High Risk Of Pneumococcal Infections Research Articles

Pneumococcal carriage, serotype distribution, and antimicrobial susceptibility in Papua New Guinean children vaccinated with PCV10 or PCV13 in a head-to-head trial

BackgroundChildren in Papua New Guinea (PNG) are at high risk of pneumococcal infections. We investigated pneumococcal carriage rates, serotype distribution, and antimicrobial susceptibility in PNG children after vaccination with 10-valent or 13-valent pneumococcal conjugate vaccines (PCV10; PCV13). MethodsInfants (N = 262) were randomized to receive 3 doses of PCV10 or PCV13 at 1-2-3 months of age, followed by pneumococcal polysaccharide vaccination (PPV) or no PPV at 9 months of age. Nasopharyngeal swabs (NPS) collected at ages 1, 4, 9, 10, 23 and 24 months were cultured using standard bacteriological procedures. Morphologically distinct Streptococcus pneumoniae colonies were serotyped by the Quellung reaction. Antimicrobial susceptibility was determined by Kirby-Bauer disc diffusion and minimum inhibitory concentration (MIC). ResultsS. pneumoniae was isolated from 883/1063 NPS collected at 1–23 months of age, including 820 serotypeable (64 different serotypes) and 144 non-serotypeable isolates. At age 23 months, 93.6% (95%CI 86.6–97.6%) of PCV10 recipients and 88.6% (95%CI 80.1–94.4%) of PCV13 recipients were pneumococcal carriers, with higher carriage of PCV10 serotypes by PCV10 recipients (19.8%, 95%CI 12.2–29.5) than PCV13 recipients (9.3%, 95%CI 4.1–17.3) (p = 0.049). There were no other statistically significant differences between PCV10 and PCV13 recipients and children receiving PPV or no PPV. Nearly half (45.6%) of carried pneumococci were non-susceptible to penicillin based on the meningitis breakpoint (MIC ≥ 0.12 µg/mL), but resistance was rare (1.1%) using the non-meningitis cut-off (MIC ≥ 8 µg/mL). Non-susceptibility to trimethoprim-sulfamethoxazole (SXT) was common: 23.2% of isolates showed intermediate resistance (MIC 1/19–2/38 µg/mL) and 16.9% full resistance (MIC ≥ 4/76 µg/mL). PCV serotypes 14 and 19A were commonly non-susceptible to both penicillin (14, 97%; 19A, 70%) and SXT (14, 97%; 19A, 87%). ConclusionEven after PCV10 or PCV13 vaccination, children living in a high-risk setting such as PNG continue to experience high levels of pneumococcal colonization, including carriage of highly antimicrobial-resistant PCV serotypes.The study is registered with ClinicalTrials.gov (CTN NCT01619462).

A phase 3 randomized, double-blind, comparator-controlled study to evaluate safety, tolerability and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine, in allogeneic hematopoietic cell transplant recipients (PNEU-STEM).

Individuals who receive allogeneic hematopoietic cell transplant (allo-HCT) are immunocompromised and at high risk for pneumococcal infections, especially in the months following transplant. This study evaluated the safety and immunogenicity of V114 (VAXNEUVANCE™), a 15-valent pneumococcal conjugate vaccine (PCV), when given to allo-HCT recipients. Participants received 3 doses of V114 or PCV13 in one-month intervals starting 3-6 months after allo-HCT. Twelve months after HCT, participants received either PNEUMOVAXTM 23 or a fourth dose of PCV (if they experienced chronic graft versus host disease). Safety was evaluated as the proportion of participants with adverse events (AEs). Immunogenicity was evaluated by measuring serotype-specific immunoglobulin G (IgG) geometric mean concentrations (GMCs) and opsonophagocytic activity (OPA) geometric mean titers (GMTs) for all V114 serotypes in each vaccination group. A total of 274 participants were enrolled and vaccinated in the study. The proportions of participants with AEs and serious AEs were generally comparable between intervention groups, and the majority of AEs in both groups were of short duration and mild-to-moderate intensity. For both IgG GMCs and OPA GMTs, V114 was generally comparable to PCV13 for the 13 shared serotypes, and higher for serotypes 22F and 33F at Day 90. V114 was well tolerated in allo-HCT recipients with a generally comparable safety profile to PCV13. V114 induced comparable immune responses to PCV13 for the 13 shared serotypes, and higher for V114 serotypes 22F and 33F. Study results support use of V114 in allo-HCT recipients.

Opsonophagocytic activity against Streptococcus pneumoniae in Indigenous and non-Indigenous patients with severe chronic kidney disease immunized with 13-valent pneumococcal conjugate vaccine

Adults with chronic kidney disease (CKD) are at high risk of pneumococcal infections and recommended to receive pneumococcal immunization. Some studies suggest that previous immunization with 23-valent pneumococcal polysaccharide vaccine (PPV23) may decrease the immunogenicity of 13-valent pneumococcal conjugate vaccine (PCV13). Via quantitation of serum IgG, IgM, and IgA specific to 7 pneumococcal serotypes (3, 6B, 9V, 14, 19A, 19F, 23F), we recently found that the response to PCV13 in previously PPV23 immunized patients with severe CKD was inferior compared to PPV23 naïve patients. As a follow-up of the previous study, we assessed the titers of opsonizing antibodies specific to 13 vaccine serotypes in sera collected as per the original clinical trial protocol.Opsonophagocytic activity (OPA) titers were determined in 57 previously PPV23-immunized (Group 1) and 72 PPV23-naïve (Group 2) patients pre- and post-PCV13 immunization (days 28 and 365).Pre-immunization, the geometrical mean titers (GMT) for 3/13 serotype-specific antibodies were significantly higher in Group 1 than in Group 2. PCV13 induced a significant GMT rise in both groups; an increase in 5/13 serotype-specific GMTs in Group 1 and 12/13 GMTs in Group 2 was present at one year post-immunization. Fold increase in GMTs by day 28 ranged between 2.4 (serotype 1) and 24.6 (serotype 6A) in Group 1, and between 4.3 (serotype 3) and 67.0 (serotype 6A) in Group 2. The fold increase was significantly larger in Group 2 than in Group 1 for serotypes 1, 4, 7F, and 18C. Patients of Indigenous ethnic background had significantly higher GMT for serotypes 6B and 23F at baseline, and for serotypes 5, 6B, 14, 18C, 19A, 19F, and 23F at Day 28 post-immunization, compared to the non-Indigenous counterpart.Conclusions: Patients with severe CKD developed functionally active pneumococcal antibodies post-PCV13 immunization. Previously administered PPV23 had a negative impact on several serotype-specific OPA responses to PCV13 that lasted for at least one year post-immunization.ClinicalTrials.gov ID: NCT02370069.

Immunogenicity and safety of the 13-valent pneumococcal conjugate vaccine in 23-valent pneumococcal polysaccharide vaccine-naïve and previously immunized adult patients with severe chronic kidney disease

Individuals with chronic kidney disease (CKD) are at high risk of pneumococcal infections and recommended to receive the 23-valent pneumococcal polysaccharide vaccine (PPV23). Although the 13-valent pneumococcal conjugate vaccine (PCV13) has been found to have higher immunogenicity compared to PPV23 in adults with some immunocompromising conditions, previous PPV23 immunization may decrease the immunogenicity of PCV13. We assessed immunogenicity and safety of PCV13 in 74 PPV23-naïve and 58 previously PPV23-immunized (>1 year ago) patients with severe (stage 4–5) CKD. Serum IgG, IgM, and IgA specific to seven serotypes, i.e. 3, 6B, 9V, 14, 19A, 19F, 23F were quantified pre- and 4 weeks and one year post-immunization.Baseline concentrations for most serotype-specific IgG and IgM, and serotype 3-specific IgA were higher in previously PPV23-immunized compared to PPV23-naïve patients. Immunization with PCV13 significantly increased almost all serotype-specific IgG, all IgA and some IgM; an increase in some serotype-specific IgG and IgM lasted for one year. Fold increases in antibody concentrations and the proportion of individuals with >2-fold increase post-immunization were generally larger in PPV23-naïve than previously immunized patients for most serotype-specific IgG and some IgA. The data show that in patients with CKD who received previous PPV23 immunization over one year ago, the antibody response to PCV13 was inferior compared to pneumococcal vaccine naïve study participants. In both groups, the lowest response to PCV13 was found for serotype 3. Patients of Indigenous ethnic background demonstrated a superior immune response to PCV13 compared to the non-Indigenous counterpart that could partially be related to Indigenous study participants' younger age. Although we found that previous PPV23 immunization could contribute to the more frequent occurrence of systemic adverse events post PCV13 immunization, those did not exceed the mild to moderate range.

An observational study of the reactogenicity and immunogenicity of 13-valent pneumococcal conjugate vaccine in women of childbearing age in Papua New Guinea

BackgroundMaternal immunization with pneumococcal conjugate vaccine (PCV) may protect young infants in high-risk settings against the high risk of pneumococcal infections in early life. The aim of this study was to determine the safety and immunogenicity of 13-valent PCV (PCV13) in healthy women of childbearing age in PNG.MethodsAs part of this observational study, 50 non-pregnant women of childbearing age (18-45 yrs. old) living in the highlands of PNG were vaccinated with a single dose of PCV13. Local and systemic reactogenicity were assessed 24–48 h after vaccination. Venous blood samples were collected before and 1 month after vaccination to measure PCV13 serotype-specific IgG antibody concentrations.ResultsNo severe adverse effects were reported during the 1-month follow-up period. IgG antibody concentrations significantly increased after vaccination for all PCV13 serotypes. One month after vaccination IgG antibody levels ≥2.5 μg/mL were reached in at least 75% of women for all PCV13 serotypes, except serotype 3, and ≥ 5 μg/mL in at least 75% of women for 7 serotypes (serotypes 6B, 9 V, 14, 18C, 19A, 19F and 23F).ConclusionPCV13 is safe and immunogenic in women of childbearing age living in a high-risk setting in PNG. This supports the implementation of studies to investigate the safety and immunogenicity of maternal PCV vaccination in high-risk settings as a strategy to protect infants in these settings against the high risk of pneumococcal infections in early life.Trial registrationNCT04183322. Registered 3 December 2019 - Retrospectively registered

Experience with 13-valent conjugated pneumococcal vaccine in HIV-infected patients

Evaluate the effect of PCV13 vaccination on the composition of the microflora of the upper respiratory tract and the immune system in HIV-infected patients. 100 patients with HIV-infection were included in the study. The patients underwent immunological examination and the collection of biomaterial from the posterior pharyngeal wall for microbiological examination. After obtaining the results of the examinations, PCV13 was intramuscularly administered. 7 days after the introduction of the vaccine, an assessment of adverse events was carried out, after 3 months, microbiological and immunological examinations were repeated. Immediately after the administration of PCV13, 5% of patients felt pain during the administration. Local reactions were reported in 6 patients. One participant showed a rise in temperature to 38.3C over 2 days. Before vaccination, 16 strains of S. pneumoniae were seeded in patients. 3 months after the administration of PCV13, pneumococcus was isolated in 8 patients. 3 months after immunization, the median level of populations and subpopulations of lymphocytes became higher than the pre-vaccination. Our results show high risk of pneumococcal infections in HIV-positive patients. A tendency towards a decrease in the level of S. pneumoniae carriage was revealed 3 months after the administration of PCV13. The high level of enterobacteria carriage in HIV-positive patients is noteworthy. There is a pronounced positive effect from the use of PCV13 in HIV-positive patients on cellular factors of the immune system. The use of PCV13 is a safe and effective method for the prevention of S. pneumoniae infections.

Immunogenicity and Immune Memory after a Pneumococcal Polysaccharide Vaccine Booster in a High-Risk Population Primed with 10-Valent or 13-Valent Pneumococcal Conjugate Vaccine: A Randomized Controlled Trial in Papua New Guinean Children

We investigated the immunogenicity, seroprotection rates and persistence of immune memory in young children at high risk of pneumococcal disease in Papua New Guinea (PNG). Children were primed with 10-valent (PCV10) or 13-valent pneumococcal conjugate vaccines (PCV13) at 1, 2 and 3 months of age and randomized at 9 months to receive PPV (PCV10/PPV-vaccinated, n = 51; PCV13/PPV-vaccinated, n = 52) or no PPV (PCV10/PPV-naive, n = 57; PCV13/PPV-naive, n = 48). All children received a micro-dose of PPV at 23 months of age to study the capacity to respond to a pneumococcal challenge. PPV vaccination resulted in significantly increased IgG responses (1.4 to 10.5-fold change) at 10 months of age for all PPV-serotypes tested. Both PPV-vaccinated and PPV-naive children responded to the 23-month challenge and post-challenge seroprotection rates (IgG ≥ 0.35 μg/mL) were similar in the two groups (80–100% for 12 of 14 tested vaccine serotypes). These findings show that PPV is immunogenic in 9-month-old children at high risk of pneumococcal infections and does not affect the capacity to produce protective immune responses. Priming with currently available PCVs followed by a PPV booster in later infancy could offer improved protection to young children at high risk of severe pneumococcal infections caused by a broad range of serotypes.

Immunogenicity, safety and tolerability of anti-pneumococcal vaccination in systemic lupus erythematosus patients: An evidence-informed and PRISMA compliant systematic review and meta-analysis.

The immunological perturbations associated with systemic lupus erythematosus (SLE) put many patients at a higher risk of infections, including pneumococcal pneumonia. However, the uptake and utility of anti-pneumococcal vaccines in SLE patient is both controversial and not completely agreed upon. Indeed, several epidemiological studies of anti-pneumococcal vaccine safety and efficacy in SLE have reported short-term immunogenicity with elevated anti-pneumococcal antibody titres but inconsistent long-term findings, with some studies finding poor responses, mainly for long-term immune protection. Moreover, the safety and efficacy of the pneumococcal vaccine in SLE patients remains controversial due to the different types of anti-pneumococcal vaccines, and the heterogeneity of SLE patients. Several reviews addressing anti-pneumococcal vaccination in SLE patients exist, however, to the best of our knowledge, the present is the first systematic review and meta-analysis. To better understand the efficacy and safety of pneumococcal vaccination in SLE, a comprehensive literature search was performed identifying 18 studies, which have been included in the present systematic review and meta-analysis. All studies were designed as longitudinal investigations, 2, in particular, were of high quality, being randomized, double-blind trials (RCTs). Four studies had control groups. Total sample size included 601 participants. Vaccine immunogenicity in terms of subjects with protective antibody titers ranged from 36% to 97.6%. According to our systematic review and metanalysis, high erythrocyte sedimentation rate (ESR), older age, earlier SLE onset, high disease activity, and immunosuppressive therapy were predictors of poor immunogenicity, although belimumab was found to have no significant impact. With regard to safety, no serious adverse events were found, with up to one third of cases reporting mild/low-grade complaints. In conclusion, due to the high risk of pneumococcal infection in SLE patients and given the safety and, at least partial, effectiveness, according to our systematic review and meta-analysis, in such patients, preventive strategies mainly by immunization, are required in all age groups and, in those needing immunosuppressive therapy, immunization should be given prior the initiation of the treatment. PROSPERO registration code CRD42018103605.

Immunogenicity and persistence of the 13-valent Pneumococcal Conjugate Vaccine (PCV13) in patients with untreated Smoldering Multiple Myeloma (SMM): A pilot study

Smoldering multiple myeloma (SMM) is an asymptomatic clonal plasma cell disorder that frequently progress to multiple myeloma (MM), a disease at high risk of pneumococcal infections. Moreover, if the polysaccharide vaccine is poorly immunogenic in MM, the 13-valent conjugated vaccine has never been tested in clonal plasma cell disorders. We evaluated its immunogenicity for 7 serotypes in 20 patients ≥ 50 years of age with smoldering multiple myeloma (SMM) pre and post routine-vaccination with PCV13.Concentrations of IgG specific for 7 serotypes were measured at baseline, 1, 6, and 12 months after vaccination by standardized ELISA and an Opsonophagocytic Assay (OPA). The primary endpoint was the proportion of patients responding to at least 5 of the 7 serotypes by ELISA at one month.At 1 month post vaccination, 12 patients (60%) were responders by ELISA, among whom 8 were also responders by OPA. At 6 months, 6 (30% of total) of the 12 responders had persistent immunity, and only 2 (10% of total) at 12 months. These results suggested a partial response in this population and a rapid decrease in antibody levels in the first months of vaccination.Although one injection of the 13-valent pneumococcal conjugate vaccine is immunogenic in some patients with SMM, the response is transient. Repeated injections are likely to be needed for effective and sustained protection.

The spleen

The spleen

An experience of vaccination against pneumococcal infection of adults at Krasnoyarsk krai

The aim of the study was to investigate efficacy of specific prevention of pneumococcal infection in high-risk group patients living at Krasnoyarsk krai. Methods. The study involved 12,080 patients with a high risk of pneumococcal infection including patients with chronic lung diseases, chronic heart failure (CHF) and diabetes mellitus. A special questionnaire was developed which included medical history for the previous 1 year and for 1 year after the vaccination. Results. CHF was diagnosed in 41.08% of patients, diabetes was diagnosed in 28.44%, chronic lung diseases were diagnosed in 30.07%; 2.4% of patients had pneumonia. PCV13 vaccine (Prevenar 13) was used in 9,986 patients (82.67%) including 5,070 patients (41.97%) vaccinated against flu and pneumococcus simultaneously. PPV23 (Pneumo-23) vaccine was used in 1,967 patients (16.28%) including 1,181 patients (9.83%) vaccinated against flu and pneumococcus simultaneously. Due to the broad-scale vaccination against pneumococcal infection, exacerbation rate reduced trice, number of hospitalisations related to exacerbations reduced by 11.5 times, morbidity of pneumonia reduced by 4.8 times, morbidity of acute respiratory infections and flu reduced by 6.6 times. Conclusion. The results confirmed high efficacy and safety of 13-valent conjugate pneumococcal vaccine and 23-valent polysaccharide pneumococcal vaccine. The vaccination allowed reducing morbidity of respiratory infection and decrease number of hospitalisations due to exacerbations of chronic diseases.

Anti-epidemic activities to prevent pneumococcal infections in flooded areas of the Amur region

The aim of this study was to analyze CAP epidemiology and morbidity in the Amur region, to evaluate anti-epidemic measures for prevention of pneumococcal infections in flooded areas and medical and socioeconomic benefits of vaccination of children with risk factors for pneumococcal disease. Material and methods. Common morbidity of pneumonia was analyzed in the Amur region. To evaluate clinical and epidemiological efficacy of pneumococcal vaccination with PCV13 in 2014–2017, 5,000 children aged 2 to 5 yrs with high risk of pneumococcal infection were involved into a special follow-up programme. Clinical, epidemiological, social, hygienic, economic and statistical analyses were used. Results. The total incidence of pneumonia in population of the Amur region reached the peak value (897.3 per 100,000) in 2009; this was associated with influenza pandemic. CAP incidence decreased by 43.8% in 2010–2014. Morbidity of CAP had certain age-related and seasonal differences and was closely related to morbidity of acute respiratory viral infection. Results of microbiological monitoring of CAP pathogens in the Amur region were also discussed. Morbidity of pneumonia and acute respiratory infections decreased in 2014 in 69.4% of children vaccinated with PCV13. Morbidity of CAP reduced by 2,014 cases in 2014 that prevented economic loss of 94 billion RUB. Conclusion. Clinical and economic monitoring of CAP and pneumococcal vaccination with PCV13 in the Amur region have significant medical and socioeconomic efficacy.

Global Pneumococcal Disease and Policies for Control

Global Pneumococcal Disease and Policies for Control

The Spectrum of Invasive Pneumococcal Disease in Adults in the XXI Century

Streptococcus pneumoniae is the most common cause of community-acquired pneumonia and bacterial meningitis in adults. Despite the availability of potent antibiotics and the development of different pneumococcal vaccines, the burden of pneumococcal infections in terms of morbidity, hospitalizations, mortality, and healthcare costs continues to be tremendous. The different pneumococcal serotypes play an important role in some aspects of pneumococcal epidemiology. The introduction of the 7-valent conjugate vaccine among children led to important changes not only in the epidemiology but also in the clinical outcomes and mortality of invasive pneumococcal disease in adults. Moreover, with the widespread use of immunosuppressive and immunomodulating therapies for different medical conditions, we may expect an increase in the number of patients at a high risk of pneumococcal infections in the following years. The influence of immunosuppression as a risk factor for invasive pneumococcal disease, the changes in the dynamics of pneumococcal serotypes, the influence of pneumococcal serotypes on the clinical presentation of pneumococcal invasive disease, and the role of pneumococcal vaccines are some of the important issues that are discussed in this review.

Technical Report: Prevention of Pneumococcal Infections, Including the Use of Pneumococcal Conjugate and Polysaccharide Vaccines and Antibiotic Prophylaxis

Pneumococcal infections are the most common invasive bacterial infections in children in the United States. The incidence of invasive pneumococcal infections peaks in children younger than 2 years, reaching rates of 228/100,000 in children 6 to 12 months old. Children with functional or anatomic asplenia (including sickle cell disease [SCD]) and children with human immunodeficiency virus infection have pneumococcal infection rates 20- to 100-fold higher than those of healthy children during the first 5 years of life. Others at high risk of pneumococcal infections include children with congenital immunodeficiency; chronic cardiopulmonary disease; children receiving immunosuppressive chemotherapy; children with immunosuppressive neoplastic diseases; children with chronic renal insufficiency, including nephrotic syndrome; children with diabetes; and children with cerebrospinal fluid leaks. Children of Native American (American Indian and Alaska Native) or African American descent also have higher rates of invasive pneumococcal disease. Outbreaks of pneumococcal infection have occurred with increased frequency in children attending out-of-home care. Among these children, nasopharyngeal colonization rates of 60% have been observed, along with pneumococci resistant to multiple antibiotics. The administration of antibiotics to children involved in outbreaks of pneumococcal disease has had an inconsistent effect on nasopharyngeal carriage. In contrast, continuous penicillin prophylaxis in children younger than 5 years with SCD has been successful in reducing rates of pneumococcal disease by 84%. Pneumococcal polysaccharide vaccines have been recommended since 1985 for children older than 2 years who are at high risk of invasive disease, but these vaccines were not recommended for younger children and infants because of poor antibody response before 2 years of age. In contrast, pneumococcal conjugate vaccines (Prevnar) induce proposed protective antibody responses (>.15 microg/mL) in >90% of infants after 3 doses given at 2, 4, and 6 months of age. After priming doses, significant booster responses (ie, immunologic memory) are apparent when additional doses are given at 12 to 15 months of age. In efficacy trials, infant immunization with Prevnar decreased invasive infections by >93% and consolidative pneumonia by 73%, and it was associated with a 7% decrease in otitis media and a 20% decrease in tympanostomy tube placement. Adverse events after the administration of Prevnar have been limited to areas of local swelling or erythema of 1 to 2 cm and some increase in the incidence of postimmunization fever when it is given with other childhood vaccines. Based on data in phase 3 efficacy and safety trials, the US Food and Drug Administration has provided an indication for the use of Prevnar in children younger than 24 months.

Prevention of pneumococcal infection by immunization with capsular polysaccharides of Streptococcus pneumoniae: current status of polyvalent vaccines.

Because of the continuing morbidity and mortality resulting from pneumococcal infection, a program was instituted to redevelop polyvalent vaccines consisting of capsular polysaccharides of Streptococcus pneumoniae. Vaccines containing 50 microgram each of the capsular polysaccharides of as many as 13 pneumococcal types have been shown to be safe, antigenic, and 78.5% effective in the prevention of type-specific putative pneumococcal pneumonia and of type-specific pneumococcal bacteremia in adults. In a population in which pneumococcal pneumonia predominated, the total incidence of radiologically confirmed pneumonia, irrespective of cause, was reduced by 54.3% by use of a tridecavalent vaccine. The efficacy of vaccine in the prevention of infection during the first two years of life is under investigation. The vaccine is recommended for those at high risk of pneumococcal infection or of a fatal outcome from such illness.