Albert M. Collier

Respiratory-syncytial-virus infections, reinfections and immunity. A prospective, longitudinal study in young children.

To better understand acquired immunity to respiratory-syncytial-virus infections, we analyzed data from a 10-year study of respiratory illness in normal children who were followed longitudinally from early infancy. Immunity was measured in terms of failure to become infected or reduction in severity of clinical illness upon reinfection. Outbreaks of infections occurred seven times over the 10-year-period. During epidemics the attack rate for first infection was 98 per cent. The rate for second infections (75 per cent) was modestly reduced (P less than 0.001); that for third infections was 65 per cent. Age and history of infection both influenced illness. Immunity induced by a single infection had no demonstrable effect on illness associated with reinfection one year later; however, a considerable reduction in severity occurred with the third infection. These observations suggest that amelioration of illness--rather than prevention of infection--may be a realistic goal for immunoprophylaxis.

A Longitudinal Study of Respiratory Viruses and Bacteria in the Etiology of Acute Otitis Media with Effusion

We analyzed data from a 14-year longitudinal study of respiratory infections in young children to determine the relative importance of viral respiratory infection and nasopharyngeal colonization with Streptococcus pneumoniae and Haemophilus influenzae as factors influencing the occurrence of acute otitis media with effusion. The incidence of this disorder was increased in children with viral respiratory infections (average relative risk, 3.2; P less than 0.0001). Infection with respiratory syncytial virus, influenza virus (type A or B), and adenovirus conferred a greater risk of otitis media than did infection with parainfluenza virus, enterovirus, or rhinovirus. Colonization of the nasopharynx with Str. pneumoniae or H. influenzae had a lesser effect on the incidence of the disease (average relative risk; 1.5; P less than 0.01). Infections with the viruses more closely associated with acute otitis media (respiratory syncytial virus, adenovirus, and influenza A or B) were correlated with an increased risk of recurrent disease. Prevention of selected otitis-associated viral infections should reduce the incidence of this disease.

The etiologic and epidemiologic spectrum of bronchiolitis in pediatric practice.

To develop a broad understanding of the causes and patterns of occurrence of wheezing associated respiratory infections, we analyzed data from an 11-year study of acute lower respiratory illness in a pediatric practice. Although half of the WARI occurred in children less than 2 years of age, wheezing continued to be observed in 19% of children greater than 9 years of age who had lower respiratory illness. Males experienced LRI 1.25 times more often than did females; the relative risk of males for WARI was 1.35. A nonbacterial pathogen was recovered from 21% of patients with WARI; respiratory syncytial virus, parainfluenza virus types 1 and 3, adenoviruses, and Mycoplasma pneumoniae accounted for 81% of the isolates. Patient age influenced the pattern of recovery of these agents. The most common cause of WARI in children under 5 years of age was RSV whereas Mycoplasma pneumoniae was the most frequent isolate from school age children with wheezing illness. The data expand our understanding of the causes of WARI and are useful to diagnosticians and to researchers interested in the control of lower respiratory disease.

Acquired Ciliary Defects in Nasal Epithelium of Children with Acute Viral Upper Respiratory Infections

Ciliary function and mucociliary clearance are primary mechanisms of defense in the respiratory tract. We found that infections by several common respiratory viruses in children were associated with ciliary abnormalities that could be detected on ultrastructural examination of the nasal epithelium. Dysmorphic ciliary forms involving microtubular aberrations were observed most often in the early stages of illness in focal sites of the nasal mucosa. Normal epithelial organization and ciliary ultrastructure appeared to be reestablished during the convalescent period, from 2 to 10 weeks after infection. These observations suggest that interference with ciliogenic mechanisms leading to transient, compromised mucociliary clearance may represent a fundamental pathophysiologic disturbance in some respiratory viral infections.

Occurrence of Diplococcus pneumoniae in the upper respiratory tract of children

The patterns of colonization of D. pneumoniae were studied over a 46-month period in a group of young children in a day-care center. Forty-four percent of nasal cultures yielded D. pneumoniae. The most frequently isolated serotypes--6, 19, and 23--accounted for 49% of the isolates; the nine most common serotypes included 80% of the isolates. Individual serotypes frequently were carried for several months. Reacquisition of a serotype previously carried occurred frequently. There was limited spread of serotypes among the children despite prolonged contact.

Biologic effects of Mycoplasma pneumoniae and other mycoplasmas from man on hamster tracheal organ culture.

Summary The applicability of organ culture systems to the study of mycoplasma infections is illustrated by the experiments described. Tracheal organ culture provided a controllable environment for analysis of the interaction between M. pneumoniae and the natural target cell of this pathogen, the ciliated respiratory epithelium. Mycoplasma pneumoniae produced distinct cytopathology in this system that was not seen with other human mycoplasmas tested. In addition, virulent M. pneumoniae produced tissue damage more effectively than did an attenuated strain. The observations suggest that this experimental model may be useful for the analysis of factors contributing to organism pathogenicity.

Attachment of Mycoplasma pneumoniae to respiratory epithelium.

The attachment of radioisotope-labeled Mycoplasma pneumoniae to hamster tracheal rings in organ culture was examined by radioautography and liquid scintillation counting. Radioautographs of individual rings exposed for 8 h to (3H) thymidine-labeled virulent M. pneumoniae revealed a dense extracellular collection of emulsion grains along the luminal surface of epithelial cells. Similar exposure of rings to isotope-labeled avirulent M. pneumoniae resulted in no accumulation of emulsion grains. The numbers of attached virulent mycoplasmas, as measured by liquid scintillation counting of infected rings, were found to increase in a nearly linear fashion over an 8-h incubation period. Viability of the mycoplasmas and metabolic integrity of the tracheal rings were important for optimal attachment. Pretreatment of rings with neuraminidase or sodium periodate significantly impaired orgainism adherence. These data suggest a specificity of interation between virulent M. pneumoniae and tracheal epithelial cells that can be further examined through the use of isotopically labeled mycoplasmas.

Effect of upper respiratory tract infection on eustachian tube ventilatory function in the preschool child.

A prospective tympanometric and microbiologic study of 28 pre-schoolchildren was undertaken to better define the effect of acute URI on induction of eustachian tube dysfunction. Significant negative middle ear pressure was present in 12.7% of tympanograms from well children. However, abnormal tympanograms were detected during 74.7% of acute URIs. The abnormality was present on day 1 or 2 of illness in the majority of cases; 10.1% of illnesses were complicated by OME. Respiratory viruses or Sp were etiologically implicated in 40.5% of illnesses; isolation rates of Pn and HF from well and ill children were similar. Although colonization of the nasopharynx of well children with Pn or HF was associated with a higher incidence of abnormal middle ear pressure, colonization with Pn or HF during URI did not influence the frequency of tympanogram abnormality.

Nucleotide sequence of the MgPa (mgp) operon of Mycoplasma genitalium and comparison to the P1 (mpp) operon of Mycoplasma pneumoniae

The attachment of Mycoplasma genitalium and Mycoplasma pneumoniae to ciliated epithelium involves two surface proteins designated MgPa and P1, respectively. We have previously cloned and sequenced the P1 (mpp) operon of M. pneumoniae, and report here the use of P1-derived probes to clone and sequence a 10.4-kb region of M. genitalium DNA that, by analogy to the P1 operon, contains the MgPa (mgp) operon. The deduced amino acid sequences of the 29-kDa (ORF-1), MgPa (160-kDa) and 114-kDa (ORF-3) proteins of the MgPa operon show extensive homologies with those of the 28-kDa, P1 (170-kDa) and 130-kDa proteins, respectively, encoded by the P1 operon. The common features and homology of these operons are consistent with previous observations that the MgPa and P1 proteins share cross-reactive epitopes, as well as similar biological function. The gene order of the MgPa operon is ORF-1, MgPa, ORF-3, with intervening regions of 6 and 1 nt, respectively. A consensus ribosome-binding site (RBS) sequence is found before ORF-1 and a sequence indicative of a transcription terminator is located beyond ORF-3; the absence of such sequences adjacent to the MgPa gene suggests that the operon is transcribed as a polycistronic message. The RBS sequence is followed by sequences of dyad symmetry that have the potential to form two alternative stem-and-loop structures, which could be involved in controlling initiation of translation.

Postnatal Development of Tracheal Surface Epithelium and Submucosal Glands in the Ferret

We explored the usefulness of the postnatal ferret as a model for early developmental events in the large airways, using light and scanning electron microscopy. In the first 28 postnatal days, ferret tracheal surface epithelium and glands undergo dramatic growth and development. Tracheal surface area increases 8-fold. At birth, ciliated cells are sparse (9.4 +/- 1.2% of total epithelial cells). A significant increase in ciliated cells is observed at weekly intervals and by day 28 the ciliated cell is the predominant cell type (54.2 +/- 2.8% of total epithelial cells). Secretory cells decrease from 66.4 +/- 1.0% at birth to 22.2 +/- 2.8% of total epithelial cells. Histochemical staining of the granules of the epithelial secretory cells changes from predominantly non-acidic (staining with PAS but not Alcian blue) to predominantly acidic (staining also with Alcian blue). During the same time interval, tracheal glands develop from intraepithelial cellular aggregates devoid of secretory granules at birth into complex, submucosal tubuloacinar structures composed predominantly of cells containing non-acidic secretory granules at 28 days. Therefore, infant ferrets offer an opportunity to examine the structural and functional components of the mucociliary clearance mechanism at developmental stages which occur prenatally in many laboratory animals and in humans.