Determination of avidity of IgG against protein antigens from Streptococcus pneumoniae: assay development and preliminary application in clinical settings.

The measurement of antibody levels is a common test for the diagnosis of Streptococcus pneumoniae infection in research. However, the quality of antibody response, reflected by avidity, has not been adequately evaluated. We aimed to evaluate the role of avidity of IgG against eight pneumococcal proteins in etiologic diagnosis. Eight pneumococcal proteins (Ply, CbpA, PspA1 and 2, PcpA, PhtD, StkP-C, and PcsB-N) were used to develop a multiplex bead-based avidity immunoassay. The assay was tested for effects of the chaotropic agent, multiplexing, and repeatability. The developed assay was applied to paired samples from children with or without pneumococcal disease (n = 38 for each group), determined by either serology, polymerase chain reaction (PCR), or blood culture. We found a good correlation between singleplex and multiplex assays, with r ≥ 0.94.The assay was reproducible, with mean inter-assay variation ≤ 9% and intra-assay variation < 6%. Children with pneumococcal disease had lower median avidity indexes in the acute phase of disease for PspA1 and 2 (p = 0.042), PcpA (p = 0.002), PhtD (p = 0.014), and StkP-C (p < 0.001). When the use of IgG avidity as a diagnostic tool for pneumococcal infection was evaluated, the highest discriminative power was found for StkP-C, followed by PcpA (area under the curve [95% confidence interval, CI]: 0.868 [0.759-0.977] and 0.743 [0.607-879], respectively). The developed assay was robust and had no deleterious influence from multiplexing. Children with pneumococcal disease had lower median avidity against five pneumococcal proteins in the acute phase of disease compared to children without disease.

A randomized, controlled trial of tonsillectomy in periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome.

OBJECTIVE: We carried out a prospective, randomized, controlled trial to clarify the effect of tonsillectomy on the clinical course of periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome. STUDY DESIGN: Twenty-six consecutive children (mean age 4.1 years) with at least 5 PFAPA attacks were recruited from 3 tertiary care pediatric hospitals during 1999-2003 and randomly allocated to tonsillectomy or follow-up alone. They were all followed up with symptom diaries for 12 months. Tonsillectomy was allowed after 6 months in the control group if the attacks recurred. RESULTS: Six months after randomization all 14 children in the tonsillectomy group and 6/12 children in the control group (50%) were free of symptoms (difference 50%, 95% confidence interval 23% to 75%, P < .001). Tonsillectomy was performed on 5/6 of the patients in the control group who still had symptoms after 6 months. The remaining unoperated child in the control group had recurrences of the fever episodes throughout the follow-up, but the symptoms became less severe, and the parents did not choose tonsillectomy. CONCLUSION: Tonsillectomy appeared to be effective for treating PFAPA syndrome. The fever episodes ceased without any intervention in half of the control subjects. We conclude that although the mechanisms behind this syndrome are unknown, tonsillectomy can be offered as an effective intervention for children with PFAPA.

Oral prednisolone is an effective adjuvant therapy for acute otitis media with discharge through tympanostomy tubes.

OBJECTIVE: To determine the efficacy of a short course of oral prednisolone as an adjuvant therapy for acute otitis media draining through tympanostomy tubes. STUDY DESIGN: In a randomized, double-blind, placebo-controlled study, children with acute discharge (<48 hours) through tympanostomy tubes received either prednisolone (2 mg/kg/d; n = 23) or placebo (n = 27) for 3 days. All children received amoxicillin/clavulanate (40/10 mg/kg/d) for 7 days. The children were examined daily at the study clinic until the drainage ceased. RESULTS: The median duration of otorrhea in the prednisolone group was 1.0 days (25% to 75% range, 1.0 to 2.0 days), compared with 3.0 days (25% to 75% range, 2.0 to 4.0 days) in the children receiving placebo (P <.001). The duration of otorrhea was

Short-term use of amoxicillin-clavulanate during upper respiratory tract infection for prevention of acute otitis media.

We performed a randomized, double-blind, placebo-controlled study to determine whether acute otitis media could be prevented by antibiotic therapy initiated promptly after the appearance of symptoms of upper respiratory tract infection. One hundred four children aged 1 to 4 years received a 7-day course of either amoxicillin-clavulanate or placebo. Acute otitis media developed in 9 (18%) of the 50 children receiving amoxicillin clavulanate and in 12 (22%) of the 54 children receiving placebo (p = 0.59).

Respiratory virus infection as a cause of prolonged symptoms in acute otitis media.

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.

Rapid diagnosis of adenoviral tonsillitis: a prospective clinical study.

Adenovirus antigen was detected by radioimmunoassay in the nasopharyngeal specimens of 30 of 74 children with febrile exudative tonsillitis. In the other 44 children, the cause of tonsillitis was identified in 16 (beta-hemolytic streptococci or Epstein-Barr, parainfluenza, or herpes simplex viruses). The clinical picture of adenoviral tonsillitis was difficult to differentiate from that of streptococcal disease; 20 of the patients had originally been given antibiotics. In 68% of patients without complications, the serum concentration of C-reactive protein was less than 20 mg/L, suggesting a viral disease. No other hematologic test was found helpful in identifying the adenoviral tonsillitis. The rapid detection of adenovirus antigen permitted withdrawal of unnecessary and ineffective antibiotic treatment in most patients.

Intrafamilial spread of pertussis.

Intrafamilial spread of pertussis was evaluated in 21 families (97 individuals) of patients with whooping cough diagnosed by culture or by ELISA serology. During follow-up (average six months), an infectivity rate of 83% was established by an ELISA within these families. However, 46% of the secondary cases were asymptomatic. Most of the asymptomatic cases were in adults or vaccinated children. Unvaccinated infants had classic whooping cough and were exposed to pertussis by their vaccinated siblings or parents. The incidence of classic symptoms of pertussis decreased with age, and atypical pertussis was usually culture negative but rapidly diagnosed by measurement of the IgM- and IgA-class antibodies by ELISA.

Measles vaccination after exposure to natural measles.

When an extensive measles epidemic broke out in Turku in late 1975, the availability of a previous study on measles vaccination reactions in 442 children permitted a comparative evaluation to be made on reactions to and the efficacy of measles vaccine (Schwartz strain) administered after exposure to natural measles. In a preliminary study, nine children were vaccinated one to 14 days after exposure to natural measles but before prodromal symptoms appeared. Only one of these nine children developed symptoms and signs comparable to those of the natural disease. In five day-care centers the children were vaccinated when five or more children out of 30 to 40 at each center had measles. In only five of 74 exposed children were the signs and symptoms comparable to those of natural measles. No marked differences in signs and symptoms after the vaccinations were observed between the exposed and nonexposed children. It is concluded that vaccination is safe, can usually prevent measles, even when administered after a prolonged interval following exposure to natural disease, and can usually control an epidemic in progress.