Efficacy of an 11-valent pneumococcal conjugate vaccine against radiologically confirmed pneumonia among children less than 2 years of age in the Philippines: a randomized, double-blind, placebo-controlled trial. Effectiveness of heptavalent pneumococcal conjugate vaccine in children younger than five years of age for prevention of pneumonia. The impact of a 9-valent pneumococcal conjugate vaccine on the public health burden of pneumonia in HIV-infected and -uninfected children. Impact of the pneumococcal conjugate vaccine on otitis media. Clinical efficacy of anti-pneumococcal vaccination in patients with COPD. Adjunctive corticosteroid therapy for Pneumocystis carinii pneumonia in AIDS: a randomized European multicenter open label study. Protective effects of the 23-valent pneumococcal polysaccharide vaccine in the elderly population: the EVAN-65 study. Clinic HIV-focused features and prevention of Pneumocystis carinii pneumonia. Effectiveness of pneumococcal polysaccharide vaccine against pneumonia and cost analysis for the elderly who receive seasonal influenza vaccine in Japan. A randomized trial of two postexposure prophylaxis regimens to reduce mother-to-child HIV-1 transmission in infants of untreated mothers.
Pneumococcus is a leading cause of childhood pneumonia worldwide. Pneumococcal conjugate vaccines (PCV) have demonstrated efficacy against childhood invasive pneumococcal disease (IPD) and pneumonia in the United States and Africa. No information is available from Asia on the impact of PCV on childhood pneumonia.
                We conducted a randomized, placebo-controlled, double-blind trial in Bohol, the Philippines (ISRCTN 62323832). Children 6 weeks to <6 months of age were randomly allocated to receive 3 doses of either an 11-valent PCV (11PCV, sanofi pasteur, Lyon, France) or a saline placebo, with a minimum interval of 4 weeks between doses to determine vaccine efficacy (VE) against the primary outcome of a child experiencing first episode of community-acquired radiologically defined pneumonia in the first 2 years of life. Secondary end points were clinical pneumonia, IPD, safety, and immunogenicity.
                Twelve thousand one hundred ninety-one children were enrolled. By per protocol (PP) analysis, 93 of 6013 fully vaccinated 11PCV recipient children had a first episode of radiologic pneumonia compared with 120 of 6018 placebo recipients. VE against radiologically defined pneumonia for the PP cohort of children 3 to 23 months old was 22.9% (95% CI: -1.1, 41.2; P = 0.06), for the prespecified subgroups of children 3 to 11 months of age, 34.0% (95% CI: 4.8, 54.3; P = 0.02), and of those 12 to 23 months old, 2.7% (95% CI: -43.5, 34.0; P = 0.88). By intent-to-treat (ITT) analysis, 119 of 6097 11PCV recipient children had an episode of radiologic pneumonia compared with 141 of 6094 placebo recipients. VE against radiologic pneumonia for the ITT cohort of children <2 years old was 16.0% (95% CI -7.3, 34.2; P = 0.16), for a subgroup of children <12 months of age, 19.8% (95% CI: -8.8, 40.8; P = 0.15). VE against clinical pneumonia by PP was not significant (VE 0.1%; 95% CI -9.4, 8.7; P = 0.99). IPD was rare: only 3 cases of IPD due to vaccine serotypes were observed during the study. 11PCV was immunogenic and well tolerated. Among 11PCV recipients, a small excess of serious adverse respiratory events was observed in the first 28 days after the first and second dose of vaccine, and of nonrespiratory events after the first dose. An excess of pneumonia episodes in 11PCV recipients in the month following the second dose of vaccination was the principal reason for lower VE by ITT analysis than by PP analysis.
                In PP analysis, a 22.9% reduction of community-acquired radiologically confirmed pneumonia in children younger than 2 years of age in the 11-valent tetanus-diphtheria toxoid-conjugated PCV vaccinated group was observed; a reduction similar as observed in other PCV trials. We could not demonstrate any VE against clinical pneumonia. Our finding confirms for the first time that in a low-income, low-mortality developing country in Asia, at least one-fifth of radiologically confirmed pneumonia is caused by pneumococcus, and thus preventable by PCV. Whether PCV should be included in national program in such settings, however, depends on careful country specific disease burden measurement and cost-effectiveness calculation. To determine the effectiveness of the Wyeth heptavalent pneumococcal conjugate vaccine against clinical and radiograph-confirmed pneumonia in children.
                The heptavalent CRM(197) pneumococcal conjugate vaccine (PCV) was given to infants at 2, 4, 6 and 12 to 15 months of age in a randomized, double blind trial. Children were randomized to receive either the CRM(197) PCV (vaccine group) or the meningococcal type C CRM(197) conjugate vaccine (control group). The primary outcome of this trial was invasive pneumococcal disease. In addition children with the clinical diagnosis of pneumonia in the study population were identified through review of automated inpatient, emergency and outpatient databases. The subset of the cohort of these children who had chest radiographs obtained at the time of diagnosis was identified, and the original reading of their radiographs by the radiologist was obtained from automated databases. Rates of clinically diagnosed pneumonia, of pneumonia with a radiograph obtained regardless of result, of pneumonia with positive radiograph (consolidation, empyema or parenchymal infiltrate) and of pneumonia with only perihilar infiltrates were compared between vaccinated and nonvaccinated groups. In addition risk of disease pneumonia was evaluated by race and ethnicity.
                The incidence of a first pneumonia episode in the control group was 55.9 per 1000 person-years. A radiograph was obtained in 61% of episodes, a positive radiograph in 21% and perihilar findings in an additional 5%. In per protocol follow-up of children given PCV, first episodes of all clinically diagnosed pneumonia were reduced by 4.3% [95% confidence interval (CI), -3.5, 11.5%, = 0.27], episodes with a radiograph were reduced by 9.8% (CI 0.1, 18.5%, < 0.05) and episodes with a positive radiograph were reduced by 20.5% (CI 4.4, 34.0, = 0.02). In the intent to treat analysis including all episodes after randomization, episodes with a positive radiograph were reduced by 17.7%, =.01). The greatest impact was in the first year of life with a 32.2% reduction and a 23.4% reduction in the first 2 years, but only a 9.1% reduction in children >2 years of age. Asians, blacks and Hispanics were at higher risk of pneumonia than were whites, but there was no evidence of ethnic variation in PCV effectiveness. Ten of the 11 cases of pneumococcal pneumonia with a positive blood culture were in the control group.
                The pneumococcal conjugate vaccine tested was effective in reducing the risk of pneumonia in young children. Pneumococcal conjugate vaccine (PnCV) may be used as a probe to define the burden of pneumococcal disease and better characterize the clinical presentation of pneumococcal pneumonia.
                This study used a 9-valent PnCV to define different end points of vaccine efficacy and the preventable burden of pneumococcal pneumonia in 39,836 children who were randomized in a double-blind, placebo-controlled trial in South Africa.
                Whereas the point-estimate of vaccine efficacy was greatest when measured against the outcome of vaccine-serotype specific pneumococcal bacteremic pneumonia (61%; P = .01), the sensitivity of blood culture to measure the burden of pneumococcal pneumonia prevented by vaccination was only 2.6% in human immunodeficiency virus (HIV)-uninfected children and 18.8% in HIV-infected children. Only 37.8% of cases of pneumococcal pneumonia prevented by PnCV were detected by means of chest radiographs showing alveolar consolidation. A clinical diagnosis of pneumonia provided the best estimate of the burden of pneumococcal pneumonia prevented through vaccination in HIV-uninfected children (267 cases prevented per 100,000 child-years) and HIV-infected children (2573 cases prevented per 100,000 child-years).
                Although outcome measures with high specificity, such as bacteremic pneumococcal pneumonia, provide a better estimate as to vaccine efficacy, the burden of disease prevented by vaccination is best evaluated using outcome measures with high sensitivity, such as a clinical diagnosis of pneumonia. The heptavalent pneumococcal conjugate vaccine (PCV) is recommended for infants to protect against invasive disease, but its impact on otitis might also have public health importance.
                To examine the impact of PCV on the incidence of otitis media, frequent otitis media and tympanostomy tube procedures and to assess whether the effectiveness of the vaccine wanes after age 24 months and varies by race, sex or season.
                From 1995 to 1998, 37 868 children at Kaiser Permanente in Northern California were randomized to receive PCV or a control vaccine in a double blind trial and were followed through April 1999.
                Children received a primary series at 2, 4 and 6 months of age and a booster at 12 to 15 months.
                Visits for otitis, frequent visits for otitis and tympanostomy tube procedures. Otitis was ascertained from diagnosis checklists routinely marked by physicians.
                Control children averaged 1.8 otitis visits per year. Children given PCV had fewer otitis visits than control children in every age group, sex, race and season examined. Intention-to-treat analysis permitted rejection of the null hypothesis that PCV is ineffective against otitis media (P < 0.0001). In children who completed the primary series per protocol, PCV reduced otitis visits by 7.8% [95% confidence interval (CI), 5.4 to 10.2%] and antibiotic prescriptions by 5.7% (CI 4.2 to 7.2%). Frequent otitis was reduced by amounts that increased with otitis frequency, from a 10% reduction in the risk of 3 visits to a 26% reduction in the risk of 10 visits within a 6-month period. Tube placements were reduced by 24% (CI 12 to 35%).
                In children followed up to 3.5 years, PCV provided a moderate amount of protection against ear infections while reducing frequent otitis media and tube procedures by greater amounts. 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. Fifty-nine human immunodeficiency virus type-1-infected patients with a microscopically proven first episode of moderate to severe Pneumocystis carinii pneumonia (PCP) were enrolled into a randomized European multicenter study. The effect of adjunctive corticosteroid (CS) therapy was assessed on (a) survival to discharge, (b) need for mechanical ventilation, and (c) survival at day 90. CS was given within 24 h of standard therapy as intravenous methylprednisolone 2 mg/kg body weight daily for 10 days. All patients received cotrimoxazole as standard treatment. Inclusion criteria were a PaO2 less than 9.0 kPa (67.5 mm Hg) and/or a PaCO2 less than 4.0 kPa (30.0 mm Hg) while breathing room air. During the acute episode of PCP, 9 (31%) of the 29 control patients died versus 3 (10%) of the 30 CS patients; p = 0.01. Mechanical ventilation was necessary in 15 patients; 12 (41%) in the control group and 3 (10%) in the CS group; p = 0.01. The 90-day survival was 69% in controls versus 87% in CS patients; p = 0.07. Based on these data we conclude that adjunctive CS therapy for moderate to severe PCP in AIDS patients reduces the acute mortality and the need for mechanical ventilation. The 23-valent polysaccharide pneumococcal vaccine (PPV) is currently recommended for elderly persons and persons who are at high risk of infection. However, the effectiveness of the 23-valent PPV remains controversial. We assessed the effectiveness of this vaccine in older adults.
                A prospective cohort study was conducted from January 2002 through April 2005; it included all community-dwelling individuals aged >or=65 years who were assigned to 1 of 8 primary health care centers in Tarragona, Spain (11,241 subjects). The primary outcomes were invasive pneumococcal disease, pneumococcal pneumonia, overall pneumonia rate, and death due to pneumonia. All cases were validated by a check of the clinical records. The association between pneumococcal vaccination and the risk of each outcome was evaluated by means of multivariate Cox proportional hazard models, adjusted for age, sex, comorbidity, immunocompetence, and influenza vaccine status.
                Pneumococcal vaccination was associated with significant reductions in the risk of hospitalization for pneumonia (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.59-0.92) and in the overall pneumonia rate (HR, 0.79; 95% CI, 0.64-0.98). The incidence of invasive pneumococcal disease was low (64 cases per 100,000 person-years), and a considerable protective effect against invasive pneumococcal disease did not attain statistical significance (HR, 0.60; 95% CI, 0.22-1.65). However, the vaccine showed a significant effectiveness of 45% to prevent pneumococcal pneumonia (HR, 0.55; 95% CI, 0.34-0.88). Finally, vaccination was associated with a significant 59% reduction in the risk of death due to pneumonia among vaccinated subjects (HR, 0.41; 95% CI, 0.23-0.72).
                These results indicate that the 23-valent PPV effectively prevented pneumococcal pneumonia (with or without bacteremia) and decreased the rates of overall pneumonia and of mortality due to pneumonia in older adults, providing new arguments for systematic vaccination in the elderly population. To examine the association of clinic HIV-focused features and advanced HIV care experience with Pneumocystis carinii pneumonia (PCP) prophylaxis and development of PCP as the initial AIDS diagnosis.
                Nonconcurrent prospective study.
                New York State Medicaid Program.
                Medicaid enrollees diagnosed with AIDS in 1990-1992.
                We collected patient clinical and health care data from Medicaid files, conducted telephone interviews of directors of 125 clinics serving as the usual source of care for study patients, and measured AIDS experience as the cumulative number of AIDS patients treated by the study clinics since 1986. Pneumocystis carinii pneumonia prophylaxis in the 6 months before AIDS diagnosis and PCP at AIDS diagnosis were the main outcome measures. Bivariate and multivariate analyses adjusted for clustering of patients within clinics. Of 1,876 HIV-infected persons, 44% had PCP prophylaxis and 38% had primary PCP. Persons on prophylaxis had 20% lower adjusted odds of developing PCP (95% confidence interval [CI] 0.64, 0.99). The adjusted odds of receiving prophylaxis rose monotonically with the number of HIV-focused features offered by the clinic, with threefold higher odds (95% CI 1.6, 5.7) for six versus two or fewer such features. Patients in clinics with three HIV-focused features had 36% lower adjusted odds of PCP than those in clinics with one or none. Neither clinic experience nor specialty had a significant association with prophylaxis or PCP.
                PCP prevention in our study cohort appears to be more successful in clinics offering an array of HIV-focused features. To determine the clinical efficacy and cost-saving effect of pneumococcal polysaccharide vaccine (PPV) against community-acquired pneumonia (CAP), an open-label, randomized clinical trial was conducted involving 786 Japanese subjects older than 65 years of age receiving a routine influenza vaccine during the 2-year period. Study subjects were randomly assigned to either a PPV group (n=394) or to a non-PPV group (n=392). The incidence, admission and the medical cost for all-cause pneumonia were compared between these two groups. PPV vaccination significantly reduced the incidence of admission for all-cause pneumonia for subjects older than 75 years of age (41.5%, P=0.039) and for those who had difficulty walking (62.7%, P=0.005), but not for all study subjects older than 65 years of age (P=0.183), for the 2-year period. The Kaplan-Meier survival curves for subjects who had difficulty walking free from all-cause pneumonia demonstrated a significant difference (P=0.0146) between the two groups. PPV vaccination significantly reduced medical costs for all study subjects during the first year period (P=0.027). Our present data demonstrated that PPV was effective for all-cause pneumonia for study subjects older than 75 years of age, although the effect was not significant for all study subjects older than 65 years of age.
                Copyright © 2010 Elsevier Ltd. All rights reserved. Single-dose nevirapine (NVP) prophylaxis to mother and infant is widely used in resource-constrained settings for preventing mother-to-child transmission (MTCT) of HIV-1. Where women do not access antenatal care or HIV testing, postexposure prophylaxis to the infant may be an important preventative strategy.
                This multicentre, randomized, open-label clinical trial (October 2000 to September 2002) in South Africa compared single-dose NVP with 6 weeks of zidovudine (ZDV), commenced within 24 h of delivery among 1051 infants whose mothers had no prior antiretroviral therapy. HIV-1 infection rates were ascertained at birth, and at 6 and 12 weeks of age. Kaplan-Meier survival methods were used to estimate HIV-1 infection rates in an intention-to-treat analysis.
                Overall, 6 week and 12 week MTCT probability was 12.8% [95% confidence interval (CI),10.5-15.0] and 16.3% (95% CI,13.4-19.2), respectively. At 12 weeks, among infants who were not infected at birth, 24 (7.9%) infections occurred in the NVP arm and 41 (13.1%) in the ZDV arm (log rank P = 0.06). Using multivariate analysis, factors associated with infection following birth were ZDV use [odds ratio (OR), 1.8; 95% CI,1.1-3.2; P = 0.032), maternal CD4 cell count < 500 x 10(6) cells/l (OR, 2.5; 95% CI,1.3-5.0; P = 0.007), maternal viral load > 50 000 copies/ml (OR, 3.6; 95% CI,2.0-6.2; P < 0.0001) and breastfeeding (OR, 2.2; 95% CI,1.3-3.8; P = 0.006).
                A single-dose of NVP given to infants offers protection against HIV-1 infection and should be a strategy used in infants of mothers with untreated HIV infection.
PCV is effective in preventing IPD, X-ray defined pneumonia, and clinical pneumonia among HIV-1 negative and HIV-1 positive children under two years. The impact was greater for VT-IPD than for all serotypes-IPD, and for X-ray defined pneumonia than for clinical pneumonia. An 11% reduction with a 95% CI of -1% to 21% and a P = 0.08 is compatible with reduction in all-cause mortality.