Pekka Karma

Efficacy of a Pneumococcal Conjugate Vaccine against Acute Otitis Media

BACKGROUNDnEar infections are a common cause of illness during the first two years of life. New conjugate vaccines may be able to prevent a substantial portion of cases of acute otitis media caused by Streptococcus pneumoniae.nnnMETHODSnWe enrolled 1662 infants in a randomized, double-blind efficacy trial of a heptavalent pneumococcal polysaccharide conjugate vaccine in which the carrier protein is the nontoxic diphtheria-toxin analogue CRM197. The children received either the study vaccine or a hepatitis B vaccine as a control at 2, 4, 6, and 12 months of age. The clinical diagnosis of acute otitis media was based on predefined criteria, and the bacteriologic diagnosis was based on a culture of middle-ear fluid obtained by myringotomy.nnnRESULTSnOf the children who were enrolled, 95.1 percent completed the trial. With the pneumococcal vaccine, there were more local reactions than with the hepatitis B vaccine but fewer than with the combined whole-cell diphtheria-tetanus-pertussis and Haemophilus influenzae type b vaccine that was administered simultaneously. There were 2596 episodes of acute otitis media during the follow-up period between 6.5 and 24 months of age. The vaccine reduced the number of episodes of acute otitis media from any cause by 6 percent (95 percent confidence interval, -4 to 16 percent [the negative number indicates a possible increase in the number of episodes]), culture-confirmed pneumococcal episodes by 34 percent (95 percent confidence interval, 21 to 45 percent), and the number of episodes due to the serotypes contained in the vaccine by 57 percent (95 percent confidence interval, 44 to 67 percent). The number of episodes attributed to serotypes that are cross-reactive with those in the vaccine was reduced by 51 percent, whereas the number of episodes due to all other serotypes increased by 33 percent.nnnCONCLUSIONSnThe heptavalent pneumococcal polysaccharide-CRM197 conjugate vaccine is safe and efficacious in the prevention of acute otitis media caused by the serotypes included in the vaccine.

The seven-valent pneumococcal conjugate vaccine reduces tympanostomy tube placement in children.

Background: The novel pneumococcal conjugate vaccine, PncCRM, has been shown to prevent acute otitis media caused by vaccine serotypes and to reduce otitis surgery. Our aim was to assess long term efficacy of the vaccine on tympanostomy tube placements. Methods: Children with complete follow-up in the Finnish Otitis Media Vaccine Trial up to 24 months of age and still living in the study area (1490 of 1662 randomized at 2 months of age) were invited to a single visit at 4–5 years of age. The children had been vaccinated at 2, 4, 6 and 12 months of age with PncCRM or hepatitis B vaccine (control). Tympanostomy tube placements reported by parents at the visit were verified from hospital and private medical center records. Additionally, tympanostomy tube placements of all children were verified from the hospital discharge registry. Vaccine efficacy (VE) was estimated by comparing all events of tympanostomy tube placement between vaccine groups. Results: During the vaccine trial (2–24 months of age), VE (95% confidence interval) in preventing tympanostomy tube placement was only 4% (– 19–23%). Altogether 756 children were enrolled for the follow-up study. After 24 months of age, the rate of surgery was 3.5 per 100 person-years in the PncCRM and 5.7 per 100 person-years in the control children, giving VE of 39% (4–61%). In the hospital-based data of all children (N = 1490), VE of 44% was obtained (19–62%). Conclusions: Receipt of PncCRM vaccine at infancy was associated with a reduction in tympanostomy tube placement from 2 to 4–5 years of age.

Association of Clinical Signs and Symptoms with Bacterial Findings in Acute Otitis Media

In acute otitis media (AOM), a means of prediction of the bacterial pathogen based on symptoms and signs would be valuable in selecting appropriate antimicrobial treatment. Children in the control arm (n=831) in the Finnish Otitis Media Vaccine Trial were prospectively observed in a study clinic setting from the age of 2 to 24 months. In patients with AOM, myringotomy with aspiration was performed, and middle ear fluid samples were cultured for bacterial pathogens. Symptoms and signs of respiratory infections were thoroughly recorded. Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae were the most common bacterial pathogens. Pneumococcal AOM was associated with more-severe AOM characterized by fever and earache. AOM due to H. influenzae was associated with eye symptoms and findings. Accurate prediction of a bacterial cause of infection based on symptoms and signs of AOM was not possible, but a specific cause was predicted in some situations, with a high probability of applicability to clinical practice.

Androgen Receptors in Laryngeal Carcinoma

To study androgen receptors in normal and malignant laryngeal tissue, high affinity, limited capacity androgen receptors were assayed from the cytosol fraction of laryngeal carcinomas of 18 male patients and of nonneoplastic laryngeal tissue of 5 male patients. Immediately after removal, the samples were frozen with dry ice and stored at -70°C. a specific radioligand, [3H]methyltrienolone incubation and dextran-coated charcoal method was used. Five laryngeal carcinomas showed androgen receptors. the number of receptor sites varied from 1.6 to 4.2 fmoles/mg protein, and the dissociation coefficient (KD) from 2.6 to 0.7 10−9 M. Androgen receptors stood at—70°C for at least 4-5 months. 13 laryngeal carcinomas were receptor negative. Nonneoplastic laryngeal tissue contained 1.0-10.5 fmoles androgen receptors/mg cytosol protein and their KD was 0.2-2.1 10−9 M. This study indicates that some laryngeal carcinomas contain androgen receptors and these cases might be amenable to antiandrogen therapy.

Occurrence of Tracheal Carcinoma in Finland

During the period 1967-1985, 95 primary tracheal carcinomas occurred in Finland. The mean annual incidence rate was one per one million inhabitants, the male:female ratio being 7:3. There was a significant increase of the disease by increasing age with the exception of 70-79 years. The most common location was the lower third of the trachea. Over two-thirds of the tumours were squamous carcinomas. Smoking seems to be an important risk factor at least in males.

Treatment of Primary Tracheal Carcinoma in Finland in 1967–1985

The treatment results of all the 95 primary tracheal carcinomas recorded by the Finnish Cancer Registry in 1967-1985 are evaluated. Six of the 95 patients were treated by surgery, 60 received radiotherapy and 29 were left untreated or received only palliative endoscopic or cytostatic therapy. The prognosis of the disease was poor. Among the 44 squamous cell carcinoma patients treated by radiotherapy, the median survival time after the diagnosis was 8 months (range 1-81 months). Complete response to radiotherapy was a favourable prognostic sign; after complete response the survival rates at 1, 2 and 5 years were 45%, 18% and 9% respectively. Patients with adenocystic carcinoma had the best prognosis.

PCR Assay for Detecting Streptococcus pneumoniae in the Middle Ear of Children with Otitis Media with Effusion

We compared a newly developed pneumococcal polymerase chain reaction (PCR) for Streptococcus pneumoniae (Pnc) to bacterial culture in 123 middle ear effusion (MEE) samples of 123 children with otitis media with effusion (OME). For the pneumococcal PCR assay, DNA of MEE samples was purified by a QIAamp blood kit. The outer primers used amplified a 348 basepair region of the pneumolysin gene, and the inner a 208. Pnc was cultured in 14 (11%) and pneumolysin PCR was positive in 57 (46%) of the 123 MEE samples. All the culture positive samples were also PCR-positive. Both the samples with culturable Pnc and with positive pneumolysin PCR increased with shorter duration of OME and a greater number of acute otitis media during the preceding 6 months. In conclusion, pneumolysin PCR suggests pneumococcal involvement in MEE even in OMEs with no evidence of Pnc in culture, and thus offers a good diagnostic tool when a more accurate and sensitive pneumococcal diagnosis is needed.

Bacteriological Findings and Persistence of Middle Ear Effusion in Otitis Media with Effusion

The bacteriology of middle ear effusion (MEE) of asymptomatic otitis media with effusion (OME) was studied in 165 children, aged 5 months to 12 years, from the MEE samples obtained during tympanostomy under general anaesthesia in 1993-1994. MEE had persisted for 1 to 12 (mean 3.5) months. Major otitis pathogens (S. pneumoniae, H. Influenzae, B. catarrhalis and S. pyogenes) were cultured in 41% of the children under 2 years of age and in 17% of older children (p < 0.001). Respiratory infections and attacks of acute otitis media (AOM) during the last 6 months were also more frequent in children younger than 2 years (p < 0.001). The proportion of S. pneumoniae (25%) and H. influenzae (38%), but not of other bacteria, was higher in the children with less than 2 months persistence of MEE as compared with those with a longer duration (8% and 3%) (p < 0.01). After 2 months, the occurrence of different bacteria remained relatively unchanged until 6 months persistence of MEE, and thereafter no pathogens were culturable. Among the children adenotomized earlier, the proportion of those with major otitis pathogens in MEE was 8% compared with 32% in non-adenotomized children (p = 0.02). S. pneumoniae, B. catarrhalis or S. pyogenes were not culturable in any of the adenotomized children, while MEE grew them in 25% of the non-adenotomized children (p < 0.001). Since the MEE bacteriology of OME with less than 2 months persistence resembles that of AOM, it may be that these cases represent a transitory phase between AOM and an established OME.

Comparison of serum antibodies to pneumolysin with those to pneumococcal capsular polysaccharides in children with acute otitis media

BACKGROUNDnStreptococcus pneumoniae is a major bacterial pathogens in acute otitis media. Pneumolysin is a species-specific protein toxin produced intracellularly by all clinically relevant pneumococcal strains, and antibodies to pneumolysin should therefore represent pneumococcal involvement in the disease, regardless of the serotype.nnnMETHODSnAntibodies to pneumococcal pneumolysin and capsular polysaccharides were measured by enzyme immunoassay in acute and convalescent sera of 121 children with acute otitis media. A pneumococcal otitis episode was defined by a positive middle ear fluid culture and/or pneumolysin PCR.nnnRESULTSnMedian age of the 10 children who developed a seroconversion response to pneumolysin was 1 year 8 months, and of the 21 children responding to polysaccharides it was 2 years 9 months. Eight of the 10 seroconversion responses to pneumolysin were of IgA class alone, whereas 17 of the 21 polysaccharide responses were of IgG class alone or IgG together with IgM and/or IgA. Of the 41 children with a pneumococcal otitis episode, 13 (39%) showed a seroconversion response, 3 (7%) to pneumolysin and 11 (27%) to capsular polysaccharides. The children with a pneumococcal otitis episode had lower titers of acute phase IgG to the capsular polysaccharide pool of S. pneumoniae (containing types 6B, 14, 19F and 23F), as compared with the titers in children with otitis caused by other pathogens and pneumococci only in the nasopharynx or not found at all (P = 0.04).nnnCONCLUSIONSnSerum antibodies to pneumolysin can be detected at an earlier age than those to the capsular polysaccharides. However, a seroconversion is rare and therefore of no diagnostic value. The presence of serum IgG to the pneumococcal capsular polysaccharides seems beneficial in the prevention of pneumococcal otitis.

The Site of Impulse Generation in Transcranial Magnetic Stimulation of the Facial Nerve

The facial nerve can be stimulated in its intracranial course through transcranial magnetic stimulation (TMS). We studied the site of impulse generation produced by TMS by comparing the latencies of the muscle evoked potentials (MEPs) elicited with TMS and intracranial electrical stimulation (IES) of the facial nerve during neurosurgical posterior fossa procedures. In a series of 25 patients, the mean latency of the TMS elicited MEPs, recorded in the orbicularis oris muscle, was 5.0 ms (SD 0.58). Also IES of the distal part of the facial nerve in the internal acoustic meatus showed a mean latency of 5.0 ms (SD 0.68). Proximal IES in the root entry zone of the facial nerve, and intermediate IES between root entry zone and meatus, produced MEPs with significantly longer latencies compared to TMS and distal IES (p < 0.05). The findings suggest that the TMS induced facial nerve activation, leading to a MEP response, takes place within the internal acoustic meatus.