Viral-bacterial interaction in acute otitis media.
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Biomedical subjects
Publications and source records attributed to O Ruuskanen.
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Molecular epidemiologic studies have shown that during respiratory syncytial virus (RSV) epidemics several subgroups of viruses cocirculate. On the other hand, very similar strains can be found from widely separated countries at the same time. Nosocomial outbreaks make no exception because multiple sources of virus have also been found within one outbreak. Management of RSV infections has thus far varied largely but based on the recent reports some conclusions can be drawn. Beta-Sympathomimetics have been shown to be of benefit in the treatment of bronchiolitis whereas there is no data to support the use of systemic corticosteroids. Use of ribavirin cannot be recommended in common practice but it seems to have some beneficial effect in the high-risk patients. Mortality risk in the high-risk patients seems to have decreased in latest analyses compared with earlier reports. This has been attributed to improved supportive intensive care management and advances in cardiac surgery. Gammaglobulin has potential both in short-term prophylaxis and treatment of RSV infections. Development of a safe and effective vaccine is one of the main topics in RSV research. Despite some encouraging reports of active prophylaxis, such as use of recombinant fusion protein or temperature-sensitive mutants, we will probably not see a vaccine in clinical practice in the near future.
Treatment of the infections caused by the respiratory syncytial virus (RSV) has varied largely in different centres. Recently, however, management practices have become more clear based on a number of studies. An infant with RSV bronchiolitis should be hospitalized in case of insufficient oxygenation, as measured by pulse oximetry, and additional oxygen should be supplied. Mist treatment and physiotherapy are not beneficial. Bronchodilators seem to be the drug of choice in most infants with bronchiolitis. Use of corticosteroids has not been supported by data received from most studies although they are generally used. Ribavirin should be used only with high-risk patients such as immunosuppressed children. Despite the common prescription of antibiotics, they should only be given to patients with verified bacterial infection. In the future, immunotherapy including aerosolized IgG may be an alternative in treatment of RSV infections. Until an efficient vaccine is brought to clinical use, the best way to limit nosocomial spread of infections is to use cohort nursing and gowns.
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Six different antigen preparations for use in an enzyme immunoassay (EIA) to detect IgM, IgA and IgG antibodies to Bordetella pertussis were evaluated using sera from 13 randomly selected culture-positive patients and from 87 patients with suspected pertussis during a pertussis outbreak. Based on results in 80 healthy control sera a specificity limit of 99.9% was selected. Sera from all culture-positive patients reacted with at least one of the antigens. The sensitivity of the EIA using the individual antigen preparations was 85% for filamentous hemagglutinin, 92% for pertussis toxin, 62% for 69 kDa outer membrane protein, 85% for a pool of these three antigens, 54% for sonicated whole bacteria and 69% for 21 kDa pertussis toxin subunit S1. In the outbreak patient group 49 (56%) of the initial sera reacted with at least one of five antigen preparations. The EIA using sonicated bacteria detected only 41% of all seropositive cases compared with 51% using filamentous hemagglutinin, 61% using pertussis toxin, 65% using 69 kDa OMP and 65% using pooled antigen. It is concluded that either the pooled antigen or pertussis toxin antigen are suitable antigen preparations for use in the EIA for diagnosis of pertussis.
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An international workshop to review the epidemiology, diagnosis, treatment, and prevention of respiratory viral infections was held in Turku, Finland, in May 1991. This workshop emphasized the following points. (1) In epidemiological studies of influenza virus, serological, clinical, and gene-sequencing methods have been used to produce a full picture of genetic evolution. Less complete information exists about other viruses, although new data on respiratory syncytial virus are emerging. (2) Tools for the diagnosis of respiratory viral infections have been developed in conjunction with the use of solid-phase immunoassays. A role remains for tissue culture in surveillance and epidemiological studies. Detection of bacterial involvement in respiratory infections has been more difficult. (3) Treatment of infections due to respiratory viruses has advanced with the use of amantadine and aerosolized ribavirin. On the other hand, many viruses remain refractory to treatment. Means for preventing influenza are established, but barriers to the development of other viral vaccines--including the existence of multiple serotypes, imperfect natural immunity, and paradoxical hypersensitivity--have proven difficult to surmount.
A polymerase chain reaction (PCR) assay amplifying a segment of a repeated gene element of Bordetella pertussis was compared with culture and enzyme immunoassay (EIA) for the diagnosis of pertussis. The PCR assay was specific for B. pertussis in tests with a panel of other bacteria and with an extensive collection of specimen material from healthy persons and children with respiratory infections other than pertussis. The PCR assay was used in the analysis of 117 nasopharyngeal swabs collected from children at an elementary school at which a pertussis outbreak occurred. Fifty-six (48%) of the 117 swabs were positive, including those for all six culture-positive cases. The PCR method was then applied to analyze another pertussis outbreak. Of 40 nasopharyngeal aspirates taken from 37 clinically susceptible pertussis patients and from three asymptomatic contacts, the PCR identified 18 (45%), including all 3 culture-positive and 5 (35%) of the 14 seropositive patients. The most consistent and reliable diagnosis by positive PCR result was observed with those patients experiencing symptoms within 1 to 6 weeks of sample collection. We conclude that PCR is a rapid, sensitive, and specific means of diagnosing pertussis, especially during the first weeks of disease. The assay can be performed with both nasopharyngeal swabs and aspirates.
Shedding of respiratory syncytial virus (RSV) in nasopharyngeal aspirates (NPA) of hospitalized children with acute respiratory infection was studied using direct antigen detection by time-resolved fluoroimmunoassay, rapid identification of infectious virus in centrifugally inoculated cell cultures by immunoperoxidase staining and conventional virus culture. Sequential NPAs, in which also local RSV-specific IgA response was measured, were collected from children with proven RSV infection. The shedding pattern was similar for both infectious virus and viral antigen. The overall agreement of the three methods was good (81%) in diagnostic specimens collected on admission, but markedly reduced (46%) in follow-up specimens. Secretory IgA was abundant in specimens giving discrepant or negative results only. The proportion of patients who shed RSV was high (> or = 87%) in the first week after onset of symptoms, and decreased sharply in the second week. An opposite temporal pattern was found in the proportion of patients with detectable RSV-IgA in their secretions. Sequentially isolated strains were antigenically stable as determined by their reactivity with a large panel of monoclonal antibodies. The findings suggest that RSV shedding should be monitored by using more than one method for virus detection.
A prospective eight-month study was carried out in 50 children admitted to hospital for radiologically confirmed community-acquired pneumonia. A potential causative agent of infection was identified in 44 (88%) cases. Using virus isolation, virus antigen detection and enzyme immunoassay serology, respiratory virus infection was diagnosed in 30 (60%) patients. Antibody assays for seven bacteria and antigen detection from serum and urine for Streptococcus pneumoniae produced evidence of bacterial infection in 31 (62%) cases. Streptococcus pneumoniae (38%), respiratory syncytial virus (30%) and Mycoplasma pneumoniae (20%) were the most common causative agents. A mixed infection was diagnosed in 25 (50%) episodes. Nine patients failed to respond to antibiotics within 24 h after onset of treatment. Three of them had a pure viral infection, three a mixed viral-bacterial infection, two a Mycoplasma pneumoniae infection mixed with other bacteria and one a pure Mycoplasma pneumoniae infection. All three Mycoplasma pneumoniae infections were initially treated with penicillin.
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We studied a new approach to the prevention of acute otitis media through the administration of influenza vaccine to 187 day-care center children aged 1 to 3 years before the influenza A epidemic of 1988-1989. The control group consisted of 187 unvaccinated children of similar age and background. During the 6-week study period, influenza A infection was diagnosed in five (3%) of 187 vaccinees and in 29 (16%) of 187 controls. Acute otitis media developed in three (60%) of five vaccinees with an influenza A infection compared with 18 (67%) of 27 controls (excluded were two children with a double viral infection). The incidence of acute otitis media associated with influenza A was reduced by 83% in the vaccinees. The total number of children with acute otitis media in the vaccine group was 35, compared with 55 in the control group, disclosing a 36% reduction among the vaccinees. We conclude that influenza vaccination decreases the incidence of acute otitis media in children during an influenza A epidemic, suggesting also that other vaccines against respiratory viruses may be an effective way to reduce the incidence of acute otitis media.
An acellular pertussis vaccine which contains highly purified pertussis toxoid (PT) and filamentous haemagglutinin (FHA) has been developed. These proteins have been shown to be stable, with essentially no significant reversion of the pertussis toxoid after a new detoxification procedure. Two clinical trials using this vaccine as a booster in 45 healthy adults have been performed. Results show that the vaccine was well tolerated, causing essentially mild, transient symptoms after administration. It induced an increase in anti-PT and anti-FHA antibody titres in all vaccinees.
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Fifty four patients aged from 1 to 6 years who had had recurrent attacks of wheezy bronchitis were prospectively followed up for three months to find out if there was an association between different viral respiratory infections and episodes of wheezing. Of the 115 episodes of upper or lower respiratory tract symptoms, virus or Mycoplasma pneumoniae infection were diagnosed in 52 (45%). Thirty four of rhinoviruses. The patients had an average of 2.1 episodes of respiratory tract symptoms the total mean (SD) duration of which was 30 (2) days of the 92 days that followed. Wheezing occurred during 76 (66%) of the 115 episodes and during a third of these the patient was admitted to hospital because of severe dyspnoea. Wheezing started a mean (SD) of 43 (7) hours after the first symptoms of respiratory infection and persisted for 3.8 (4.2) days in patients in whom virus infection was diagnosed. The incidence of wheezing was not associated with IgE mediated atopy, with positive virological tests, or with fever during virus infection, but was associated with parental smoking and more than one sibling.
We studied respiratory viruses in 22 children with acute otitis media who had failed to improve after at least 48 hours of antimicrobial therapy. The mean duration of preenrollment antimicrobial therapy was 4.8 days. For comparison we studied 66 children with newly diagnosed acute otitis media. Respiratory viruses were isolated from middle ear fluid or from the nasopharynx, or both, significantly more often in the patients unresponsive to initial antimicrobial therapy than in the comparison patients (68% vs 41%, p less than 0.05). Viruses were recovered from the middle ear fluid in 32% of the study patients and from 15% of the comparison group. Bacteria were isolated from the middle ear fluid of four (18%) children in the study group; one child had an isolate resistant to initial antimicrobial therapy. All four children with bacteria in the middle ear fluid had evidence of concomitant respiratory virus infection. Our results indicate that respiratory virus infection is often present in patients with acute otitis media unresponsive to initial antimicrobial therapy, and may explain the prolongation of symptoms of infection. Resistant bacteria seem to be a less common cause of failure of the initial treatment.