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New developments in the treatment of viral respiratory tract infections.

Most respiratory tract infections are viral in origin, yet until recently only a few effective therapies had been developed. This reflected the large number of causative agents and the generally benign course of most infections. However, increasing numbers of serious respiratory infections have been seen in recent years, due to the rising prevalence of immunodeficient patients and the emergence of previously unrecognised pathogens. Better understanding of viral structure, and novel methods of drug design and discovery are leading to the development of potentially valuable new treatments, particularly for influenza and respiratory syncytial virus infection.

Journal Article↗

Acute lower respiratory tract infections and respiratory syncytial virus in infants in Guinea-Bissau: a beneficial effect of BCG vaccination for girls community based case-control study.

Among measles unvaccinated infants in Guinea-Bissau, we tested whether case infants with acute lower respiratory tract infection (ALRI), especially ALRI caused by respiratory syncytial virus (RSV), were more likely to be Bacille Calmette Guerin (BCG)-unvaccinated and to have no scar after BCG vaccination than were control infants without symptoms of ALRI. Three hundred and eighty-six case infants with ALRI were identified at a paediatric clinic (N=84), a health centre (N=82), and in a community morbidity surveillance system (N=220). Control infants were matched on sex, age, and district and were also measles unvaccinated. In ALRI case infants, the adjusted OR of being BCG unvaccinated was 2.87 (1.31-6.32), 1.72 (0.48-6.19) in boys and 4.45 (1.48-13.4) in girls. Among BCG vaccinated ALRI case infants, the adjusted OR of having no BCG scar was 1.54 (0.86-2.75), 0.93 (0.45-1.91) in boys and 2.70 (1.21-6.02) in girls. In ALRI case infants with RSV infection, similar trends were observed. BCG vaccination may have a non-targeted protective effect against ALRI, the effect being most marked in girls.

BCG Vaccine↗

Antibiotics for preventing respiratory tract infections in adults receiving intensive care.

OBJECTIVES: Pneumonia is an important cause of mortality in intensive care units. The objective of this review was to assess the effects of antibiotics for preventing respiratory tract infections and overall mortality in adults receiving intensive care. SEARCH STRATEGY: We searched MEDLINE, proceedings of scientific meetings and reference lists of articles from January 1984 to September 1997. We also contacted investigators in the field. SELECTION CRITERIA: Randomised trials of antibiotic prophylaxis for respiratory tract infections and deaths among adult intensive care unit patients. DATA COLLECTION AND ANALYSIS: Trials were assessed for quality and investigators contacted for additional information. MAIN RESULTS: Overall 33 trials involving 5727 people were included. There was variation in the antibiotics used, patient characteristics and the risk of respiratory tract infections and mortality in the control groups. In 16 trials (involving 3493 patients) of a topical and systemic antibiotic combination, the average rates of respiratory tract infections and deaths in the control group were 33% and 28% respectively. There was a significant reduction of both respiratory tract infections (odds ratio 0.36, 95% confidence interval 0.30 to 0. 43) and total mortality (odds ratio 0.80, 95% confidence interval 0. 68 to 0.93). On average five patients needed to be treated to prevent one infection and 23 treated to prevent one death. In 17 trials (involving 2366 patients) of topical antimicrobials the rates of respiratory tract infections and deaths in the control groups were 30% and 24% respectively. There was a significant reduction of respiratory tract infections (odds ratio 0.57, 95% confidence interval 0.46 to 0.69) but not in total mortality (odds ratio 1.01, 95% confidence interval 0.84 to 1.22). REVIEWER'S CONCLUSIONS: A combination of topical and systemic prophylactic antibiotics can reduce respiratory tract infections and overall mortality in adult patients receiving intensive care. [This abstract has been prepared centrally.]

Adult↗

Procalcitonin, C-reactive protein and leukocyte count in children with lower respiratory tract infection.

BACKGROUND: Lower respiratory tract infection is the most common infection leading to unnecessary antibiotic treatment in children. Etiologic diagnosis is not immediately achieved, and the pathogen remains unidentified in a large number of cases. Neither clinical nor laboratory factors allow for a rapid distinction between bacterial and viral etiology. The aim of our study was to evaluate the reliability of procalcitonin (PCT), C-reactive protein (CRP) and leukocyte count in distinguishing pneumococcal, atypical and viral lower respiratory tract infection. METHODS: PCT, CRP and leukocyte count were measured in children with microbiologically documented diagnoses of lower respiratory tract infection. The results were compared of children with pneumococcal, atypical and viral etiologies. RESULTS: PCT and CRP showed significant correlation with a bacterial etiology of lower respiratory tract infection. No significance was found for leukocyte count. Using a cutoff point of 2 ng/ml for PCT and 65 mg/l for CRP, the sensitivities and specificities for distinguishing bacterial from viral lower respiratory tract infections were 68.6 and 79.4% for PCT and 79.1 and 67.1% for CRP. The sensitivities and specificities for distinguishing pneumococcal from other etiologies were 90.3 and 74.1% for PCT and 90.3 and 60% for CRP, respectively. CONCLUSIONS: High PCT and CRP values show a significant correlation with the bacterial etiology of lower respiratory tract infection. PCT and CRP show good sensitivity for distinguishing pneumococcal from other etiologies. PCT shows higher specificity than CRP. PCT and CRP can help make decisions about antibiotic therapy in children with lower respiratory tract infections.

Biomarkers↗

Wheezing following lower respiratory tract infections with respiratory syncytial virus and influenza A in infancy.

We examined the incidence of subsequent wheezing in 292 children, hospitalized for influenza A or respiratory syncytial virus (RSV) lower respiratory tract infection, during two consecutive seasons (November-December, 1993 and March-April, 1995). Questionnaires concerning episodes of wheezing and known risk factors for wheezy bronchitis were mailed to parents 1 year after hospitalization. Sixty per cent of parents reported two or more episodes of wheezing following either influenza A or RSV. Hospitalization as a result of wheezing was necessary in 15% of the patients. The severity of the primary infection, as indicated by the need for treatment in the intensive care unit (ICU), was correlated with later wheezing. No additional significant risk factors predicting later wheezing could be identified.

Asthma↗

Antimicrobial drugs for respiratory tract infections.

The respiratory tract of small animals is exposed to a large number of potential pathogens. If endogenous defense mechanisms are not able to remove the invading microorganism, infection may result. The veterinarian must then determine if antimicrobial therapy is appropriate and, if so, which drug to use, at which dose, and for how long. This article discusses the therapeutic problems that arise when deciding on antimicrobial therapy in small animal respiratory disease.

Animals↗

Rapid detection of respiratory viruses by centrifugation enhanced cultures from children with acute lower respiratory tract infections.

BACKGROUND: Acute respiratory tract infection (ARI) is the major cause of morbidity and mortality in young children in developing countries. Information on viral aetiology in ARI in India is very limited. OBJECTIVE: The aim of the study was to define the role of viruses in acute lower respiratory tract infections (ALRTI) in children in India using centrifugation enhanced cultures followed by indirect immunofluorescence (IIF). STUDY DESIGN: Nasopharyngeal aspirates (NPAs) were collected from children from September 1995 to April 1997, attending paediatric clinic of All India Institute of Medical Sciences (AIIMS) with symptoms of ALRTI. Virus isolation was done by centrifugation enhanced cultures using HEp-2, LLC-MK2 and MDCK cells. The viruses were identified at 24-48 h post inoculation by IIF staining using monoclonal antibodies to respiratory syncytial virus (RSV), parainfluenza virus (PIV), influenza virus and adenovirus. RESULTS: Of 200 NPA samples, 89 (44.5%) were positive for one or more viral pathogens. RSV was detected in 34 (17%) of all ALRTI cases followed by influenza viruses in 29 (14.5%), PIVs in 23 (11.5%) and adenoviruses in three (1.5%). In 79 children with bronchiolitis, RSV was most frequently isolated (25%) pathogen, while in bronchopneumonia cases (101) the most common viral pathogen was influenza virus (17%). In eight cases (4%) of ALRTI dual infections were detected. In 100 NPA specimens IIF staining on direct cell smears was carried out and viruses were detected in only 17%. RSV and influenza virus infection peaked from September to December, where as PIV infections were more frequent from January to April. CONCLUSION: Respiratory viruses accounted for 44.5% of cases of ALRTI in India and the results of viral aetiology could be given in 24-48 h using centrifugation enhanced cultures. RSV was the most common viral agent associated with ALRTI in children under 5 years of age with greater association with bronchiolitis.

Adenoviruses, Human↗

Host-pathogen relationships in respiratory tract infections.

The respiratory tract is continuously exposed to inhaled particles. The mucous membrane and the mechanisms of sneezing, coughing, and mucociliary clearance are the first line of defense. For the bronchioli and alveoli, the phagocytic cells are the cornerstone of defense against invading microorganisms. Alveolar macrophages and polymorphonuclear leukocytes are responsible for phagocytosis. For optimal phagocytosis, antibodies and complement are needed; phagocytic cells possess receptors for the Fc fragment of the immunoglobulin (IgG) molecule and complement. Receptors for cytokines are also present. These cytokines are important for activating the alveolar macrophage and recruiting other phagocytic cells and lymphocytes to the site of infection. Alveolar macrophages also contain cytophilic antibodies, IgG molecules that are bound to the cell via the F(ab)2 fragments. These cytophilic antibodies can interfere with the process of phagocytosis. They can bind to bacteria containing an Fc receptor (eg, Staphylococcus aureus protein A) and therefore provide the alveolar macrophage with a means to bind and digest staphylococci. Pulmonary surfactant proteins enhance the uptake of bacteria and viruses by alveolar macrophages and viruses. Thus surfactant contributes to the defense mechanisms of the lung. Phagocytic cells can injure alveoli. During the process of phagocytosis, toxic oxygen species and enzymes, needed for killing bacteria, are produced. These toxic substances may leak out of the cell and damage the surrounding tissues. All these phenomena contribute to the processes of inflammation. The function of phagocytic cells is decreased in smokers and by certain air pollutants. Phagocytic cells are crucial for the elimination of microorganisms.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacteria↗