Young Malaysian children with lower respiratory tract infections show low incidence of chlamydial infection

OBJECTIVE: The incidence of Chlamydia pneumoniae and Chlamydia trachomatis infection was studied among infants and young children admitted to hospital for the management of lower respiratory tract infections, over a 12 month period. METHODOLOGY: Respiratory secretions were examined for chlamydiae by cell culture, enzyme-linked immunosorbent assay and polymerase chain reaction-enzyme immunoassay. Sera were tested by micro-immunofluorescence for chlamydial IgG, IgM and IgA. Other bacterial and viral pathogens were also looked for by standard cultural and serological methods. RESULTS: Of 87 patients aged 2 months-3 years, an aetiologic diagnosis was made in 41 (47.1%). C. pneumoniae and C. trachomatis were each detected in 1 (1.2%) of the patients. Among common bacterial pathogens, Haemophilus influenzae (13.8%) and Streptococcus pneumoniae (8.1%) were the most frequently identified. Respiratory viruses and elevated Mycoplasma pneumoniae antibodies were found in 10.3% and 9.1% of patients, respectively. CONCLUSION: Chlamydiae are infrequent causes of community-acquired acute lower respiratory tract infections in infants and very young children in Malaysia.     

Epidemiology of acute bronchopulmonary infections in children

In infants and young children acute lower respiratory infection is the most common cause of morbidity and death especially in developing countries. Factors that contribute to the increased susceptibility to respiratory pathogens include young age, season, sex, indoor pollution, large family size, malnutrition, low immunocompetence, socioeconomic disadvantage. The epidemiology of acute respiratory infections in childhood seems similar worldwide. In all countries, respiratory syncytial virus, parainfluenzae virus 1 and 3 influenzae A and B viruses and adenovirus are reported to be the main causes of acute respiratory infections. Six microorganisms are responsible of 90% of documented acute bacterial pulmonary infections, Streptococcus pneumoniae, Mycoplasma pneumoniae, Chlamydia pneumoniae, Chlamydia trachomatis, Haemophilus influenzae, Staphylococcus. Mixed viral and bacterial infections occur frequently (30%). The role of respiratory viruses in predisposing to colonization and invasion of bacterial organisms has often been suggested. In recent years acquired resistance against antibiotic for H. influenzae and S. pneumoniae has emerged.     

Iodine-123-BMIPP myocardial washout and cardiac work during exercise in normal and ischemic hearts

Due to the changes in the frequency of penicillin-resistant strains of S. pneumoniae, it is necessary to perform surveillance studies of bacterial resistance. Isolates from the upper respiratory tract of asymptomatic children have been useful. There is no information about the difference between isolates from children with and without upper respiratory tract infection (URTI). The objective of the authors in this paper is to establish the prevalence of carrier-state, serotype and antimicrobial resistance of S. pneumoniae isolates from children with and without acute upper respiratory tract infection (URTI) in a rural area in Mexico. A cross-sectional comparative study was performed in Tlaxcala, Mexico. Children from one month 5 years of age were included. Nasopharyngeal swabs were obtained. Identification was done by international microbiology standards. Serotyping was done by the capsular Quellung test. The susceptibility testing was performed by the agar dilution method. Four-hundred and fifty patients were included. S. pneumoniae was isolated in 134 children (29.7%). Frequency of carriers was greater in patients with URTI (107/323) than without URTI (27/127) (33.1% vs. 21.1% p = 0.012, OR 1.84, IC 95% 1.1-3.08). The six most frequent serotypes were: 6B (16.4%); 19F (11.9%); 19A (6.7%); 14, 23F, and 35 (5.2% each), with no difference among the groups. Only 3% of the strains had high level resistance to penicillin, and 12.6% had intermediate resistance, and for ampicillin 4%, amoxicillin 4%, amoxicillin-clavulanate 4%, ceftriaxone 3%, cefotaxime 1.5%, erythromycin 6%, miocamycin 3%, chloramphenicol 4%, and vancomycin 0%. Trimethoprim-sulfamethoxazole resistance was very high (42%). In conclusion, colonization is higher in children with URTI. Five of the most frequent serotypes identified in this study were the same as those identified in patients with S. pneumoniae invasive diseases in Mexico City. In Tlaxcala, Mexico, beta-lactams could be the drug of choice for the treatment of S. pneumoniae lower respiratory tract infections. It is necessary to perform clinical assays to evaluate the efficacy of trimethoprim-sulfamethoxazole due to the high resistance in vitro.     

A clinical study of chronic lower respiratory infection with Haemophilus influenza by transtracheal aspiration

We have performed a clinical study on chronic lower respiratory tract infection (CLRTI) with Haemophilus influenzae (H. influenzae) by transtracheal aspiration (TTA) and analyzed clinical factors of the acute exacerbation. In 40 episodes (38 cases) of H. influenzae isolated from CLRTI, monobacterial infection with H. influenzae were 21 episodes and polymicrobial infection were 19 episodes. We classified the disease into acute exacerbated (27 episodes) and stable (13 episodes) phase and the former episodes were divided into bronchitis type (7 episodes) and pneumonia type (20 episodes). Polymicrobial infections were seen more in the pneumonia type (13 episodes) than in the bronchitis type (2 episodes). The principal organism detected with H. influenzae were alpha-Streptococcus and Neisseria sp. in the bronchitis type and S. pneumoniae in the pneumonia type. The acute exacerbated cases were divided into the following 4 patterns; 1. polymicrobial infection with continuous infection of P. aeruginosa, 2. monomicrobial infection after acute upper respiratory tract infection, 3. polymicrobial infection with S. pneumoniae after continuous infection of H. influenzae, 4. bacterial replacement by P. aeruginosa after acute exacerbation. The results of the study suggests that polymicrobial infection is an important chronic lower respiratory tract infection when caused H. influenzae.     

In vivo study on the immunomodulating effects of OM-85 BV on survival, inflammatory cell recruitment and bacterial clearance in Klebsiella pneumonia

Oral administration of the bacterial extract OM-85 BV has been shown to prime alveolar macrophages (AM) in such a way that they secrete significantly more nitric oxide, tumor necrosis factor-alpha and interleukin-1beta upon in vitro stimulation with lipopolysaccharide (LPS). As increased cytokine secretion by AM may account for the therapeutic effect of OM-85 BV in respiratory tract infections, we studied the effect of orally administered OM-85 BV on the outcome of Klebsiella pneumoniae-induced pneumonia. Mice received a daily oral dose of OM-85 BV (350 mg/kg body weight) for 5 days and were intratracheally infected with 333, 1000 or 3333 CFU K. pneumoniae on day 8. It was shown that OM-85 BV pretreatment of mice has no effect on bacterial clearance, neutrophil recruitment and survival in this acute respiratory tract infection. Also, OM-85 BV treatment had no protective effect in a recurrent infection with K. pneumoniae. It is concluded that AM activation by oral treatment with OM-85 BV is not sufficient to play a protective role in respiratory tract infection with K. pneumoniae.     

Rapid diagnosis of respiratory Chlamydia pneumoniae infection by nested touchdown polymerase chain reaction compared with culture and antigen detection by EIA

Chlamydia pneumoniae is a common cause of respiratory tract infection and community-acquired pneumonia. During an extensive outbreak of C. pneumoniae in northern Sweden, 319 respiratory samples from 129 persons were collected. Sputum, throat, and nasopharyngeal samples were obtained and analyzed by nested touchdown polymerase chain reaction (PCR), EIA, and culture in Hep-2 and McCoy cells. Serology was performed by complement fixation and microimmunofluorescence tests. By PCR, 30 patients were diagnosed with C. pneumoniae compared with 26 positive by EIA and 23 by culture. The finding of C. pneumoniae in the respiratory samples was accompanied by serology indicating acute infection in 26 (96%) of 27 patients for whom adequate sera were available. Nested PCR was sensitive and reliable for diagnosing acute respiratory C. pneumoniae infection. Sputum samples had the highest diagnostic efficacy, and the nested type of PCR was superior to one-step PCR. EIA and culture were less sensitive than nested PCR.     

Etiology of pneumonia and other common childhood infections requiring hospitalization and parenteral antimicrobial therapy. SE-TU Study Group

The etiology of acute lower respiratory tract infections (mostly pneumonia) in children is well characterized, but these are only some of the community-acquired infections warranting parenteral antimicrobial therapy. We prospectively evaluated all such infections among children aged 3 months to 15 years by use of blood cultures, examination of nasopharyngeal aspirates, and serologies for 15 viral, 7 bacterial, and 1 protozoal agent. Immunocompromised patients and those with urinary tract infection, meningitis, or osteoarticular infection were excluded. In all, 170 children were included. The pathogenic agent was identified in 62% of the cases. Bacteria were detected in 54%, and a pneumococcus was found in 59% of the cases identified. Viruses were found in 15% overall. Sole bacterial or viral infections were detected in 47.1% and 8.1%, respectively. Since thorough screening established the etiology in less than two-thirds of patients ill enough to be hospitalized and treated parenterally, better diagnostics are needed, especially to identify those who would truly benefit from antimicrobial therapy.     

Clinical predictors of hypoxaemia in Gambian children with acute lower respiratory tract infection: prospective cohort study

OBJECTIVES: To determine clinical correlates and outcome of hypoxaemia in children admitted to hospital with an acute lower respiratory tract infection. DESIGN: Prospective cohort study. SETTING: Paediatric wards of the Royal Victoria Hospital and the hospital of the Medical Research Council's hospital in Banjul, the Gambia. SUBJECTS: 1072 of 42 848 children, aged 2 to 33 months, who were enrolled in a randomised trial of a Haemophilus influenzae type b vaccine in the western region of the Gambia, and who were admitted with an acute lower respiratory tract infection to two of three hospitals. MAIN OUTCOME MEASURES: Prevalence of hypoxaemia, defined as an arterial oxygen saturation <90% recorded by pulse oximetry, and the relation between hypoxaemia and aetiological agents. RESULTS: 1072 children aged 2-33 months were enrolled. Sixty three (5.9%) had an arterial oxygen saturation <90%. A logistic regression model showed that cyanosis, a rapid respiratory rate, grunting, head nodding, an absence of a history of fever, and no spontaneous movement during examination were the best independent predictors of hypoxaemia. The presence of an inability to cry, head nodding, or a respiratory rate >/= 90 breaths/min formed the best predictors of hypoxaemia (sensitivity 70%, specificity 79%). Hypoxaemic children were five times more likely to die than non-hypoxaemic children. The presence of malaria parasitaemia had no effect on the prevalence of hypoxaemia or on its association with respiratory rate. CONCLUSION: In children with an acute lower respiratory tract infection, simple physical signs that require minimal expertise to recognise can be used to determine oxygen therapy and to aid in screening for referral. The association between hypoxaemia and death highlights the need for early recognition of the condition and the potential benefit of treatment.     

Diagnosis of Mycoplasma pneumoniae pneumonia in pediatric patients by polymerase chain reaction (PCR)

Polymerase chain reaction (PCR) testing was performed on respiratory tract specimens obtained by throat swab in 21 children admitted to the hospital with suspected Mycoplasma pneumoniae pneumonia. Of 13 patients with a clinical condition compatible with mycoplasma infection and an immunological response to M. pneumoniae, 11 were positive by PCR. Eight patients were negative by serology and/or had a clinical condition not compatible with mycoplasma infection, and all were negative by PCR. The antibody response to M. pneumoniae was delayed for a week or more in 3 (23%) of the 13 patients with documented mycoplasma infection. These results suggest that PCR performed on a respiratory tract specimen obtained by a throat swab may be useful in the initial evaluation of children with suspected M. pneumoniae pneumonia, especially in patients in whom the serological response is delayed.     

Pneumococcal immune complexes in the diagnosis of lower respiratory infections in children

BACKGROUND: In recent years serologic methods have been applied to assess pneumococcal etiology of pneumonia and other respiratory tract infections. Antigen and antibody assays have shown to be insensitive, especially in young children. The aim of this study was to evaluate the usefulness of circulating immune complexes in the diagnosis of pneumococcal lower respiratory infection in children. MATERIAL AND METHODS: Pneumococcal immune complexes (IC) containing antibodies to species-specific C-polysaccharide, to mixtures of type-specific capsular polysaccharides or to a protein antigen, pneumolysin, were studied in the sera of 449 children with lower respiratory tract infection. RESULTS: Circulating ICs were found in 68 (15%) children; 46 (68%) of them were demonstrated in acute and 43 in convalescent serum. In 5 (7%) of the 68 IC-positive patients pneumococcal antigen was present in acute serum; those patients formed 18% of the 28 cases with antigenemia. An antibody response between paired sera to any of the 3 pneumococcal antigens studied was observed in 14 (21%) IC-positive children; they formed 23% of the 60 cases with an antibody response. In total ICs were positive in 51% of all the 134 pneumococcal cases diagnosed by any method. CONCLUSIONS: We conclude that the measurement of circulating ICs is more sensitive than other serologic methods for the diagnosis of pneumococcal lower respiratory infection. In infants, however, it was as insensitive as antigen and antibody assays.     

Efficacy and tolerance of coamoxiclav in community-acquired lower respiratory tract infections in children

Amoxyclav (amoxycillin/potassium clavulanate, A/PC) was used in the treatment of 55 children with acute bronchitis and pneumonia. The drug was administered in a dose of 20-40 mg/kg body weight a day in 3 portions. The treatment course was 4 to 10 days. The treatment was performed under careful clinicoroent-genologic control. The clinical picture of the disease in the children was characterized by a moderate process which made it possible to treat the children as outpatients. The clinical efficacy amounted to 90.5 per cent. The isolates of Streptococcus pneumoniae, Streptococcus pyogenes, Staphylococcus aureus and Haemophilus influenzae proved to be susceptible to A/PC. It may be used as the 1st class agent in the treatment of children with lower respiratory tract infection.     

Community-acquired pneumonia: prospective study of 101 adult, immunocompetent patients for 1 year

BACKGROUND: A one year prospective study was carried out to assess the etiology of community-acquired pneumonia (CAP), and also to know the incidence, characteristics and evolution of infection by Chlamydia pneumoniae; and the effectiveness of DNA probes in CAP due to Mycoplasma pneumoniae and Legionella. METHODS: One hundred and ten patients with a diagnosis of CAP in the emergency department were studied. Serologic studies were performed, and also tests commonly used for the diagnosis of respiratory tract pathogens in respiratory samples, including serology and culture of Chlamydia pneumoniae and DNA probes for Mycoplasma pneumoniae and Legionella. RESULTS: In 72 cases (71.3%) some pathogen was found and in 5 cases more than one microorganism was involved. The etiology was bacterial in 31% of the cases, with S. pneumoniae being the most frequent (19 cases). Forty percent of the cases were "atypical" pneumonias with 33 cases of M. pneumoniae and 5 by Chlamydia pneumoniae. Diagnostic data of viral pneumonia were found in 2 cases. DNA probes were not useful for the diagnosis of pneumonia by Legionella pneumophila and had low effectiveness (31.8%) in Mycoplasma pneumoniae CAP. CONCLUSIONS: a) M. pneumoniae was the most frequent pathogen (33%). b) DNA probes for M. pneumoniae had low sensitivity in sputum (31.8%) and none in pharyngeal exudate. c) Acute infection by C. pneumoniae was diagnosed in 5 cases. Previous data of infection were recorded in 60.4% of the patients. d) Bacterial pneumonia (31%) was underestimated due to a low rate of bacteremic cases (7.9%) and the low number of positive cultures with definitive diagnostic value. e) The evolution was good except in two cases (death due to staphylococcal pneumonia with alcohol withdrawal syndrome and multiorganic failure by disseminated chicken-pox).     

Azithromycin. A review of its use in paediatric infectious diseases

Azithromycin is an azalide antimicrobial agent active in vitro against major pathogens responsible for infections of the respiratory tract, skin and soft tissues in children. Pathogens that are generally susceptible to azithromycin include Haemophilus influenzae (including ampicillin-resistant strains), Moraxella catarrhalis, Chlamydia pneumoniae, Chlamydia trachomatis, Mycoplasma pneumoniae, Legionella spp., Streptococcus pyogenes and Streptococcus agalactiae. Azithromycin is also generally active against erythromycin- and penicillin-susceptible Streptococcus pneumoniae and methicillin-susceptible Staphylococcus aureus. Azithromycin is administered once daily, achieves clinically relevant concentrations at sites of infection, is slowly eliminated from the body and has few drug interactions. In children, azithromycin is usually given as either a 3-day course of 10 mg/kg/day or a 5-day course with 10 mg/kg on the first day, followed by 5 mg/kg/day for a further 4 days. These standard regimens were as effective as amoxicillin/clavulanic acid, clarithromycin, cefaclor and amoxicillin in the treatment of children with otitis media. Azithromycin was also as effective as either phenoxymethylpenicillin (penicillin V), erythromycin, clarithromycin or cefaclor against streptococcal pharyngitis or tonsillitis in children, but appears to result in more recurrence of infection than phenoxymethylpenicillin in this indication, necessitating a dosage of 12 mg/kg/day for 5 days. Community-acquired pneumonia, bronchitis and other respiratory tract infections in children responded as well to azithromycin as to amoxicillin/clavulanic acid, cefaclor, erythromycin or josamycin. Azithromycin was similar or superior to ceftibuten in mixed general practice populations of patients. However, symptoms of lower respiratory tract infections resolved more rapidly with azithromycin than with erythromycin, josamycin or cefaclor. Skin and soft tissue infections responded as well to azithromycin as to cefaclor, dicloxacillin or flucloxacillin, and oral azithromycin was as effective as ocular tetracycline in treating trachoma. Although not as well tolerated as phenoxymethylpenicillin in the treatment of streptococcal pharyngitis, azithromycin is at least as well tolerated as most other agents used to treat respiratory tract and other infections in children and was better tolerated than amoxicillin/clavulanic acid. Adverse events that do occur are mostly gastrointestinal and tend to be mild to moderate in severity. CONCLUSIONS: Azithromycin is an effective and well tolerated alternative to first-line agents in the treatment of respiratory tract, skin and soft tissue infections in children, offerring the convenience of a short, once-daily regimen.     

Intractable respiratory infections

Silent aspiration would be major factor which predispose the bacterial infections in aged patients. Sixty-seven strains were isolated from culture positive cases. Anaerobes, S. pneumoniae, S. aureus, P. aeruginosa were the more frequently isolated strains of bacteria. Gram-negative rods were apparent in 39%, and Anaerobes were 19%, of 67 strains. Patients with diffuse panbronchiolitis are frequently affected by P. aeruginosa superinfection. The patients with longer duration, more severe lung function and more deteriorated roentgenological findings developed P. aeruginosa superinfection more easily. These infection in the lower respiratory tract significantly affect the prognosis of DPB patients. Using long-term administration of erythromycin against DPB, acute exacerbation were controlled in some patients and the frequency of their admission to hospital was lessened.     

Comparison of two serological methods and a polymerase chain reaction-enzyme immunoassay for the diagnosis of acute respiratory infections with Chlamydia pneumoniae in adults

Chlamydia pneumoniae is a common respiratory tract pathogen. Serological methods currently used for the diagnosis of C. pneumoniae infection lack specificity, give ambiguous results from a single serum sample and often provide only a retrospective diagnosis. A prospective study was undertaken to assess whether PCR could be a useful addition to the serological techniques routinely practised for diagnosis. This study investigated 68 adult patients with a diagnosis of acute respiratory infection. Acute and convalescent serological determination of antibodies to C. pneumoniae were performed by means of an rELISA test and a micro-immunofluorescence (MIF) test. Nasopharyngeal aspirates or bronchoalveolar lavage specimens and bronchial aspirates obtained from the 68 patients were evaluated by PCR-enzyme immunoassay (PCR-EIA) for the presence of C. pneumoniae and by immunofluorescence assay and cell culture for virus identification. Mycoplasma pneumoniae serology was also performed. Eight patients (11.8%) were positive by either rELISA or PCR-EIA, or both, with an infection rate of 5 (18.5%) of 27 in patients with community-acquired pneumonia, 2 (9%) of 22 in asthmatic patients and 1 (5%) of 19 in patients with an exacerbation of chronic obstructive pulmonary disease. Serological evidence of acute infection was found in four of these patients with the rELISA test and in three others with the MIF test. PCR-EIA detected C. pneumoniae DNA in four specimens, but there were concordant results with both rELISA and PCR-EIA in only one patient A positive PCR-EIA was also obtained in a patient who did not show an antibody response in acute serum. The discrepancy between serological and PCR-EIA results reflects the difficulties in routine laboratory diagnosis of C. pneumoniae infection and the necessity for further studies with optimised techniques.     

Respiratory syncytial virus infection in tropical and developing countries

Little is known about the epidemiology of respiratory syncytial virus (RSV) infection in tropical and developing countries; the data currently available have been reviewed. In most studies, RSV was found to be the predominant viral cause of acute lower respiratory tract infections (ALRI) in childhood, being responsible for 27-96% of hospitalised cases (mean 65%) in which a virus was found. RSV infection is seasonal in most countries; outbreaks occur most frequently in the cold season in areas with temperate and Mediterranean climates and in the wet season in tropical countries with seasonal rainfall. The situation on islands and in areas of the inner tropics with perennial high rainfall is less clear-cut. The age group mainly affected by RSV in developing countries is children under 6 months of age (mean 39% of hospital patients with RSV). RSV-ALRI is slightly more common in boys than in girls. Very little information is available about the mortality of children infected with RSV, the frequency of bacterial co-infection, or the incidence of further wheezing after RSV. Further studies on RSV should address these questions in more detail. RSV is an important pathogen ill young children in tropical and developing countries and a frequent cause of hospital admission. Prevention of RSV infection by vaccination would have a significant impact on the incidence of ALRI in children in developing countries.     

Virological aspects of human immunodeficiency virus infection

At the cellular level, the respiratory tract has a variety of defense mechanisms to prevent bacterial infection. Recent data have demonstrated that the respiratory epithelium plays a very active role in host defense. In this review we start by examining the respiratory epithelia and its function in mucociliary clearance, and extend our review to include its role in the secretion and regulation of inflammatory cytokines and production of antimicrobial factors. Furthermore, we examine how recent advances in understanding cystic fibrosis have provided useful insights into the pathogenesis of lower respiratory tract infection. In addition, we examine how two common respiratory pathogens, Streptococcus pneumoniae and Pseudomonas aeruginosa, subvert the defense mechanisms at the cellular level. Finally, we attempt to identify new or potential therapeutic approaches that have arisen from some of the insights into the pathogenesis of lower respiratory tract infections.     

Pathogens isolated during treatment failures in otitis

OBJECTIVES: A prospective study in the Paris region to evaluate the clinical and bacteriologic epidemiology of acute otitis media in infants in whom oral antibiotic therapy resulted in clinical failure. METHODS: The study included 186 children with a mean age of 17.5 +/- 13.1 months. Two-thirds of them attended a day-care center and 40.8% had a history of recurrent otitis media. The most frequently prescribed prior antibiotics were amoxicillin-clavulanic acid (43% of cases), an oral third generation cephalosporin (22.6%), erythromycin-sulfisoxazole (11.8%) and a first generation cephalosporin (10.2%). The average duration of antibiotic therapy was 6.9 +/- 2.65 days. Specimens for bacterial cultures included 188 samples of middle ear fluid obtained by tympanocentesis and 37 collected from otorrhea fluid. RESULTS: One hundred forty-one samples (62.7%) from 126 children yielded 170 bacterial isolates. In 60 children (32.3%) the culture of the ear pus was sterile. Among the 170 bacterial isolates: 67 (39.4%) were Streptococcus pneumoniae (59 patients), of which 77.6% had reduced susceptibility to penicillin (PRSP with penicillin MIC > or = 0.125 mg/l); 61 (35.9%) were Haemophilus influenzae (56 patients) of which 49.2% were beta-lactamase producers; and 8 were Moraxella catarrhalis (8 patients), of which 87.5% were beta-lactamase producers. Thirty-six patients were infected by S. pneumoniae with penicillin MIC > or =1 mg/l. In our study attending day-care center (P = 0.04), temperature >38 degrees C with signs of otalgia (P = 0.02), age <2 years (P = 0.048) and prior antibiotic treatment with erythromycin-sulfisoxazole (P = 0.006) were independently predictive risk factors for patients infected with penicillin-resistant S. pneumoniae. Pneumococcal serogroups 23, 14 and 19 were predominant (25.4, 25.4 and 23.8%, respectively). Penicillin resistance was mainly associated with serogroups 23 and 14. CONCLUSIONS: Penicillin-resistant S. pneumoniae isolates are frequently responsible for therapeutic failure in cases of acute otitis media in the Paris region.     

Etiology of respiratory tract infection in adults in a general practice setting

A prospective study was conducted over a 3-month winter period in three general practice clinics in an urban population in southern Israel to identify the etiological agents of respiratory tract infections (RTI) in adults. RTI was defined as an acute febrile illness with cough, coryza, sore throat or hoarseness. Serum samples were taken from all patients in both the acute and convalescent phases of their illness. Tests were conducted for detection of 17 microorganisms known to cause RTI, including serological tests for 16 known pathogens. An etiological diagnosis was established in 80 (66%) of the 122 patients who participated in the study. The distribution of the etiological agents was as follows: influenza B virus in 27 (22%) patients. Chlamydia pneumoniae in 22 (18%), Legionella spp. in 15 (12%), Mycoplasma pneumoniae in 13 (11%), influenza A virus in 11 (9%), Bordetella pertussis in 9 (7%), adenovirus in 4, Epstein Barr virus in 4, Haemophilus influenzae in 3, beta-hemolytic streptococci in 3, Streptococcus pneumoniae in 2, respiratory syncytial virus in 2, parainfluenza 1 virus in 2 and parainfluenza 2 virus in 1. No patients were found to be infected with Coxiella burnetii, Moraxella catarrhalis or parainfluenza 3 virus. More than one pathogen was identified in 27 (34%) patients in whom an etiological diagnosis was established. It is concluded that RTI is caused by a broad spectrum of etiological agents, a considerable number of patients having evidence of infection with more than one pathogen. The therapeutic significance of these findings should be elucidated in further studies.