Datasets:

CShorten

/

CORD19-Chunk-2

like 0

The Immunology of Bovine Respiratory Disease: Recent Advancements

Bovine respiratory disease (BRD) remains a leading cause of morbidity, mortality, and economic loss to the cattle industry. The continued high prevalence of the disease underlines a gap in understanding of the host immune response to respiratory infection. The host immune response is beneficial and detrimental, required for clearing the disease but often leading to tissue damage and long-term defects in lung function. This article highlights advancements made in understanding innate and adaptive immunity in BRD, factors that predispose animals to BRD, and novel intervention strategies that may lead to changes in the approach to treating and controlling BRD.

Veranstaltungstipps

Use of high frequency oscillatory ventilator in neonates with respiratory failure: the clinical practice in Taiwan and early multimodal outcome prediction

High-frequency oscillatory ventilation (HFOV) can be a rescue for neonates with refractory respiratory failure or an early elective therapy for preterm infants with severe respiratory distress syndrome (RDS). However, little is known about the current evolution and therapeutic limitations of HFOV. We therefore aimed to describe its use in clinical practice and predict the risk of mortality for neonates receiving HFOV. A retrospective observational study of all neonates treated with HFOV in a quaternary referral NICU between January 2007 and December 2016 was conducted. We classified these patients into five subgroups based on primary respiratory diagnoses. We performed the logistic regression and decision tree regression analyses to identify independent factors of 30-day mortality following HFOV. A total of 1125 patients who were ever supported on HFOV were enrolled, of whom 64.1% received HFOV as a rescue therapy, 27.2% received it as an elective therapy, and 8.7% received it for air leak. An average oxygenation index (OI) greater than 25 in the first 24 hours after the initiation of HFOV and patients with secondary pulmonary hypertension were found to have the greatest risk of in-hospital mortality (p < 0.0001). The overall in-hospital mortality rate was 25.8% (290/1125). Decision tree regression analysis revealed that neonates with refractory respiratory failure who had a pre-HFOV OI value higher than 20.5 and OI values higher than 21.5, 23.5 and 34 at 2 hours, 6 hours, and 12 hours after the use of HFOV, respectively, had a significantly increased risk of 30-day mortality. We identified the predictors and cutoff points of OI before and after the initiation of HFOV in neonates with respiratory failure, which can be clinically used as a reference for 30-day mortality. Further efforts are still needed to optimize the outcomes.

Antibodies against a short region of PfRipr inhibit Plasmodium falciparum merozoite invasion and PfRipr interaction with Rh5 and SEMA7A

Plasmodium falciparum merozoite invasion into erythrocytes is an essential step of the blood-stage cycle, survival of parasites, and malaria pathogenesis. P. falciparum merozoite Rh5 interacting protein (PfRipr) forms a complex with Rh5 and CyRPA in sequential molecular events leading to erythrocyte invasion. Recently we described PfRipr as a conserved protein that induces strain-transcending growth inhibitory antibodies in in vitro assays. However, being a large and complex protein of 1086 amino acids (aa) with 87 cysteine residues, PfRipr is difficult to express in conventional expression systems towards vaccine development. In this study we sought to identify the most potent region of PfRipr that could be developed to overcome difficulties related to protein expression, as well as to elucidate the invasion inhibitory mechanism of anti-PfRipr antibodies. Using the wheat germ cell-free system, Ecto- PfRipr and truncates of approximately 200 aa were expressed as soluble proteins. We demonstrate that antibodies against PfRipr truncate 5 (PfRipr_5: C(720)-D(934)), a region within the PfRipr C-terminal EGF-like domains, potently inhibit merozoite invasion. Furthermore, the antibodies strongly block PfRipr/Rh5 interaction, as well as that between PfRipr and its erythrocyte-surface receptor, SEMA7A. Taken together, PfRipr_5 is a potential candidate for further development as a blood-stage malaria vaccine.

Nonantibiotic Adjunctive Therapies for Community-Acquired Pneumonia (Corticosteroids and Beyond): Where Are We with Them?

Community-acquired pneumonia (CAP) is a leading cause of hospitalization, morbidity, and mortality. Despite advances in antibiotic treatments, mortality among patients with CAP is still high. For this reason, interest has been focused on nonantibiotic therapeutic measures directed to the host response rather than the microorganism. The development of an efficacious adjunctive treatment has important implications for reducing mortality in CAP. Some clinical studies performed in the last decade have shown a clinically beneficial effect of corticosteroids, possibly by diminishing local and systemic inflammatory host response. Recent meta-analyses showed faster resolution of symptoms, shorter time to clinically stability, reduction of mechanical ventilation needed, and reduction of mortality in the most severe population, although some methodological limitations must be taken into account. In addition, some studies using statins also suggested improved outcomes due to its anti-inflammatory effect in CAP, although this requires further research. Other adjunctive therapies such as immunoglobulins and stem cells are being explored, but are not yet in the stage of clinical trials. In summary, the use of corticosteroids and other adjuvant treatments are promising in CAP, but more studies are needed to determine their impact on mortality.

Community-Acquired Pneumonia in the Asia-Pacific Region

Community-acquired pneumonia (CAP) is an important cause of mortality and morbidity worldwide. Aging population, dense urbanization, and poor access to health care make the Asia-Pacific region vulnerable to CAP. The high incidence of CAP poses a significant health and economic burden in this region. Common etiologic agents in other global regions including Streptococcus pneumoniae, Mycoplasma pneumoniae, Haemophilus influenzae, Chlamydophila pneumoniae, Staphylococcus aureus, and respiratory viruses are also the most prevalent pathogens in the Asia-Pacific region. But the higher incidence of Klebsiella pneumoniae and the presence of Burkholderia pseudomallei are unique to the region. The high prevalence of antimicrobial resistance in S. pneumoniae and M. pneumoniae has been raising the need for more prudent use of antibiotics. Emergence and spread of community-acquired methicillin-resistant S. aureus deserve attention, while the risk has not reached significant level yet in cases of CAP. Given a clinical and socioeconomic importance of CAP, further effort to better understand the epidemiology and impact of CAP is warranted in the Asia-Pacific region.

Adenovirus: Epidemiology, Global Spread of Novel Serotypes, and Advances in Treatment and Prevention

Adenoviruses (AdVs) are DNA viruses that typically cause mild infections involving the upper or lower respiratory tract, gastrointestinal tract, or conjunctiva. Rare manifestations of AdV infections include hemorrhagic cystitis, hepatitis, hemorrhagic colitis, pancreatitis, nephritis, or meningoencephalitis. AdV infections are more common in young children, due to lack of humoral immunity. Epidemics of AdV infection may occur in healthy children or adults in closed or crowded settings (particularly military recruits). The disease is more severe and dissemination is more likely in patients with impaired immunity (e.g., organ transplant recipients, human immunodeficiency virus infection). Fatality rates for untreated severe AdV pneumonia or disseminated disease may exceed 50%. More than 50 serotypes of AdV have been identified. Different serotypes display different tissue tropisms that correlate with clinical manifestations of infection. The predominant serotypes circulating at a given time differ among countries or regions, and change over time. Transmission of novel strains between countries or across continents and replacement of dominant viruses by new strains may occur. Treatment of AdV infections is controversial, as prospective, randomized therapeutic trials have not been conducted. Cidofovir is the drug of choice for severe AdV infections, but not all patients require treatment. Live oral vaccines are highly efficacious in reducing the risk of respiratory AdV infection and are in routine use in the military in the United States, but currently are not available to civilians.

Avian Influenza A Viruses: Evolution and Zoonotic Infection

Although efficient human-to-human transmission of avian influenza virus has yet to be seen, in the past two decades avian-to-human transmission of influenza A viruses has been reported. Influenza A/H5N1, in particular, has repeatedly caused human infections associated with high mortality, and since 1998 the virus has evolved into many clades of variants with significant antigenic diversity. In 2013, three (A/H7N9, A/H6N1, and A/H10N8) novel avian influenza viruses (AIVs) breached the animal-human host species barrier in Asia. In humans, roughly 35% of A/H7N9-infected patients succumbed to the zoonotic infection, and two of three A/H10N8 human infections were also lethal; however, neither of these viruses cause influenza-like symptoms in poultry. While most of these cases were associated with direct contact with infected poultry, some involved sustained human-to-human transmission. Thus, these events elicited concern regarding potential AIV pandemics. This article reviews the human incursions associated with AIV variants and the potential role of pigs as an intermediate host that may hasten AIV evolution. In addition, we discuss the known influenza A virus virulence and transmission factors and their evaluation in animal models. With the growing number of human AIV infections, constant vigilance for the emergence of novel viruses is of utmost importance. In addition, careful characterization and pathobiological assessment of these novel variants will help to identify strains of particular concern for future pandemics.

Enterovirus D68 and Human Respiratory Infections

Enterovirus D68 (EV-D68) is a member of the species Enterovirus D in the genus Enterovirus of the Picornaviridae family. EV-D68 was first isolated in the United States in 1962 and is primarily an agent of respiratory disease. Infections with EV-D68 have been rarely reported until recently, when reports of EV-D68 associated with respiratory disease increased notably worldwide. An outbreak in 2014 in the United States, for example, involved more than 1,000 cases of severe respiratory disease that occurred across almost all states. Phylogenetic analysis of all EV-D68 sequences indicates that the circulating strains of EV-D68 can be classified into two lineages, lineage 1 and lineage 2. In contrast to the prototype Fermon strain, all circulating strains have deletions in their genomes. Respiratory illness associated with EV-D68 infection ranges from mild illness that just needs outpatient service to severe illness requiring intensive care and mechanical ventilation. To date, there are no specific medicines and vaccines to treat or prevent EV-D68 infection. This review provides a detailed overview about our current understanding of EV-D68-related virology, epidemiology and clinical syndromes, pathogenesis, and laboratory diagnostics.

Human Respiratory Syncytial Virus: Infection and Pathology

The human respiratory syncytial virus (hRSV) is by far the major cause of acute lower respiratory tract infections (ALRTIs) worldwide in infants and children younger than 2 years. The overwhelming number of hospitalizations due to hRSV-induced ALRTI each year is due, at least in part, to the lack of licensed vaccines against this virus. Thus, hRSV infection is considered a major public health problem and economic burden in most countries. The lung pathology developed in hRSV-infected individuals is characterized by an exacerbated proinflammatory and unbalanced Th2-type immune response. In addition to the adverse effects in airway tissues, hRSV infection can also cause neurologic manifestations in the host, such as seizures and encephalopathy. Although the origins of these extrapulmonary symptoms remain unclear, studies with patients suffering from neurological alterations suggest an involvement of the inflammatory response against hRSV. Furthermore, hRSV has evolved numerous mechanisms to modulate and evade the immune response in the host. Several studies have focused on elucidating the interactions between hRSV virulence factors and the host immune system, to rationally design new vaccines and therapies against this virus. Here, we discuss about the infection, pathology, and immune response triggered by hRSV in the host.

Parainfluenza Virus Infection

Human parainfluenza viruses (HPIVs) are single-stranded, enveloped RNA viruses of the Paramyoviridaie family. There are four serotypes which cause respiratory illnesses in children and adults. HPIVs bind and replicate in the ciliated epithelial cells of the upper and lower respiratory tract and the extent of the infection correlates with the location involved. Seasonal HPIV epidemics result in a significant burden of disease in children and account for 40% of pediatric hospitalizations for lower respiratory tract illnesses (LRTIs) and 75% of croup cases. Parainfluenza viruses are associated with a wide spectrum of illnesses which include otitis media, pharyngitis, conjunctivitis, croup, tracheobronchitis, and pneumonia. Uncommon respiratory manifestations include apnea, bradycardia, parotitis, and respiratory distress syndrome and rarely disseminated infection. Immunity resulting from disease in childhood is incomplete and reinfection with HPIV accounts for 15% of respiratory illnesses in adults. Severe disease and fatal pneumonia may occur in elderly and immunocompromised adults. HPIV pneumonia in recipients of hematopoietic stem cell transplant (HSCT) is associated with 50% acute mortality and 75% mortality at 6 months. Though sensitive molecular diagnostics are available to rapidly diagnose HPIV infection, effective antiviral therapies are not available. Currently, treatment for HPIV infection is supportive with the exception of croup where the use of corticosteroids has been found to be beneficial. Several novel drugs including DAS181 appear promising in efforts to treat severe disease in immunocompromised patients, and vaccines to decrease the burden of disease in young children are in development.

Herpesvirus Respiratory Infections in Immunocompromised Patients: Epidemiology, Management, and Outcomes

Among immunocompromised individuals, members of the human Herpesviridae family are frequently encountered pathogens. Cytomegalovirus, herpes simplex virus 1 and 2, varicella zoster virus, Epstein–Barr virus, and human herpesvirus-6, -7, and -8 all establish latency after infection and can reactivate during periods of immunosuppression, leading to both direct and indirect adverse effects on the host including severe organ dysfunction as well as allograft rejection and loss after transplantation. While not all herpesviruses are primary respiratory pathogens, many of their manifestations include involvement of the respiratory tract. This article discusses the individual viruses, their epidemiology, and clinical manifestations as well as recommended treatment and preventive strategies.

Phylogeography and genetic diversity of the copepod family Cyclopidae (Crustacea: Cyclopoida) from freshwater ecosystems of Southeast Nigeria

BACKGROUND: Copepods are key components of aquatic ecosystems and can help regulate the global carbon cycle. Much attention has been paid to the species diversity of copepods worldwide, but the phylogeography and genetic diversity of copepods in Nigeria is unexplored. RESULTS: Using a mitochondrial cytochrome c oxidase subunit I marker, we preformed phylogenetic and phylogeographic analyses for Cyclopidae copepods in Southeast Nigeria. A high species diversity of Cyclopidae in Nigeria: 5 species of Tropocyclops, 5 species of Mesocyclops and 2 species of Thermocyclops from Cyclopidae were identified in 15 populations. Moreover, we detected 18 unique haplotypes, which fell into two distinct clades. Pairwise genetic distances (uncorrected p-distances) among the species of Cyclopidae ranged from 0.05 to 0.257. Several species co-existed in the same lake, and some haplotypes were shared among different geographic populations, suggesting a dispersal of Cyclopidae in our sampling region. Finally, we found that the population genetic diversity for each species of Cyclopidae was low in Nigeria. CONCLUSIONS: Our findings explored the species diversity and distribution of copepods within the family Cyclopidae for 15 Nigerian freshwater ecosystems: a high species diversity of Cyclopidae copepods was detected over a small geographic sampling range. Results from this study contribute to a better understanding of copepod diversity of Nigerian freshwater ecosystems.

Monitoring Leishmania infection and exposure to Phlebotomus perniciosus using minimal and non-invasive canine samples

BACKGROUND: In endemic areas of zoonotic leishmaniosis caused by L. infantum, early detection of Leishmania infection in dogs is essential to control the dissemination of the parasite to humans. The aim of this study was to evaluate the serological and/or molecular diagnostic performance of minimally and non-invasive samples (conjunctiva cells (CS) and peripheral blood (PB)) for monitoring Leishmania infection/exposure to Phlebotomus perniciosus salivary antigens in dogs at the beginning and the end of sand fly seasonal activity (May and October, respectively) and to assess associated risks factors. METHODS: A total of 208 sheltered dogs from endemic areas of leishmaniosis were screened. Leishmania DNA detection in PB on filter paper and CS was performed by nested-PCR (nPCR), while the detection of anti-Leishmania antibodies was performed using IFAT and ELISA. The exposure to P. perniciosus salivary antigens (SGH, rSP01 and rSP03B + rSP01) was measured by ELISA. RESULTS: Ninety-seven (46.6%) and 116 (55.8%) of the 208 dogs were positive to Leishmania antibodies or DNA by at least one test at the beginning and end of the sand fly season, respectively. IFAT and ELISA presented a substantial agreement in the serodiagnosis of leishmaniosis. Discrepant PB nPCR results were obtained between sampling points. Leishmania DNA was detected in CS of 72 dogs at the end of the phlebotomine season. The presence of antibodies to the parasite measured by ELISA was significantly higher in dogs presenting clinical signs compatible with leishmaniosis at both sampling points. Phlebotomus perniciosus salivary antibodies were detected in 179 (86.1%) and 198 (95.2%) of the screened dogs at the beginning and end of the phlebotomine season, respectively. CONCLUSIONS: The association between ELISA positivity and clinical signs suggests its usefulness to confirm a clinical suspicion. CS nPCR seems to be an effective and non-invasive method for assessing early exposure to the parasite. PB nPCR should not be used as the sole diagnostic tool to monitor Leishmania infection. The correlation between the levels of antibodies to P. perniciosus saliva and Leishmania antibodies suggests the use of a humoral response to sand fly salivary antigens as biomarkers of L. infantum infection. [Image: see text]

The role of molecular diagnosis in acute respiratory tract infection

Clustering of Feline Coronaviruses in Multicat Households

Simultaneous detection and typing of human metapneumovirus strains in nasopharyngeal secretions and cell cultures by monoclonal antibodies

Seasonal respiratory virus testing in management of adult cystic fibrosis patients

Absence of Melaka-virus in European children with respiratory disease

Respiratory Viral and Atypical Pneumonias

Comments on “Impact of bronchoalveolar lavage multiplex polymerase chain reaction on microbiological yield and therapeutic decisions in severe pneumonia in intensive care unit”

A highly efficient in vivo plasmid editing tool based on CRISPR-Cas12a and phage λ Red recombineering

Respiratory viruses and acute asthma in children

Broad reactivity of the Luminex xTAG Respiratory Virus Panel (RVP) assay for the detection of human rhinoviruses

IV, 6. Calicivirus RNA recombination

RNA recombination apparently contributed to the evolution of CVs. Nucleic acid sequence homology or identity and similar RNA secondary structure of CVs and non-CVs may provide a locus for recombination within CVs or with non-CVs should co-infections of the same cell occur. Natural recombinants have been demonstrated among other enteric viruses, including Picornaviridae (Kirkegaard and Baltimore, 1986; Furione et al., 1993), Astroviridae (Walter et al., 2001), and possibly rotaviruses (e.g., Desselberger, 1996; Suzuki et al., 1998), augmenting the natural diversity of these pathogens and complicating viral gastroenteritis prevention strategies based upon traditional vaccines. Such is the case for CVs and Astroviridae, whose recombinant strains may be a common portion of naturally circulating strains. The taxonomic — and perhaps biologic — limits of recombination are defined by the suggested recombination of Nanovirus and CV, viruses from hosts of different biologic orders; the relationship of picornaviruses and CVs, viruses in different families, as recombination partners; and the intra-generic recombination between different clades of NLVs.

Atypical respiratory pathogens

The main atypical pathogens in respiratory tract infections are classified on the basis of their ability to cause atypical pneumonia. This is not a well-defined clinical entity, and it is evident that atypical pathogens can sometimes cause ‘typical’ pneumonias and vice versa. This emphasizes the need for microbiological diagnosis, since it affects the selection of proper treatment, in which β-lactam antibiotics and aminoglycosides are not effective. Moreover, mixed infections caused by atypical and typical pathogens together are common. At this moment rapid and sensitive diagnostic methods are lacking. Besides numerous viruses, the main bacterial pathogens causing atypical pneumonias are Mycoplasma pneumoniae, two chlamydial species, Chlamydia pneumoniae and C. psittaci, one rickettsia, Coxiella burnetti, and several Legionella species. The majority of these pathogens cause upper respiratory tract infections more often than overt pneumonias. An atypical agent, Chlamydia pneumoniae, has also been associated with chronic inflammatory conditions in the cardiovascular system. The most recently discovered pathogen in atypical pneumonias is a hantavirus causing hantavirus pulmonary syndrome.

First report of two consecutive respiratory syncytial virus outbreaks by the novel genotypes ON-1 and NA-2 in a neonatal intensive care unit()

OBJECTIVE: Respiratory syncytial virus is a pathogen frequently involved in nosocomial outbreaks. Although several studies have reported nosocomial outbreaks in neonatal intensive care units, molecular epidemiology data are scarce. Here, the authors describe two consecutive respiratory syncytial virus outbreaks caused by genotypes ON-1 and NA-2 in a neonatal intensive care unit in São Paulo, Brazil. METHODS: A prospective search for respiratory syncytial virus was performed after diagnosing the index case and four other symptomatic newborns in the neonatal intensive care unit. Nasopharyngeal aspirate samples of all patients in the neonatal intensive care unit were tested for 17 respiratory viruses using real-time reverse transcriptase polymerase chain reaction. Genotyping was performed using nucleotide sequencing. RESULTS: From May to August 2013, two different outbreaks were detected in the neonatal intensive care unit. A total of 20 infants were infected with respiratory syncytial virus-A (ten and 14 with ON-1 and NA-2 genotypes, respectively). The mean age of the infants was 10 days, mean birth weight was 1,961 g, and the mean gestational age was 33 weeks. Risk factors (heart disease, lung disease, and prematurity) were present in 80% and 85.7% of infants in the ON-1 and NA-2 groups, respectively. In total, 45.8% of infants were asymptomatic and 20.8% required mechanical ventilation. Coinfections were not detected during the outbreaks. CONCLUSIONS: Infants in a neonatal intensive care unit who develop abrupt respiratory symptoms should be tested for respiratory viruses, especially respiratory syncytial virus. Even in the absence of severe symptoms, respiratory syncytial virus detection can prevent nosocomial transmission through infection control measures. A better understanding of respiratory syncytial virus molecular epidemiology is essential for developing new vaccines and antiviral drugs against respiratory syncytial virus.

Bronchiectasis: working together for better evidence

Feline infectious diseases: Our curiosity could be their salvation

Food-borne and water-borne diseases under climate change in low- and middle-income countries: Further efforts needed for reducing environmental health exposure risks

This paper provides a view of the major facts and figures related to infectious diseases with a focus on food-borne and water-borne diseases and their link with environmental factors and climate change. The global burden of food-borne diseases for 31 selected hazards was estimated by the World Health Organization at 33 million disability-adjusted life years (DALYs) in 2010 with 40% of this burden concentrated among children under 5 years of age. The highest burden per population of food-borne diseases is found in Africa, followed by Southeast Asia and the Eastern Mediterranean sub-regions. Unsafe water used for the cleaning and processing of food is a key risk factors contributing to food-borne diseases. The role of quality and quantity of water to the general burden of infectious diseases deserves attention, particularly in low- and middle-income countries, as its effects go beyond the food chain. Water-related infectious diseases are a major cause of mortality and morbidity worldwide, and climate change effects will exacerbate the challenges for the public health sector for both food-borne and water-borne diseases. Selected case studies from Africa and Asia show that (i) climate change extreme events, such as floods, may exacerbate the risks for infectious diseases spreading through water systems, and (ii) improvements related to drinking water, sanitation and hygiene could result in a significant reduction of intestinal parasitic infections among school-aged children. There is a need to better anticipate the impacts of climate change on infectious diseases and fostering multi-stakeholder engagement and multi-sectoral collaborations for integrated interventions at schools, community and household levels. The paper calls for giving priority to improving the environmental conditions affecting food-borne and water-borne infectious diseases under climate change.

Viral pharyngitis

Classical and molecular techniques for the diagnosis of viral gastroenteritis()

Ribavirin

Randomised, controlled trial of effectiveness of ampicillin in mild acute respiratory infections in Indonesian children

The recommended treatment for mild acute respiratory infections (ARI) in children is supportive care only, but many physicians, especially in developing countries, continue to prescribe antibiotic treatment because they believe it prevents progression to more severe ARI. To find out whether ampicillin treatment conferred any benefit over supportive care alone, a randomised, controlled trial was carried out among 889 children (under 5 years) with mild ARI in Indonesia. 447 were randomly allocated ampicillin (25-30 mg/kg body weight three times daily for 5 days) plus supportive care (continued breastfeeding, clearing of the nose, and paracetamol to control fever); 442 were allocated supportive care only. The treatment groups were almost identical after randomisation in terms of age, sex, level of parental education, history of measles immunisation, and fever. After 1 week the percentages cured were nearly identical (204 [46%] ampicillin; 209 [47%] control), as were the percentages of cases progressing to moderate ARI (56 [13%] vs 53 [12%]). The effect of treatment was not modified by age, sex, measles immunisation status, or the educational level of the parents. At the 2-week follow-up, the percentages cured were 62% (277) in the ampicillin group and 58% (256) in the control group; 14% of both groups had progressed to moderate ARI; and 24% (107) and 28% (123), respectively, still had mild ARI. None of the differences in outcome between the ampicillin and control groups was statistically significant. Thus, ampicillin plus supportive care offers no benefit over supportive care alone for treatment of mild ARI in young Indonesian children.

The wheezing infant

Wheeze is a symptom and not a diagnosis. It is extremely common in infancy; 20-30% of children have experienced recurrent episodic wheezing by the age of 12 months. Wheezing may result from widespread peripheral airway narrowing or, less commonly, from localized central disease. Excluding recurrent viral wheezing and asthma-like symptoms, all other specific causes of wheezing (e.g. cystic fibrosis, congenital airway disorders, chronic lung disease of prematurity) affect only 2-3% of the population. Although wheezing disease preceded by acute viral bronchiolitis early in infancy features prominently in most articles on childhood asthma, it affects, at most, 1% of the population. The increased prevalence of reported wheezing in industrialized countries until the mid-1990s, accompanied by an increase in the number of hospital admissions for wheezing, represents a true increase in the problem rather than simply increased awareness. In the UK, wheezing in pre-school children accounts for about 25% of acute hospital admissions in childhood, and almost 50% during epidemics of respiratory syncytial virus (RSV) infection.

Virus-virus and virus-bacterium associations in the etiology of tuberculous and nontuberculous pneumopatia, during influenza season

Impact of a poorly performing point-of-care test during the 2017-2018 influenza season

T cell sensitization to proteolipid protein in myelin basic protein-induced relapsing experimental allergic encephalomyelitis

(SJL/J × PL/J)F(1) mice immunized with myelin basic protein (MBP) develop an autoimmune demyelinating disease termed relapsing experimental allergic encephalomyelitis (rEAE). The acute stage of disease is mediated by CD4(+) T cells specific for MBP amino acids 1–9. To determine the immunologic bases for disease relapse, host sensitization to additional autoantigens of the central nervous system was measured. Results indicate that most animals develop T cell reactivity to endogenous myelin proteolipid protein (PLP) during rEAE. However, PLP-specific immunity does not appear to accound for expression of relapse episodes of demyelination. relapse episodes of demyelination.

GASTROINTESTINAL AND NUTRITIONAL PROBLEMS IN CHILDREN WITH IMMUNODEFICIENCY AND AIDS

SCANDINAVIAN EPIDEMIC NEPHROPATHY AND KOREAN HÆMORRHAGIC FEVER

Infectious wastes: Myths and realities

Virus evolution

The epidemiology of respiratory infections in children()

Viral cytopathogenicity correlated with integration of ubiquitin-coding sequences()

The RNA genomes of cytopathogenic bovine viral diarrhea virus (BVDV) isolates contain insertions highly homologous to cellular sequences. For two of them the insert was identified as ubiquitin coding sequence. The genome of BVDV Osloss contains exactly one ubiquitin gene monomer. In the case of BVDV CP1 the cellular insertion comprises one complete ubiquitin gene and part of a second monomer. The host cell-derived element in the CP1 genome is embedded in a large duplication of about 2.4 kb of viral sequences. Cellular insertion and duplication were not found in the genome of NCP1, the noncytopathogenic counterpart of CP1. These results strongly suggest that recombination between viral and cellular RNA is responsible for development of the cytopathogenic viruses, which is linked to pathogenesis of a lethal disease in cattle.

VIRUS-LIKE PARTICLES IN INFECTIOUS HEPATITIS

Cold calling

Vaccination against flu viruses is well established and reasonably successful…

Contrasting effects of immunosuppression on herpes simplex virus type I (HSV I) induced central nervous system (CNS) demyelination in mice

We previously reported that lip inoculation of Herpes simplex virus type I (HSV I) in specific strains of mice would induce multifocal brain demyelination (MBD). The mechanisms mediating the development of MBD are unknown. In this study, five inbred strains of mice (C57BL/6J, Balb/cByJ, A/J, SJL/J, PL/J) immunosuppressed with either irradiation (IR), cyclophosphamide (CY), or cyclosporin A (CP) along with three immune deficient strains (C57BL/6J nu/nu, Balb/cByJ nu/nu, C57BL/6J bg/bg) were lip inoculated with HSV I to determine the effect of immunosuppression on viral spread throughout the brain and the development of demyelination during the acute stage of infection. Mortality increased in all groups when compared with controls but was greatest in A/J, SJL/J, and PL/J strains, where all mice died before day 6 PI. In contrast with immunocompetent C57BL/6J mice where virus is restricted to the brainstem, virus spread throughout the brain of immunosuppressed C57BL/6J, C57BL/6J nu/nu, and C57BL/6J bg/bg mice. Despite viral spread throughout the brain of immunosuppressed C57BL/6J, C57BL/6J nu/nu, Balb/cByJ and Balb/cByJ nu/nu mice, MBD did not develop. MBD did develop however, in both HSV I infected C57BL/6J bg/bg and CP treated Balb/cByJ mice. Immunosuppression of HSV I infected Balb/cByJ mice prevents the development of demyelination at the trigeminal root entry zone (TREZ) of the brainstem while in Balb/cByJ nu/nu mice, the extent of demyelination at TREZ was reduced and delayed when compared with immunocompetent controls. These results suggest that the immune system plays an important role in limiting viral spread in the brain as well as in the development of demyelination at TREZ and of MBD throughout the brain during the acute phase of infection. Virus alone does not induce MBD in this animal model of virus induced CNS demyelination but is a prerequisite for its development.

How ‘hidden’ reading frames are expressed

Secondary reading frames, ‘hidden’ under other reading frames, are used for coordinated expression of proteins in several eukaryotic viruses. In some genes, ribosomal frameshifting and initiation or reinitiation of protein synthesis on internal AUG codons are translational mechanisms allowing access to such ‘hidden’ reading frames. In others, secondary reading frames are translated from alternatively spliced or edited mRNAs.

Expression patterns of the ectopeptidases aminopeptidase N/CD13 and dipeptidyl peptidase IVICD26: immunoultrastructural topographic localization on different types of cultured cells

Aminopeptidase N/CD13 and dipeptidyl peptidase IV/CD26 are widespread membrane-bound peptidases involved in fundamental biological processes. Using cryo-ultramicrotomy of cultured cells followed by indirect immunogold labelling, both enzymes appeared to be strongly and regularly labelled on the cell surfaces of human synovial fibroblasts, T-Iymphocytes and colon carcinoma cells Caco-2. In the cytoplasm of the synovial fibroblasts gold-labelled vesicle-like structures were found, which we consider to be potential transport vesicles. An abundant and regular expression of CD13 was detected on cultured renal parenchymal cells. On the renal carcinoma cell line Caki-l cells we found a low, non-homogeneous and clustered CD13-labelling. On cultured renal parenchymal cells and the Caki-l cells CD26 could not be observed. The expression pattern of CD26 on renal carcinoma cell line Caki-2 cells showed also a slightly clustered distribution. A low density CD26-labelling was present on the squamous cell carcinoma cell line UM-SCC-22B. CD13 was absent in Caki-2 and UMSCC-22B cells. The presence of both enzymes on the cultured cells enables their ultrastructural investigation under different growth conditions and their involvement in cell-cell interactions. For this purpose, however, further investigations are necessary.

Avsunviroidae family: Viroids containing hammerhead ribozymes

This chapter focuses on the second viroid family, whose members are also referred to as hammerhead viroids, taking into account their most outstanding feature. If the word “small” is the first to come to mind when considering viroids, perhaps the second word is “hammerhead,” because this class of ribozymes, which because of its structural simplicity has an enormous biotechnological potential, is described in avocado sunblotch viroid (ASBVd) as well as in a viroid-like satellite RNA. The most outstanding feature of the Avsunviroidae members is their potential to adopt hammerhead structures in both polarity strands and to self-cleave in vitro accordingly. Viroids differ from viruses not only in their genome size but also in other fundamental aspects, prominent among which is the lack of messenger activity of both viroid RNAs and their complementary strands.

Mouse neuropathogenic poliovirus strains cause damage in the central nervous system distinct from poliomyelitis

Poliomyelitis as a consequence of poliovirus infection is observed only in primates. Despitea host range restricted to primates, experimental infection of rodents with certain genetically well defined poliovirus strains produces neurological disease. The outcome of infection of mice with mouse-adapted poliovirus strains has been described previously mainly in terms of paralysis and death, and it was generally assumed that these strains produce the same disease syndromes in normal mice and in mice transgenic for the human poliovirus receptor (hPVR-tg mice). We report a comparison of the clinical course and the histopathological features of neurological disease resulting from intracerebral virus inoculation in normal micewith those of murine poliomyelitis in hPVR-tg mice. The consistent pattern of clinical deficits in poliomyelitic transgenic mice contrasted with highly variable neurologic disease that developed in mice infected with different mouse-adapted polioviruses. Histopathological analysis showed a diffuse encephalomyelitis induced by specific poliovirus serotype 2 isolates in normal mice, that affected neuronal cell populations without discrimination, whereas in hPVR-tg animals, damage was restricted to spinal motor neurons. Mouse neurovirulent strains of poliovirus type 2 differed from mouse neurovirulent poliovirus type 1 derivatives in their ability to induce CNS lesions. Our findings indicate that the characteristic clinical appearance and highly specific histopathological features of poliomyelitis are mediated by the hPVR. Our data lead us to conclude that the tissue tropism of mouse-adapted poliovirus strains in normal mice is fundamentally different from that of poliovirus in hPVR-tg mice and primates, and that this is indicative of an as yet unknown mechanism of adsorption and uptake of the virus into cells of the murine CNS.

Alphaviruses — vectors for the expression of heterologous genes

DNA viruses and retroviruses are well established as vectors for the expression of heterologous genes, but there is increasing interest in the possibilities of using RNA viruses, which do not replicate through a DNA intermediate, for this purpose. This article summarizes some of the general properties of RNA viruses and concentrates on one class of RNA viruses — the alphaviruses — and their potential as expression vectors.

VI, 3. Molecular biology and epidemiology of Aichi virus and other diarrhoeogenic enteroviruses

The virion of the Aichi virus contains a single-stranded RNA molecule as the genome. The homology of Aichi virus structural proteins (VP0, VP3, and VP1) with corresponding polypeptides of other picornaviruses varies between 19% and 32%. The epidemiology of the Aichi virus as a medically important pathogen has not been well defined. Stool samples from adult patients in six oyster-associated gastroenteritis outbreaks were examined for variation, based on their reactivity with a monoclonal antibody raised against the standard strain (A486/88) and on reverse transcription–polymerase chain reactions (RT-PCR) of three genomic regions. Antibody to the Aichi virus could be detected using a neutralization test and an enzyme-linked immunosorbent assay (ELISA). These methods were used for the identification of Aichi virus infection in paired serum samples. The chapter concludes with a discussion on other diarrheagenic enteroviruses.

The disruption of infectious bronchitis virus (IBV-41 strain) with Triton X-100 detergent

Immunoblotting and dot blotting

Effects of immunopotentiating agents on alveolar macrophage properties

Infectious respiratory diseases in man and in domestic animals are characterized by the presence of a large number of different microorganisms: viruses, bacterias, mycoplasmas. It is therefore necessary to stimulate non-specific defense mechanisms in the lung and especially alveolar macrophages (AM). These cells, located in the alveolar air-spaces, play a major role in the lung clearance mechanisms and exert antibacterial, antiviral and antitumoral activities. Activation of alveolar macrophages was studied in vitro with lipopolysaccharide (LPS), lymphokines or mycobacterial derivatives (MDP). Rodent alveolar macrophages were rendered cytotoxic by in vitro exposure to LPS, free MDP or liposome-encapsulated MDP derivatives. In vivo, intravenously administered liposomes containing lipophilic MDP derivatives induced cytotoxic alveolar macrophages and protected mice against the development of pulmonary metastases.

Ambisense Rna Genomes of Arenaviruses and Phleboviruses

This chapter reviews the evidence that shows that arenaviruses and members of one genus of the Bunyaviridae (phleboviruses) have some proteins coded in subgenomic, viral-sense mRNA species and other proteins coded in subgenomic, viral-complementary mRNA sequences. This unique feature is discussed in relation to the implications it has on the intracellular infection process and how such a coding arrangement may have evolved. The chapter presents a list of the known members of the arenaviridae, their origins, and the vertebrate hosts from which isolates have been reported. It discusses the structural components, the infection cycle, and genetic attributes of arenaviruses. In order to determine how arenaviruses code for gene products, the S RNA species of Pichinde virus and that of a viscerotropic strain of LCM virus (LCM-WE) have been cloned into DNA and sequenced. The arenavirus S RNA is described as having an ambisense strategy, to denote the fact that both viral and viral-complementary sequences are used to make gene products. The chapter discusses the infection cycle, the structural and genetic properties of bunyaviridae member.

Viral-Bacterial Synergistic Interaction in Respiratory Disease

Humans and animals are constantly inoculated with various microorganisms resident in the upper respiratory tract and by inhaled aerosols, yet pneumonia is a relatively rare event. This implies the existence of very efficient defense mechanisms that are capable of eliminating the vast majority of microorganisms before they colonize and multiply to sufficient levels, resulting in clinical diseases. In order to overcome this continuous barrage of microorganisms, there is a complex array of defense mechanisms present in the upper and lower respiratory tract capable of eradicating these organisms. However, in individuals suffering from a variety of diseases, including virus infections, colonization occurs rapidly with subsequent development of pneumonia. Thus, it is estimated that 90% of bacterial pneumonias develop after a viral infection. Furthermore, individuals suffering from a viral pneumonia have a 40% chance of developing bacterial pneumonia. The reasons for the increased colonization of the lung by bacteria following virus infections are related to the surface properties of epithelial cells lining the respiratory tract, the physiological environment of the respiratory tract, and the alteration of the specific and nonspecific defense mechanisms of the lung that occurs as a result of virus infection.

Viral Enteritis

Viral enteritis, rotavirus enteritis in particular, has emerged as the major cause of infant diarrhea throughout the world. A new understanding of the causes and mechanisms of viral diarrhea has provided the basis for new approaches to active and preventive therapy. The administration of rational oral fluids and early provisions of nutrients have been beneficial in acute cases. Work to develop vaccines for human rotavirus has been promising, but a safe vaccine of proven effectiveness is not yet available.

299S1 DGHM Abstracts

Clinical, virologic, and serologic evidence of Epstein-Barr virus infection in association with childhood pneumonia()

To explore the association of Epstein-Barr virus infection with childhood pneumonia we studied two patients whose mononucleosis-like illnesses were accompanied by pneumonia; both had virologic and serologic evidence of current or recent EBV infection. We then analyzed the sera of 71 children (age range, 14 months to 9 years) with pulmonary infiltrates for the presence of four classes of antibody to EBV. Antibody responses consistent with current or recent EB virus infection were found in 15. Two children had IgM antibodies to the EBV viral antigen at titers ≥1:160, indicating current infection, and all 15 patients had antibody to components of the early antigen complex, suggesting recent infection. A fourfold rise or drop in one or more EBV-specific antibody classes was noted in eight patients within 30 days following onset of clinical illness. Few patients had clinical features suggesting infectious mononucleosis. Eight of the 15 with serologic evidence of current or recent EBV infection also had clinical or serologic evidence of infection with another pathogen-bacterial, viral, or mycoplasmal. Thus, in childhood pneumonia, EBV may be a primary, co-primary, or secondary pathogen; it may be reactivated in the course of infection with another agent, or possibly, by suppressing immune function, it may precipitate infection with some other organism.

Colostral transfer of bovine immunoglobulin E and dynamics of serum IgE in calves

The role of IgE in protective immunity is becoming understood, therefore the colostral transfer of IgE and the age-dependent changes of IgE levels may be important for neonatal immunity. To investigate this question, serum samples were collected from range-fed Hereford cows and their calves from birth through 9 months of age. The sera were assayed for total IgE by enzyme-linked immunosorbent assay (ELISA). Calves were found to have significant levels of IgE during the first week postpartum, indicating colostral transfer of IgE. Thereafter, serum levels declined rapidly within 3 weeks from birth. The IgE levels began to increase after 12 weeks of age, and in some cases reached adult levels. The passive transfer of maternal IgE through colostrum may be important in providing early protection from disease, especially against intestinal parasites.

Viral respiratory diseases in children: Classification, etiology, epidemiology, and risk factors()()()

The epidemiology, molecular structure, cell tropism, and pathophysiology of many human disease-causing viruses have been painstakingly and elegantly characterized during the past 50 years. Vaccines and antiviral drugs of varying efficacy were developed and tested. Despite the relegation of smallpox to a freezer chest and the progress in the control of measles and hepatitis B, the viruses that cause respiratory tract infections remain significant causes of illness and death in pediatric populations worldwide. This discussion surveys the virus groups that contain nearly 200 distinct viruses that cause sporadic and epidemic respiratory infections in children. The epidemiology of infection with the influenza A and B, parainfluenza, and respiratory syncytial viruses and adenoviruses and their impact on infants and children and the groups at highest risk for morbid outcomes are discussed. (J PEDIATR 1994;124:S13-S6)

Effective Use of the Diagnostic Laboratory in Dairy Practice

Infectious disease in athletes

Multiplex RT-nested PCR differentiation of gill-associated virus (Australia) from yellow head virus (Thailand) of Penaeus monodon

A multiplex RT-nested PCR has been developed to detect and differentiate the closely related prawn viruses, gill-associated virus (GAV) from Australia and yellow head virus (YHV) from Thailand. RT-PCR using primers to conserved sequences in the ORF1b gene amplified a 794 bp region of either GAV or YHV. Nested PCR using a conserved sense primer and either a GAV- or YHV-specific antisense primer to a divergent sequence differentially amplified a 277 bp region of the primary PCR amplicon. Multiplexing the YHV antisense primer with a GAV antisense primer to another divergent sequence allowed the viruses to be distinguished in a single nested PCR. Nested PCR enhanced detection sensitivity between 100- and 1000-fold and GAV or YHV RNA was detectable in ∼10 fg lymphoid organ total RNA. The multiplex RT-nested PCR was also able to co-detect GAV and YHV RNA mixed over a wide range of concentrations to simulate potential dual-infection states. The robustness of the test was examined using RNA samples from Penaeus monodon prawns infected either chronically or acutely with GAV or YHV and collected at different locations in Eastern Australia and Thailand between 1994 and 1998. GAV- (406 bp) or YHV-specific (277 bp) amplicons were differentially generated in all cases, including five YHV RNA samples in which no primary RT-PCR amplicon was detected. Sequence analysis of GAV and YHV PCR amplicons identified minor variations in the regions targeted by the virus-specific antisense primers. However, none occurred at positions that critically affected the PCR.

Viral proteases as targets for chemotherapeutic intervention

Many viruses encode proteinases that are essential for infectivity, and are consequently attractive chemotherapeutic targets. The biochemistry and structure of the human immunodeficiency virus proteinase have been characterized extensively, and potent peptide-mimetic inhibitors have been developed. Techniques and strategies used to improve the efficiency of these compounds are likely to be applicable to other viral proteinases.

Laboratory Diagnosis of Swine Diseases

Evidence for the existence of IL-4 and IFNγ secreting cells in the T cell repertoire of naive mice

The kinetics with which IgE responses develop in vivo following immunization of experimental animals indirectly support the existence of IL-4-secreting T cells as a normal component of the T cell repertoire. At the same time, studies of IL-4-secreting cell frequencies directly ex vivo have argued that T cells with the potential to become IL-4 secretors exist in vivo, in the form of precursors requiring stimulation and 4 – 12 days of culture as well as restimulation with mitogen or Ag before they become detectable as lymphokine-secreting cells. We demonstrate here that intravenous administration of low doses of anti-CD3 mAb 145-2C11 results in IL-4 production within 60 min of stimulation as demonstrated by Northern analysis of mRNA and a sensitive, selective bioassay (CT.4S cell proliferation) of biologically active IL-4 protein. Production of IL-4 is paralleled by IFNγ synthesis, displaying similar kinetics. These findings, consistent with the presence of mature cells capable of IL-4 and IFNγ synthesis in the T cell repertoire of naive mice, are supported by the observation that stimulation of spleen cells from naive mice with anti-CD3 mAb in vitro for 12 h also results in strong IL-4 and IFNγ mRNA and protein synthesis. The data support and extend those obtained through analysis of cytokine mRNA synthesis alone, thereby providing evidence that “fresh” T cells are indeed capable of producing IL-4 directly ex vivo and are consistent with the existence of IL-4-secreting cells as a normal component of the T cell repertoire of naive mice.

Ste24: An Integral Membrane Protein Zinc Metalloprotease with Provocative Structure and Emergent Biology

Ste24, an integral membrane protein zinc metalloprotease, is found in every kingdom of eukaryotes. It was discovered approximately 20 years ago by yeast genetic screens identifying it as a factor responsible for processing the yeast mating a-factor pheromone. In animals, Ste24 processes prelamin A, a component of the nuclear lamina; mutations in the human ortholog of Ste24 diminish its activity, giving rise to genetic diseases of accelerated aging (progerias). Additionally, lipodystrophy, acquired from the standard highly active antiretroviral therapy used to treat AIDS patients, likely results from off-target interactions of HIV (aspartyl) protease inhibitor drugs with Ste24. Ste24 possesses a novel “α-barrel” structure, consisting of a ring of seven transmembrane α-helices enclosing a large (> 12,000 Å(3)) interior volume that contains the active-site and substrate-binding region; this “membrane-interior reaction chamber” is unprecedented in integral membrane protein structures. Additionally, the surface of the membrane-interior reaction chamber possesses a strikingly large negative electrostatic surface potential, adding additional “functional mystery.” Recent publications implicate Ste24 as a key factor in several endoplasmic reticulum processes, including the unfolded protein response, a cellular stress response of the endoplasmic reticulum, and removal of misfolded proteins from the translocon. Ste24, with its provocative structure, enigmatic mechanism, and recently emergent new biological roles including “translocon unclogger” and (non-enyzmatic) broad-spectrum viral restriction factor, presents far differently than before 2016, when it was viewed as a “CAAX protease” responsible for cleavage of prenylated (farnesylated or geranylgeranylated) substrates. The emphasis of this review is on Ste24 of the “Post-CAAX-Protease Era.”

Design of the first highly potent and selective aminopeptidase N (EC 3.4.11.2) inhibitor

A series of phosphinic compounds mimicking the transition state of substrates hydrolysed by aminopeptidase N (EC 3.4.11.2) were synthesized. These new compounds have potent inhibitory activities with Ki values in the nanomolar range. These derivatives behave as the most potent APN inhibitors designed to date.

Vγ9Vδ2 T cell-mediated non-cytolytic antiviral mechanisms and their potential for cell-based therapy

In healthy adult Homo sapiens, the most frequent circulating γδ T cells (Vγ9Vδ2) respond to pyrophosphomonoesters, alkylamines (together referred to as non-peptidic antigens, NpAgs) and nitrogen-containing bisphosphonates. The seemingly very low toxicity of bisphosphonate and pyrophosphomonoester drugs in vivo, may allow novel approaches to the immunotherapy of viral infections. For example, these drugs can be used to stimulate Vγ9Vδ2 T cells to release antiviral molecules that directly suppress virus replication without destroying the virus-replicating cells. In addition, the soluble molecules released by γδ T cells could boost the antiviral potency of cytotoxic T lymphocytes (CTLs) and promote antigen presentation. The relative therapeutic value of drug-induced direct antiviral and immunoregulatory activities may depend on the infecting virus as well as on the nature of protective immune responses.

OTC product: Kleenex Anti-Viral tissue

An invited commentary on: “Evidence based management guideline for the COVID-19 pandemic - Review article”

Opportunities for rapid viral diagnosis

A rapid, quantitative assay for titration of bovine virus diarrhoea-mucosal disease virus()

An end point dilution microtitration assay is described that can be used for the titration of both cytopathic and non-cytopathic isolates of bovine virus diarrhoea-mucosal disease virus. Indirect immunofluorescence is used to detect infected MDBK cells in the wells of Terasaki plates. The virus titre is derived from the number of uninfected wells, using the Poisson distribution. The assay is simple, fast and economical. Titres of cytopathic virus determined by the microtitration assay and standard plaque assay are equivalent.

Seasonality and prevalence of rotavirus in Al-Ain, United Arab Emirates

Background: Rotaviruses are the single most important causative agent of acute neonatal enteritis in most avian and mammalian species including humans. Rotaviruses infections have also been shown to be associated with the elderly, immunocompromised individuals and more recently with epidemic diarrheal illness in adults. Objectives: To study the incidence and the effect of seasonality on the prevalence of rotaviruses in Al-Ain, United Arab Emirates. Study design: A total of 650 stool samples submitted to the laboratories of two University Teaching Hospitals (Al-Ain and Tawam) and a private hospital (Oasis) were examined for the presence of rotaviruses from January 1990–December, 1992, using a commercially available latex agglutination assay. The meteorological data (temperature, relative humidity and rainfall) recorded during the sampling period was analyzed statistically to examine the effect of seasonality on the prevalence of rotavirus cases in Al-Ain, United Arab Emirates. Results: Rotavirus was detected in 21.4% of the samples examined. The predominant number of positive cases (35%) were in the 7–12 months age group. It was interesting to find rotavirus-positive cases in as low an age group as <3 months (3.6%) and as high as 10 years (8.04%). There was no significant difference on infection rates between male and female groups in the study. However, there was a significant difference between the national (38.18%) and non-national children (61.28%). The higher rate of the latter may be due to import of infections. There appeared to be a seasonal pattern of rotavirus occurrence in the cases studied, with a marked increase in the number of positive cases during the months when the relative humidity was low (25–45%) and there was no rainfall. Conclusions: Rotavirus was detected in all age groups with a predominance in 7–12 month age groups, and a higher incidence in non-nationals. There was a marked increase in the number of positive cases during the months when the relative humidity was low (25–45%) and there was no rainfall. These findings are discussed in relation to the epidemiology and prophylaxis of rotavirus infections.

HIV genetic variation: Life at the edge

New Developments in Fungal Virology

Although viruses are widely distributed in fungi, their biological significance to their hosts is still poorly understood. A large number of fungal viruses are associated with latent infections of their hosts. With the exception of the killer-immune character in the yeasts, smuts, and hypovirulence in the chestnut blight fungus, fungal properties that can specifically be related to virus infection are not well defined. Mycoviruses are not known to have natural vectors; they are transmitted in nature intracellularly by hyphal anastomosis and heterokaryosis, and are disseminated via spores. Because fungi have a potential for plasmogamy and cytoplasmic exchange during extended periods of their life cycles and because they produce many types of propagules (sexual and asexual spores), often in great profusion, mycoviruses have them accessible to highly efficient means for transmission and spread. It is no surprise, therefore, that fungal viruses are not known to have an extracellular phase to their life cycles. Although extracellular transmission of a few fungal viruses have been demonstrated, using fungal protoplasts, the lack of conventional methods for experimental transmission of these viruses have been, and remains, an obstacle to understanding their biology. The recent application of molecular biological approaches to the study of mycoviral dsRNAs and the improvements in DNA-mediated fungal transformation systems, have allowed a clearer understanding of the molecular biology of mycoviruses to emerge. Considerable progress has been made in elucidating the genome organization and expression strategies of the yeast L-A virus and the unencapsidated RNA virus associated with hypovirulence in the chestnut blight fungus. These recent advances in the biochemical and molecular characterization of the genomes of fungal viruses and associated satellite dsRNAs, as they relate to the biological properties of these viruses and to their interactions with their hosts are the focus of this chapter.

Reovirus infection in adult mice: the virus hemagglutinin determines the site of intestinal disease

Reovirus type 1, strain Lang, and type 3, strain Dearing, induced site-specific intestinal lesions in the adult mouse after intravenous inoculation. Reovirus type 1 caused inflammation and epithelial changes such as loss of nuclear polarity, villus blunting and crypt hyperplasia restricted to the ileum. In contrast, reovirus type 3 induced duodenitis, jejunitis, and ulcerative colitis. In the duodenum and jejunum, the epithelial cells appeared normal, but hemorrhage and inflammation in the lamina propria was present. In the colon, superficial ulceration, crypt abscesses, and intraluminal hemorrhage was observed. Segregation analysis using reassorant clones derived from reoviruses 1 and 3, suggested the viral hemagglutinin, encoded by genome segment S1, to be the major viral determinant of site specific intestinal disease following intravenous inoculation.

Amantadine for chronic hepatitis C: a magic bullet or yet another dead duck?

[32] Families of cysteine peptidases

This chapter presents families of cysteine peptidases. The activity of all cysteine peptidases depends on a catalytic dyad of cysteine and histidine. The order of the cysteine and histidine residues (Cys/His or His/Cys) in the linear sequence differs between families and this is among the lines of evidence suggesting that cysteine peptidases have had many separate evolutionary origins. The families C1, C2, and C10 can be described as “papainlike,” and form clan CA. The papain family contains peptidases with a wide variety of activities, including endopeptidases with broad specificity, endopeptidases with narrow specificity, aminopeptidases, and peptidases with both endopeptidase and exopeptidase activities. Papain homologs are generally either lysosomal or secreted proteins. The calpain family includes the calcium-dependent cytosolic endopeptidase calpain, which is known from birds and mammals, and the product of the sol gene in Drosophila. Calpain is a complex of two peptide chains. Picornains are a family of polyprotein-processing endopeptidases from single-stranded RNA viruses. Each picornavirus has two picornains (2A and 3C).

Improved cutaneous genetic immunization by microneedle array delivery of an adjuvanted adenovirus vaccine

Clinically distinguishable syndromes caused by viruses

Ribavirin efficacy in an in vivo model of Crimean-Congo hemorrhagic fever virus (CCHF) infection()

After intraperitoneal (i.p.) infection of infant mice with CCHF virus, virus titers in liver remained significantly higher than in other organs except blood (serum). Within the liver, virus antigen was first found by immunofluorescence (IFA) in Kupffer cells followed by more extensive hepatic spread. Later, virus was found in other organs including brain and heart. Ribavirin treatment significantly reduced infant mouse mortality and extended the geometric mean time to death. Ribavirin treatment reduced CCHF virus growth in liver and significantly decreased, but did not prevent, viremia. Despite a substantial viremia, infection of other organs including brain and heart was not detected in ribavirin-treated mice. A hepatotropic virus subpopulation with less neurovirulence than the parent was isolated from liver of ribavirin-treated mice (single dose, 100 mg/kg). After serial passage in placebo-treated mice, the exclusive hepatotropism was lost.

Virus-induced autoimmunity: Molecular mimicry as a route to autoimmune disease

Improvements in obtaining and characterizing mouse cerebrospinal fluid(): Application to mouse hepatitis virus-induced encephalomyelitis

This report describes advances in techniques for analyzing cellular and humoral immune components in the cerebrospinal fluid (CSF) of the mouse that are applicable to other laboratory animals. CSF studies undertaken during experimental infection of mice with JHM strain virus (JHMV) of mouse hepatitis virus are presented. A critical pitfall which can lead to erroneous or invalid results is contamination of the CSF by even minute quantities of blood. Means of avoiding this contamination are attention to anatomical reference points, the use of a micropipet, and prior intracardiac perfusion of animals with phosphate-buffered saline. Cells in the CSF were typed as either B, T, polymorphonuclear, or mononuclear cells by the combination of a microcytotoxicity assay and histologic stains. A radioimmunoassay (RIA) allowed quantification of antibodies to JHMV in the CSF and indicated the presence of intrathecal synthesis of antibody in chronically infected mice. The combined use of these sensitive methods makes possible CSF analysis in individual mice rather than in pooled groups.

Does muscle activation occur by direct mechanical coupling of transverse tubules to sarcoplasmic reticulum?

Our knowledge of the physiological and biochemical constituents of skeletal muscle excitation has increased greatly during the last few years but this has not led to a consensus of the physiological mode of muscle activation. Three hypotheses of transmission, involving either transmitter-receptor interaction or direct mechanical coupling, are still under active consideration. The hypothesis of direct mechanical coupling currently being evaluated proposes that the dihydropyridine receptor in the transverse tubules serves as a voltage sensor that communicates directly with the junctional foot protein/Ca(2+) channel of sarcoplasmic reticulum to initiate opening of the channel.

The spectrum of severe wheezing in childhood()

Chapter 8 Paramyxoviruses

The paramyxoviruses are a heterogeneous group of viruses causing a variety of clinical diseases in humans, animals, and birds. This chapter examines in more detail the structure and properties of the important human viruses in this group, namely measles, respiratory syncytial virus (RSV), mumps and parainfluenza viruses I-V. They are all enveloped, negative-stranded, riboviruses of helical symmetry. It is suggested that susceptible children, adolescents, and adults should be vaccinated against mumps, unless vaccination is contraindicated. Mumps vaccine can be of particular value to children approaching puberty and for adolescents and adults, especially males who have not had mumps in childhood. Ribavirin therapy may be particularly beneficial for children at risk for severe and often fatal RSV infection, such as infants with congenital heart disease. Attenuated measles vaccines have been developed empirically by selection of host range mutants, and are widely and successfully used throughout the world. Using the vaccine, some countries may soon eliminate measles as an endogenous virus but continued problems are anticipated, particularly in adults with viruses re-introduced by visitors from abroad. Basic studies on new antivirals are continuing (particularly with oligopeptides) but antiviral compounds are unlikely to have extended use in the clinic, except perhaps in tropical areas where the disease may be life threatening. However, a vaccination programme in these areas is preferable, and is an urgent need.

O manejo do absorvedor de CO(2) durante o uso do aparelho de anestesia como respirador mecânico em pacientes com COVID-19

Crossed immunoelectrophoresis: Qualitative and quantitative considerations

Invented 20 years ago, crossed immunoelectrophoresis (X-IEP) today is a technique of unusual power and myriad application. It combines very high resolution with exquisite specificity by alloying 2-dimensional electrophoresis with immunoprecipitation for symbiotic new potentialities. The consequent matchless quantitative/qualitative capabilities of X-IEP for analyzing antigens in complex mixtures, particularly by their idiomatic internal comparisons, are still not widely recognized. Because of this and the supposed complications of its use and interpretation, X-IEP is more rarely used than it should be. This essay discusses contemporary X-IEP with the particular aims of demonstrating that it is not difficult to use and of explaining with selected examples why it is peculiarly powerful for analyzing antigen mixtures like the body fluids, tissue and cell extracts, and microbial homogenates.

Greater frequency of viral respiratory infections in asthmatic children as compared with their nonasthmatic siblings()

A longitudinal clinical and microbiologic surveillance was conducted from October to May, 1971–1972, on 16 children with infectious asthma and 15 of their nonasthmatic siblings. Asthmaticchildren experienced a significantly greater frequency of viral respiratory infections than did nonasthmatic ones (5.1 vs. 3.8 per subject). This increased incidence appeared to be largely the result of a greater number of rhinovirus infections. While respiratory infections of identical etiology that occurred concurrently in an asthmatic and his sibling were equivalent in severity, illnesses were longer (but not significantly so) in asthmatic children.

Master author index

Expression in Escherichia coli and purification of biologically active L proteinase of foot-and-mouth disease virus

The foot-and-mouth disease virus (FMDV) Lb gene was cloned into bacterial expression vectors under the control of a T7 RNA polymerase promoter. The Lb protein was expressed in both an in vitro transcription-translation system and in Escherichia coli. In vitro expression of a construct containing the Lb gene fused to a portion of the VP4 and 3D genes demonstrated cis cleavage activity that could be blocked by the thiol protease inhibitor E-64. Lb expressed in E. coli was purified from the soluble fraction by metal chelation chromatography. Purified Lb had trans cleavage activity at the L/P1 junction and cleaved the p220 component of the cap-binding protein complex.

VIRUSES AND GASTROENTERITIS

Respiratory illness caused by picornavirus infection: a review of clinical outcomes

Background: Respiratory infections result from invasion of the respiratory tract, mainly by viruses, and are the leading cause of acute morbidity in individuals of all ages worldwide. During peak season, picornaviruses cause 82% of all episodes of acute nasopharyngitis (the common cold), the most frequent manifestation of acute respiratory infection, and produce more restriction of activity and physician consultations annually than any other viral or bacterial source of respiratory illness. Objective: This article reviews the clinical impact and outcomes of picornavirus-induced respiratory infections in specific populations at risk for complications. It also discusses the potential economic impact of the morbidity associated with picornavirus-induced respiratory infection. Methods: Relevant literature was identified through searches of MEDLINE, OVID, International Pharmaceutical Abstracts, and Lexis-Nexis. The search terms used were picornavirus, rhinovirus, enterovirus, viral respiratory infection, upper respiratory infection, disease burden, economic, cost, complications, asthma, COPD, immunocompromised, elderly, otitis media, and sinusitis. Additional publications were identified from the reference lists of the retrieved articles. Conclusions: Based on the clinical literature, picornavirus infections are associated with severe morbidity as well as considerable economic and societal costs. Future research should focus on identifying patterns of illness and the costs associated with management of these infections. New treatments should be assessed not only in terms of their ability to produce the desired clinical outcome, but also in terms of their ability to reduce the burden of disease, decrease health care costs, and improve productivity.

[33] Using confocal microscopy to study virus binding and entry into cells

The chapter presents a discussion on the study of virus binding and entry into cells by using confocal microscopy. For the study new approaches to study vaccinia virus (VV), binding and entry based on confocal microscopy are developed. These techniques do not require virus purification or labeling and generate data that reveal the absolute numbers of virus particles that have bound to or have entered into individual cells. The chapter describes these techniques and then illustrates with some of the results obtained. These methods should be applicable to any virus larger than 50 nm. The chapter discusses the way these techniques have generated data that cannot be obtained with classical binding or entry assays. Vaccina virus is the prototype of the poxvirus family. These are DNA viruses that replicate in the cell cytoplasm and have genomes between 150 and 300 kbp. These techniques are presented with a study of the binding and entry of VV. The methods have been particularly useful for studying VV because this virus produces two different forms of infectious virion that are antigenically and biologically distinct and are produced in widely differing amounts. Moreover, the extracellular enveloped virus (EEV) form of VV cannot be purified from contaminating IMV without disrupting the integrity of the outer envelope.

Nonculturable agents of viral gastroenteritis

Regulation of Tobamovirus Gene Expression

This chapter discusses tobacco mosaic virus (TMV) strains U1, OM, L, CGMMV, 0, and Cc. The production of each TMV protein is regulated differently, both in amounts and times of production. The chapter discusses some of the strategies that tobamoviruses uses to control gene expression: (1) different subgenomic RNA promoter/leader sequences control timing of expression of genes, (2) genes expressed via subgenomic mRNAs are expressed in decreasing amounts with increasing distances from the 3' terminus, and (3) TMV mRNAs appear to be translationally regulated differently from host mRNAs. Genome organization affects gene expression, but it appears to be equally important for the efficiency of replication and the ability of the genomic structure to be stably propagated. Different virus groups have evolved different gene arrangements. Tobamovirus genes expressed via subgenomic mRNAs appear to be expressed in increasing amounts when positioned nearer the 3’ terminus.