The evidence for using conjugate vaccines to protect HIV-infected children against pneumococcal disease

Pneumococcal conjugate vaccines (PCVs) are a potentially useful complement to existing treatment strategies in HIV-infected children, for whom pneumococcal infections are common and serious. This Review summarises available data on the burden of pneumococcal disease and the safety and efficacy of PCVs in HIV-infected children. The data demonstrate that children with HIV have significantly increased risk of pneumococcal disease compared with uninfected children; the serotypes included in currently licensed or near-licensure conjugate vaccines include most serotypes that cause invasive pneumococcal disease (IPD) in HIV-infected children and adults; PCVs provide substantial protection against IPD and clinical pneumonia when given to HIV-infected infants; and HIV-infected adults gain an indirect benefit when children in the community are vaccinated. PCV should be considered as an important intervention for improving the lives of HIV-infected children.     

Trends in mortality and antibiotic resistance among HIV-infected patients with invasive pneumococcal disease

Objectives The aim of the study was to describe trends and risk factors for mortality and changes in antibiotic resistance, serotypes and clones among HIV‐infected patients with invasive pneumococcal disease (IPD). Methods A prospective study of 199 episodes of IPD occurring in a cohort of 4011 HIV‐infected patients was carried out. Predictors of mortality included clinical and microbiological data. The 7‐valent pneumococcal conjugate vaccine (PCV7) for children was introduced in late 2001. Time periods were classified for mortality studies as pre‐ (1986–1996), early (1997–2001) and late (2002–2007) highly active antiretroviral therapy (HAART) era, and for serotype studies as pre‐PCV7 (1986–2001) and PCV7 (2002–2007) era. Results Of 199 IPD episodes, 71 (36%) occurred in HIV‐infected patients with associated comorbidities (mainly liver cirrhosis; 52 of 71), which increased in recent years. The incidence of IPD decreased from the pre‐HAART era to the early HAART era and then remained stable in the late HAART era (24.1, 8.4 and 7.4 episodes per 1000 patient‐years, respectively). Rates of 30‐day mortality have risen over the three periods (8, 19 and 25%, respectively; P=0.017). In multiple logistic regression analysis, predictors of mortality were shock at presentation [odds ratio (OR) 7.01; 95% confidence interval (CI) 2.05–23.87] and associated comorbidities (OR 4.27; 95% CI 1.53–11.92). In the PCV7 era, IPD caused by non‐PCV7 serotypes increased, and resistance to betalactams decreased. The most frequent genotypes were Spain^9V‐ST156, Spain^23F‐ST81, ST88^19F, Sweden¹‐ST304 and Spain^6B‐ST90. Conclusions In the late HAART era, the incidence of IPD has not significantly decreased. Mortality from IPD has risen in association with an increase in comorbidities such as liver cirrhosis. New vaccination strategies are needed to diminish the burden of IPD in the HIV‐infected population.     

Pneumococcal Vaccination in Adults: What Can We Learn From Observational Studies That Evaluated PCV13 and PPV23 Effectiveness in the Same Population?

IntroductionFifteen and 20-valent pneumococcal conjugate vaccines (PCV15; PCV20) were recently licensed to prevent pneumococcal disease in adults. In the absence of efficacy or effectiveness data for these new vaccines, studies comparing 23-valent pneumococcal polysaccharide vaccine (PPV23) and PCV13 might help inform decision-making on how to best implement expanded-valency PCVs. Comparing PPV23 and PCV13 is problematic, as no head-to-head clinical trials evaluated efficacy. Comparing effectiveness results across observational studies that vary by population, design, and outcomes is difficult. To address these limitations, we undertook a narrative review of studies that assessed PPV23 and PCV13 vaccine effectiveness (VE) in the same adult populations.MethodsWe conducted a literature search in PubMed and Google Scholar and screened 525 studies using a standardized evaluation framework.ResultsNine studies met inclusion criteria, all from high-income countries. None evaluated invasive pneumococcal disease (IPD) alone. VE against vaccine-type pneumococcal pneumonia ranged from 2 to 6% for PPV23 and 41 to 71% for PCV13. VE against pneumococcal pneumonia or severe pneumococcal disease (IPD or pneumococcal pneumonia) ranged from ?10 to 11% for PPV23, 40 to 79% for PCV13, and 39 to 83% for sequential PCV13/PPV23. VE against all-cause pneumonia or lower respiratory tract infection ranged from ?8 to 3% for PPV23 and 9 to 12% for PCV13.ConclusionsOverall, PCV13 demonstrated better protection than PPV23 against pneumococcal disease and all-cause respiratory outcomes in the included studies. Where evaluated, sequential PCV13/PPV23 vaccination showed little benefit over PCV13 alone. Results support the use of PCVs to protect against pneumococcal disease and respiratory infections in adults.     

Emergence of invasive pneumococcal disease caused by nonvaccine serotypes in the era of 7-valent conjugate vaccine.

BACKGROUND: Little is known about the epidemiology of invasive pneumococcal disease (IPD) after the introduction of 7-valent pneumococcal conjugate vaccine (PCV7) in Spain and other European countries. METHODS: We performed a 10-year prospective study including all children with culture-proven IPD admitted to Sant Joan de Deu Hospital, a children's center in the southern area of Barcelona, Catalonia, Spain. PCV7 was introduced in June 2001, and the current estimate of PCV7 coverage is 45%-50%. RESULTS: Comparing the prevaccine period (1997-2001) with the vaccine period (2002-2006), among children aged <2 years, the rate of IPD increased from 32.4 episodes per 100,000 population to 51.3 episodes per 100,000 population (an increase of 58%; 95% confidence interval, 2%-145%), and among children aged 2-4 years, the rate increased from 11.3 episodes per 100,000 population to 26.5 episodes per 100,000 population (an increase of 135%; 95% confidence interval, 31%-320%). At clinical presentation, the rate of pneumonia and/or empyema among children aged <5 years increased from 3.6 episodes per 100,000 population to 15.1 episodes per 100,000 population (an increase of 320%; 95% confidence interval, 98%-790%). These increased rates of IPD were caused by non-PCV7 serotypes, which represented 38% and 72% of infecting serotypes in the prevaccine and vaccine periods, respectively (P=.001). Penicillin resistance decreased from 48% in the prevaccine period to 27% in the vaccine period (P=.005). In the vaccine period, there was an emergence of previously established virulent clones of non-PCV7 serotypes 1 and 5. There was also an increase in the prevalence of serotypes 19A and 6A expressed with different clonal types, including Spain(23F)-1 and Spain(6B)-2. CONCLUSIONS: Since the introduction of PCV7 for children, there has been an emergence of IPD caused by virulent clones of non-PCV7 serotypes that has been associated with significant clinical changes and a decrease in antibiotic resistance.     

Burden of invasive pneumococcal disease and serotype distribution among Streptococcus pneumoniae isolates in young children in Europe: impact of the 7-valent pneumococcal conjugate vaccine and considerations for future conjugate vaccines

ObjectivesThe overall reported burden of invasive pneumococcal disease (IPD) varies among countries in Europe. This review describes the epidemiology and serotype distribution of IPD in European children from studies published from 1990 to 2008.MethodsAverages were derived from all studies from all countries that had available data.ResultsBefore widespread immunization with 7-valent pneumococcal conjugate vaccine (PCV7), the overall mean annual incidence of IPD in children aged <2 years was 44.4/100 000. The mean case fatality rate for IPD was 3.5%, and resistant rates were approximately 23% for penicillin G (minimum inhibitory concentration ≥2 mg/l), 41% for erythromycin, and 9% (≤5 years) for third-generation cephalosporins. The most common serotypes causing IPD were 14, 6B, 19F, and 23F, all of which are included in PCV7. Vaccine serotype coverage ranged from 37% to 100% for PCV7, with mean increases in coverage of 7% and 16% for investigational 10- and 13-valent pneumococcal conjugate vaccines, respectively. The most common IPD isolates since PCV7 introduction in Belgium, France, Germany, Greece, Norway, Portugal, Spain, and the UK were serotypes 1, 19A, 3, 6A, and 7F.ConclusionsWith routine effective use of PCV7, a general decline in IPD, antibiotic non-susceptibility, and vaccine serotypes has been observed. The most common IPD isolates since PCV7 introduction are serotypes 1, 19A, 3, 6A, and 7F, highlighting the need for inclusion of these serotypes in future vaccine formulations.     

Incidence of invasive pneumococcal disease among elderly people in Southern Catalonia, Spain, 2002-2009: an increase in serotypes not contained in the heptavalent conjugate vaccine

Population-based surveillance study conducted among persons ≥ 65 years old in Southern Catalonia, Spain during 2002-2009. All cases with isolation of pneumococcus from normally sterile bodily fluids were included. Incidence rates of invasive pneumococcal disease (IPD) as well as rates of infections caused by serotypes included in the heptavalent pneumococcal conjugate vaccine (PCV7) and the 23-valent polysaccharide pneumococcal vaccine (PPV23) were compared for early (2002-2005) and contemporary (2006-2009) periods. Mean incidence rate (per 100,000 population-year) of IPD across study period was 48.0 [95% CI (confidence interval): 30.1-72.5]. Incidence rates for PCV7 serotypes slightly decreased by 21% between 2002-2005 and 2006-2009 (from 9.2 to 7.3; p = 0.511) whereas rates of IPD due to nonPCV7 serotypes largely increased by 172% (from 15.6 to 42.4; p < 0.001) during the same period. For PPV23 but nonPCV7 types, incidence rates increased by 146% (from 10.9 to 26.9; p < 0.001) whereas rates for nonPPV23 serotypes increased by 237% (from 4.6 to 15.5; p = 0.001). As an overall effect of these changes, the incidence of all IPD increased by a significant 69% (95% CI: 29%-110%). Specific incidence rates of serotypes 6A (from 1.7 to 4.1; p = 0.182), 7F (from 1.7 to 5.7; p = 0.052) and 19A (from 0.6 to 6.2; p = 0.004) substantially increased between both periods. According to these findings, Southern Catalonia region can be classified as a mesoendemic area of pneumococcal infections among elderly people, with a recent increase incidence of some nonPCV7 serotypes (especially 19A).     

Routine Pneumococcal Vaccination of Children Provokes New Patterns of Serotypes Causing Invasive Pneumococcal Disease in Adults and Children

IntroductionRoutine vaccination of infants with protein-conjugated 7-valent pneumococcal vaccine (PCV7) begun in 2000 initiated a sea change of prevalent serotypes (STs) in invasive pneumococcal disease (IPD). The authors investigated in 1 community all STs causing IPD during 5 years before (PRE) and 2, 5-year periods after (POST1 and POST2) its initiation and found that PCV7 adversely affected ST coverage of 23-valent pneumococcal polysaccharide vaccine (PPV23) among adults.MethodsFrom 1996–2010, 620 consecutive Streptococcus pneumoniae IPD strains from adults (521) and children (99) hospitalized with IPD in Huntington, WV, were collected. Each strain was typed by Quellung reaction. The Marshall University Institutional Review Board approved this study.ResultsBy 6 to 10 years after the initiation of PCV7, IPD in children decreased significantly, whereas IPD in adults increased significantly. In both adults and children, IPD due to PCV7 STs decreased significantly. In adults with IPD, PCV7 STs were replaced by several non-PCV7 STs including STs contained in PPV23 but not in PCV7 and STs not contained in either vaccine. IPD due to 4 nonsusceptible STs included in PCV7 decreased from PRE to POST1 and POST2. IPD due to nonsusceptible STs not included in PCV7 increased from PRE to POST1 and POST2.ConclusionsRoutine PCV7 decreased IPD in children but not in adults. Predominant STs changed—children exhibited fewer PCV7 STs and adults exhibited fewer PCV7 and PPV23 STs—reducing vaccine coverage and increasing the risk of replacement STs causing IPD in adults.     

Clinical and microbiological characteristics of unusual manifestations of invasive pneumococcal disease

Introduction

Invasive pneumococcal disease (IPD) typically presents as bacterial pneumonia, meningitis or primary bacteraemia. However, Streptococcus pneumoniae can produce infection at any level of the body (endocarditis, arthritis, spontaneous bacterial peritonitis, etc.), which is also known as unusual IPD (uIPD). There are very limited data available about the clinical and microbiological profile of these uncommon manifestations of pneumococcal disease. Our aim was to analyse clinical forms, microbiological profile, epidemiology and prognosis of a cohort of patients with unusual invasive pneumococcal disease (uIPD).

Incidence of pneumococcal infections among children under 15 years in southern Catalonia throughout the heptavalent conjugate vaccine era, 2002–2009

Purpose

Updating epidemiological studies to document current incidences of pneumococcal diseases are greatly needed in the current era of new pneumococcal conjugate vaccines (PCVs). The aim of this study is to analyze the incidence and distribution of different serotypes causing pneumococcal infections among the pediatric population in southern Catalonia, Spain, throughout the 2002–2009 PCV7 eras.

Methods

A population-based surveillance study was conducted among children aged ≤14 years in the region of Tarragona (Catalonia, Spain) during the period 2002–2009. All cases of pneumococcal infections (invasive and non-invasive cases) were included in the study. Incidence rates (per 100,000 population-year) and prevalence of infections caused by serotypes included in different PCV formulations were calculated for the 2002–2005 and 2006–2009 periods.

Results

Globally, across the total 2002–2009 period, the incidence of pneumococcal infections was 48.2 per 100,000 children-year (22.4 and 25.8 for invasive and non-invasive infections, respectively). Between 2002–2005 and 2006–2009, the incidence rates largely decreased among children aged <2 years (from 171 to 111 per 100,000 children-year; p = 0.059), but they did not substantially vary among children aged 2–14 years. The percentages of cases caused by serotypes included in PCV7 (60.0 vs. 16.7 %; p < 0.001), PCV10 (75.0 vs. 47.4 %; p = 0.028), and PCV13 (85.0 vs. 70.5 %; p = 0.190) decreased in both periods.

Conclusion

In this study, which was conducted in a setting with intermediate PCV7 uptakes, a considerable protective direct effect of vaccination occurred among young infants, but an indirect protective effect did not emerge in the rest of the pediatric population. Despite new PCVs with higher serotype coverage, an important proportion of pneumococcal infections is still not covered by these vaccines.     

Serotype changes and antimicrobial nonsusceptibility rates of invasive and non-invasive Streptococcus pneumoniae isolates after implementation of 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in Bulgaria

The 10-valent pneumococcal conjugate vaccine (PCV10) has been included in Bulgarian Childhood Immunization Program since 2010. This study aimed to assess serotype distribution and antimicrobial resistance of 198 invasive and non-invasive Streptococcus pneumoniae strains that had been isolated in Bulgaria during 2011–2016 from patients with invasive (IPD) and non-invasive (NIPD) pneumococcal diseases. The most common invasive serotypes were 3 (10.1%), 19F (4.0%), and 7F (3.0%). A significant decrease in the proportion of invasive vaccine types (VTs) from 64.2% to 35.2% was found in comparison with pre-vaccine era. The most common serotypes among middle ear fluids were 3, 19A and 19F (5.6% each), and VTs fell down from 66.4% to 40.0% in post-PCV10 period. Among respiratory isolates, the most prevalent serotypes were some emergent serotypes such as 15A/B/C (5.0%), 19A, and 6C (4.0% each). VTs decreased significantly (16.3%) among vaccinated children compared to unvaccinated children and adults (44.0%). Two non-VTs (19A and 6C) have increased significantly more (p < 0.05) in vaccinated children than in unvaccinated patients. The rates of antibiotic nonsusceptible S. pneumoniae in Bulgaria remained high in post-PCV10 era. Among all source of isolates, antimicrobial nonsusceptibility rates were: oral penicillin – 46.5%, trimethoprim-sulfamethoxazole – 45.4%, erythromycin – 43.9%, tetracycline – 37.4%, and multidrug-resistance (MDR) was 44%. The most common MDR serotypes were 19F, 19A, 6A/C, 15A/B/C and 23A. Our results proved that PCV10 vaccination substantially reduced VTs pneumococcal IPD and NIPD. There has been a shift in the distribution of S. pneumoniae serotypes mostly in vaccinated children but also in the whole population and strong serotype-specific antibiotic resistance was observed after vaccine implementation. Therefore, it is important to continue monitoring serotype changes and pneumococcal resistance among all patient ages in addition to aid in determining the long-term effectiveness of PCV10 interventions.     

Impact of prior pneumococcal vaccination on clinical outcomes in HIV-infected adult patients hospitalized with invasive pneumococcal disease

Background

Recent studies in hospitalized patients with community‐acquired pneumonia have found a lower risk of bacteraemia and better clinical outcomes in patients who had previously received the 23‐valent pneumococcal polysaccharide vaccine (PPV) in comparison with unvaccinated individuals. The aim of this study was to assess the influence of prior PPV on clinical outcomes in HIV‐infected adult patients hospitalized with invasive pneumococcal disease (IPD).

Methods

This was an observational study of all consecutive HIV‐infected adults hospitalized with IPD from January 1996 to October 2007 in three hospitals in Spain. Baseline characteristics and clinical outcome‐related variables were compared according to prior PPV vaccination status.

Results

A total of 162 episodes of IPD were studied. In 23 of these (14.2%), patients had previously received PPV. In both vaccinated and unvaccinated patients, most of the causal serotypes were included in the 23‐valent PPV (76.9% and 84.1%, respectively). Overall, 25 patients (15.4%) died during hospitalization, 21 patients (13%) required admission to an intensive care unit (ICU) and 34 patients (21%) reached the composite outcome of death and/or admission to the ICU. None of the 23 patients who had previously received PPV died or required ICU admission, in comparison with 25 (18%; P=0.026) and 21 (15.1%; P=0.046), respectively, of the unvaccinated patients. The length of hospital stay for vaccinated patients was significantly shorter (8.48 vs. 13.27 days; P=0.011).

Conclusions

Although 23‐valent PPV failed to prevent IPD in some HIV‐infected patients, vaccination produced beneficial effects on clinical outcomes by decreasing illness severity and mortality related to IPD.     

Evolución de la enfermedad neumocócica invasora y sus serotipos en la Comunidad de Madrid

Introduction

Streptococcus pneumoniae is an important cause of morbidity. Vaccination is the most effective measure to prevent it. The aim of this study is to analyse the evolution of invasive pneumococcal disease (IPD).

Invasive pneumococcal disease in children<5 years of age in rural Mozambique

Objectives To estimate the incidence and epidemiological characteristics of invasive pneumococcal disease (IPD) in children <5 years of age living in a rural area of southern Mozambique. Methods As part of the clinical management of children admitted to Manhiça District Hospital, prospective surveillance for invasive bacterial disease was conducted from June 2001 to May 2003. The level of antibiotic resistance of the isolates was also analysed. Results Pneumococcus was the most commonly isolated bacterium, accounting for 212 episodes. The estimated crude incidence rate of IPD in the study area among children <5 years of age was 416/100 000 per child‐year at risk. The youngest age group (<3 months) had the highest incidence (779/100 000). Cases were detected during both rainy and dry seasons. The most common clinical diagnosis was pneumonia, made in 146/212 (69%) of the episodes of IPD. The overall case fatality rate was 10%, being highest among children with pneumococcal meningitis (5/9 = 56%). Pneumococcal isolates were highly susceptible to penicillin (86% susceptible and 14% with intermediate resistance) and chloramphenicol (98% susceptible). In contrast, up to 37% of the isolates tested were non‐susceptible to cotrimoxazole. Conclusions Incidence rates of IPD and associated mortality shown in this study highlight the need for pneumococcal vaccines in rural Africa, which must be effective in infants and young children.     

Epidemiology of pneumococcal diseases in Spain after the introduction of pneumococcal conjugate vaccines

In Spain, the use of pneumococcal conjugate vaccines (PCVs) has led to a decrease in the incidence of vaccine serotypes causing invasive and non-invasive disease in vaccinated and unvaccinated children and adults. Further, the coverage of most of the resistant serotypes by vaccines resulted in an overall decline in antibiotic resistance.As an undesirable effect, there was an increase in the non-vaccine serotypes causing infection, especially serotypes 1, 7F and 19A after PCV7 and serotype 8 after PCV13 approval, this making the beneficial effect of vaccination less apparent.The inclusion of PCVs in childhood vaccination schedules, its approval for use in healthy adults and the increasing number of serotypes covered by the vaccines in development are strong strategies in the fight against pneumococcal disease. Nonetheless, the epidemiology of Streptococcus pneumoniae infections must be still under surveillance to detect new changes, given the high capacity for recombination and adaptability of this always-surprising microorganism.     

Invasive pneumococcal disease in children with cancer: Incidence density,risk factors and isolated serotypes

BackgroundPediatric oncology patients (POP) have a high risk of infections due to impaired immunity. Invasive pneumococcal disease (IPD) is an important cause of severe infection in these patients and it is associated with high mortality. This study aimed to evaluate the incidence and risk factors associated with IPD at a Pediatric Oncology Center in Brazil.MethodsThis was a retrospective case-control study. All IPD cases in children with cancer from 2005 through 2016 were reviewed. Each case of IPD was matched with two controls from a cohort of patients matched for year of IPD, age and disease in order to assess risk factors. The incidence density was calculated as the number of IPD per 100,000 patients-year.ResultsA total of 51 episodes of IPD in 49 patients was identified. All pneumococci were isolated from blood cultures. The median age was five years and 67% were male; mortality rate was 7.8%. The IPD incidence density rate in POP was 311.21 per 100,000 patients-year, significantly higher than the rate in the general pediatric population. Severe neutropenia was the only risk factor associated with IPD, after multivariate conditional logistic regression analysis.ConclusionAlthough pneumococcal disease decreased after the introduction of 10-valent pneumococcal vaccine in the Brazilian national immunization schedule in 2010, there was no decrease in the IPD incidence rate in our cohort. A higher coverage rate of pneumococcal vaccination in children in the general population might be necessary to reduce the incidence rate in this high-risk population.     

Chronic medical conditions associated with invasive pneumococcal diseases in inpatients in teaching hospitals in São Paulo city: Estimating antimicrobial susceptibility and serotype-coverage of pneumococcal vaccines

BackgroundChronic conditions increase the risk of invasive pneumococcal diseases (IPD). Pneumococcal vaccination remarkably reduced IPD morbimortality in vulnerable populations. In Brazil, pneumococcal vaccines are included in the National Immunization Program (PNI): PCV10 for < 2 years-old, and PPV23 for high risk-patients aged ≥ 2 years and institutionalized ≥ 60 years. PCV13 is available in private clinics and recommended in the PNI for individuals with certain underlying conditions.MethodsA retrospective study was performed using clinical data from all inpatients from five hospitals with IPD from 2016 to 2018 and the corresponding data on serotype and antimicrobial-non-susceptibility of pneumococcus. Vaccine-serotype-coverage was estimated. Patients were classified according to presence of comorbidities: healthy, without comorbidities; at-risk, included immunocompetent persons with specific medical conditions; high-risk, with immunocompromising conditions and othersResults406 IPD cases were evaluated. Among 324 cases with information on medical conditions, children < 5 years were mostly healthy (55.9%), while presence of comorbidity prevailed in adults ≥ 18 years old (> 82.0%). Presence of ≥1 risk condition was reported in ≥ 34.8% of adults. High-risk conditions were more frequent than at-risk in all age groups. Among high-risk comorbidity (n = 211), cancer (28%), HIV/AIDS (25.7%) and hematological diseases (24.5%) were the most frequent. Among at-risk conditions (n = 89), asthma (16.5%) and diabetes (8.1%) were the most frequent. Among 404 isolates, 42.9% belonged to five serotypes: 19A (14.1%), 3 (8.7%), 6C (7.7%), 4 and 8 (6.2% each); 19A and 6C expressed antimicrobial-non-susceptibility. The vaccine-serotype-coverage was: PCV10, 19.1%, PCV13, 43.8%; PCV15, 47.8%; PCV20, 62.9%; PCV21, 65.8%, and PPV23, 67.3%. Information on hospital outcome was available for 283 patients, of which 28.6% died. Mortality was 54.2% for those with meningitis.ConclusionVaccine with expanded valence of serotypes is necessary to offer broad prevention to IPD. The present data contribute to pneumococcal vaccination public health policies for vulnerable patients, mainly those with comorbidity and the elderly.     

Epidemiology, antibiotic susceptibility, and serotype distribution of Streptococcus pneumoniae associated with invasive pneumococcal disease in British Columbia - A call to strengthen public health pneumococcal immunization programs.

BACKGROUND: This study examined the epidemiology, antibiotic susceptibility and serotype distribution of Streptococcus pneumoniae associated with invasive pneumococcal disease (IPD) in British Columbia. METHODS: Six hospitals and one private laboratory network participated in a prospective, sentinel laboratory based surveillance study of IPD, between October 1999 and October 2000. At each site, S pneumoniae isolates were collected and epidemiological data were gathered using a structured questionnaire, for all cases of IPD meeting the study case definition. Isolates were serotyped and tested for antimicrobial susceptibility. Bivariate associations were analyzed and multivariate logistic regression was used to identify independent risk factors associated with hospitalization or death. RESULTS: One hundred three reports and isolates were collected. Seventy-nine per cent of cases were community-acquired, 64% required hospitalization and 5% died. Cases with one or more assessed risk factor for IPD and of female sex were independent variables associated with hospitalization or death. One-third of isolates had reduced penicillin susceptibility and 96% of these represented serotypes contained in the 23-valent pneumococcal polysaccharide vaccine (PPV-23). Overall, 89% of serotypes identified are included in the PPV-23 vaccine and 88% of isolates from children under five years of age are found in the 7-valent pneumococcal conjugate vaccine (PCV-7). Forty-one per cent of cases qualified for publicly funded pneumococcal vaccine and 34% of eligible persons were vaccinated. CONCLUSIONS: Overall, pneumococcal serotypes associated with IPD in this study closely matched serotypes included in PPV-23 products currently licensed in Canada. Most serotypes associated with IPD in children under five years of age are included in a recently licenced PCV-7. One third of isolates demonstrated reduced penicillin susceptibility, most involving serotypes included in PPV-23. Effective delivery of current public health immunization programs using PPV-23 and extending protection to infants and young children using the PCV-7 will prevent many cases of IPD.     

Pneumococcal serogroups and serotypes in severe pneumococcal pneumonia in Belgian children: theoretical coverage of the 7-valent and 9-valent pneumococcal conjugate vaccines

BACKGROUND: Although the causative pneumococcal serotypes of invasive diseases are already extensively studied, few data are available about the pneumococcal serotypes additionally isolated from broncho-alveolar lavage samples in childhood pneumonia. STUDY AIM: To identify the causative pneumococcal serotypes in culture proven childhood community acquired pneumonia (CAP) and to calculate the effectiveness of the heptavalent and nonavalent pneumococcal vaccine (7- and 9-valent PnV) in severe pneumococcal pneumonia. METHODS: All pneumococcal isolates stored from broncho-alveolar lavage, blood culture and pleural fluid in healthy children with CAP were characterized. RESULTS: Seventy children (median age 2 years 3.5 months) could be included. The most prevalent serotypes were: SGT1 (21.4%), SGT6 (20.0%), SGT19 (12.8%), SGT23 (10.0%), and SGT14 (7.1%). SGT1 was especially prevalent in complicated cases and children >5 years. This first ranking of SGT1 is not reported in invasive pneumococcal disease studies. The overall theoretical coverage of the 7-valent PnV and the 9-valent PnV for pneumococcal pneumonia was 45.7% and 72.8%. The theoretical coverage of both vaccines was equal for non-invasive pneumonia (64%) but the theoretical coverage of the 9-valent PnV for invasive pneumonia was much higher (79% vs. 37.2%). Antibiotic susceptibility to penicillin was 84%, 70% to tetracycline and 61% to erythromycin; however only one strain (MIC = 4 mg/L) was highly resistant to penicillin. CONCLUSIONS: Based on this serotyping, the theoretical coverage of the 7-valent PnV for proven pneumococcal pneumonia is good but decreases with age. A 9-valent PnV containing SGT1 could significantly increase the coverage, especially for invasive pneumonia. According to these data, penicillin remains the first choice antibiotic treatment for childhood CAP in Belgium.     

Combined schedules of pneumococcal conjugate and polysaccharide vaccines: is hyporesponsiveness an issue?

Streptococcus pneumoniae is a major cause of morbidity and mortality in children less than 5 years of age. Prevention of pneumococcal disease and death in children in the developing world through vaccination with recently developed, highly efficacious pneumococcal conjugate vaccines (PCVs) is now possible. Schedules combining PCV with 23-valent pneumococcal polysaccharide vaccine (PPV23) have been studied and proposed as a means to expand disease protection against serotypes not included in the PCVs. Studies of group A and C meningococcal polysaccharide vaccine and repeated doses of PPV23 in adults and children have shown that a state of immune tolerance, or hyporesponsiveness, can develop to repeated polysaccharide vaccine antigen exposures. In this Review, we describe the evidence for and against this hyporesponsiveness and explore the possible mechanisms for such an occurrence.     

Streptococcus pneumoniae serotype 19A in Latin America and the Caribbean: a systematic review and meta-analysis, 1990-2010

ABSTRACT: BACKGROUND: Pneumococcal conjugate vaccines (PCVs) are in the process of implementation in Latin America. Experience in developed countries has shown that they reduce the incidence of invasive and non-invasive disease. However, there is evidence that the introduction of PCVs in universal mass vaccination programs, combined with inappropriate and extensive use of antibiotics, could be associated to changes in non-PCV serotypes, including serotype 19A. We conducted a systematic review to determine the distribution of serotype 19A, burden of pneumococcal disease and antibiotic resistance in the region. METHODS: We performed a systematic review of serotype 19A data from observational and randomized clinical studies in the region, conducted between 1990 and 2010, for children under 6 years. Pooled prevalence estimates from surveillance activities with confidence intervals were calculated. RESULTS: We included 100 studies in 22 countries and extracted data from 63. These data reported 19733 serotyped invasive pneumococcal isolates, 3.8% of which were serotype 19A. Serotype 19A isolates were responsible for 2.4% acute otitis media episodes, and accounted for 4.1% and 4.4% of 4,380 nasopharyngeal isolates from healthy children and in hospitalbased/ sick children, respectively. This serotype was stable over the twenty years of surveillance in the region. A total of 53.7% Spn19A isolates from meningitis cases and only 14% from non meningitis were resistant to penicillin. CONCLUSIONS: Before widespread PCV implementation in this region, serotype 19A was responsible for a relatively small number of pneumococcal disease cases. With increased use of PCVs and a greater number of serotypes included, monitoring S. pneumoniae serotype distribution will be essential for understanding the epidemiology of pneumococcal disease.