Efficacy of pneumococcal vaccine in severe chronic obstructive pulmonary disease. Effect of a conjugate pneumococcal vaccine on the occurrence of respiratory infections and antibiotic use in day-care center attendees. Clinical efficacy of pneumococcal vaccine in the elderly: a randomized, single-blind population-based trial. Clinical efficacy of anti-pneumococcal vaccination in patients with COPD. Influenza vaccination in children with asthma: randomized double-blind placebo-controlled trial. Prophylaxis of otitis media in asthmatic children. Response to pneumococcal vaccine in chronic obstructive lung disease--the effect of ongoing, systemic steroid treatment. Efficacy of nine-valent pneumococcal conjugate vaccine against pneumonia and invasive pneumococcal disease in The Gambia: randomised, double-blind, placebo-controlled trial. A controlled evaluation of the protective efficacy of pneumococcal vaccine for patients at high risk of serious pneumococcal infections.
Although pneumococcal vaccine has been recommended for patients with chronic obstructive pulmonary disease (COPD), its efficacy in this population has not been shown. A double-blind randomized controlled trial of 14-valent pneumococcal vaccine was carried out in 189 men and women aged 40 to 89 years with a clinical diagnosis of COPD and a forced expiratory volume in 1 second of less than 1.5 L. Of the 189, 92 received the vaccine and 97 received saline placebo. In a randomly chosen subsample of those who received the vaccine the mean titres of specific IgG antibody to selected pneumococcal polysaccharide serotypes increased two- to threefold by 4 weeks after vaccination. Over a 2-year period the rates of death, hospital admissions and emergency visits and the mean length of hospital stay were not significantly different in the two groups. Although a protective effect of 14-valent pneumococcal vaccine could not be shown, the small size of the sample and the relatively low follow-up rates preclude firm conclusions about efficacy from these data alone. The elevated antibody levels before vaccination in some of the patients, suggesting prior infection with Diplococcus pneumoniae, may partly explain the findings. Incidence and severity of respiratory infections are increased in day-care center attendees. Streptococcus pneumoniae is an important contributor to these infections.
                To examine whether the use of a pneumococcal conjugate vaccine could reduce the occurrence of respiratory infections and the ensuing antibiotic drug use in the day care.
                In this double blind, randomized, controlled study performed in 8 day-care centers located in Beer-Sheva, Israel, 264 toddlers ages 12 to 35 months at enrollment were randomized to receive either a 9-valent conjugate pneumococcal vaccine (conjugated to CRM197) or a control vaccine [conjugate meningococcus C vaccine (conjugated to CRM197)] and were followed for an average of 22 months. The main outcome measures were respiratory morbidity and antibiotic use.
                An overall reduction of 7% in child months with > or = 1 reported illness episodes was observed among vaccinees (P = 0.008), and 85% of all episodes were related to the respiratory tract. Reductions of 15, 16 and 17% were observed in upper respiratory infections, lower respiratory problems and otitis media, respectively. An overall reduction of 17% in antibiotic days was observed [10% for upper respiratory infections, 20% for otitis and 47% for lower respiratory problems (P < or = 0.005 for each entity)]. The reduction in episodes and antibiotic use was greater for those <36 months of age than for the older children.
                The reduction of respiratory problems, including those not traditionally considered of pneumococcal origin and the ensuing lowered antibiotic use in day-care center attendees by pneumococcal conjugate vaccination suggest a broader benefit from the vaccine than preventing invasive disease only. To study the efficacy of pneumococcal capsular polysaccharide vaccine among the elderly by use of a population-based intervention in one township, Varkaus, Eastern Finland.
                A randomized, controlled trial in which elderly inhabitants (aged 60 years or older) of the catchment area were randomized to receive either pneumococcal and influenza vaccines (PI group = vaccinated) or influenza vaccine alone (I group = controls) and offered participation. The response rate was 67.4%. The PI group consisted of 1,364 persons and the I group of 1,473 persons. The vaccinations were performed in the municipal health center in the fall of 1982, and all elderly inhabitants were followed for 3 years for the development of radiologically confirmed pneumonia. Pneumococcal etiology was identified by serological methods.
                The incidence of pneumonia was 18.8 per 1,000 person-years in the PI group (73 pneumonia episodes) and 16.6 per 1,000 person-years in the I group (69 episodes). Pneumococcal etiology was found in 27 episodes in the PI group (incidence 7.0 per 1,000 person-years) and in 36 episodes in the I group (incidence 8.6 per 1,000 person-years). In controls (I group) the incidence of pneumococcal pneumonia was significantly higher among persons with increased risk for contracting pneumonia (19 per 1,000 person-years) than among controls with low risk status (4 per 1,000 person-years). No significant protection from pneumococcal pneumonia was found in the study group as a whole (vaccine efficacy 15%, 95% CI -43% to 50%). However, in persons with medical risk factors for contracting pneumonia, there was a statistically significant protective efficacy of 59% (95% CI, 6% to 82%).
                Pneumococcal vaccination significantly reduced the incidence of pneumococcal pneumonia in elderly persons at increased risk for contracting pneumonia. This increased/high-risk category comprised 34% of the population aged 60 years or older. Because targeted vaccination of this large group may be difficult to organize in an efficient manner, vaccinating all elderly persons may be the best strategy to prevent this rather common and often fatal disease. A study was undertaken to evaluate the clinical efficacy of the 23-valent pneumococcal polysaccharide vaccine (PPV) in immunocompetent patients with chronic obstructive pulmonary disease (COPD).
                A randomised controlled trial was carried out in 596 patients with COPD of mean (SD) age 65.8 (9.7) years, 298 of whom received PPV. The main outcome was radiographically proven community acquired pneumonia (CAP) of pneumococcal or unknown aetiology after a mean period of 979 days (range 20-1454).
                There were 58 first episodes of CAP caused by pneumococcus or of unknown aetiology, 25 in the intervention group and 33 in the non-intervention group. Kaplan-Meier survival curves for CAP did not show significant differences between the intervention and non-intervention arms (log rank test = 1.15, p = 0.28) in the whole group of patients. The efficacy of PPV in all patients was 24% (95% CI -24 to 54; p = 0.333). In the subgroup aged <65 years the efficacy of PPV was 76% (95% CI 20 to 93; p = 0.013), while in those with severe functional obstruction (forced expiratory volume in 1 second <40%) it was 48% (95% CI -7 to 80; p = 0.076). In younger patients with severe airflow obstruction the efficacy was 91% (95% CI 35 to 99; p = 0.002). There were only five cases of non-bacteraemic pneumococcal CAP, all in the non-intervention group (log rank test = 5.03; p = 0.025). Multivariate analysis gave a hazard ratio for unknown and pneumococcal CAP in the vaccinated group, adjusted for age, of 0.20 (95% CI 0.06 to 0.68; p = 0.01).
                PPV is effective in preventing CAP in patients with COPD aged less than 65 years and in those with severe airflow obstruction. No differences were found among the other groups of patients with COPD. There is little evidence that influenza vaccination reduces asthma exacerbations. We determined whether influenza vaccination is more effective than placebo in 6-18-year-old children with asthma. We performed a randomized, double-blind, placebo-controlled trial. Parenteral vaccination with inactivated influenza vaccine or placebo took place approximately November 1, and children were followed until April 1 of the next year. Airway symptoms were reported in a diary. When symptom scores reached a predefined level, a pharyngeal swab was taken. Primary outcome was the number of asthma exacerbations associated with virologically proven influenza infection. Three hundred forty-nine children were assigned placebo, and 347 were assigned vaccine. Pharyngeal swabs positive for influenza were related to 42 asthma exacerbations, 24 in the vaccine group and 18 in the placebo group, a difference of 33% favoring placebo (31% after adjustment for confounders; 95% confidence interval, -34% to 161%). Influenza-related asthma exacerbations were of similar severity in both groups; they lasted 3.1 days shorter in the vaccine group (95% confidence interval, -6.2 to 0.002 days, p = 0.06). We conclude that influenza vaccination did not result in a significant reduction of the number, severity, or duration of asthma exacerbations caused by influenza. Additional studies are warranted to justify routine influenza vaccination of children with asthma. Seventy-two asthmatic children with recurrent otitis media were studied over a 2-year interval. They were randomly divided to receive either (1) no routine medication, (2) antihistamines whenever nasally congested, (3) daily sulfisoxazole at 500 mg twice a day, (4) pneumococcal immunization and (5) both pneumococcal vaccine and 500 mg sulfisoxazole twice daily. There was no apparent benefit in the antihistamine group. There was a mean yearly reduction in otitis media of 75% in the sulfisoxazole group, 38% in the pneumococcal vaccine group and 90% in the group treated with both agents. The latter group also had a 56% reduction in frequency of acute asthmatic attacks and a 90% decrease in hospitalizations associated with otitis media. In conclusion the use of sulfisoxazole and pneumococcal vaccine appears efficacious for management of asthmatic children with recurrent otitis media. Forty-nine patients with chronic obstructive lung disease (COPD) were block-randomized in four groups to investigate, if different degrees of steroid-load influenced the effect of pneumococcal-vaccination on antibody level and clinical variables during 6 months of follow-up. The groups included 13 patients without systemic steroids for the previous 3 months, all vaccinated at entrance in the study and treated with steroids for 4 weeks. Nine patients had chronic steroid treatment both before and during the investigation; they were vaccinated at the entrance in the study. Fifteen patients without systemic steroids for the previous 3 months were vaccinated after the end of a 4-week steroid treatment. Twelve patients served as controls, and were not vaccinated. Totally, 60%-78% of vaccinated patients in the three groups had a rise in antibody level, and a later decrease compared to two of the 12 control patients (p<0.01). This difference was also significant (p<0.05) for the patients vaccinated at entrance in the hospital. No differences were observed among the clinical variables: pneumonia, exacerbations, admittance to hospital, increase in the use of steroids or beta-agonists, and the use of antibiotics. We conclude that a rise in antibody level after pneumococcal vaccination can be expected in patients with COPD despite of the use of systemic steroids. The clinical effect of vaccination is debatable. Pneumonia is estimated to cause 2 million deaths every year in children. Streptococcus pneumoniae is the most important cause of severe pneumonia. We aimed to assess the efficacy of a nine-valent pneumococcal conjugate vaccine in children.
                We undertook a randomised, placebo-controlled, double-blind trial in eastern Gambia. Children age 6-51 weeks were randomly allocated three doses of either pneumococcal conjugate vaccine (n=8718) or placebo (8719), with intervals of at least 25 days between doses. Our primary outcome was first episode of radiological pneumonia. Secondary endpoints were clinical or severe clinical pneumonia, invasive pneumococcal disease, and all-cause admissions. Analyses were per protocol and intention to treat.
                529 children assigned vaccine and 568 allocated placebo were not included in the per-protocol analysis. Results of per-protocol and intention-to-treat analyses were similar. By per-protocol analysis, 333 of 8189 children given vaccine had an episode of radiological pneumonia compared with 513 of 8151 who received placebo. Pneumococcal vaccine efficacy was 37% (95% CI 27-45) against first episode of radiological pneumonia. First episodes of clinical pneumonia were reduced overall by 7% (95% CI 1-12). Efficacy of the conjugate vaccine was 77% (51-90) against invasive pneumococcal disease caused by vaccine serotypes, 50% (21-69) against disease caused by all serotypes, and 15% (7-21) against all-cause admissions. We also found an efficacy of 16% (3-28) against mortality. 110 serious adverse events arose in children given the pneumococcal vaccine compared with 131 in those who received placebo.
                In this rural African setting, pneumococcal conjugate vaccine has high efficacy against radiological pneumonia and invasive pneumococcal disease, and can substantially reduce admissions and improve child survival. Pneumococcal conjugate vaccines should be made available to African infants. The protective efficacy of pneumococcal vaccine against systemic pneumococcal infections in adults with the current indications for the vaccine was evaluated in a case-control study. Six (7%) of the 90 cases and 16 (18%) of the matched controls had received pneumococcal vaccine for an odds ratio of 0.33 (p less than 0.05). The vaccine's protective efficacy was 67%, which remained virtually unchanged after adjusting for potential confounding variables. The vaccine's efficacy was 77% for patients at moderately increased risk of pneumococcal infections, but 0% for patients who were severely immunocompromised. The vaccine's protective efficacy was 70% (p less than 0.05) for all patients 55 years or older after controlling for indications for the vaccine in addition to age. Pneumococcal vaccine confers substantial protection against systemic pneumococcal infections on the elderly and patients with illnesses associated with a moderately increased risk of pneumococcal infections.
This review found very limited evidence to support the routine use of pneumococcal vaccine in people with asthma. A randomised trial of vaccine efficacy in children and adults with asthma is needed.