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Biomedical subjects

V M Howie

Publications and source records attributed to V M Howie.

At least 19 recordsLinked to original sources

Effect of viral respiratory tract infection on outcome of acute otitis media.

We prospectively studied 271 infants and children (2 months to 7 years of age) with acute otitis media (AOM) for viral and bacterial causes, outcome at the end of therapy, and frequency of recurrence within 1 month. Comprehensive virologic methods, including viral antigen detection, cell culture, and serologic studies, were used to diagnose viral infection of the respiratory tract, middle ear, or both. Evidence of viral infection was found in 46% (124/271) of patients with AOM. Sixty-six patients (24%) had virus or viral antigen in the middle ear fluid; 50 of these patients (76%) also had bacteria in middle ear fluid, and 16 (24%) had virus alone. More patients with AOM and combined bacterial and viral infection (51%) had persistent otitis (3 to 12 days after institution of antibiotic treatment), compared with those with only bacterial otitis (35%; p = 0.05) or patients with only viral infection (19%; p less than 0.01). Of patients with only viral infection, 4 of 10 with virus in middle ear fluid had persistent otitis, compared with none of 11 patients who had virus only in nasal wash specimens or whose viral infection was diagnosed only by serologic studies. Our data suggest that viruses interact with bacteria and that concurrent viral infection can significantly worsen the clinical course of bacterial AOM. The presence of virus in middle ear fluid may contribute to the pathogenesis and outcome of bacterial AOM. The mechanism of these interactions deserve further investigation.

Amoxicillin

Presence of cytomegalovirus and herpes simplex virus in middle ear fluids from children with acute otitis media.

Twenty-seven (10%) of 271 infants and children with acute otitis media (AOM) were found to be infected with cytomegalovirus (CMV) or herpes simplex virus type 1 (HSV). CMV or HSV, alone or in combination with bacteria or other viruses, was isolated from the middle ear fluid (MEF) of 10 patients. In three cases, CMV alone was isolated from the MEF, and in one case, HSV alone was isolated. One of the CMV cases involved an acute primary or reactivation of CMV infection, with CMV-bacterial otitis and conjunctivitis as major manifestations. One patient with AOM and stomatitis had purulent otitis associated with the presence of HSV in MEF, with no other bacterial or viral pathogens noted in MEF or nasal wash specimens. While most patients with CMV infection were probably asymptomatic excreters at the time of development of AOM, CMV did enter the middle ear. The presence of CMV in MEF was prolonged, and the patients continued to have clinical signs of otitis despite negative bacterial cultures. Among patients with bacterial otitis, a higher proportion of those who had CMV found only in nasal wash specimens had persistent bacteria in MEF, compared with those who were concurrently infected with other viruses (57% vs. 19%; P less than .04). This report is the first to suggest an etiologic role for CMV and HSV in AOM.

Acute Disease

Respiratory viruses interfere with bacteriologic response to antibiotic in children with acute otitis media.

Fifty-eight infants and children with acute otitis media were prospectively studied for bacterial and viral pathogenesis and response to antibiotic therapy. Tympanocentesis for bacterial and viral cultures of middle ear fluids (MEF) was done before and 2-4 days after beginning treatment. Patients were followed until the end of antibiotic course. Bacteria were cultured from the preantibiotic MEF in 43 cases (74%). Viruses were cultured from the preantibiotic MEF in 11 cases (19%); all of these MEFs also contained bacterial pathogens. A significantly higher proportion of patients with both virus and bacteria (50%) failed to respond with clearing of bacteria 2-4 days into therapy compared with the group with bacteria alone (13%). The patients with persistently positive viral cultures of the MEF seemed to have purulent otitis of longer duration. Presence of virus in the MEF may interfere with bacteriologic and clinical responses to antibiotic. The mechanism of interference deserves further investigation.

Acute Disease

The effect of early onset of otitis media on educational achievement.

One hundred and forty-four patients from three different pediatric practices were compared using the Science Research Associates (SRA) tests for academic achievement. First, the patients were divided into those who had had three or more attacks of otitis media and those who had had no attacks of otitis media during the first 18 months of life as recorded by their pediatricians. Matched pairs by sex, birth date, occupation of father, school attended and year of testing were made for comparison purposes. Using the one-tailed t-test, a significant difference in the composite score was found favoring the group with no recorded otitis media in the first 18 months of life. All patients were treated with antibiotics.

Achievement

Bacterial etiology of otitis media during the first six weeks of life.

Tympanocentesis was performed on 70 infants who had otitis media during the first six weeks of life. The bacteria isolated from their middle-ear effusions were Streptococcus pneumoniae (13 patients), Neisseria catarrhalis (11 patients), Hemophilus influenzae (ten patients), Enterobacteriaceae (four patients), Staphylococcus aureus (four patients), streptococci (groups A and B) (three patients), and Pseudomonas aeruginosa (two patients). Thirty patients (42.9%) had middle-ear effusions which did not contain pathogenic bacteria. Twenty-seven infants were followed for at least 12 months and 12 (44.4%) of these infants had six or more episodes of otitis media during the observation period. Further studies will be needed to establish the significance of middle-ear disease at this age and the role of therapy in improving its outcome.

Bacterial Infections

Pneumococcal polysaccharide immunization in infants and children.

By using indirect hemagglutination, the antibody responses of normal infants and children to an octavalent pneumococcal vaccine that contained pneumococcal polysaccharide types 1, 3, 6, 7, 14, 18, 19, and 23 were evaluated. By 2 years of age, there was a significant rise in hemagglutination titers to all the polysaccharide types, except type 19. By 6 to 8 months of age, five of the eight types of pneumococcal polysaccharides tested resulted in up to 60% responders and, by 2 years, a significant number responded to all pneumococcal polysaccharide types in the vaccine. Pneumococcal polysaccharide type 3 resulted in a significant antibody response as early as 3 months of age, whereas type 19 never resulted in a significant antibody response. Except for type 3, it seemed that when the other pneumococcal polysaccharides tested produced an antibody response, the degree of resonse did not subsequently change significantly with increasing age. The relationship of antibody response to age for pneumococcal polysaccharides is similar to that found for other polysaccharide vaccines. Based on the results of our study, we would recommend immunization with pneumococcal vaccine at 6 months of age with repeat immunization at 2 years of age, especially in high-risk children.

Age Factors

Antibody of polyribophate of Haemophilus influenzae type b in infants and children: effect of immunization with polyribophosphate.

Antibody to polyribophosphate, the capsular polysaccharide of Haemophilus influenzae type b, was measured in healthy ambulatory children by a radioactive antigen-binding assay. Titers fell from birth through nine months of age, then increased until six years, when they plateaued. Antibody activity was not correlated with the child's sex, ethnic status, or area of residence. Doses of 0.2-50 microgram of polyribophosphate given as single or booster doses had similar effects on antibody activity. Of 368 doses given to infants two to six months of age, 7% produced a significant antibody response; of 95 doses given to infants seven to 12 months old, 17% produced a response. The geometric mean titers of antibody resulting from immunization with polyribophosphate given at various times in relation to diphtheria-pertussistetanus vaccine did not differ significantly from one another or from titers observed in infants given only the latter vaccine. These data indicate that purified polyribophosphate will not provoke humoral immunity in young infants against H. influenzae type b and that it should no longer be considered as a candidate vaccine for this purpose.

Age Factors

Immune response to acute otitis media in children III. Implications of viral antibody in middle ear fluid.

With the technique of radioimmunodiffusion and indirect FA staining, IgA antibody to measles, mumps, rubella, and polio-1 were determined in serum and middle ear fluid (MEF) of 103 patients with otitis media. The occurrence of IgA viral antibody in MEF and its absence in simultaneously drawn serum was used as an indicator of local antibody production. Of the 401 assays performed, 41 instances of IgA antibody exclusively in MEF were found. Only four of these occurred in specimens from unimmunized patients and were directed against rubella virus. Of the 37 remaining cases, 16 each were directed against measles and polio-1 and four and one, respectively, for mumps and rubella viruses. The mean specific IgA titers were from 8- to 17-fold higher in MEF from immunized individuals than in the unimmunized and persisted for at least 9 to 19 months after immunization. The data thus indicate 1) specific immunologic sensitization of the middle ear mucosa can be achieved by parenteral as well as oral routes of immunization, and 2) specific immunologic memory exists in the middle ear mucosa. These two factors are crucial to feasibility of immunization against acute otitis media.

Antibodies, Viral

The bacteriology of pneumococcal otitis media.

The bacteriologic findings of 1205 episodes of pneumococcal otitis media are analyzed. Capsular types 6, 14, 19 and 23 have been found to account for more than half the initial and subsequent infections of the middle ear. Initial infection has been shown to be related to age, and recurrent infection with pneumococci of heterologous capsular types has been found to occur most often within six months of the initial attack. Nasopharyngeal carriage of the pneumococcal types most frequently causing otitis media may occur without causing infection, may antedate infection by as long as 13 months and may persist after infection for as long as 30 months. Recurrence of infection with a given capsular type has been identified following intervening infection with one or more heterologous capsular types. Simultaneous infection of the middle ear with two pneumococcal capsular types has been observed in 1% of the infections studied. The potential, but as yet unestablished, value of prophylactic vaccination against pneumococcal otitis media is considered.

Carrier State

The "otitis-prone" condition.

We studied the incidence of exudative otitis media in 488 patients followed up from birth. Forty-nine percent (240) of the patients had their initial episode of otitis media in the first year of life and only 12% (56) in the second year of life. Thereafter, the incidence decreased steadily. Patients having six or more episodes of otitis media before age 6 were termed "otitis prone". Fifty-seven such patients were observed and this condition was found to be significantly related to the onset of otitis media in the first year of life and to the pneumococcal cause of the initial episode.

Acute Disease

The immune response to acute otitis media in children. II. Serum and middle ear fluid antibody in otitis media due to Haemophilus influenza.

The antibody response in serum and middle ear fluid was studied in 40 children less than two years of age who had otitis media due to Haemophilus influenzae. Specific antibody in serum was determined by either a bacteriocidal test or an indirect fluorescent antibody test, and in the middle ear fluid by the latter test. For both assays the infecting bacterium of the patient was used. Half of the acute sera and three-fourths of the convalescent sera had antibody of at least one of the IgG, IgM, or IgA classes; IgG occurred most often. Fourteen patients had significant increases in specific antibody in the convalescent serum. Middle ear fluids from 22 to 29 patients had specific antibody. IgG and IgA antibodies occurred with equal frequency, but IgA antibody was found more often in middle ear fluids when IgA antibody was absent from serum. Thus it appears that infants with otitis media respond systemically and locally with specific antibody to H. influenzae.

Acute Disease

Immunology and microbiology in acute otitis media.

Various immunological parameters were measured in serum, middle ear fluid (MEF), and lymphocytes from peripheral blood and MEF of infants with acute otitis media due to S. pneumoniae or H. influenzae. Approximately half of 131 patients had IgE specific antibody to the infecting bacterium as determined by the indirect fluorescent antibody (IFA) technique. Seventy-one percent of these IgE positive patients had IgE specific antibody in the MEF. Total IgE concentration was found to be from an average of 1.5 to 3.0 times higher in the MEF when compared to the simultaneously drawn serum. In addition, antibody to pneumococcal capsular polysaccharides and to pneumococcal C-carbohydrate was demonstrated in the MEF by radioimmunoassay. When MEF specific antibody was compared to serum antibody it appeared that antibody to C-carbohydrate was more concentrated in the MEF. That this antibody was of the IgE class was suggested by IFA but not conclusively proven. Evidence exists that conditions for enhanced IgE synthesis is concomitantly associated with a decrease in T-cell activity. T-cell function in MEF derived lymphocytes as determined by rosette formation and by phytohemagglutinin (PHA) stimulation was approximately one-tenth that of the peripheral blood lymphocytes. However, that T-cells may participate in the immune response to polysaccharides was suggested by the observation that polysaccharide stimulated peripheral blood lymphocytes from infants immunized with octavalent pneumococcal capsular vaccine underwent protein synthesis two to three times that of the PHA stimulated cells. The clinical significance of this finding as well as the nature of the cell responsible for the increased protein synthesis remains to be established. It is hypothesized that acute otitis media results from local synthesis of bacteria specific IgE antibody which is enhanced by a paucity of local T-cell activity.

Acute Disease