Failures of 13-Valent Conjugated Pneumococcal Vaccine in Age-Appropriately Vaccinated Children 2-59 Months of Age, Spain.

Vaccination with the 13-valent conjugated pneumococcal disease (PCV13) has reduced invasive pneumococcal disease (IPD), but there have been reports of vaccine failures. We performed a prospective study in children aged 2-59 months who received diagnoses of IPD during January 2012-June 2016 in 3 pediatric hospitals in Catalonia, Spain, a region with a PCV13 vaccination coverage of 63%. We analyzed patients who had been age-appropriately vaccinated but who developed IPD caused by PCV13 serotypes. We detected 24 vaccine failure cases. The serotypes involved were 3 (16 cases); 19A (5 cases); and 1, 6B, and 14 (1 case each). Cases were associated with children without underlying conditions, with complicated pneumonia (OR 6.65, 95% CI 1.91-23.21), and with diagnosis by PCR (OR 5.18, 95% CI 1.84-14.59). Vaccination coverage should be increased to reduce the circulation of vaccine serotypes. Continuous surveillance of cases of IPD using both culture and PCR to characterize vaccine failures is necessary.

[Vaccines against varicella-zoster virus (VZV)]. / Vacunas frente al virus de la varicela zóster.

In Western countries, two attenuated varicella vaccines derived from the OKA strain are licensed: Varilrix® GlaxoSmithKline (OKA/RIT strain) and Varivax® Merck Sharp and Dohme (OKA/Merck strain). Currently, in Spain, varicella vaccination is only included in the Ministry of Health, Social Services and Equality official vaccination calendar for administration in adolescents who have not had the disease. Given the good results obtained in Navarra and Madrid with universal administration of the vaccine in children, it would be desirable to include the vaccine in the routine immunization schedule, with the administration of two doses at 15-18 months of age in the future. The protective efficacy of the attenuated herpes zoster vaccine was evaluated in the Shingles Prevention Study, which showed that in the short term (0-4 years) the vaccine reduced the incidence of herpes zoster by 53%, post-herpetic neuralgia by 66%, and the disease burden in immunocompetent persons aged ≥60 years by 61%. Another study demonstrated protective efficacy in persons aged 50-59 years. Over time, the protective efficacy decreases, but remains at acceptable levels, especially for post-herpetic neuralgia and the disease burden. Recently, the results of a controlled clinical trial (phase III) conducted in 18 countries to assess the protective efficacy of the inactivated subunit vaccine (glycoprotein E) adjuvanted with the adjuvant AS01B were published. The study inferred that the vaccine significantly reduced the incidence of herpes zoster in the short term (3.2 years) in people aged ≥50 years. Vaccine protection did not decrease with age at vaccination, ranging between 96.8% and 97.9% in all age groups.

Invasive pneumococcal disease in children under 60 months before and after availability of 13-valent conjugate vaccine.

BACKGROUND: Invasive pneumococcal disease (IPD) is the most important bacterial infection in young children, and the introduction of pneumococcal conjugate vaccines has changed its presentation. This study compared the incidence, characteristics and serotype distribution of IPD before and after the introduction of the pneumococcal conjugate vaccine (PCV13). METHODS: Prospective enrolment of patients with IPD aged less than 60 months and admitted to either of 2 tertiary care hospitals between January 2007 and December 2009 (pre-PCV13 period) and January 2012 and June-2016 (PCV13 period). RESULTS: We identified 493 cases, 319 in the pre-PCV13 period and 174 in the PCV13 period. The incidence of IPD decreased from 89.7 to 34.4 casos per 100 000 habitantes ( -62%; P < .001). This decrease was observed in all forms of disease except necrotising pneumonia (increase from 0.8 to 3.7 casos/100 000 population). There was a significant reduction in all serotypes included in the PCV13 and not included in the PCV7. We did not find significant differences in length of stay, mortality or the frequency of sequelae between both periods, but in the PCV13 period, the length of stay in the paediatric intensive care unit and the duration of mechanical ventilation were longer (P = .00). The incidence of serotype 3 decreased from 10.4 to 6.9 casos per 100 000 population, although it was the serotype involved most frequently in patients with severe disease. CONCLUSIONS: After the introduction of the PCV13, there has been a significant decrease in IPD cases. Serotype 3 continues to be an important cause of severe IPD.

[Invasive pneumococcal disease in children under 60 months before and after availability of 13-valent conjugate vaccine]. / Enfermedad neumocócica invasiva en niños menores de 60 meses, antes y después de la introducción de la vacuna conjugada 13-valente.

BACKGROUND: Invasive pneumococcal disease (IPD) is the most important bacterial infection in young children, and the introduction of pneumococcal conjugate vaccines has changed its presentation. This study compared the incidence, characteristics and serotype distribution of IPD before and after the introduction of the pneumococcal conjugate vaccine (PCV13). METHODS: Prospective enrolment of patients with IPD aged less than 60 months and admitted to either of 2 tertiary care hospitals between January 2007 and December 2009 (pre-PCV13 period) and January 2012 and June-2016 (PCV13 period). RESULTS: We identified 493 cases, 319 in the pre-PCV13 period and 174 in the PCV13 period. The incidence of IPD decreased from 89.7 to 34.4 cases per 100,000 population (-62%; P<.001). This decrease was observed in all forms of disease except necrotising pneumonia (increase from 0.8 to 3.7 cases/100,000 population). There was a significant reduction in all serotypes included in the PCV13 and not included in the PCV7. We did not find significant differences in length of stay, mortality or the frequency of sequelae between both periods, but in the PCV13 period, the length of stay in the paediatric intensive care unit and the duration of mechanical ventilation were longer (P=.00). The incidence of serotype 3 decreased from 10.4 to 6.9 cases per 100,000 population, although it was the serotype involved most frequently in patients with severe disease. CONCLUSIONS: After the introduction of the PCV13, there has been a significant decrease in IPD cases. Serotype 3 continues to be an important cause of severe IPD.

Necrotizing pneumonia due to Streptococcus pneumoniae in children during the period of non-systematic use of PCV13 in Catalonia, Spain.

BACKGROUND: Some studies have observed an increased incidence of necrotizing pneumonia (NP) in recent years. This might be related to the emergence of non-vaccine S. pneumoniae serotypes after PCV7 introduction although it is suggested that evolutionary factors may have modified the virulence and the interactions of pneumococci. The aim of this study was to clinically and microbiologically define NP in the population served by the three major paediatric hospitals in Barcelona (Catalonia, Spain). METHODS: A prospective observational study was conducted in patients <18 years hospitalized due to invasive pneumococcal disease (January 2012-June 2016). Data of confirmed cases of pneumococcal NP (diagnosed by culture or DNA detection and serotyped) were collected. PCV13 was not systematically administered in Catalonia during the study period, but was available in the private market so the vaccination coverage in children increased from 48.2% to 74.5%. RESULTS: 35 cases of NP were identified. 77.1% of cases were associated with empyema. In the first 4 years, a trend to a decrease in NP incidence was observed (p=0.021), especially in children <5 years (p=0.006). Serotype 3 was responsible for 48.6% of NP cases. Five patients with NP due to serotype 3 were fully vaccinated for their age with PCV13. CONCLUSIONS: Serotype 3 has a preeminent role in pneumococcal NP and was associated with all PCV13 vaccination failures. Although in our series the incidence does not seem to be increasing, evolution of pneumococcal NP rates should be monitored after inclusion of PCV13 in the systematic calendar.

Influence of socioeconomic status on community-acquired pneumonia outcomes in elderly patients requiring hospitalization: a multicenter observational study.

BACKGROUND: The associations between socioeconomic status and community-acquired pneumonia outcomes in adults have been studied although studies did not always document a relationship.The aim of this multicenter observational study was to determine the association between socioeconomic status and community-acquired pneumonia outcomes in the elderly, in the context of a public health system providing universal free care to the whole population. METHODS: A total of 651 patients aged > or =65 years hospitalized due to community-acquired pneumonia through the emergency departments of five Spanish public hospitals were recruited and followed up between May 2005 and January 2007. The primary outcomes studied were: length of stay, intensive care unit admission, overall mortality and readmission. Socioeconomic status was measured using both individual and community data: occupation [categorized in six social groups (I, II, III, IVa, IVb and V)], educational level (< or = primary level or > or = secondary level) and disposable family income of the municipality or district of residence [>12,500 euro (high municipality family income) and < or =12,500 euro (low municipality family income)]. The six social groups were further categorized as upper/middle social class (groups I-IVb) and lower class (group V).Bivariate and multivariate analyses were performed. OR and their 95% confidence intervals were calculated. All statistical tests were two tailed and statistical significance was established as p < 0.05. RESULTS: 17.7% of patients lived in a municipality or district with a high municipality family income and 63.6% were upper/middle social class (I-IVb). Only 15.7% of patients had a secondary education. The adjusted analysis showed no association between pneumonia outcomes and social class, educational level or municipality family income. However, length of stay increased significantly in patients in whom the factors, living alone and being a smoker or ex-smoker coincided (p < 0.001). CONCLUSIONS: We measured socioeconomic status using both individual and community data and found no association between social class, educational level or municipality family income and the variables of pneumonia outcomes. The lack of differences between social classes supports the provision of universal, equitable health care by the public health system.

Impact of the 13-Valent Conjugated Pneumococcal Vaccine on the Direct Costs of Invasive Pneumococcal Disease Requiring Hospital Admission in Children Aged < 5 Years: A Prospective Study.

The lack of invasive pneumococcal disease (IPD) cost studies may underestimate the eect ofpneumococcal polysaccharide conjugated vaccines (PCV). The objective of this study was to estimatethe direct costs of hospitalized IPD cases. A prospective study was made in children aged <5 yearsdiagnosed with IPD in two high-tech hospitals in Catalonia (Spain) between 2007-2009 (PCV7 period)and 2012-2015 (PCV13 period). Costs were calculated according to 2014 Catalan Health Service ratesusing diagnostic-related groups. In total, 319 and 154 cases were collected, respectively. Pneumoniahad the highest cost (65.7% and 62.0%, respectively), followed by meningitis (25.8% and 26.1%,respectively). During 2007-2015, the costs associated with PCV7 serotypes (Pearson coecient (Pc) =?0.79; p = 0.036) and additional PCV13 serotypes (Pc = ?0.75; p = 0.05) decreased, but those of otherserotypes did not (Pc = 0.23 p = 0.62). The total mean cost of IPD increased in the PCV13 period by31.4% (¿3016.1 vs. ¿3963.9), mainly due to ICU stay (77.4%; ¿1051.4 vs. ¿1865.6). During the PCV13period, direct IPD costs decreased due to a reduction in the number of cases, but cases were more severe and had a higher mean cost. During 2015, IPD costs increased due to an increase in the costsassociated with non-PCV13 serotypes and serotype 3 and this requires further investigation.

Necrotizing pneumonia due to Streptococcus pneumoniae in children during the period of non-systematic use of PCV13 in Catalonia, Spain.

BACKGROUND: Some studies have observed an increased incidence of necrotizing pneumonia (NP) in recent years. This might be related to the emergence of non-vaccine S. pneumoniae serotypes after PCV7 introduction although it is suggested that evolutionary factors may have modified the virulence and the interactions of pneumococci. The aim of this study was to clinically and microbiologically define NP in the population served by the three major paediatric hospitals in Barcelona (Catalonia, Spain). METHODS: A prospective observational study was conducted in patients <18 years hospitalized due to invasive pneumococcal disease (January 2012-June 2016). Data of confirmed cases of pneumococcal NP (diagnosed by culture or DNA detection and serotyped) were collected. PCV13 was not systematically administered in Catalonia during the study period, but was available in the private market so the vaccination coverage in children increased from 48.2% to 74.5%. RESULTS: 35 cases of NP were identified. 77.1% of cases were associated with empyema. In the first 4 years, a trend to a decrease in NP incidence was observed (p=0.021), especially in children <5 years (p=0.006). Serotype 3 was responsible for 48.6% of NP cases. Five patients with NP due to serotype 3 were fully vaccinated for their age with PCV13. CONCLUSIONS: Serotype 3 has a preeminent role in pneumococcal NP and was associated with all PCV13 vaccination failures. Although in our series the incidence does not seem to be increasing, evolution of pneumococcal NP rates should be monitored after inclusion of PCV13 in the systematic calendar.

Serotype and clonal distribution dynamics of invasive pneumococcal strains after PCV13 introduction (2011-2016): Surveillance data from 23 sites in Catalonia, Spain.

BACKGROUND: The objective of this study is to describe incidence and shifts of serotype and clonal distribution of invasive Streptococcus pneumoniae strains in four different age groups (<5 years, 5-17 years, 18-64 years and >65 years) during a period of intermediate PCV13 vaccination coverage (2011-2016) in Catalonia, Spain. METHODS: We included all pneumococcal strains systematically sent to the Catalan support laboratory for molecular surveillance of invasive pneumococcal disease (IPD) located at Hospital Sant Joan de Deu, Barcelona. Two study periods were considered: 2011-13, early PCV13 vaccination period (EVP) and 2014-2016, late vaccination period (LVP). RESULTS: A total of 2142 strains were included in the study. Five years after intermediate introduction of PCV13 in our population, a significant decrease of overall incidence of IPD in children <5 years was observed (incidence rate ratio 0.5, 95% confidence interval 0.4-0.8). However, in seniors older than 65 years, a significant increase of overall incidence of IPD was observed (IRR 1.4, 95% CI 1.1-1.7). The contribution of PCV13 vaccine serotypes to IPD declined significantly in all age groups: from 59% to 38.1% in <5 years; 82.7% to 59% in 5-17 years, 47.8% to 34.1% in 18-64 years and 48.2% to 37% in >65 years. Results found when comparing both periods were consistent with IRRs observed year by year. In children <5 years, the three major serotypes detected were 1, 24F and 19A in EVP vs 24F, 14 and 10A in LVP. Among patients 5-17 years the first three serotypes were 1, 12F and 14 both in EVP and LVP. Among adults 18-64, the three major serotypes detected were 1, 12F and 8 vs 8, 12F and 3, respectively. Finally, in patients >65 years the most frequently isolated serotypes were 3, 19A and 7F vs 3, 14 and 12F, respectively. Regarding clonal complexes (CCs) expressing mainly PCV13 serotypes, significant decreases of the proportions of CC306, CC191 and CC320 were observed, while CC156 showed a significant increase. As for CCs expressing mostly non-PCV13 serotypes, significant increases in ST989, CC53 and CC404 were showed. CONCLUSIONS: Despite low vaccine coverage in our setting a significant decrease of incidence of IPD was observed in children younger than 5 years. The modest indirect protection against vaccine serotypes causing IPD in elderly indicate the need for the inclusion of more serotypes in future high-valent PCV and vaccinating old adults should be considered.

Complicated pneumococcal pneumonia with pleural effusion or empyema in the 13-valent pneumococcal conjugate vaccine era.

AIM: The aim was to analyze the epidemiological, microbiological and clinical characteristics of patients with complicated pneumococcal pneumonia with pleural effusion (PE) or empyema. METHOD: Prospective study in three Catalan hospitals in persons aged <18 years diagnosed with complicated pneumonia with PE or empyema with isolation of Streptococcus pneumoniae in blood or pleural fluid by culture or real-time PCR between January 2012 and June 2016. Patients were divided into <2 years and 2-17 years age groups. Epidemiological, microbiological, and clinical data of patients were compared annually in both groups. PCV13 vaccination coverage increased from 48.2% in 2012 to 74.5% in 2015. RESULTS: We included 143 patients. The incidence of pneumococcal pneumonia was 6.83 cases × 10-5 persons/year in cases with PE or empyema and 2.09 cases × 10-5 person-years in cases without (rate ratio [RR]: 3.27; 2.25-4.86; P < 0.001). Empyema was more frequent than PE (79.7% vs 20.3%, P < 0.005). Of 143 cases studied, 93 (65.0%, P < 0.001) were diagnosed by real-time-PCR, 43 (30.1%) by culture and RT-PCR and 7 (4.9%) by culture only. PCV13 serotypes were more frequent in complicated than in uncomplicated pneumonia (116/142, 81.7% vs 27/45, 60.0%; P = 0.003), especially serotype 1 (41/142, 28.9% vs 6/45, 13.3%, P : 0.036). From 2012 to 2015 there was a significant reduction in serotype 1 (16/43, 37.2% vs 3/27, 11.1%, P = 0.026), and a trend to an increase in non-PCV13 serotypes (6/43, 14% vs 9/27, 33.3%, P = 0.054). CONCLUSIONS: A directly proportional relationship was observed between the reduction in pneumonia complicated with PE or empyema and a significant reduction in PCV13 serotypes, especially serotype 1, coinciding with increased PCV13 coverage.

Effectiveness of the 13-valent pneumococcal conjugate vaccine in preventing invasive pneumococcal disease in children aged 7-59 months. A matched case-control study.

BACKGROUND: The 13-valent pneumococcal conjugate vaccine (PCV13) was licensed based on the results of immunogenicity studies and correlates of protection derived from randomized clinical trials of the 7-valent conjugate pneumococcal vaccine. We assessed the vaccination effectiveness (VE) of the PCV13 in preventing invasive pneumococcal disease (IPD) in children aged 7-59 months in a population with suboptimal vaccination coverage of 55%. METHODS: The study was carried out in children with IPD admitted to three hospitals in Barcelona (Spain) and controls matched by hospital, age, sex, date of hospitalization and underlying disease. Information on the vaccination status was obtained from written medical records. Conditional logistic regression was made to estimate the adjusted VE and 95% confidence intervals (CI). RESULTS: 169 cases and 645 controls were included. The overall VE of ≥1 doses of PCV13 in preventing IPD due to vaccine serotypes was 75.8% (95% CI, 54.1-87.2) and 90% (95% CI, 63.9-97.2) when ≥2 doses before 12 months, two doses on or after 12 months or one dose on or after 24 months, were administered. The VE of ≥1 doses was 89% (95% CI, 42.7-97.9) against serotype 1 and 86.0% (95% CI, 51.2-99.7) against serotype 19A. Serotype 3 showed a non-statistically significant effectiveness (25.9%; 95% CI, -65.3 to 66.8). CONCLUSIONS: The effectiveness of ≥1 doses of PCV13 in preventing IPD caused by all PCV13 serotypes in children aged 7-59 months was good and, except for serotype 3, the effectiveness of ≥1 doses against the most frequent PCV13 serotypes causing IPD was high when considered individually.

Herpes zoster and postherpetic neuralgia in Catalonia (Spain).

The objective of the study was to analyze the descriptive epidemiology and costs of herpes zoster (HZ) and postherpetic neuralgia (PHN) in people aged ≥50 years in Catalonia (Spain). The incidence of HZ in Catalonia was estimated by extrapolating the incidence data from Navarre (Spain) to the population of Catalonia. The incidence of PHN was estimated according to the proportion of cases of HZ in the case series of the Hospital del Sagrado Corazón de Barcelona that evolved to PHN. Drug costs were obtained directly from the prescriptions included in the medical record (according to official prices published by the General Council of the College of Pharmacists). The cost of care was obtained by applying the tariffs of the Catalan Health Institute to the number of outpatient visits and the number and duration of hospital admissions. The estimated annual incidence of HZ was 31 763, of which 21 532 (67.79%) were in patients aged ≥50 years. The respective figures for PHN were 3194 and 3085 (96.59) per annum, respectively. The mean cost per patient was markedly higher in cases of PHN (916.66 euros per patient) than in cases of HZ alone (301.52 euros per patient). The cost increased with age in both groups of patients. The estimated total annual cost of HZ and its complications in Catalonia was € 9.31 million, of which 6.54 corresponded to HZ and 2.77 to PHN. This is the first Spanish study of the disease burden of HZ in which epidemiological data and costs were collected directly from medical records. The estimated incidence of HZ is probably similar to the real incidence. In contrast, the incidence of PHN may be an underestimate, as around 25% of patients in Catalonia attend private clinics financed by insurance companies. It is also probable that the costs may be an underestimate as the costs derived from the prodromal phase were not included. In Catalonia, HZ and PHN cause an important disease burden (21 532 cases of HZ and 3085 de PHN with an annual cost of € 9.31 million) in people aged ≥50 years, in whom vaccination is indicated.

Economic benefits of inactivated influenza vaccines in the prevention of seasonal influenza in children.

The aim of this study was to systematically review published studies that evaluated the efficiency of inactivated influenza vaccination in preventing seasonal influenza in children. The vaccine evaluated was the influenza-inactivated vaccine in 10 studies and the virosomal inactivated vaccine in 3 studies. The results show that yearly vaccination of children with the inactivated influenza vaccine saves money from the societal and family perspectives but not from the public or private provider perspective. When vaccination does not save money, the cost-effectiveness ratios were very acceptable. It can be concluded, that inactivated influenza vaccination of children is a very efficient intervention.

Results of the rubella elimination program in Catalonia (Spain), 2002-2011.

Rubella is usually a mild disease with nonspecific symptoms, but can cause congenital rubella syndrome (CRS) when infection occurs during pregnancy. The objective of this study was to evaluate the sensitivity and positive predictive value of different data sources used for surveillance purposes in the Rubella Elimination Program of Catalonia between 2002 and 2011. The Urgent Notification to the Statutory Disease Reporting System, the Individualized Disease Reporting System, screening for other viruses included in the Measles Elimination Program, the Microbiological Reporting System and the Minimum Hospital Discharge Data were evaluated. 100 suspected cases of postnatal rubella and 6 suspected cases of CRS were detected. For postnatal rubella, Urgent Notification had the highest sensitivity (32.5%; 95%CI 18.6-49.1), followed by the Virus screening in Measles Elimination Program (25%; 95%CI 12.7-41.2). Virus screening in the Measles Elimination Program had the highest PPV (76.9%; 95%CI 46.1-94.9), followed by the Individualized Disease Reporting System (57.1%; 95%CI 28.9-82.3). For CRS cases, the Individualized Disease Reporting System had the highest sensitivity (100%, 95%CI 29.2-100) and the highest PPV (60%; 95%CI 14.7-100). Most confirmed postnatal cases (25 cases, 48.1%) were in the 25-44 y age group followed by the 15-24 y age group (11 cases, 21.2%). The highest values of sensitivity and PPV for the detection of confirmed cases corresponded to activities that were specifically introduced in the measles and rubella elimination programs.

Are risk factors associated with invasive pneumococcal disease according to different serotypes?

The aim of this study was to investigate risk factors for the most common serotypes of invasive pneumococcal disease (IPD). A total of 293 IPD cases were analyzed in children aged 3-59 mo in a community with intermediate vaccination coverage with the 7-valent pneumococcal vaccine (PCV7). IPD cases were reviewed during 2007-2009 in two pediatric hospitals in Catalonia (Spain). A multivariate analysis using unconditional logistic regression was performed to estimate the adjusted odds ratio. PCV7 coverage was 45.4%. Pneumonia with empyema (64.5%) was the most frequent clinical manifestation. The most common serotypes were: serotype 1 (21.2%), 19A (16.0%), 3 (12.6%) and 7F/A (6.8%). 70.0% of serotypes found were included in the 13-valent conjugate vaccine (PCV13), 39.2% in the 10-valent conjugate vaccine and 8.1% in the PCV7. PCV7 was protective in IPD cases due to PCV7-serotypes (aOR: 0.15, 95% CI:0.04-0.55). Serotype 1 was positively associated with attending day care or school (aOR: 3.55, 95% CI: 1.21-10.38) and age 24-59 mo (aOR: 7.70, 95% CI:2.70-21.98). Serotype 19A was positively associated with respiratory infection in the previous month (aOR: 2.26, 95% CI: 1.03-4.94), non-penicillin susceptible IPD (aOR: 1.89, 95% CI:1.13-3.16) and negatively associated with age 24-59 mo (aOR: 0.19, 95% CI:0.09-0.41). Serotype 3 was positively associated with vaccination (aOR: 4.87, 95% CI:2.05-11.59). No factors were associated with serotype 7F/A. Vaccination with pneumococcal vaccines including more serotypes may reduce the risk of disease in our setting.

Effectiveness of the WC/rBS oral cholera vaccine in the prevention of traveler's diarrhea: a prospective cohort study.

OBJECTIVE: Traveler's diarrhea (TD) is the most frequent disease among people from industrialized countries who travel to less developed ones, especially sub-Saharan Africa, Southern Asia and South America. The most common bacteria causing TD is enterotoxigenic Escherichia coli (ETEC). The WC/rBS cholera vaccine (Dukoral) has been shown to induce cross-protection against ETEC by means of the B subunit of the cholera toxin. The aim of the study was to evaluate the effectiveness of the WC/rBS cholera vaccine in preventing TD. METHODS: Between May 1 and September 30 (2007), people seeking pre-travel advice in ten Spanish international vaccination centers were included in a prospective cohort study of travelers to cholera risk countries. The incidence rates of TD were adjusted for variables whose frequencies were statistically different (entry point 0.10) between the vaccinated and non-vaccinated cohorts. FINDINGS: The vaccinated cohort (n = 544 travelers) included people vaccinated with the WC/rBS cholera vaccine, and the non-vaccinated cohort (n = 530 travelers) by people not vaccinated. The cumulative incidence rate of TD was 1.69 in vaccinated and 2.14 in non-vaccinated subjects. The adjusted relative risk of TD in vaccinated travelers was 0.72 (95% CI: 0.58-0.88) and the adjusted vaccination effectiveness was 28% (95% CI: 12-42). CONCLUSIONS: The WC/rBS cholera vaccine prevents TD in 2 out of 7 travelers (preventive fraction: 28%). The number needed to vaccinate (NNV) to prevent 1 case of TD is 10.

Clinical presentation of invasive pneumococcal disease in Spain in the era of heptavalent conjugate vaccine.

BACKGROUND: The aim of this study was to analyze the rate of incidence, clinical presentation, serotype, and clonal distribution of invasive pneumococcal disease (IPD) in the era of heptavalent pneumococcal conjugate vaccine (PCV7) in Barcelona, Spain. METHODS: This was a prospective study comprising all children <5 years with IPD who were managed in 2 tertiary-care, pediatric hospitals between January 2007 and December 2009. IPD was defined as the presence of clinical findings of infection together with isolation or detection of DNA of Streptococcus pneumoniae in a sterile fluid sample. RESULTS: In this study, 319 patients (53.3% male), mean age 29.6 months, were included. Comparing rates in 2007 and 2009 (76.2 and 109.9 episodes/100,000 population, respectively), an increase of 44% (95% confidence interval, 10%-89%) was observed. The main clinical presentation was pneumonia (254 episodes, 79.6%), followed by meningitis (29, 9.1%), and bacteremia (25, 7.8%).The diagnosis was made by positive culture in 123 (38.6%) patients and in 196 (61.4%) by real-time polymerase chain reaction. Serotype study was performed in 300 episodes, and 273 (91%) were non-PCV7 serotypes. The most frequent serotypes were 1 (20.7%), 19A (15.7%), and 3 (12.3%). A minimal inhibitory concentration ≥0.12 µg/mL to penicillin was detected in 34.4% of isolates. Sequence type 306 expressing serotype 1 was the most frequent clonal type detected (20.3% of studied strains). CONCLUSIONS: IPD continues to increase in Barcelona, and the rate is higher than previously reported as a result of low sensitivity of bacterial culture. Non-PCV7 serotypes were responsible for 91% of episodes and pneumonia was the main clinical presentation.

Pneumococcal polysaccharide vaccination for adults: new perspectives for Europe.

Vaccination is the only public-health measure likely to reduce the burden of pneumococcal diseases. In 2010, a group of European experts reviewed evidence on the burden of pneumococcal disease and the immunogenicity, clinical effectiveness and cost-effectiveness of vaccination with 23-valent pneumococcal polysaccharide vaccine (PPV23). They also considered issues affecting the future use of PPV23 and pneumococcal conjugate vaccines in the elderly and adults at high risk of pneumococcal disease. PPV23 covers 80-90% of the serotypes responsible for invasive pneumococcal disease in Europe. Primary vaccination and revaccination with PPV23 are well tolerated, induce robust, long-lasting immune responses in elderly adults and are cost effective. Ensuring protection against pneumococcal disease requires monitoring of the changing epidemiology of pneumococcal serotypes causing invasive pneumococcal disease and improving vaccine coverage. In the future, it will be critically important for pneumococcal vaccination recommendations for elderly adults to be based on comparative evaluations of PPV23 and newer pneumococcal conjugate vaccines with regard to their long-term immunogenicity, clinical effectiveness and cost-effectiveness.