Risk Of Invasive Pneumococcal Infection Research Articles

Retained Splenic Function in an Indian Population with Homozygous Sickle Cell Disease May Have Important Clinical Significance.

Background and Objectives:To determine whether the persistence of splenomegaly characteristic of the Asian haplotype of homozygous sickle cell (SS) disease is associated with continued splenic function, a comparison of patients from Odisha, India, and Jamaica.Materials and Methods:Indian patients were examined in a cross-sectional study and compared with the Jamaican Cohort Study from birth. Splenomegaly was assessed in both populations with standard methods. Splenic function was assessed in both by counts of pitted red blood cells determined by differential interference contrast microscopy in the same laboratory.Results:In Jamaica, the spleen became palpable in 55% of patients during the 1st year of life and the prevalence declined thereafter, whereas in Indian patients, the prevalence rose steeply after the age of 4 years. Raised pitted red cell counts, consistent with loss of splenic function, were common after 2 years in Jamaicans but did not increase in Indians until after the age of 5 years.Interpretation and Conclusions:The maximal risk of invasive pneumococcal infection in SS disease falls sharply after the age of 3 years, and persistence of splenic function in Odisha patients beyond this age may explain the apparent absence of pneumococcal septicemia in Indian patients and questions the role of pneumococcal prophylaxis.

Immunogenicity of the Currently Recommended Pneumococcal Vaccination Schedule in Patients With Inflammatory Bowel Disease.

Patients with inflammatory bowel disease (IBD) are at increased risk of invasive pneumococcal infections. Therefore, vaccination with the 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) 2 months later is recommended. However, the level of immunogenicity induced by this vaccination schedule in IBD patients with and without immunosuppressive medication remains unclear. We prospectively assessed the immunogenicity of PCV13 followed by PPSV23 in IBD patients by measuring serotype-specific pneumococcal immunoglobulin G antibody concentrations at baseline and 4-8 weeks postvaccination. Response to vaccination was defined as a postvaccination antibody concentration ≥1.3 μg/mL for 70% of the measured serotypes. We analyzed the immunogenic effect of 4 different medication regimens: (1) conventional immunomodulators (ie, oral prednisolone >10 mg/day, thiopurines, methotrexate); (2) anti-tumor necrosis factor agents; (3) combination therapy; and (4) no treatment with immunosuppressive agents (control group). One hundred forty-one IBD patients were included, of whom 37 were controls. Adequate response to vaccination was 59% (61/104) in patients using immunosuppressive agents (groups 1-3) vs 81% (30/37) in controls (odds ratio, 0.33 [95% confidence interval, .13-.82]). A combination of different immunosuppressive drugs most severely impaired the immune response to pneumococcal vaccination (response, 52% [15/29]). Although the sequential vaccination schedule of PCV13 followed by PPSV23 is safe, immunogenic, and thus beneficial in the majority of IBD patients, those receiving immunosuppressive agents, and especially those receiving combination therapy, have an impaired immune response compared to controls. Therefore, preferably, vaccinations should be administered before the initiation of immunosuppressive therapy. Dutch trial register #6315.

Invasive pneumococcal infections in children following transplantation in the pneumococcal conjugate vaccine era.

Pediatric recipients of hematopoietic stem cell and solid organ transplants are at increased risk of invasive pneumococcal infections (IPI). Data on IPI in this population are scarce. To our knowledge, this is the first study describing the epidemiology of IPI among pediatric transplant recipients in the pneumococcal conjugate vaccine (PCV) era. We identified transplant recipients with IPI at 8 children's hospitals in the U.S. from our surveillance database (2000-2014). Pneumococcal isolates were collected prospectively. Serotyping and antibiotic susceptibility were performed in a central laboratory. Categorical variables were analyzed by Fisher's exact test and continuous variables with nonparametric tests. Indirect cohort study design was used to calculate vaccine effectiveness. We identified 65 episodes of IPI in transplant recipients. Recurrent IPI was observed in 10% of transplant recipients. The IPI crude incidence rate in solid organ transplant recipients was higher than in the general population. Most IPI episodes occurred >6months after transplantation. Bacteremia and pneumonia were the most common presentations. Meningitis was unusual. No case fatalities were observed. Serotype 19A was the most common serotype (n=10), followed by 6C (n=7). In 2010-2014, 37% of IPI was caused by PCV13 serotypes. Four cases of vaccine breakthrough were identified. Most isolates were susceptible to penicillin and ceftriaxone. Pneumococcal conjugate and polysaccharide immunization rates were low. Pediatric transplant recipients remain at increased risk of IPI in the vaccine era. Most cases presented as a late post-transplant infection. The interval between transplantation and IPI may allow adequate time for pneumococcal immunization.

Antibiotic resistance of Streptococcus pneumoniae colonising the nasopharynx of HIV-exposed Tanzanian infants.

To determine antibiotic susceptibility of colonising pneumococcal serotypes in HIV-exposed infants before the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13), because HIV-exposed infants are at increased risk of invasive pneumococcal infections. Antibiotic susceptibility of 104 pneumococcal isolates, cultured from the nasopharynx from Tanzanian HIV-exposed infants, was determined using the disc diffusion method and the E-test according to EUCAST version 4.0 (2014) criteria. A total of 69.2% of isolates were intermediately susceptible for benzyl penicillin (MIC 0.06-2mg/l ); no high-level resistance was found. All isolates but one were susceptible to ampicillin. Regarding non-beta-lactam antibiotics, 19.2% of isolates were resistant to doxycycline, 3.8% to erythromycin and 97.1% to trimethoprim/sulfamethoxazole. A total of 15.4% of isolates were resistant to three antibiotic classes or more. There were no differences in antibiotic susceptibility between vaccine and non-vaccine serotypes. Reduced susceptibility of colonising pneumococcal isolates for commonly used antibiotics is common in HIV-exposed Tanzanian infants. High-dose penicillin and ampicillin remain appropriate first choices for non-meningeal pneumococcal infections in this group.

Tu1186 Risk of Invasive Pneumococcal Infection in Patients With Inflammatory Bowel Disease: A Nationwide Danish Cohort Study

Tu1186 Risk of Invasive Pneumococcal Infection in Patients With Inflammatory Bowel Disease: A Nationwide Danish Cohort Study

DOP092 Risk of invasive pneumococcal infection in patients with inflammatory bowel disease: A nationwide Danish cohort study

DOP092 Risk of invasive pneumococcal infection in patients with inflammatory bowel disease: A nationwide Danish cohort study

Asthma and Risk of Community-Associated Blood Stream Infection Due to Staphylococcus aureus: A Population-Based Case-Control Study

Patients with asthma harbor an increased risk of invasive pneumococcal infection (IPD). It is unknown whether there is a similar association between asthma and community-associated blood stream infection (BSI) caused by Staphylococcus aureus.

Air Pollution And Environmental Tobacco Smoking During Infancy May Increase The Risk Of Bronchiolitis

M O N D A Y 623 Asthma and Risk of Community-Associated Blood Stream Infection Due to Staphylococcus aureus: A Population-Based Case-Control Study J. Lee, H. Yang, W. Atrouni, L. Baddour, B. Yawn, Y. Juhn; Department of Pediatrics,Samsung Changwon Hospital, Changwon-si, REPUBLIC OF KOREA, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, Department of Pediatrics,Soonchunhyang University Hospital, Seoul, REPUBLIC OF KOREA, Division of Infectious Diseases, Department of Internal Medicine,University of Kansas Medical Center, Kansas, KS, Division of Infectious Diseases, Department of Medicine,Mayo Clinic, Rochester, MN, Department of Research, Olmsted Medical Center, Rochester, MN. RATIONALE: Patients with asthma harbor an increased risk of invasive pneumococcal infection (IPD). It is unknown whether there is a similar association between asthma and community-associated blood stream infection (BSI) caused by Staphylococcus aureus. METHODS: Subjects were adult residents of Olmsted County, MN, who developed community-associated BSI caused by S. aureus between 1998 and 2005; three ageand sex-matched controls were also evaluated. The associations between asthma and community-associated BSI caused by S. aureus were assessed by Fischer exact test. RESULTS: Of the 43 BSI cases, 70% were male, 86% were Caucasians, and the median age was 59 years. Five (11.6%) of them were asthmatics as compared to 9 (7%) of 129 controls (p50.34). Compared to non-asthmatics, asthmatics had a lower ICU admission rate (34% vs 0%, p50.3) and lower Pitt-bacteremia scores (2.362.7 vs. 0.860.5, p50.13), a shorter hospital stay (13.6614.7 days vs. 11.462.1 days,p50.59), and lower mortality rates (13.0% vs. 0.0%, p51.0), but these differences were not statistically significant. CONCLUSIONS: Unlike IPD, asthma is not significantly associated with risk and severity of BSI caused by S. aureus. Designation of specific pathogenmay be one of several key factors in an association of asthmawith risk and severity of BSI. However, a small sample size significantly limited the current investigation.

Asthma and Severity of Blood Stream Infection Caused by Escherichia coli: A Population-Based Study

M O N D A Y 623 Asthma and Risk of Community-Associated Blood Stream Infection Due to Staphylococcus aureus: A Population-Based Case-Control Study J. Lee, H. Yang, W. Atrouni, L. Baddour, B. Yawn, Y. Juhn; Department of Pediatrics,Samsung Changwon Hospital, Changwon-si, REPUBLIC OF KOREA, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, Department of Pediatrics,Soonchunhyang University Hospital, Seoul, REPUBLIC OF KOREA, Division of Infectious Diseases, Department of Internal Medicine,University of Kansas Medical Center, Kansas, KS, Division of Infectious Diseases, Department of Medicine,Mayo Clinic, Rochester, MN, Department of Research, Olmsted Medical Center, Rochester, MN. RATIONALE: Patients with asthma harbor an increased risk of invasive pneumococcal infection (IPD). It is unknown whether there is a similar association between asthma and community-associated blood stream infection (BSI) caused by Staphylococcus aureus. METHODS: Subjects were adult residents of Olmsted County, MN, who developed community-associated BSI caused by S. aureus between 1998 and 2005; three ageand sex-matched controls were also evaluated. The associations between asthma and community-associated BSI caused by S. aureus were assessed by Fischer exact test. RESULTS: Of the 43 BSI cases, 70% were male, 86% were Caucasians, and the median age was 59 years. Five (11.6%) of them were asthmatics as compared to 9 (7%) of 129 controls (p50.34). Compared to non-asthmatics, asthmatics had a lower ICU admission rate (34% vs 0%, p50.3) and lower Pitt-bacteremia scores (2.362.7 vs. 0.860.5, p50.13), a shorter hospital stay (13.6614.7 days vs. 11.462.1 days,p50.59), and lower mortality rates (13.0% vs. 0.0%, p51.0), but these differences were not statistically significant. CONCLUSIONS: Unlike IPD, asthma is not significantly associated with risk and severity of BSI caused by S. aureus. Designation of specific pathogenmay be one of several key factors in an association of asthmawith risk and severity of BSI. However, a small sample size significantly limited the current investigation.

Risk of invasive pneumococcal infections among working age adults with asthma

BackgroundInformation about the risk of invasive pneumococcal infection (IPI) among adults with asthma is limited and inconsistent. To evaluate this association, a population-based case–control study was conducted.MethodsCases of IPI (Streptococcus...

Loss of Discrete Memory B Cell Subsets Is Associated with Impaired Immunization Responses in HIV-1 Infection and May Be a Risk Factor for Invasive Pneumococcal Disease

Invasive pneumococcal infection is an important cause of morbidity and mortality in HIV-1-infected individuals. B cells play an important role in maintaining serologic memory after infection. IgM memory B cells are significantly reduced in HIV-1-infected patients and their frequency is similar to that observed in other patient groups (splenectomized individuals and patients with primary Ab deficiency) who are also known to have an increased risk of invasive pneumococcal infection. Antiretroviral therapy does not restore marginal zone B cell percentages. Immunization with the 23-valent polysaccharide pneumococcal vaccine shows that HIV-1-infected patients have impaired total IgM and IgG pneumococcal vaccines compared with healthy controls. Loss of switched memory B cells was associated with impaired tetanus toxoid IgG vaccine responses. Results of this study demonstrate that defects in B cell memory subsets are associated with impaired humoral immune responses in HIV-1 patients who are receiving antiretroviral therapy and may be a contributory factor to the increased risk of invasive pneumococcal infection observed in HIV-1 infection.

Randomised revaccination with pneumococcal polysaccharide or conjugate vaccine in asplenic children previously vaccinated with polysaccharide vaccine

Asplenic children are at high risk of invasive pneumococcal infection. In this group, the American Academy of Pediatrics recommends a single revaccination with the 23-valent polysaccharide vaccine (PSV23) 3-5 years after a previous PSV23 dose. Despite potential advantages, there are few data available regarding the safety and immunogenicity of the heptavalent pneumococcal conjugate vaccine (PCV7) in this population. The aim of the study was to prospectively determine and to compare, in asplenic children, the vaccine specific antibody titres against the seven serotypes included in the PCV7 after administration of one dose of PCV7 or of PSV23, 3 years or more after an initial vaccination with PSV23. In this randomised, single-centre study, antibody titres were monitored at baseline, at 1 and 6 months after revaccination in 21 children with anatomic or functional asplenia. Response was considered as positive when there was a four-fold increase in antibody titres from baseline. The most frequently reported adverse events were local reactions in 7/11 of PCV7 subjects and in 5/8 of PSV23 subjects, and general reactions (loss of appetite, sleepiness) in 5/11 of PCV7 subjects and in 1/8 of PSV23 subjects; without any serious adverse events. One child in the PCV7 group had increased temperature (38.4 degrees C). At least half of the PCV7 children responded to four or five serotypes, while more than half of the PSV23 subjects responded to less than 3 serotypes (p=0.285). After 1 month, the immune response for serotype 23F was significantly greater after PCV7 vaccination than after PSV23 vaccination (p=0.036). PCV7 revaccination is safe and immunogenic in asplenic children previously vaccinated with PSV23, and could provide appropriate booster response in this high-risk population. The clinical repercussion on invasive pneumococcal diseases remains to be demonstrated.

Impaired anti-pneumococcal polysaccharide antibody production and invasive pneumococcal infection following heart transplantation

An increased risk of invasive pneumococcal infection has been described among adult heart transplant (HT) recipients. Vaccination has been recommended before HT but the appropriate time for revaccination is not known. In a preliminary analysis of a prospective study involving a cohort of 32 HT recipients receiving daclizumab and triple immunosuppresion therapy, a progressive decline in pneumococcal polysaccharide antibody (anti-PPS) levels was observed during the first year after HT. One of the patients who was found to have a decrease in the levels of anti-PPS developed severe pneumococcal meningitis 20 months after HT. Before HT he had received non-conjugated 23-valent pneumococcal vaccine and showed a normal post-immunization anti-PPS production. The data suggest that long-term immunologic monitoring might be useful to recognize impairment of antibody responses under immunosuppressive therapy in HT.

Invasive Pneumococcal Infections in Adult Lung Transplant Recipients

An increased risk of invasive pneumococcal infection (IPI) has been described among kidney or heart transplant recipients, but the epidemiology of IPI among lung transplant recipients has not been previously reported. We undertook a single center, retrospective cohort study to define the incidence, timing, clinical, and microbiologic features of IPI in lung transplant patients. Fourteen out of 220 recipients (6.4%) developed IPI at a median of 1.3 years after transplantation (incidence rate: 22.7 cases per 1000 person-years). All patients were receiving trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis at the time of diagnosis, and 10 (71%) had TMP-SMX-resistant isolates. All isolates were from the 23 valent polysaccharide vaccine-associated serogroups. The high incidence of IPI in lung transplant recipients is similar to that reported in kidney and heart recipients. Alternative prevention strategies, including use of the conjugated pneumococcal vaccine, should be explored in future studies.

Decreased serum opsonic activity against Streptococcus pneumoniae in human immunodeficiency virus-infected Ugandan adults.

Type-specific immunoglobulin G (IgG) to pneumococcal capsular polysaccharide (CPS) and opsonic activity against Streptococcus pneumoniae were evaluated in serum samples from 36 Ugandan adults with community-acquired pneumonia and 58 asymptomatic Ugandan adults with or without human immunodeficiency virus type 1 (HIV-1) infection. The levels of serum IgG to CPS were significantly higher in HIV-1-infected subjects than in HIV-uninfected subjects. Serum samples from HIV-1-infected subjects that had lower IgG titers demonstrated higher opsonic activity against type 3 (titers of 7) and type 9 (titers of 7-11) pneumococcal strains. Plasma HIV-1 load also correlated inversely with serum opsonic activity against these strains, and peripheral blood CD4+ lymphocyte numbers also tended to correlate with serum opsonic activity in asymptomatic HIV-1-infected adults. Our findings suggest that the opsonic activity of type-specific IgG is impaired in the serum of HIV-1-infected African adults, which may expose them to a serious risk of invasive pneumococcal infections.

Pneumococcal disease in the elderly: what is preventing vaccine efficacy?

The effective prevention of Streptococcus pneumoniae infection has a renewed priority in an era in which the emergence of antibacterial-resistant strains has the potential to further compromise efforts to reduce early mortality from invasive pneumococcal infection. Although the 23-valent pneumococcal polysaccharide (PPS) vaccine was approved in the US to prevent respiratory and invasive infection in the elderly and other high-risk populations, the protective efficacy of this vaccine for the growing population of adults aged >65 years remains controversial. The apparent effectiveness of pneumococcal immunisation in clinical studies of elderly adults has varied depending upon whether a reduction in pneumococcal colonisation, pneumonia, bacteraemia or death was used as an outcome. Clinical studies of vaccine efficacy to date suggest that the current pneumococcal vaccine is 56 to 81% effective at preventing invasive pneumococcal infection, and may have additive benefit to influenza vaccine in preventing community-acquired pneumonia, particularly in elderly adults with an increased risk of serious pneumonia requiring hospitalisation. Possible reasons for incomplete protection from pneumococcal infection after immunisation include infection with non-vaccine serotypes, inadequate or ineffective antibody responses, waning of antibody responses, or compromised nonhumoral host defences. Further studies are needed to determine whether: (i) elderly adults who respond poorly to the 23-valent pneumococcal vaccine can be identified prior to immunisation and targeted for study with improved pneumococcal vaccines; (ii) specific nutrient deficiencies can be identified and corrected to improve the immune responsiveness of elderly adults to the PPS vaccine; (iii) newer protein-conjugate or DNA pneumococcal vaccines may be more uniformly immunogenic for elderly adults; and (iv) whether smoking cessation reduces the risk of invasive pneumococcal infection in elderly adults.

The epidemiology of pneumococcal infection in children in the developing world.

Pneumonia causes about three million deaths a year in young children, nearly all of which are in developing countries. Streptococcus pneumoniae (the pneumococcus) is the most important bacterial cause of pneumonia in young children and so is likely to be responsible for a high proportion of these deaths. The pneumococcus is also responsible for a substantial proportion of the 100,000-500,000 deaths that occur from meningitis in children each year. The incidence of invasive pneumococcal disease in children in the developing world is several times higher than in industrialized countries. This discrepancy may, in part, be due to socio-economic differences but genetic factors may also play a role. Children with sickle cell disease have a substantially increased risk of invasive pneumococcal infection and a search is being made for other possible genetic risk factors. Infection with human immunodeficiency virus (HIV) also predisposes to invasive pneumococcal disease and so the incidence of this disease in young children is expected to rise as increasing numbers of African and Asian children are born with a perinatally acquired HIV infection. Until recently, pneumococcal infections could be treated effectively with penicillin, a cheap and safe antibiotic. However, pneumococci that are resistant to penicillin are becoming prevalent in many countries, necessitating a change to more costly antibiotics which may be beyond the reach of the health services of poor, developing countries. The spread of antibiotic resistance has provided an added stimulus to the development of vaccines that might be able to prevent pneumococcal disease in infants. Recently developed polysaccharide-protein conjugate vaccines show promise and are now undergoing field trials. How deployment of these vaccines will influence the balance between invasive pneumococcal infections and asymptomatic nasopharyngeal carriage of pneumococci is uncertain.

Pneumococcal Colonization and Antibiotic Resistance

Patients with HIV infection have about a 100-fold increased risk of invasive pneumococcal infection. Because the development of clinical disease depends in part on the frequency of carriage of invasive serotypes, these Houston researchers determined pneumococcal colonization rates of adults with HIV at a variety of different CD4-cell counts and compared this rate with noninfected controls. Researchers recruited 103 HIV-infected patients and …

Pneumococcal bacteremia in Monroe County, New York.

Knowledge of the epidemiology of pneumococcal disease is critical for public health planning, evaluation of preventive strategies, and development of immunization recommendations. We studied the incidence and case-fatality rates of pneumococcal bacteremia as a proxy for pneumococcal disease in Monroe County, New York, from 1985 through 1989 by reviewing the laboratory and clinical care records of all cases occurring among residents. There were 671 cases identified, for an overall yearly rate of 18.8 per 100,000. The rates were highest in the very young, in the very old, and in non-White populations. Age-specific rates were consistently higher in Blacks than in Whites. Predisposing medical conditions were present in 61% of cases. Case-fatality rates were 15% overall, 27% in those with predisposing medical conditions, and approximately 30% in Blacks older than 55 years and Whites older than 65 years. This study documents the incidence of and mortality from pneumococcal bacteremia. It supports previous observations that Black populations have an increased risk of invasive pneumococcal infection and suggests that immunization should be considered for Blacks older than 55 years.