High Risk Of Invasive Pneumococcal Disease Research Articles

Penicillin Prophylaxis in Patients With Sickle Cell Disease Beyond Age 5 Years.

Patients with sickle cell disease (SCD) are at increased risk for invasive pneumococcal disease (IPD) caused by Streptococcus pneumoniae. Immunization and antimicrobial prophylaxis may prevent this complication, and landmark clinical trials support discontinuation of antimicrobial prophylaxis at age 5 years. However, antimicrobial prophylaxis continues in some patients indefinitely. The objective of this study was to evaluate the incidence of culture-positive IPD and other infections in the setting of penicillin prophylaxis in the pediatric SCD population. This was a single-center, retrospective cohort study of patients with SCD who continued antimicrobial prophylaxis with penicillin, compared with those whose antimicrobial prophylaxis was discontinued. Included patients were aged 5 to 18 years during the study period and had no history of IPD or surgical splenectomy. Patient charts were reviewed for demographics, immunizations, penicillin prescription history, and microbiologic culture data. Antimicrobial prophylaxis continued beyond age 5 years in 65% of patients, a higher percentage of whom had hemoglobin SS or S beta-zero disease. No patients whose antimicrobial prophylaxis was discontinued experienced IPD; 1 patient who continued antimicrobial prophylaxis died of S pneumoniae sepsis. Rates of other infections were comparable between groups (21% in prophylaxis versus 18% in no prophylaxis). These results support appropriate de-prescribing of antimicrobial prophylaxis in patients with SCD who are not at high risk for IPD. Further multicenter studies are needed to evaluate consequences of antimicrobial prophylaxis with alternative agents on antibiotic resistance, examine provider rationale for continuation of antimicrobial prophylaxis, and assess quality of life effects (e.g., medication adherence, adverse drug reactions) of antimicrobial prophylaxis.

Improving Pneumococcal Vaccination Rates in High-risk Children in Specialty Clinics.

Pediatric patients with immunocompromising or certain chronic medical conditions have an increased risk of acquiring invasive pneumococcal disease (IPD). The 23-valent pneumococcal polysaccharide vaccine (PPSV23) is recommended for patients ≥2 years at high risk for IPDs. The aim of this project was to improve PPSV23 vaccination rates for children at high risk for IPD who were seen in 3 specialty clinics from ∼20% to 50% over a 12-month period. The project team included quality improvement champions from the divisions of rheumatology, infectious diseases, and pulmonology in addition to leaders from our population health management subsidiary. Several initiatives were implemented, starting with review of patient inclusion criteria per the vaccination recommendations, that led to the design and deployment of an automated weekly previsit planning report. Additionally, we implemented a process to stock pneumococcal vaccines and shared best practices among the divisions. We monitored improvement through times series and run charts of PPSV23 vaccination rates. The initial PPSV23 vaccination rate for applicable high-risk patients was ∼20%. There was an increase in vaccination rate to ∼60%. All 3 divisions showed improvements in their individual PPSV23 vaccination rates. Using quality improvement methodology, we increased PPSV23 vaccination rates in 3 pediatric specialty clinics, and this improvement was sustained. We will continue to identify best practices and actively recruit additional divisions because we have the opportunity to reach >9000 high-risk patients.

Risk of invasive pneumococcal disease in patients with asplenia/hyposplenism: A nationwide population-based study in Korea, 2009–2018

ObjectivesWe aimed to determine the incidence and relative risk (RR) of invasive pneumococcal disease (IPD) in patients with asplenia/hyposplenism, using a nationwide population-based database. MethodsFrom 2009 to 2018, all claimed cases of newly diagnosed asplenia/hyposplenism in the National Health Insurance Service in South Korea were included. The incidence and RR of IPD in asplenia/hyposplenism patients were investigated using the Korean Center for Disease Control criteria. ResultsFifty-seven IPD cases were identified among 21,376 patients with 82,748 person-years of exposure. The cumulative 8-year IPD incidence was 0.5%; 45.6% of the infections occurred within two years after an asplenia/hyposplenism diagnosis. The age-standardised incidence rate was 104.5 per 100,000 person-years (95% confidence interval [CI], 103.6–105.4). Patients aged <5 years had a 15.1-times higher risk of IPD than those aged ≥60 years (95% CI: 5.8–39.5, p < 0.0001). The RR of IPD was 32.0 times higher in patients with asplenia/hyposplenism than in the general population (95% CI, 21.7–47.0); the standardized incidence ratio was 17.9(95% CI, 11.8–26.0). ConclusionsThis large population-based study highlights the high IPD incidence rate and RR in Korean patients with asplenia/hyposplenism. Increased awareness and effective prevention strategies are needed for these high-risk populations, especially children aged <5 years.

Asthma and the Risk of Invasive Pneumococcal Disease: A Meta-analysis.

Invasive pneumococcal disease (IPD) and pneumonia are a leading cause of morbidity and mortality throughout the world, and asthma is the most common chronic disease of childhood. To evaluate the risk of IPD or pneumonia among children with asthma after the introduction of pneumococcal conjugate vaccines (PCVs). Four electronic databases were searched. We selected all cohorts or case-control studies of IPD and pneumonia in populations who already received PCV (largely 7-valent pneumococcal conjugate vaccine), but not 23-valent pneumococcal polysaccharide, in which authors reported data for children with asthma and in which healthy controls were included, without language restriction. Two reviewers independently reviewed all studies. Primary outcomes were occurrence of IPD and pneumonia. Secondary outcomes included mortality, hospital admissions, hospital length of stay, ICU admission, respiratory support, costs, and additional medication use. Five studies met inclusion criteria; of those, 3 retrospective cohorts (∼26 million person-years) and 1 case-control study (N = 3294 children) qualified for the meta-analysis. Children with asthma had 90% higher odds of IPD than healthy controls (odds ratio = 1.90; 95% confidence interval = 1.63-2.11; I2 = 1.7%). Pneumonia was also more frequent among children with asthma than among controls, and 1 study reported that pneumonia-associated costs increased by asthma severity. None of the identified studies had information of asthma therapy or compliance. Despite PCV vaccination, children with asthma continue to have a higher risk of IPD than children without asthma. Further research is needed to assess the need for supplemental 23-valent pneumococcal polysaccharide vaccination in children with asthma, regardless of their use of oral steroids.

Invasive Pneumococcal Disease in UK Children

Invasive pneumococcal disease (IPD) has declined significantly since the introduction of pneumococcal conjugate vaccines (PCVs). It is not known whether certain infant populations remain at higher risk of IPD in countries with established 13-valent PCV (PCV13) programs. We aimed to describe the epidemiology, clinical characteristics, serotype distribution, and outcomes of IPD in infants, and to estimate the relative risk of PCV13-type, non-PCV13-type, and overall IPD in premature infants compared to term infants during a 4-year period after the PCV13 program was established. This was a prospective, enhanced national surveillance of laboratory-confirmed IPD in England in infants aged <1 year diagnosed during 2013-2016. There were 517 cases of IPD (incidence: 19/100000 infants). Incidence was significantly higher in premature infants compared with those born at term (49/100000 vs 17/100000; incidence rate ratio [IRR], 2.87; P < .001), with infants born before 28 weeks' gestation having the highest incidence (150/100000; IRR, 8.8; P < .001). Of the 454 IPD cases with serotyped isolates, most were caused by non-PCV13 serotypes (369 cases, 71.4%), with 85 cases (16.4%) due to PCV13 serotypes. There were 31 deaths (case fatality rate [CFR], 6.2% [95% confidence interval, 4.3%-8.6%]). Premature infants did not have a higher CFR than term infants (P = .62). IPD incidence in infants remains lower than rates reported prior to PCV7 introduction in England. The risk of IPD remains significantly higher in premature infants compared to infants born at term, for both PCV13 and non-PCV13 serotypes. Any changes to the infant PCV13 immunization schedule may disproportionally affect premature infants.

Neonatal invasive pneumococcal disease: New Zealand experience in the era of pneumococcal vaccination.

Invasive pneumococcal disease (IPD) became a notifiable disease in New Zealand in 2008, and in the same year pneumococcal conjugate vaccine (PCV) was added to the childhood immunisation schedule. This was a retrospective study of IPD in infants aged <90 days reported to the national notifiable disease database, EpiSurv, from 1 January 2009 to 31 December 2013. All cases had Streptococcus pneumoniae isolated from a normally sterile site. IPD incidence was calculated for babies aged <90 and <30 days using the number of national IPD cases with a denominator of annual infant live births. Clinical, demographic and outcome data were reviewed for infants aged less than seven days (early onset). There were 29 cases of IPD in infants aged <90 days and 19 cases in infants aged <30 days. Of the nine early-onset cases, six occurred within the first 48 h. Six of the early-onset cases were infants of NZ Maori ethnicity. One infant died six hours after birth. Three infants developed long-term neurological or respiratory sequelae. Isolates from five of the early-onset cases were S. pneumoniae serotypes not covered by the PCV in use at the time of infection. Maternal vaccination with 23-valent pneumococcal vaccine would have covered 84% (16 of 19) of serotypes responsible for the cases in infants <30 days old. Strategies such as maternal vaccination or accelerated neonatal vaccination may be beneficial to protect neonates at high risk of IPD.

Risk of underlying chronic medical conditions for invasive pneumococcal disease in adults

PurposeIn the United States, the 13-valent pneumococcal conjugate vaccine is recommended in persons ⩾65years of age, and persons ⩽65years of age with immunocompromising (IC) conditions. For invasive pneumococcal disease (IPD) prevention in those ⩽65 with non-IC medical conditions, the 23-valent polysaccharide vaccine is recommended. This group is at higher risk of IPD than the general population, but the level of risk is not well-quantified. We estimated IPD risk by individual underlying medical conditions, and by total number of conditions, for persons ⩾18years of age. We calculated the relative risks (RR) of various medical conditions, comparing the incident IPD cases to the general study population, and used Poisson regression models to estimate an IPD RR, adjusting for other conditions. We also examined IPD incidence by number of conditions diagnosed in each calendar year, using a risk-stacking model. ResultsUnderlying medical conditions with the highest adjusted RR for IPD were chronic liver disease (RR 2.1, 95% CI 1.5–2.8) and chronic obstructive pulmonary disease (COPD; RR 2.1, 95% CI 1.8–2.5). IPD risk increased with increasing number of medical conditions: adjusted RR, 2.2 (95% CI 1.9–2.5) 1 condition, 2.9 (2.5–3.5) for 2 conditions, and 5.2 (4.4–6.1) for 3 conditions. ConclusionsFor persons with a single, non-IC medical condition, IPD risk was twice that for the general KPNC population. Persons with multiple, non-IC chronic conditions exhibited increased IPD risk with each additional condition. Such information may inform discussions on recommendations for adult pneumococcal immunization and prevention.

Invasive Bacterial Diseases in Northern Canada, 2006-2013.

Northern populations were at a high risk of developing invasive bacterial diseases (IBDs). Since the last published study that described IBDs in Northern Canada, a number of vaccines against some bacterial pathogens have been introduced into the routine childhood immunization schedule. To describe the epidemiology of IBDs in Northern Canada from 2006 to 2013. Data for 5 IBDs (invasive pneumococcal disease (IPD), invasive Haemophilus influenzae disease (Hi), invasive Group A streptococcal disease (iGAS), invasive meningococcal disease (IMD) and invasive Group B streptococcal disease (GBS)) were extracted from the International Circumpolar Surveillance (ICS) program and the Canadian Notifiable Diseases Surveillance System. Incidence rates were calculated per 100,000 population per year. During the study period, the incidence rates of IPD ranged from 16.84-30.97, iGAS 2.70-17.06, Hi serotype b 0-2.78, Hi non-b type 2.73-8.53, and IMD 0-3.47. Except for IMD and GBS, the age-standardized incidence rates of other diseases in Northern Canada were 2.6-10 times higher than in the rest of Canada. Over the study period, rates decreased for IPD (p=0.04), and iGAS (p=0.01), and increased for Hi type a (Hia) (p=0.004). Among IPD cases, the proportion of pneumococcal conjugate vaccine (PCV)7 serotypes decreased (p=0.0004) over the study period. Among Hi cases, 69.8% were Hia and 71.6% of these were in children under than 5 years. Of 13 IMD cases, 8 were serogroup B and 2 of them died. Northern population in Canada, especially infants and seniors among First Nations and Inuit, are at a high risk of IPD, Hi and iGAS. Hia is the predominant serotype in Northern Canada.

Summary of the National Advisory Committee on Immunization's Statement on the re-immunization with polysaccharide 23-valent pneumococcal vaccine.

Individuals who are 2 years of age and over and at high risk for invasive pneumococcal disease (IPD) (defined as those with functional or anatomic asplenia or sickle cell disease; hepatic cirrhosis; chronic renal failure or nephrotic syndrome; HIV infection; and immunosuppression related to disease or therapy) are recommended to receive one lifetime booster dose of polysaccharide 23-valent pneumococcal vaccine (Pneu-P-23) vaccine, in addition to age- and risk-specific recommendations for the conjugate 13-valent pneumococcal vaccine (Pneu-C-13). Adults aged 65 years and over are also considered at high risk for invasive pneumococcal disease (IPD). To determine the optimal time between initial vaccination with Pneu-P-23 and subsequent booster doses to protect against IPD in those at high risk for IPD. The National Advisory Committee on Immunization (NACI) conducted a systematic review of the literature on booster doses of pneumococcal vaccine for individuals at high risk for IPD disease. NACI reviewed the evidence considering the target population, safety, immunogenicity, efficacy, effectiveness of the vaccines, vaccine schedules, and other aspects of the overall immunization strategy, and then approved three specific recommendations. For all individuals aged 2 years and over who are at high risk for IPD and who have received a dose of Pneu-P-23, re-vaccination with a second dose of Pneu-P-23 should be provided five years after the initial dose of Pneu-P-23. They should also have previously received age-appropriate doses of 13-valent conjugate pneumococcal vaccine. There is currently insufficient evidence to determine the optimal timing and number of Pneu-P-23 boosters in high-risk adults. One lifetime booster of Pneu-P-23 is currently recommended for individuals at high risk for IPD, five years after the previous dose. Given the increased risk of IPD in adults aged 65 years and older and the rapid decline in antibodies following Pneu-P-23, all individuals should receive one dose of Pneu-P-23 at age 65 years-as long as five years have passed since the previous Pneu-P-23 dose. No additional booster dose is currently recommended for this age group, if they have no medical conditions that put them at high risk for IPD. The new and complete set of current recommendations for pneumococcal vaccines will be published in the updated "Pneumococcal" chapter in the Canadian Immunization Guide in the near future.

The role of mannose-binding lectin in pneumococcal infection

The role of mannose-binding lectin (MBL) deficiency (MBL2; XA/O and O/O genotypes) in host defences remains controversial. The surfactant proteins (SP)-A1, -A2 and -D, other collectins whose genes are located near MBL2, are part of the first-line lung defence against infection. We analysed the role of MBL on susceptibility to pneumococcal infection and the existence of linkage disequilibrium (LD) among the four genes. We studied 348 patients with pneumococcal community-acquired pneumonia (P-CAP) and 2,110 controls. A meta-analysis of MBL2 genotypes in susceptibility to P-CAP and to invasive pneumococcal disease (IPD) was also performed. The extent of LD of MBL2 with SFTPA1, SFTPA2 and SFTPD was analysed. MBL2 genotypes did not associate with either P-CAP or bacteraemic P-CAP in the case-control study. The MBL-deficient O/O genotype was significantly associated with higher risk of IPD in a meta-analysis, whereas the other MBL-deficient genotype (XA/O) showed a trend towards a protective role. We showed the existence of LD between MBL2 and SP genes. The data do not support a role of MBL deficiency on susceptibility to P-CAP or to IPD. LD among MBL2 and SP genes must be considered in studies on the role of MBL in infectious diseases.

Recommendations for the Prevention of Streptococcus pneumoniae Infections in Infants and Children: Use of 13-Valent Pneumococcal Conjugate Vaccine (PCV13) and Pneumococcal Polysaccharide Vaccine (PPSV23)

Routine use of the 7-valent pneumococcal conjugate vaccine (PCV7), available since 2000, has resulted in a dramatic reduction in the incidence of invasive pneumococcal disease (IPD) attributable to serotypes of Streptococcus pneumoniae contained in the vaccine. However, IPD caused by nonvaccine pneumococcal serotypes has increased, and nonvaccine serotypes are now responsible for the majority of the remaining cases of IPD occurring in children. A 13-valent pneumococcal conjugate vaccine has been licensed by the US Food and Drug Administration, which, in addition to the 7 serotypes included in the original PCV7, contains the 6 pneumococcal serotypes responsible for 63% of IPD cases now occurring in children younger than 5 years. Because of the expanded coverage provided by PCV13, it will replace PCV7. This statement provides recommendations for (1) the transition from PCV7 to PCV13; (2) the routine use of PCV13 for healthy children and children with an underlying medical condition that increases the risk of IPD; (3) a supplemental dose of PCV13 for (a) healthy children 14 through 59 months of age who have completed the PCV7 series and (b) children 14 through 71 months of age with an underlying medical condition that increases the risk of IPD who have completed the PCV7 series; (4) "catch-up" immunization for children behind schedule; and (5) PCV13 for certain children at high risk from 6 through 18 years of age. In addition, recommendations for the use of pneumococcal polysaccharide vaccine for children at high risk of IPD are also updated.

Streptococcus pneumoniae

Genetic analyses of Streptococcus pneumoniae clinical isolates causing invasive pneumococcal disease (IPD) have revealed within the "susceptible population" a significant proportion of strains harboring a single, principally parC mutation within the quinolone-resistance determining region. The occurrence of first-step mutants predisposes S. pneumoniae to a subsequent and more rapid second-step mutation resulting in elevated levels of fluoroquinolone resistance and clinical failure. Fluoroquinolones are a common therapeutic choice for residents of long-term care facilities and/or elderly patients in the community at higher risk of IPD. Despite the advent of the pneumococcal conjugate vaccine, levofloxacin resistance among vaccine serotypes is increasing, and the majority of these isolates are closely related to widespread antibiotic-resistant clones. Use of fluoroquinolones with activity against levofloxacin-nonsusceptible isolates of S. pneumoniae should be considered in the management of IPD among elderly patients in the community and long-term care residents and among at-risk patients with chronic pulmonary infections.

The cost-effectiveness of pneumococcal conjugate vaccination in Australia

Background: Pneumococcal conjugate vaccine, 7 valent (PCV7) is the most costly vaccine yet considered for publicly funded programs. In mid 2001, Australia funded PCV7 for high-risk groups only (indigenous children and children with certain underlying medical conditions). World wide, non-industry-funded studies and studies using cost–utility measures are sparse. We undertook an independent economic analysis of PCV7 compared with no vaccination in the non high-risk Australian childhood population using cost–utility and cost-effectiveness measures. Methods: The incidence of invasive pneumococcal disease (IPD), non-bacteraemic pneumonia and otitis media was estimated using representative urban Australian data, or by extrapolation from comparable industrialised countries. A decision-analytic model was developed for a hypothetical birth cohort using the age-specific vaccine coverage from the Californian randomised controlled trial of PCV7. Health outcomes were measured by life-years saved and deaths and disability-adjusted life-years (DALYs) averted. In line with government guidelines, only direct costs were considered in 1997–1998 Australian dollars. Results: For a birth cohort of 250,000, the gross cost of vaccination is $ 78.6 million. Subtracting treatment cost savings, the net cost (discounted) is $ 61.7 million. In undiscounted terms, vaccination prevents 13.7 deaths, 11.2 (82%) from IPD and the remainder from non-bacteraemic pneumonia. The discounted cost per death avoided is $ 5.0 million, per life-year saved $ 230,130 and per DALY averted $ 121,100, giving a break-even vaccine price of $ 15.40 per dose. These estimates are most sensitive to the unit cost per dose of vaccine, estimates of incidence and vaccine efficacy against non-bacteraemic pneumonia and the discount rate. The cost per DALY reduced to $ 81,000 with a discount rate of 3% rather than 5% and to $ 90,000 with the most favourable assumptions concerning pneumonia reduction. Discussion: With a vaccine price of $ 90 per dose, mid-range estimates of impact against non-bacteraemic pneumonia, and discount rate of 5%, a PCV7 program for infants not at high risk of IPD is at the upper limit of cost per DALY previously approved under Australian pharmaceutical funding guidelines. The impact of PCV7 against non-bacteraemic pneumonia is poorly defined, but its importance to cost-effectiveness in resource rich and resource poor settings warrants further studies or analysis to give greater precision to this outcome.

The future of pneumococcal conjugate vaccines for prevention of pneumococcal diseases in infants and children.

Seven-valent pneumococcal conjugate vaccine (PCV7) was licensed in February 2000. In June 2000, the Advisory Committee on Immunization Practices and the American Academy of Pediatrics recommended the universal administration of pneumococcal conjugate vaccine for all children 23 months of age and younger and for children 24 to 59 months of age who are at high risk for serious pneumococcal disease. Since then, >23 million doses have been administered in the United States. Postlicensure surveillance of invasive pneumococcal disease (IPD) in the United States from the Active Bacterial Core Surveillance program at the Centers for Disease Control and Prevention and the Northern California Kaiser Permanente Vaccine Study Center has reported a decline in IPD and in pneumococcal disease incidence as a result of vaccine serotypes, respectively. During this period, issues critical to the long-term success of PCV7 have become more relevant: Will PCV7 be as effective in groups of children who are at high risk for IPD as in healthy children? Will nonvaccine types replace vaccine serotypes in the nasopharynx and in disease? Why are the results of the clinical trials different for IPD and for acute otitis media? How many doses of PCV7 and what concentrations of antibody are necessary for protection? Will universal administration of PCV7 to children younger than 2 years reduce antimicrobial drug resistance and alter prescribing patterns of physicians for febrile infants? Have there been unanticipated adverse events or benefits observed? The purpose of this report is to review the current data available to address these questions and to identify gaps that will require additional knowledge to determine the ultimate value of pneumococcal conjugate vaccines in reducing the burden of pneumococcal disease in infants and children.