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The virology of acute upper respiratory tract infections is presented in a survey. The first part includes general properties of viruses (structure, replication, maturation, classification), aetiological and immunological problems of viral infections. The different respiratory viruses and their clinical picture in particular are summarized in the second part.
Upper respiratory tract infections are the most common types of infectious diseases among adults. It is estimated that each adult in the United States experiences two to four respiratory infections annually. The morbidity of these infections is measured by an estimated 75 million physician visits per year, almost 150 million days lost from work, and more than $10 billion in costs for medical care. Serotypes of the rhinoviruses account for 20 to 30 percent of episodes of the common cold. However, the specific causes of most upper respiratory infections are undefined. Pneumonia remains an important cause of morbidity and mortality for nonhospitalized adults despite the widespread use of effective antimicrobial agents. There are no accurate figures on the number of episodes of pneumonia that occur each year in ambulatory patients. In younger adults, the atypical pneumonia syndrome is the most common clinical presentation; Mycoplasma pneumoniae is the most frequently identified causative agent. Other less common agents include Legionella pneumophila, influenza viruses, adenoviruses, and Chlamydia. More than half a million adults are hospitalized each year with pneumonia. Persons older than 65 years of age have the highest rate of pneumonia admissions, 11.5 per 1,000 population. Pneumonia ranks as the sixth leading cause of death in the United States. The pathogens responsible for community-acquired pneumonias are changing. Forty years ago, Streptococcus pneumoniae accounted for the majority of infections. Today, a broad array of community-acquired pathogens have been implicated as etiologic agents including Legionella species, gram-negative bacilli, Hemophilus influenzae, Staphylococcus aureus and nonbacterial pathogens. Given the diversity of pathogenic agents, it has become imperative for clinicians to establish a specific etiologic diagnosis before initiating therapy or to consider the diagnostic possibilities and treat with antimicrobial agents that are effective against the most likely pathogens.
STUDY OBJECTIVE: The aim of the study was to seek for a possible association between the incidence of upper respiratory tract infections and air temperature and humidity in the home. DESIGN: Recordings of temperature and relative humidity were made in living rooms and children's bedrooms over a six month period and related to incidence of upper respiratory tract infection. SETTING: The study was carried out in one general practice of 10,000 patients. PATIENTS: 297 children aged 24-59 months were studied, selected in random order from the practice age-sex register. MEASUREMENTS AND MAIN RESULTS: Temperature and humidity recordings were made with thermohygrograph recorders over six days. Upper respiratory tract infections were recorded (a) retrospectively over the previous 12 months, and (b) during the study period. Past history of acute otitis media and recent family history of respiratory infection were also obtained. No significant association was found between the variables, although the bedrooms of children with reported upper respiratory tract infections were cooler overnight than those of non-infected children (mean difference 0.8 degrees C, 95% confidence limits 0.7 degrees C). No association was found between reported or recorded upper respiratory tract infections and age or type of home, family size, level of occupancy, social class, or smoking habits. Only 15 children (5%) were identified by their parents as having had asthma, but 58 (19.5%) had had a "wheezy chest". A greater proportion of children who wheezed slept in cooler bedrooms, had gas fires rather than central heating, and had more smokers in the house. CONCLUSIONS: No association between upper respiratory tract infection and domestic temperature or humidity levels could be shown in this study. Since dampness is repeatedly presented as a health risk, further study is required.
Human metapneumovirus (hMPV) is a newly described human pathogen associated with respiratory disease. A real-time reverse transcriptase-polymerase chain reaction method was developed to detect this virus. This reports present the first 2 cases of hMPV disease diagnosed in Norway. Both patients were children with serious lower airway disease.
Seven hundred fifty patients with acute upper or lower respiratory tract infections were randomly assigned to receive 2 gm of erythromycin ethylsuccinate daily or 1.125 gm of clavulanate-potentiated amoxicillin daily in a single-blind, multicenter study. The efficacy of each formulation was similar, with close to 90% of patients in each treatment group being reported as either cured or improved. Gastrointestinal symptoms were the most commonly reported side effects, their overall incidence being similar in both treatment groups. However, diarrhea occurred more than twice as often in the amoxicillin group than the erythromycin group. In each group, the number of patients failing to complete treatment was similar; the main reasons cited for discontinuation were gastrointestinal symptoms. The results indicate that both erythromycin ethylsuccinate and clavulanate-potentiated amoxicillin are well tolerated and are equally effective for routine empirical treatment of acute respiratory tract infections.
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Twenty patients admitted to hospital with serious lower respiratory tract infections entered an open study of 400 mg enoxacin given orally twice a day for a minimum of seven days. Clinical signs and symptoms were completely cured or improved in six of eight patients with pneumonia, in nine of ten patients with bronchitis, and in two patients with bronchiectasis. Enoxacin was effective in eradicating the initial pathogens in 10 of 12 patients with positive cultures. Enoxacin was well tolerated. Only one treatment-related side-effect was observed during the study. Nine patients received concurrent treatment with theophylline, but no signs of theophylline toxicity were seen. Enoxacin is a safe and effective alternative to parenteral treatment of lower respiratory tract infections.
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Over the last decade, the spectrum of organisms causing community-acquired acute lower respiratory tract infections has changed. Streptococcus pneumoniae now causes approximately 30% of outpatient acute pneumonia-less than in former decades-whereas Mycoplasma pneumoniae is found in both young and elderly patients. The Enterobacteriaceae and Staphylococcus aureus are now seen more frequently as respiratory tract pathogens in community-acquired pneumonia patients, and they are the major organisms causing pneumonia in residents of homes for the elderly or nursing homes, and in immuno-compromised patients. Agents that were previously considered non-pathogenic for the respiratory tract include serotypes of Haemophilus influenzae other than type b, H. parainfluenzae and Moraxella (Branhamella) catarrhalis; these organisms affect mainly patients with underlying cardiopulmonary disease. Legionella species can cause sporadic as well as epidemic disease of the lower respiratory tract. Chlamydia pneumoniae is a newly recognized pathogen responsible for mild to severe upper and lower respiratory tract infections. In 60-80% of cases, hospital-acquired pneumonias are caused by Gram-negative bacilli and S. aureus. These organisms colonize the mucosal membranes of the upper respiratory tract and penetrate into the lower tract by aspiration or intubation.
Patients with lower respiratory tract infections [pneumonia (n = 16), bronchiectasis (n = 5) and acute exacerbations of chronic bronchitis (n = 44)] were treated daily with amoxycillin/clavulanic acid given either 1.2 g intravenously three times daily or 625 mg orally three times daily for 7-15 days. Symptoms, signs and sputum volume and colour were monitored daily. Chest X-ray, sputum culture and Gram-stain examinations were also carried out on days 1 and 5, and immediately after the end of the treatment. There was a clinical improvement, as indicated by the incidence of cough, dyspnoea and rales, and by sputum volume and colour in 90.8% of the patients. Microbiological improvement, as indicated by the complete elimination of sputum pathogens and pus cells, was achieved in the same proportion of patients (90.8%). In one patient, an adverse side-effect, diffuse exanthema, was noted. Amoxycillin/clavulanic acid possesses a high clinical and microbiological efficacy for lower respiratory tract infections.
BACKGROUND: Chlamydia pneumoniae infection can cause acute respiratory illnesses (including sinusitis, bronchitis, and pneumonia) that are sometimes associated with wheezing. Little is known about whether acute infection in a previously unexposed, nonasthmatic individual can produce persistent wheezing leading to a diagnosis of chronic asthma. OBJECTIVE: We sought to determine whether patients with acute C. pneumoniae respiratory tract infections would develop chronic asthma. METHODS: A consecutive series of 163 primary care outpatient adolescents and adults (average age 43, 45% male) who had acute wheezing illnesses or chronic asthma were evaluated for C. pneumoniae infection by serologic testing. A subgroup of these patients also had nasopharyngeal cultures for C. pneumoniae. RESULTS: Twenty patients (12%) were diagnosed with C. pneumoniae infection defined by serology (15), culture isolation (3), or both (2). Of these 20, 10 patients wheezed for the first time and 6 of them subsequently developed chronic asthma (5) or chronic bronchitis (1) along with a serologic profile suggesting chronic infection. The other 10 patients diagnosed with C. pneumoniae infection already had a diagnosis of chronic asthma. In these patients initial serologic findings suggested chronic rather than acute infection. CONCLUSIONS: Acute C. pneumoniae respiratory tract infections in previously unexposed, nonasthmatic individuals can result in chronic asthma. Patients previously diagnosed with chronic asthma should be evaluated for possible chronic C. pneumoniae infection.
The clinical efficacy and tolerability of ceftriaxone in the treatment of pneumonia and other lower respiratory tract infections were evaluated in 827 patients (515 pneumonia, 312 other lower respiratory tract infections) reported in the international literature (daily dose: 1 of 2 g.i.v. or i.m. in most patients). Therapeutic success was achieved in 738 patients (89.2%). Microbiological results were evaluated in 295 patients. Eradication of the most common respiratory pathogens was achieved in 100% of cases and of Enterobacteriaceae in 85.7%-100%. Adverse effects occurred in 4.9% of patients. A large multicenter trial was carried out in Italy using a single daily dose of 1-2 g by i.v. or i.m. Six hundred ninety-six patients were admitted to the study (370 pneumonia, and 326 other lower respiratory tract infections). Therapeutic success was achieved in 668 cases (96%). Pathogens were eradicated in 88% of cases (184 pts evaluated). Side effects were observed in 4.6% of cases.
Some of the newer quinolone derivatives (e.g., ciprofloxacin, enoxacin, fleroxacin, ofloxacin, pefloxacin, and amifloxacin) can be administered intravenously. Parenteral quinolone therapy is indicated primarily for patients receiving intensive care or in the early postoperative phase, for perioperative prophylaxis, and for patients with disturbed absorption. With respect to pharmacokinetic parameters, there are no substantial differences between parenteral and oral preparations of the quinolones. The quinolones have a long elimination half-life, a high volume of distribution, low protein-binding capacity, renal as well as extrarenal elimination, and limited biotransformation. Thus far, the limited data concerning the clinical efficacy and safety of quinolones are available only for the parenteral forms of ciprofloxacin, pefloxacin, and ofloxacin. The data available indicate good to excellent clinical and antimicrobiologic responses in patients with complicated urinary tract infections; respiratory tract infections; intraabdominal, bone and joint, skin and soft tissue infections; and difficult-to-treat infections (e.g., septicemia, nosocomial pneumonia, and fever of unknown origin in neutropenic patients).
Bordetella pertussis, Bordetella parapertussis, and Bordetella bronchiseptica are closely related subspecies that cause respiratory tract infections in humans and other mammals and express many similar virulence factors. Their lipopolysaccharide (LPS) molecules differ, containing either a complex trisaccharide (B. pertussis), a trisaccharide plus an O-antigen-like repeat (B. bronchiseptica), or an altered trisaccharide plus an O-antigen-like repeat (B. parapertussis). Deletion of the wlb locus results in the loss of membrane-distal polysaccharide domains in the three subspecies of bordetellae, leaving LPS molecules consisting of lipid A and core oligosaccharide. We have used wlb deletion (Deltawlb) mutants to investigate the roles of distal LPS structures in respiratory tract infection by bordetellae. Each mutant was defective compared to its parent strain in colonization of the respiratory tracts of BALB/c mice, but the location in the respiratory tract and the time point at which defects were observed differed significantly. Although the Deltawlb mutants were much more sensitive to complement-mediated killing in vitro, they displayed similar defects in respiratory tract colonization in C5(-/-) mice compared with wild-type (wt) mice, indicating that increased sensitivity to complement-mediated lysis is not sufficient to explain the in vivo defects. B. pertussis and B. parapertussis Deltawlb mutants were also defective compared to wt strains in colonization of SCID-beige mice, indicating that the defects were not limited to interactions with adaptive immunity. Interestingly, the B. bronchiseptica Deltawlb strain was defective, compared to the wt strain, in colonization of the respiratory tracts of BALB/c mice beginning 1 week postinoculation but did not differ from the wt strain in its ability to colonize the respiratory tracts of B-cell- and T-cell-deficient mice, suggesting that wlb-dependent LPS modifications in B. bronchiseptica modulate interactions with adaptive immunity. These data show that biosynthesis of a full-length LPS molecule by these three bordetellae is essential for the expression of full virulence for mice. In addition, the data indicate that the different distal structures modifying the LPS molecules on these three closely related subspecies serve different purposes in respiratory tract infection, highlighting the diversity of functions attributable to LPS of gram-negative bacteria.
A total of 256 patients were admitted in Germany into a Pan-European multi centre trial of doxycycline in the treatment of infections of the respiratory tract. The diagnoses showed a preponderance of lower respiratory tract infections compared with other European countries, due largely to the fact that the participating physicians were pulmonary or internal medicine specialists. Doxycycline was given in a dose of 200 mg initially followed by 100 mg daily for 5-10 days (only the occasional patient varied from this regimen). Side-effects were uncommon (2.5-3.5%) and affected only the gastrointestinal tract. Four patients had to change antibiotic therapy, not because of side-effects but because of possible bacterial resistance in these patients. The results were comparable with those from the rest of Europe: 88% of patients had a good or very good response. Nine patients were treated for longer than 14 days and only eight patients did not show improvement.
Health and economic burden of recurrent respiratory tract infections (RTIs) in early childhood is considerable. A systematic review of licensed influenza and pneumococcal vaccines showed substantial efficacy in children, but the health-economic impact of such vaccines among pre-school children with recurrent RTIs is unknown. We therefore, designed a double-blind randomized controlled trial to determine the effectiveness and costs of a combined influenza and pneumococcal vaccination program among a primary care based cohort of children with recurrent episodes of RTI aged between 18 and 72 months. We will enroll 690 children over three consecutive years (2003--2005) who will be randomly allocated to receive vaccinations against influenza and pneumococcal disease, influenza alone or hepatitis B in a similar schedule. Follow up by parental diaries, tympanic temperature measurements, questionnaires and interviews is planned until May 2006. Primary outcome is number of febrile RTIs. Other outcomes include duration and severity of RTI episodes, medical consumption, safety and costs.