Significance of Legionella pneumophila in human respiratory pathology

The etiological structure of acute pneumonia and acute respiratory diseases was studied with a view to establishing the proportion of L. pneumophila among other causative agents of such diseases. A total of 299 patients were examined over time. The etiological diagnosis based on the data of serological examination was made in 70.6% of the patients with acute pneumonia and in 65% of the patients with acute respiratory viral infections and influenza. In the etiology of pneumonia, the leading role was found to belong to influenza A (H3N2) and B viruses, as well as to adenovirus, while in the etiology of acute respiratory viral infections and influenza, to influenza B virus, adenovirus and Mycoplasma pneumoniae. The importance of L. pneumophila in the etiology of acute pneumonia and acute respiratory diseases was shown. The proportion of L. pneumophila proved to be, on the average, 9.9% in acute pneumonia and 9.8% in acute respiratory diseases. L. pneumophila occurred most frequently in mixed infections in combination with adenovirus and influenza B virus. Diseases of Legionella etiology were found to have a seasonal character, occurring mostly in winter and spring.     

Acute respiratory disease in the United States Army in the Republic of Vietnam, 1965-1970.

Respiratory tract infections represented one of the commonest illnesses that occurred among U.S. Army personnel stationed in the Republic of Vietnam. Between 1965 and 1970 the years of this review, respiratory tract infections ranked approximately equal to diarrheal disease as a cause of hospitalization or assignment to quarters. Rates varied between 20 and 110 per 1000 troops per year. The specific casual agents responsible for acute respiratory diseases in Vietnam were not defined. Limited observations suggest that members of the adenovirus group and respiratory syncytial viruses were involved. During the fall of 1968, influenza due to the A2 Hong Kong strain (H3N2) was widespread, but it was not associated with marked increases in rates of hospitalization or mortality. Mycoplasma pneumoniae was the most common demonstrable causative agent in soldiers admitted to hospitals with pneumonia, 42% in one series.     

Etiology of acute pneumonia occurring against a background of influenza and other acute respiratory viral infections

The etiology of acute pneumonia (AP) was studied in 229 patients who had the disease simultaneously with influenza (106 patients), other viral and mycoplasmal infections (48 patients), and without concomitant acute viral infections (75 patients). The use of the quantitative microbiological method and the indirect immunofluorescence test with autostrains or Streptococcus pneumoniae strains of serotypes 2, 3, and 6, prevailing in Leningrad in patients with acute inflammatory diseases of the lungs, made it possible to find out the pneumococcal etiology of AP in 95% of patients irrespective of the presence of acute respiratory viral infections. The etiological role of opportunistic bacteria was revealed in 13 AP patients (5.7%); in 2 of them the causative agent of AP was Staphylococcus aureus and in 11, various species of Gram-negative enterobacteria. The latter were the cause of complications in 8 cases of pneumococcal pneumonia.     

Global prevalence and case fatality rate of Enterovirus D68 infections,a systematic review and meta-analysis

A substantial amount of epidemiological data has been reported on Enterovirus D68 (EV-D68) infections after the 2014 outbreak. Our goal was to map the case fatality rate (CFR) and prevalence of current and past EV-D68 infections. We conducted a systematic review (PROSPERO, CRD42021229255) with published articles on EV-68 infections in PubMed, Embase, Web of Science and Global Index Medicus up to January 2021. We determined prevalences using a model random effect. Of the 4,329 articles retrieved from the databases, 89 studies that met the inclusion criteria were from 39 different countries with apparently healthy individuals and patients with acute respiratory infections, acute flaccid myelitis and asthma-related diseases. The CFR estimate revealed occasional deaths (7/1353) related to EV-D68 infections in patients with severe acute respiratory infections. Analyses showed that the combined prevalence of current and past EV-D68 infections was 4% (95% CI = 3.1–5.0) and 66.3% (95% CI = 40.0–88.2), respectively. The highest prevalences were in hospital outbreaks, developed countries, children under 5, after 2014, and in patients with acute flaccid myelitis and asthma-related diseases. The present study shows sporadic deaths linked to severe respiratory EV-D68 infections. The study also highlights a low prevalence of current EV-D68 infections as opposed to the existence of EV-D68 antibodies in almost all participants of the included studies. These findings therefore highlight the need to implement and/or strengthen continuous surveillance of EV-D68 infections in hospitals and in the community for the anticipation of the response to future epidemics.     

Digging through the Obstruction: Insight into the Epithelial Cell Response to Respiratory Virus Infection in Patients with Cystic Fibrosis

Respiratory virus infections are common but generally self-limiting infections in healthy individuals. Although early clinical studies reported low detection rates, the development of molecular diagnostic techniques by PCR has led to an increased recognition that respiratory virus infections are associated with morbidity and acute exacerbations of chronic lung diseases, such as cystic fibrosis (CF). The airway epithelium is the first barrier encountered by respiratory viruses following inhalation and the primary site of respiratory viral replication. Here, we describe how the airway epithelial response to respiratory viral infections contributes to disease progression in patients with CF and other chronic lung diseases, including the role respiratory viral infections play in bacterial acquisition in the CF patient lung.     

Diagnosis and treatment of viral diseases in recipients of allogeneic hematopoietic stem cell transplantation

Viral infections are important causes of morbidity and mortality after allogeneic stem cell hematopoietic transplantation (allo-HSCT). Although most viral infections present with asymptomatic or subclinical manifestations, viruses may result in fatal complications in severe immunocompromised recipients. Reactivation of latent viruses, such as herpesviruses, is frequent during the immunosuppression that occurs with allo-HSCT. Viruses acquired from community, such as the respiratory and gastrointestinal viruses, are also important pathogens of post-transplant viral diseases. Currently, molecular diagnostic methods have replaced or supplemented traditional methods, such as viral culture and antigen detection, in diagnosis of viral infections. The utilization of polymerase chain reaction facilitates the early diagnosis. In view of lacking efficacious agents for treatment of viral diseases, prevention of viral infections is extremely valuable. Application of prophylactic strategies including preemptive therapy reduces viral infections and diseases. Adoptive cellular therapy for restoring virus-specific immunity is a promising method in the treatment of viral diseases.     

Respiratory Viruses—Current Status and Future Prospects

The application of tissue culture technology has revealed several new groups of viruses, comprising scores of different serotypes, as important causes of upper and lower respiratory tract disease in man. Other agents as yet unrecognized undoubtedly exist.Present epidemiologic data, although still incomplete, point up the unique importance of certain of these viruses in respiratory diseases.The particular type and severity of respiratory syndrome produced by a virus is determined by the immune status of the host, by the presence of complicating disease and by characteristics intrinsic in the infecting agent itself.Respiratory virus control might be particularly beneficial in certain groups, particularly persons with allergic sensitivity and chronic pulmonary disease.For control of viral respiratory disease, active immunization would provide significant protection but highly polyvalent vaccines might be necessary. Adjuvants could be helpful in this regard.Certain vaccines formerly in use were produced from strains of viruses which have recently been shown to be oncogenic in animals. In addition, hybridization of viruses can occur, resulting in the incorporation of the oncogenic potential of one agent into the genetic constitution of another. The significance of these biologic phenomena to vaccination programs has yet to be defined.Passive immunization would provide short-lived protection and would find application only in uniquely susceptible populations or at times of augmented risk. Active immunization of pregnant women, however, could provide increased breadth and duration to the transplacental passive immunity in the newborn.Interferon-inducing agents could potentially provide broad spectrum antiviral protection, but the extent and duration of their effectiveness are unknowns.Certain chemical agents have been shown to have prophylactic and therapeutic effects against a limited number of clinically severe viral diseases. Finally, limited data suggest that climatic control in places of public gathering might be worth evaluating as a means of controlling the spread of viral respiratory infections.     

Pneumococcal and chlamydial infections in a closed community

An epidemic outbreak of acute respiratory infection (295 patients) in an organized group of young people was observed in December-May 1997-1998. Pneumococcal etiology was established by means of indirect immunofluorescence reaction in cases of outpatient pneumonia (81.9%), acute bronchitis (80%) and acute respiratory diseases (92.5%). Respiratory chlamydiosis caused by Chlamydia pneumoniae was detected in enzyme immunoassay with the use of immunoComb Chlamydia Bivalent IgG in patients with pneumonia (66.7%), acute bronchitis (60%) and acute respiratory diseases (50%). Synergic relationship between pneumococcal and chlamydial infections was noted.     

Netilmicin in the treatment of bacterial respiratory tract infections

Netilmicin - a semisynthetic aminoglycoside - was administered to 33 patients with the acute or chronic lower respiratory tract or pulmonary infections in a daily dose of 5 mg/kg body weight for 10 days. A principle criterium of patients classification to netilmicin therapy were sensitive bacterial strains either in sputum or in BAL liquid. A significant clinical improvement was noted in 88% of the treated patients. However, elimination of pathogens from the sputum was achieved only in 52% of these patients. No improvement was observed in 4% of the treated patients. No adverse reactions were noted. Netilmicin proved safe and effective antibacterial agent in patients with respiratory infections.     

Morbidity study of acute respiratory diseases to assess the indications for ambulatory care at a student polyclinic

The methods of the retrospective epidemiological analysis of morbidity rate among students attending a specialized polyclinic for students have made it possible to establish the fact that acute respiratory diseases of non-influenza etiology are of the greatest socio-economic importance for students living under the conditions of a hostel. Such importance of these infections is linked with the autonomous character of the epidemic process due to the "mixing" factor, the intensive realization of the drop mechanism of infection transfer, and high morbidity risk in the absence of immunoprophylactic remedies. The results of this study indicate that the student body may be considered a group of primary necessity for prophylactic medical examination aimed at the early detection of the consequences of the past disease and at the organization of timely and effective treatment of young people.     

The aetiology of SARS: Koch's postulates fulfilled

Proof that a newly identified coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV) is the primary cause of severe acute respiratory syndrome (SARS) came from a series of studies on experimentally infected cynomolgus macaques (Macaca fascicularis). SARS-CoV-infected macaques developed a disease comparable to SARS in humans; the virus was re-isolated from these animals and they developed SARS-CoV-specific antibodies. This completed the fulfilment of Koch's postulates, as modified by Rivers for viral diseases, for SARS-CoV as the aetiological agent of SARS. Besides the macaque model, a ferret and a cat model for SARS-CoV were also developed. These animal models allow comparative pathogenesis studies for SARS-CoV infections and testing of different intervention strategies. The first of these studies has shown that pegylated interferon-alpha, a drug approved for human use, limits SARS-CoV replication and lung damage in experimentally infected macaques. Finally, we argue that, given the worldwide nature of the socio-economic changes that have predisposed for the emergence of SARS and avian influenza in Southeast Asia, such changes herald the beginning of a global trend for which we are ill prepared.     

Combining Healthcare-Based and Participatory Approaches to Surveillance: Trends in Diarrheal and Respiratory Conditions Collected by a Mobile Phone System by Community Health Workers in Rural Nepal

BackgroundSurveillance systems are increasingly relying upon community-based or crowd-sourced data to complement traditional facilities-based data sources. Data collected by community health workers during the routine course of care could combine the early warning power of community-based data collection with the predictability and diagnostic regularity of facility data. These data could inform public health responses to epidemics and spatially-clustered endemic diseases. Here, we analyze data collected on a daily basis by community health workers during the routine course of clinical care in rural Nepal. We evaluate if such community-based surveillance systems can capture temporal trends in diarrheal diseases and acute respiratory infections.MethodsDuring the course of their clinical activities from January to December 2013, community health workers recorded healthcare encounters using mobile phones. In parallel, we accessed condition-specific admissions from 2011–2013 in the hospital from which the community health program was based. We compared diarrhea and acute respiratory infection rates from both the hospital and the community, and assigned three categories of local disease activity (low, medium, and high) to each week in each village cluster with categories determined by tertiles. We compared condition-specific mean hospital rates across categories using ANOVA to assess concordance between hospital and community-collected data.ResultsThere were 2,710 cases of diarrhea and 373 cases of acute respiratory infection reported by community health workers during the one-year study period. At the hospital, the average weekly incidence of diarrhea and acute respiratory infections over the three-year period was 1.8 and 3.9 cases respectively per 1,000 people in each village cluster. In the community, the average weekly rate of diarrhea and acute respiratory infections was 2.7 and 0.5 cases respectively per 1,000 people. Both diarrhea and acute respiratory infections exhibited significant differences between the three categories of disease rate burden (diarrhea p = 0.009, acute respiratory infection p = 0.001) when comparing community health worker-collected rates to hospital rates.ConclusionCommunity-level data on diarrhea and acute respiratory infections modestly correlated with hospital data for the same condition in each village each week. Our experience suggests that community health worker-collected data on mobile phones may be a feasible adjunct to other community- and healthcare-related data sources for surveillance of such conditions. Such systems are vitally needed in resource-limited settings like rural Nepal.     

An explosive outbreak of respiratory streptococcal infection with a droplet transmission mechanism

The data obtained in the study of an explosive outbreak of acute respiratory diseases, tonsillitis and scarlet fever in one of schools in Moscow have made it possible to exclude the alimentary mechanism of its development and to demonstrate the role of the droplet mechanism of transmission in the appearance of its outbreak. The epidemiological analysis of the outbreak has permitted the formulation of the hypothesis on the conditions of the formation and spread of the epidemic variant of the infective agent; this hypothesis corresponds to the available data in literature on the qualitative changes of the infective agent in the course of the epidemic process. The study has shown that the prophylaxis of the explosive outbreaks of respiratory streptococcal infections must be ensured by the system of epidemiological surveillance with timely intervention into the epidemiological process at its early stages.     

Interferonogenic properties of prodigiozan and its effectiveness in treating acute respiratory diseases in children

The capacity of prodigiozan to stimulate interferon production in the cell culture of the human palatine tonsil lymphocytes was studied. The interferonogenic properties of prodigiozan administered in the form of aerosols to children were also investigated. The efficacy of the prodigiozan aerosols in treatment of children with viral respiratory diseases was estimated. It was shown that prodigiozan stimulated interferon production in the cell culture of the tonsil lymphocytes (the titers of 1 : 2--1 : 8) and induced formation of endogenic interferon in the host (in the tonsils and blood serum) 24 hours after the aerosol administration. 100 micrograms of prodigiozan administered in the form of aerosols in a single dose or in 2 doses at an interval of 1--2 days had a pronounced therapeutic effect 1--2 days after the administration. The use of prodigiozan in treatment of children with acute viral respiratory infections promoted a decrease in the frequency of complications, such as pneumonia and otitis. The data are indicative of the validity of prodigiozan in treatment of children with acute respiratory infections.     

Repurposing the estrogen receptor modulator raloxifene to treat SARS-CoV-2 infection

The ongoing coronavirus disease 2019 (COVID-19) pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) necessitates strategies to identify prophylactic and therapeutic drug candidates to enter rapid clinical development. This is particularly true, given the uncertainty about the endurance of the immune memory induced by both previous infections or vaccines, and given the fact that the eradication of SARS-CoV-2 might be challenging to reach, given the attack rate of the virus, which would require unusually high protection by a vaccine. Here, we show how raloxifene, a selective estrogen receptor modulator with anti-inflammatory and antiviral properties, emerges as an attractive candidate entering clinical trials to test its efficacy in early-stage treatment COVID-19 patients.Subject terms: Infectious diseases, Drug development     

Aetiology of Acute Respiratory Tract Infections in Hospitalised Children in Cyprus

In order to improve clinical management and prevention of viral infections in hospitalised children improved etiological insight is needed. The aim of the present study was to assess the spectrum of respiratory viral pathogens in children admitted to hospital with acute respiratory tract infections in Cyprus. For this purpose nasopharyngeal swab samples from 424 children less than 12 years of age with acute respiratory tract infections were collected over three epidemic seasons and were analysed for the presence of the most common 15 respiratory viruses. A viral pathogen was identified in 86% of the samples, with multiple infections being observed in almost 20% of the samples. The most frequently detected viruses were RSV (30.4%) and Rhinovirus (27.4%). RSV exhibited a clear seasonality with marked peaks in January/February, while rhinovirus infections did not exhibit a pronounced seasonality being detected almost throughout the year. While RSV and PIV3 incidence decreased significantly with age, the opposite was observed for influenza A and B as well as adenovirus infections. The data presented expand our understanding of the epidemiology of viral respiratory tract infections in Cypriot children and will be helpful to the clinicians and researchers interested in the treatment and control of viral respiratory tract infections.     

Epidemiological trial of the prophylactic effectiveness of the interferon inducer dipyridamole with respect to influenza and acute respiratory diseases

The epidemiological effectiveness of dipyridamol, an interferon-inducing agent used for the prevention of influenza and viral acute respiratory diseases, was tested in 4 epidemiological trials, 3 of them carried out as double blind trials. Observations were made in groups of adults (a research institute, a factory) and children (a kindergarten, a school), comprising 1040 subjects in the test groups and 771 subjects in the control groups. The drug was used during the whole epidemic period (January--March 1983) according to the following schedule: 1 oral administration in 8 days, in doses of 8 mg for adults, 50 mg for schoolchildren and 24 mg for children in the kindergarten. The epidemiological effectiveness of the drug was evaluated by comparing the total morbidity rates in influenza and acute respiratory diseases in the test and control groups. The results of 4 trials showed a pronounced epidemiological effectiveness of dipyridamol. The values of the epidemiological effectiveness index of the drug were 2.38 in the kindergarten, 1.55 at the school, 7.42 at the factory and 2.16 at the research institute. The results of the study of dipyridamol suggest that further investigations should be made with a view to use it for the mass prevention of influenza and acute respiratory diseases.     

Evaluation of amyxin effect in prophylaxis of acute respiratory viral infections

The results of the evaluation of the oral inductor of endogenic interferon (amyxin), manufactured in Russia are presented. The use of amyxin was found to produce a drop in morbidity in acute respiratory virus infections (ARVI) among medical workers 3.4 times, i.e. the preparation exhibited a pronounced prophylactic effect with respect to ARVI. The use of the preparation was accompanied by a decrease in the number of manifest forms of ARVI. Persons given the preparation often had ARVI in a mild or asymptomatic form.