investigated the prevalence of HCoVs among Brazilian outpatients and hospitalised patients with respiratory illnesses during 2009 and 2010. To identify the HCoVs, pancoronavirus and species-specific reverse-transcriptase polymerase chain reaction assays were performed. Five of 394 samples were positive for HCoVs (1.2%): 1/182 (0.5%) outpatients and 4/212 (1.8%) hospitalised patients. The OC43 and NL63 HCoVs were identified. Two patients were admitted to the intensive care unit. Underlying chronic disease was reported in cases and one diabetic adult died. HCoVs can cause lower respiratory infections and hospitalisation. Patients with pre-existing conditions and respiratory infections should be evaluated for HCoV infections.

Respiratory infection in congenital cardiac disease. Hospitalizations in young children in Spain during 2004 and 2005: the CIVIC Epidemiologic Study.

OBJECTIVES To evaluate the rate of hospitalization for acute respiratory tract infection in children less than 24 months with haemodynamically significant congenital cardiac disease, and to describe associated risk factors, preventive measures, aetiology, and clinical course. MATERIALS AND METHODS We followed 760 subjects from October 2004 through April 2005 in an epidemiological, multicentric, observational, follow-up, prospective study involving 53 Spanish hospitals. RESULTS Of our cohort, 79 patients (10.4%, 95% CI: 8.2%-12.6%) required a total of 105 admissions to hospital related to respiratory infections. The incidence rate was 21.4 new admissions per 1000 patients-months. Significant associated risk factors for hospitalization included, with odds ratios and 95% confidence intervals shown in parentheses: 22q11 deletion (8.2, 2.5-26.3), weight below the 10th centile (5.2, 1.6-17.4), previous respiratory disease (4.5, 2.3-8.6), incomplete immunoprophylaxis against respiratory syncytial virus (2.2, 1.2-3.9), trisomy 21 (2.1, 1.1-4.2), cardiopulmonary bypass (2.0, 1.1-3.4), and siblings aged less than 11 years old (1.7, 1.1-2.9). Bronchiolitis (51.4%), upper respiratory tract infections (25.7%), and pneumonia (20%) were the main diagnoses. An infectious agent was found in 37 cases (35.2%): respiratory syncytial virus in 25, Streptococcus pneumoniae in 5, and Haemophilus influenzae in 4. The odds ratio for hospitalization due to infection by the respiratory syncytial virus increases by 3.05 (95% CI: 2.14 to 4.35) in patients with incomplete prophylaxis. The median length of hospitalization was 7 days. In 18 patients (17.1%), the clinical course of respiratory infection was complicated and 2 died. CONCLUSIONS Hospital admissions for respiratory infection in young children with haemodynamically significant congenital cardiac disease are mainly associated with non-cardiac conditions, which may be genetic, malnutrition, or respiratory, and to cardiopulmonary bypass. Respiratory syncytial virus was the most commonly identified infectious agent. Incomplete immunoprophylaxis against the virus increased the risk of hospitalization.

Kartagener syndrome: an uncommon cause of neonatal respiratory distress?

We report a newborn with respiratory distress and situs inversus totalis. The diagnosis of primary ciliary dyskinesia was confirmed by both ultrastructural and functional investigations. The immotile cilia syndrome was suspected because of respiratory distress, situs inversus, abnormal nasal discharge and hyperinflated chest X-ray. We suggest that ultrastructural and functional investigations of the respiratory mucosa should be done in any newborn with respiratory distress without explanation for the respiratory problems. Establishment of the correct diagnosis at an early stage may allow to improve the prognosis provided prophylactic physiotherapy, vaccinations, and aggressive antibiotic treatment of intercurrent respiratory infections are instituted. CONCLUSION Despite its rarity, primary ciliary dyskinesia should be considered in unexplained cases of neonatal distress.

Neonatal treatment with recombinant ectodysplasin prevents respiratory disease in dogs with X-linked ectodermal dysplasia.

Patients with defective ectodysplasin A (EDA) have X-linked hypohidrotic ectodermal dysplasia (XLHED; OMIM#305100), a condition comprising hypotrichosis, inability to sweat, abnormal teeth, and frequent pulmonary infections. The XLHED dogs show the same clinical signs as humans with the disorder, including frequent respiratory infections that can be fatal. The respiratory disease in humans and dogs is thought to be due to the absence of tracheal and bronchial glands which are a vital part of the mucociliary clearance mechanism. In our XLHED model, the genetically missing EDA was replaced by postnatal intravenous administration of recombinant EDA resulting in long-term, durable corrective effect on adult, permanent dentition. After treatment with EDA, significant correction of the missing tracheal and bronchial glands was achieved in those dogs that received higher doses of EDA. Moreover, successful treatment resulted in the presence of esophageal glands, improved mucociliary clearance, and the absence of respiratory infection. These results demonstrate that a short-term treatment at a neonatal age with a recombinant protein can reverse a developmental disease and result in vastly improved quality of life.

Respiratory distress in a one-month-old child suffering brachial plexus palsy.

This paper describes a one-month-old girl presenting with respiratory and growth failure due to diaphragmatic paralysis associated with left brachial plexus palsy after forceps delivery. Despite continuous positive pressure ventilation and nasogastric feeding, the situation did not improve and a laparoscopic diaphragmatic plication had to be performed. When dealing with a child born with brachial plexus palsy, one must think of this possible association and if necessary proceed to the complementary radiological examinations. The treatment must avoid complications like feeding difficulties and failure to thrive, respiratory infections or atelectasis. It includes intensive support and a good evaluation of the prognosis of the lesion to decide the best moment for a surgical therapy.

Ewing sarcoma of the rib: respiratory tract infection as initial symptoms in a 14-year-old boy. Functional medical imaging findings

Ewing sarcoma or primitive neuroectodermal tumor (PNET) of bone is the second most common pediatric malignant bone tumor. The median age at diagnosis is 15 years and there is a male predilection of 1.5/1. The authors present the case of a 14-year-old boy with Ewing sarcoma situated on the left ninth rib which was being investigated for respiratory tract infection. Pleurisy is the most common misdiagnosis. Our case illustrates the importance of recognizing exceptional features when interpreting FDG PET or scintigraphy to prevent the misinterpretation of metastases as other etiologies, such as infection.

Receptors and endocytosis of coxsackievirus A9

Coxsackievirus A9 (CV-A9) belongs to human enteroviruses within family Picornaviridae, which are the main cause of aseptic meningitis. In addition, CV-A9 causes a wide range of other clinical manifestations of acute disease including respiratory infections, myocarditis, encephalitis and severe generalized infections in newborns. In this study, the functions of integrins αVβ6 and αVβ3 in the attachment and cellular entry of CV-A9 were analyzed. Further, virus and cell surface interactions and endocytosis of CV-A9 were studied in specific cell lines. Also, a method for production of GFP-expressing CV-A9 particles by long PCR-mediated mutagenesis and in vivo transcription was developed. The results indicated that RGD-motif (arginine-glycine-asparagine) that resides in the viral capsid is important for CV-A9 infection particularly in cell lines expressing integrin αVβ6 and that this integrin serves as a high affinity attachment receptor for the virus. CV-A9 is also capable of infecting certain cell lines independently of αV-integrins by binding to the cell surface HSPA5 protein. Regardless of the attachment stage, the internalization of the virus occurs via the same entry pathway and is dependent on β2M, dynamin, and Arf6 but independent of clathrin and caveolin-1. Furthermore, the virus internalization occurs within Arf6-containing vesicles suggesting that Arf6 is central mediator of CV-A9 endocytosis. While in this study the results of CV-A9 endocytosis were based on microscopical visualization within individual fixed cells, a rapid method for generation of a virus for real-time imaging was also described.

Th-1 and Th-2 cytokine production in infants with virus-associated wheezing

Wheezing associated with respiratory viral infections in infancy is very common and results in high morbidity worldwide. The Th1/Th2 pattern of immune response in these patients remains unclear and previous studies have shown controversial results. The aim of the present study was to compare the type of Th1/Th2 cytokine response between infants with acute bronchiolitis, recurrent wheezing and upper respiratory infections from a developing country. Infants younger than 2 years of age admitted to Hospital São Lucas, Porto Alegre, RS, Brazil, between May and November 2001, with an acute episode of wheezing associated with viral respiratory infection were selected. Subjects with upper respiratory infections from the emergency department were selected for the control group. Interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) levels from nasal aspirates were determined by ELISA from peripheral mononuclear cell cultures. Twenty-nine subjects with acute bronchiolitis, 18 with recurrent wheezing and 15 with upper respiratory infections were enrolled. There were no differences in family history of atopy or parental smoking between groups. Oxygen requirement was similar for the acute bronchiolitis and recurrent wheezing groups. The percentage of positive tests for the cytokines studied and the IFN-gamma/IL-4 ratio was similar for all groups. Comparison of the polarized Th1/Th2 cytokine results for the various groups showed no specific pattern of cytokine production. Infants with wheezing from a developing country do not show any specific predominant pattern of Th1/Th2 cytokine production, suggesting that multiple factors may be involved in the pathogenesis of this illness.

Molecular analysis of the bovine coronavirus S1 gene by direct sequencing of diarrheic fecal specimens

Bovine coronavirus (BCoV) causes severe diarrhea in newborn calves, is associated with winter dysentery in adult cattle and respiratory infections in calves and feedlot cattle. The BCoV S protein plays a fundamental role in viral attachment and entry into the host cell, and is cleaved into two subunits termed S1 (amino terminal) and S2 (carboxy terminal). The present study describes a strategy for the sequencing of the BCoV S1 gene directly from fecal diarrheic specimens that were previously identified as BCoV positive by RT-PCR assay for N gene detection. A consensus sequence of 2681 nucleotides was obtained through direct sequencing of seven overlapping PCR fragments of the S gene. The samples did not undergo cell culture passage prior to PCR amplification and sequencing. The structural analysis was based on the genomic differences between Brazilian strains and other known BCoV from different geographical regions. The phylogenetic analysis of the entire S1 gene showed that the BCoV Brazilian strains were more distant from the Mebus strain (97.8% identity for nucleotides and 96.8% identity for amino acids) and more similar to the BCoV-ENT strain (98.7% for nucleotides and 98.7% for amino acids). Based on the phylogenetic analysis of the hypervariable region of the S1 subunit, these strains clustered with the American (BCoV-ENT, 182NS) and Canadian (BCQ20, BCQ2070, BCQ9, BCQ571, BCQ1523) calf diarrhea and the Canadian winter dysentery (BCQ7373, BCQ2590) strains, but clustered on a separate branch of the Korean and respiratory BCoV strains. The BCoV strains of the present study were not clustered in the same branch of previously published Brazilian strains (AY606193, AY606194). These data agree with the genealogical construction and suggest that at least two different BCoV strains are circulating in Brazil.