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INTRODUCTION: In Argentina, vaccination with 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23; PCV13 → PPSV23) has been recommended for all adults aged ≥ 65 years and younger adults with chronic medical ("moderate-risk") or immunocompromising ("high-risk") conditions since 2017. With the approval of a 20-valent PCV (PCV20), we evaluated the cost-effectiveness of PCV20 versus current recommendations for moderate-/high-risk adults aged 18-64 years and all adults 65-99 years. METHODS: A probabilistic cohort model was used to project lifetime outcomes and costs associated with invasive pneumococcal disease (IPD) and all-cause non-bacteremic pneumonia (NBP), and the expected impact of vaccination. Clinical outcomes were projected annually based on Argentinean data. Economic costs were estimated based on cases and corresponding medical costs (adjusted to 2023 USD) and costs of vaccine and administration. Cost-effectiveness of PCV20 was evaluated versus the current strategy, PCV13 → PPSV23, and alternatively, versus sequentially administered 15-valent PCV and PPSV23 (PCV15 → PPSV23), and presented as cost per quality-adjusted life year gained; a healthcare system perspective was used. Costs and benefits were discounted at 3%/year. RESULTS: PCV20 in lieu of PCV13 → PPSV23 among moderate-/high-risk adults aged 18-64 years and all adults 65-99 years (N = 13.4M) prevented 3838 IPD, 4377 inpatient NBP, and 6003 outpatient NBP cases, and 1865 disease-related deaths; relative to PCV15 → PPSV23 the corresponding reductions were 2775, 3285, 4518, and 1348. PCV20 was projected to be the dominant strategy versus PCV13 → PPSV23 and PCV15 → PPSV23 as overall costs were lower by $87.6M and $80.8M, respectively. In probabilistic sensitivity analyses, PCV20 was dominant (i.e., more effective, less costly) in 100% of 1000 simulations. CONCLUSIONS: Analyses suggest implementing a PCV20 vaccination program in moderate-/high-risk adults aged 18-64 years and all adults ≥ 65 years-in lieu of PCV13 → PPSV23-would yield substantial reductions in pneumococcal disease and would be cost saving to the Argentinean healthcare system.

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Pneumococcal pneumonia has a high disease burden in both children and adults. Older adults and those with certain underlying conditions are more susceptible to severe pneumococcal disease resulting in considerable economic burden on the healthcare system. In Argentina, vaccination with 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) a year later is recommended for all adults aged ≥ 65 years and adults aged 18­64 years with underlying risk conditions. Despite vaccination efforts, prevalence of pneumococcal disease remains high. Two higher-valent PCVs­15-valent PCV (PCV15) and 20-valent PCV (PCV20)­are available for use in adults with PCV20 offering additional serotype coverage. This study assessed the cost-effectiveness of replacing current (PCV13 → PPSV23) and alternative (PCV15 → PPSV23) vaccination strategies with PCV20 alone. The use of PCV20 was evaluated among Argentinean adults aged 18­64 years with underlying risk conditions and all adults aged 65­99 years (N = 13 million). Over a lifetime time horizon, compared to PCV13 → PPSV23, PCV20 use would avert 14,218 cases and 1865 deaths, and increase quality-adjusted life years by 8655. Compared to PCV15 → PPSV23, PCV20 reduced cases and deaths by 10,578 and 1348, respectively, and increased quality-adjusted life years by 6341. In both comparisons, PCV20 use was cost saving with $87.6 million and $80.8 million lower costs compared to PCV13 → PPSV23 and PCV15 → PPSV23, respectively. Results of the cost-effectiveness analyses suggest that the use of PCV20 is a cost-saving strategy, reducing overall costs to the healthcare system and improving public health.

RESUMEN

Streptococcus pneumoniae causes serious illnesses, such as pneumonia, bacteremia, and meningitis, mainly in immunocompromised individuals and those of extreme ages. Currently, pneumococcal conjugate vaccines (PCVs) are the best allies against pneumococcal diseases. In Brazil, the 10-valent and 13-valent PCVs have been available since 2010, but the threat of antimicrobial resistance persists and has been changing over time. We conducted a systematic review of the literature with works published since 2000, generating a parallel between susceptibility data on isolates recovered from colonization and invasive diseases before and after the implementation of PCVs for routine childhood use in Brazil. This systematic review was based on the Cochrane Handbook for Systematic Reviews of Interventions and Preferred Reporting Items for Systematic Literature Reviews and Meta-Analyses (PRISMA) guidelines. Despite the inclusion of PCVs at a large scale in the national territory, high frequencies of non-susceptibility to important drugs used in pneumococcal diseases are still observed, especially penicillin, as well as increasing resistance to macrolides. However, there are still drugs for which pneumococci have a comprehensive sensitivity profile.

RESUMEN

BACKGROUND: In 2010, Brazil introduced the ten-valent pneumococcal conjugate vaccine (PCV10) in the national infant immunization program. Limited data on the long-term impact of PCV10 are available from lower-middle-income settings. We examined invasive pneumococcal disease (IPD) in Salvador, Bahia, over 11 years. METHODS: Prospective laboratory-based surveillance for IPD was carried out in 9 hospitals in the metropolitan region of Salvador from 2008 to 2018. IPD was defined as Streptococcus pneumoniae cultured from a normally sterile site. Serotype was determined by multiplex polymerase chain reaction and/or Quellung reaction. Incidence rates per 100,000 inhabitants were calculated for overall, vaccine-type, and non-vaccine-type IPD using census data as the denominator. Incidence rate ratios (IRRs) were calculated to compare rates during the early (2010-2012), intermediate (2013-2015), and late (2016-2018) post-PCV10 periods in comparison to the pre-PCV10 period (2008-2009). RESULTS: Pre-PCV10, overall IPD incidence among all ages was 2.48/100,000. After PCV10 introduction, incidence initially increased (early post-PCV10 IRR 3.80, 95% CI 1.18-1.99) and then declined to 0.38/100,000 late post-PCV10 (IRR 0.15; 95% CI 0.09-0.26). The greatest reductions in the late post-PCV10 period were observed in children aged ≤2 years, with no cases (IRR not calculated) and those ≥60 years (IRR 0.11, 95% CI 0.03-0.48). Late post-PCV10, significant reductions were observed for both PCV10 serotypes (IRR 0.02; 95% CI 0.0-0.15) and non-PCV10 serotypes (IRR 0.27; 95%CI 0.14-0.53). Non-PCV10 serotypes 15B, 12F, 3, 17F, and 19A became predominant late post-PCV10 without a significant increase in serotype-specific IPD incidence compared to pre-PCV10. CONCLUSION: Significant declines in IPD, including among adults not eligible for vaccination, suggest direct and indirect protection up to nine years after PCV10 introduction, without evidence of significant replacement disease. Continued surveillance is needed to monitor changes in non-vaccine serotypes and inform decisions about introducing higher valent PCVs.

Asunto(s)

Infecciones Neumocócicas , Lactante , Niño , Adulto , Humanos , Brasil/epidemiología , Estudios Prospectivos , Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas , Serogrupo , Incidencia , Vacunas Conjugadas

RESUMEN

Worldwide, conjugated pneumococcal vaccines (PCVs) have proven effective against invasive pneumococcal disease, but non-invasive pneumonia is a major cause of mortality in young children and serotypes vary geographically, affecting effectiveness. We analyze nationwide death certificate data between 2003-2017 to assess the impact of PCVs on pneumonia mortality among young children from Peru. We report descriptive statistics and perform timeseries analysis on annual mortality rates (AMRs) and monthly frequencies of pneumonia deaths. Children under 5 years of age accounted for 6.2% (n = 10,408) of all pneumonia deaths (N = 166,844), and 32.3% (n = 3363) were children between 1-4 years of age, of which 95.1% did not report pneumonia etiology. Comparing periods before and after PCV introduction in 2009, mean AMRs dropped 13.5% and 26.0% for children between 1-4 years of age (toddlers/preschoolers), and children under 1 year of age (infants), respectively. A moderate correlation (Spearman's r = 0.546, p < 0.01) in the monthly frequency of pneumonia deaths was estimated between both age groups. Quadratic regression suggests a change in direction around 2005 (highest pneumonia mortality) for both age groups, but percentage change analysis identified an inflection point in 2013 for infants only, not for toddlers/preschoolers, suggesting that the impact of PCVs might be different for each age group.

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OBJECTIVE: To determinate the frequency of Streptococcus pneumoniae nasopharyngeal carriers, serotypes and antimicrobial resistance in healthy children in Lima, Peru, post-PCV13 introduction and to compare the results with a similar study conducted between 2006 and 2008 before PCV7 introduction (pre-PCV7). METHODS: A cross-sectional multicenter study was conducted between January 2018 and August 2019 in 1000 healthy children under two years of age. We use standard microbiological methods to determinate S. pneumoniae from nasopharyngeal swab, Kirby Bauer and minimum inhibitory concentration methods to determinate antimicrobial susceptibility and whole genomic sequencing to determinate pneumococcal serotypes. RESULTS: The pneumococcal carriage rate was 20.8 % vs. 31.1 % in pre-PCV7 (p < 0.001). The most frequent serotypes were 15C, 19A and 6C (12.4 %, 10.9 % and 10.9 % respectively). The carriage of PCV13 serotypes after PCV13 introduction decreased from 59.1 % (before PCV7 introduction) to 18.7 % (p < 0.001). Penicillin resistance was 75.5 %, TMP/SMX 75.5 % and azithromycin 50.0 %, using disk diffusion. Penicillin resistance rates using MIC breakpoint for meningitis (MIC ≥ 0.12) increased from 60.4 % to 74.5 % (p = 0.001). CONCLUSION: The introduction of PCV13 in the immunization program in Peru has decreased the pneumococcal nasopharyngeal carriage and the frequency of PCV13 serotypes; however, there has been an increase in non-PCV13 serotypes and antimicrobial resistance.

Asunto(s)

Antiinfecciosos , Infecciones Neumocócicas , Humanos , Niño , Lactante , Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/prevención & control , Serogrupo , Estudios Transversales , Perú/epidemiología , Portador Sano/microbiología , Streptococcus pneumoniae/genética , Nasofaringe/microbiología , Resistencia a las Penicilinas , Vacunas Neumococicas , Vacunas Conjugadas

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BACKGROUND: Chronic 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. METHODS: A 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 others RESULTS: 406 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. CONCLUSION: Vaccine 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.

Asunto(s)

Antiinfecciosos , Infecciones Neumocócicas , Niño , Adulto , Anciano , Humanos , Lactante , Adolescente , Preescolar , Serogrupo , Estudios Retrospectivos , Pacientes Internos , Brasil/epidemiología , Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/uso terapéutico , Hospitales de Enseñanza , Vacunas Conjugadas

RESUMEN

OBJECTIVE: A combination of 13-valent pneumococcal conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPSV23) is currently recommended for adults with systemic lupus erythematosus (SLE). However, data on the immunogenicity elicited by sequential pneumococcal vaccination in this patient population are scarce. In this study, we compared short-term antibody responses to both PCV13/PPSV23 (≥8-week interval) and PPSV23/PCV13 (≥12-month interval) vaccination strategies in pneumococcal vaccine-naive adults with SLE. METHODS: This longitudinal, open-label, quasi-randomized study was performed in a single-center cohort of adults (18 years or older) with SLE. In both vaccination groups, blood samples were collected immediately before administering the first dose of the pneumococcal vaccine (timepoint T0), 4-6 weeks after the priming dose (T1), and 4-6 weeks after the booster dose (T2). We focused on the 12 shared serotypes between PCV13 and PPSV23, and compared the following immunogenicity outcomes between the groups at T2: anti-pneumococcal antibody geometric mean concentration (ApAb GMC), fold increase in ApAb levels (FI-ApAb), overall seroprotection rate, and overall seroconversion rate. The protective level for each pneumococcal serotype was set at 1.3 µg/mL. We used the multi-analyte immunodetection method to determine serum levels of ApAbs. RESULTS: Thirty-four patients with SLE were screened between April 2019 and January 2020, and 16 of them (mean age: 39.4 years, 87.5% female, and 100% on immunosuppressants) had evaluable immunogenicity results at T2. The median time elapsed between the pneumococcal vaccinations was 56 days in the PCV13/PPSV23 group (n = 11 patients) and 16 months in the PPSV23/PCV13 group (n = 5 patients). Priming with PCV13 (PCV13/PPSV23 group), as opposed to PPSV23 (PPSV23/PCV13 group), yielded significantly better results regarding FI-ApAb, overall seroconversion rate, and overall seroprotection rate 4-6 weeks after each pneumococcal vaccination. A trend toward augmented ApAb GMC in the patients who received the PCV13/PPSV23 sequence was also observed. No relevant safety issues were identified with sequential pneumococcal vaccination. CONCLUSION: The PCV13-priming PPSV23-boost strategy in adults with SLE induced greater antibody responses for most immunogenicity outcomes than those elicited by the PPSV23/PCV13 strategy.

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Lupus Eritematoso Sistémico , Infecciones Neumocócicas , Adulto , Femenino , Humanos , Masculino , Anticuerpos Antibacterianos , Brasil , Estudios de Cohortes , Método Doble Ciego , Inmunogenicidad Vacunal , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas , Vacunación , Vacunas Conjugadas

RESUMEN

ABSTRACT Background: Chronic 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. Methods: A 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 others Results: 406 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. Conclusion: Vaccine 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.

RESUMEN

OBJECTIVES: Ecuador introduced the pneumococcal conjugate vaccine in 2010. A recent time series analysis has demonstrated the impact of 10-valent pneumococcal conjugate vaccine (PCV10) on hospitalized pneumococcal disease in children. We leveraged these estimates to calculate the return on investment (ROI) of PCV10 in Ecuador from 2010 to 2030 at the national and regional levels. METHODS: We used 2 approaches to estimate the economic benefits: (1) cost of illness, which includes treatment, transportation, and productivity loss averted, (2) and the value of statistical life, which reflects society's average willingness to pay to save one life. Costs of the immunization program include vaccine costs (doses, syringes, injection supplies) and immunization delivery costs (personnel, cold chain equipment and maintenance, transportation, distribution services, and other recurrent costs). We estimated the ROI by dividing the net benefits by costs. RESULTS: The ROI using the cost-of-illness approach was slightly negative in the introduction year. From 2011 to 2020, we estimated the ROI to be 0.45 (0.15-0.73). For the future decade, the ROI is estimated at 0.37 (-0.03 to 1.03). Using the value-of-statistical-life approach, the ROI was 1.46 (0.82-2.17) in the introduction year. In the first decade, the ROI was 1.01 (0.49-1.60); in the second decade, the ROI fell to 0.83 (0.23-1.78). CONCLUSIONS: The results of this study demonstrate the total economic benefits of PCV10 in Ecuador exceed immunization program costs after the introduction year. Estimates from this study will inform country policy makers and will contribute to efforts to mobilize resources for immunization.

Asunto(s)

Vacunas Neumococicas , Niño , Análisis Costo-Beneficio , Ecuador , Humanos , Vacunas Conjugadas/uso terapéutico

RESUMEN

Streptococcus pneumoniae upper respiratory infections and pneumonia are often treated with macrolides, but recently macrolide resistance is becoming an increasingly important problem. The 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in the National Immunization Program of Peru in 2015. This study aimed to evaluate the temporal evolution of macrolide resistance in S. pneumoniae isolates collected in five cross-sectional studies conducted before and after this vaccine introduction, from 2006 to 2019 in Lima, Peru. A total of 521 and 242 S. pneumoniae isolates recovered from nasopharyngeal swabs from healthy carrier children < 2 years old (2 carriage studies) and samples from normally sterile body areas from pediatric patients with invasive pneumococcal disease (IPD) (3 IPD studies), respectively, were included in this study. Phenotypic macrolide resistance was detected using the Kirby-Bauer method and/or MIC test. We found a significant increase in macrolide resistance over time, from 33.5% to 50.0% in carriage studies, and from 24.8% to 37.5% and 70.8% in IPD studies. Macrolide resistance genes [erm(B) and mef(A/E)] were screened using PCR. In carriage studies, we detected a significant decrease in the frequency of mef(A/E) genes among macrolide-resistant S. pneumoniae strains (from 66.7% to 50.0%) after introduction of PCV13. The most common mechanism of macrolide-resistant among IPD strains was the presence of erm(B) (96.0%, 95.2% and 85.1% in the 3 IPD studies respectively). Macrolide resistance was more common in serotype 19A strains (80% and 90% among carriage and IPD strains, respectively) vs. non-serotype 19A (35.5% and 34.4% among carriage and IPD strains, respectively). In conclusion, S. pneumoniae macrolide resistance rates are very high among Peruvian children. Future studies are needed in order to evaluate macrolide resistance trends among pneumococcal strains, especially now after the COVID-19 pandemic, since azithromycin was vastly used as empiric treatment of COVID-19 in Peru.

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COVID-19 , Infecciones Neumocócicas , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Niño , Preescolar , Estudios Transversales , Farmacorresistencia Bacteriana , Humanos , Lactante , Macrólidos/farmacología , Pandemias , Perú/epidemiología , Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas , Serogrupo , Streptococcus pneumoniae , Vacunas Conjugadas

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Infecciones Neumocócicas , Vacunas Neumococicas , Colombia , Humanos , Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/prevención & control , Vacunas Conjugadas

RESUMEN

Introduction The effectiveness of the 13-valent pneumococcal conjugate vaccine (PCV13) on sepsis, meningitis, pneumonia, and even acute otitis media has been proved in many studies. Nonetheless, the impact of PCV13 on otomastoiditis (OM) in children has barely been reviewed. In the past, we published a 13 years pneumococcal OM study from our hospital. This is a continuation of our active surveillance and is the first Latin American, prospective study examining the effectiveness of this vaccine on pneumococcal pediatric OM. Methods Active surveillance identifying patients < 16 years of age with OM admitted at the "Hospital General de Tijuana" was performed from October 1, 2005, to September 30, 2019. Diagnosis of OM was based on clinical exam (postauricular tenderness, erythema, and swelling causing protrusion of the auricle) and computerized tomographic signs (opacification of the mastoid air cells and middle ear). We used either conventional culturing or PCR to isolate bacterial pathogens, while to further Streptococcus pneumoniae serotype identification we used the Quellung Reaction (Statens Serum Institute®) or PCR. To assess pneumococcal conjugate vaccines effectiveness (VE), we counted cases per month before any pneumococcal conjugate vaccine was implemented (19 months surveillance), during the 7-valent pneumococcal conjugate vaccine (PCV7) use in the pediatric community (61 months surveillance), after PCV13 implementation in children (100 months surveillance), and calculated as follows: VE = 1 -(cases per month with specific pneumococcal conjugate vaccination/cases per month without any pneumococcal conjugate vaccination). Results Following 15 years of active surveillance, we identified 21 cases of OM. At admission the median age of patients was 38 months (six months to 15 years old), the median hospitalization days was 12 (5 to 115). All patients underwent mastoidectomy. Identification of bacterial pathogens was possible in 19 (90.5%), among which. Streptococcus pneumoniae was the leading cause with 15 cases (79%). PCV7 VE was 27.8%, however, after PCV13 introduction, VE increased to 68%, with only one case of pneumococcal OM in the last two years, without incremental OM cases by other bacteriae. Conclusion After 15 years of active/prospective surveillance in our hospital, a continuous and high VE (68%) of PCV13 on pediatric OM caused by Streptococcus pneumoniae has been found, with only one case in the last two years.

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BACKGROUND: Invasive pneumococcal disease (IPD) leads to thousands of pediatric deaths annually. Pneumococcal colonization precedes IPD. In 2013, the Dominican Republic introduced the 13-valent pneumococcal conjugate vaccine (PCV13) into its routine infant immunization program, with doses at ages 2, 4, and 12 months. Prevalence of pneumococcal nasopharyngeal colonization was evaluated post-PCV13 introduction. METHODS: A prospective cohort study of 125 children aged 2-35 months was conducted in a rural Dominican Republic community November 2016 through July 2017. Nasopharyngeal swabs and clinical and vaccination data were collected at enrollment and 4-6 months later. Serotypes included in PCV13 were defined as vaccine-type. Colonization rates and serotype distribution were compared at baseline and follow-up, and the association between colonization and vaccination status among the entire cohort was evaluated at each time point. RESULTS: Of 125 children enrolled, 118 (94%) completed follow-up. Overall and vaccine-type pneumococcal colonization rates were 62% and 25%, respectively, at baseline and 60% and 28% at follow-up. Among children age-eligible for 3 doses, 50% and 51% were fully vaccinated at baseline and follow-up, respectively. At baseline assessment, children up-to-date for age for PCV13 were less likely to be colonized with vaccine-type pneumococci than children not up-to-date, and the same was found for fully vaccinated children (3 doses) compared to those not fully vaccinated (odds ratios [ORs], 0.38 [95% confidence interval {CI}, .18-.79], and 0.14 [95% CI, .04-.45], respectively). The same associations were not found at follow-up assessment. CONCLUSIONS: Three years post -PCV13 introduction, vaccine-type colonization rates remained high. Low vaccination coverage for 3 PCV13 doses may have contributed. The protective effect of PCV13 on vaccine-type carriage suggests an increase in PCV13 coverage could lead to substantial declines in pneumococcal vaccine-type carriage.

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Nasofaringe/microbiología , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/administración & dosificación , Vacunas Neumococicas/inmunología , Streptococcus pneumoniae/inmunología , Vacunas Conjugadas/inmunología , Portador Sano/epidemiología , República Dominicana/epidemiología , Femenino , Humanos , Lactante , Masculino , Infecciones Neumocócicas/epidemiología , Estudios Prospectivos , Población Rural , Serogrupo , Vacunas Conjugadas/administración & dosificación

RESUMEN

BACKGROUND: Streptococcus pneumoniae, or pneumococcus, is a leading cause of morbidity and mortality in children worldwide. Pneumococcal conjugate vaccines (PCV) reduce carriage in the nasopharynx, preventing disease. We conducted a pneumococcal carriage study to estimate the prevalence of pneumococcal colonization, identify risk factors for colonization, and describe antimicrobial susceptibility patterns among pneumococci colonizing young children in Port-au-Prince, Haiti, before introduction of 13-valent PCV (PCV13). METHODS: We conducted a cross-sectional study of children aged 6-24 months at an immunization clinic in Port-au-Prince between September 2015 and January 2016. Consenting parents were interviewed about factors associated with pneumococcal carriage; nasopharyngeal swabs were collected from each child and cultured for pneumococcus after broth enrichment. Pneumococcal isolates were serotyped and underwent antimicrobial susceptibility testing. We compared frequency of demographic, clinical, and environmental factors among pneumococcus-colonized children (carriers) to those who were not colonized (noncarriers) using unadjusted bivariate analysis and multivariate logistic regression. RESULTS: Pneumococcus was isolated from 308 of the 685 (45.0%) children enrolled. Overall, 157 isolates (50.8%) were PCV13 vaccine-type serotypes; most common were 6A (13.3%), 19F (12.6%), 6B (9.7%), and 23F (6.1%). Vaccine-type isolates were significantly more likely to be nonsusceptible to ≥1 antimicrobial (63.1% vs 45.4%, P = .002). On bivariate analysis, carriers were significantly more likely than noncarriers to live in a household without electricity or running water, to share a bedroom with ≥3 people, to have a mother or father who did not complete secondary education, and to have respiratory symptoms in the 24 hours before enrollment (P < .05 for all comparisons). On multivariable analysis, completion of the pentavalent vaccination series (targeting diphtheria, pertussis, tetanus, hepatitis B, and Haemophilus influenzae type b) remained significantly more common among noncarriers. CONCLUSIONS: Nearly a quarter of healthy children surveyed in Haiti were colonized with vaccine-type pneumococcal serotypes. This baseline carriage study will enable estimation of vaccine impact following nationwide introduction of PCV13.

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Portador Sano/epidemiología , Portador Sano/microbiología , Nasofaringe/microbiología , Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/microbiología , Streptococcus pneumoniae , Antibacterianos/farmacología , Preescolar , Estudios Transversales , Femenino , Haití/epidemiología , Humanos , Lactante , Masculino , Serogrupo

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Introducción: Desde hace más de 15 años, las vacunas antineumocócicas conjugadas (PCVs) están disponibles en muchas partes del mundo, y son efectivas en la prevención de las enfermedades neumocócicas en niños. La OMS recomienda la inclusión de las PCVs en los programas de inmunización infantil en todo el mundo. Objetivo: Valorar el abordaje ético y el impacto socioeconómico de las vacunas antineumocócicas conjugadas para la decisión de uso en diferentes contextos. Material y Métodos: Se realizó una búsqueda bibliográfica en las bases de datos PubMed y SciELO, considerando informes de la web de la OMS. Desarrollo: Está globalmente considerado que para la reglamentación, el desarrollo y el uso de las PCVs，se deben tener en cuenta aspectos regulatorios, resultados de investigaciones y el consentimiento informado (CI) de los sujetos. En el contexto de países como China，la PCV13 de la empresa Pfizer es de la Clase II debido a su alto precio de importación, en otros contextos como Cuba no se ha introducido la vacunación contra neumococo por limitaciones financieras. Los equipos de investigación trabajan en el desarrollo de las PCVs para reducir el coste de la importación de estas vacunas, haciendo realidad la inclusión de las PCVs en el programa nacional de inmunización. A pesar de complejidad cada vez mayor de la investigación vacunológica, los investigadores seguirán obligados a adherirse a los principios éticos. Conclusiones: Es necesario una vacuna antineumocócica conjugada más económica para tener un impacto socio-económico más alto. Los profesionales sanitarios tienen la obligación de ser éticos y rigurosos en las investigaciones vacunológicas. Además, estas investigaciones requieren de la revisión por parte de un consejo de revisión ética a escala nacional y su seguimiento debe ser sistemático. Cabe señalar que los estudios en población infantil deben ser fuertemente regulados y controlados(AU)

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Introduction: Pneumococcal conjugate vaccines (PCVs) have been available in many parts of the world for more than 15 years and are effective in preventing pneumococcal diseases in children. The WHO recommends the inclusion of PCVs in childhood immunization programmes worldwide. Objective: To value the approach to ethics and the socioeconomic impact of the conjugate pneumococcal vaccines. Material and Methods: A bibliographic review was carried out in databases such as PubMed and SciELO, considering reports from the WHO website. Development: It is globally considered that regulatory aspects, research results and informed consent (IC) of the subjects should be taken into account for the regulation, development and use of PCVs. In the context of countries such as China，the PCV13 of the Pfizer company is Class II due to its high import price. In other contexts, such as Cuba, pneumococcal vaccination has not been introduced due to financial limitations. Research teams are working on the development of PCVs to reduce the cost of importing these vaccines, making the inclusion of PCVs in the national immunization program a reality. Despite the increasing complexity of vaccinology research, researchers will continue to be obliged to adhere to ethical principles. Conclusions: A cheaper pneumococcal conjugate vaccine would be needed to have a higher socioeconomic impact. Healthcare professionals have the obligation to be ethical and rigorous in vaccinology research. In addition, such research requires review by a national ethical review board and should be systematically monitored. It should be noted that studies in the pediatric population should be strongly regulated and controlled(AU)

Asunto(s)

Humanos , Infecciones Neumocócicas/prevención & control , Control Social Formal , Programas de Inmunización , Atención a la Salud

RESUMEN

BACKGROUND: Brazil introduced 10-valent pneumococcal conjugate vaccine (PCV10) into its immunization program in 2010. We assessed antimicrobial susceptibility of Streptococcus pneumoniae (Spn) obtained from a national surveillance system for invasive pneumococcal diseases (IPD) before/after PCV10 introduction. METHODS: Antimicrobial non-susceptible isolates were defined as intermediate or resistant. Minimum inhibitory concentrations (MICs) to penicillin and ceftriaxone were analyzed by year. Antimicrobial susceptibility rates were assessed for each three-year-period using the pre-PCV10-period as reference. Susceptibility of vaccine-types was evaluated for 2017-2019. RESULTS: 11,380 isolates were studied. Spn with penicillin ≥ 0.125 mg/L and ceftriaxone ≥ 1.0 mg/L decreased in the three-years after PCV10 introduction (2011-2013: penicillin, 28.1-22.5%; ceftriaxone, 11.3%-7.6%) versus pre-PCV10-years (2007-2009: penicillin, 33.8-38.1%; ceftriaxone, 17.2%-15.6%). After 2013, the proportion of Spn with those MICs to penicillin and ceftriaxone increased to 39.4% and 19.7% in 2019, respectively. Non-susceptibility to penicillin and ceftriaxone increased in 2014-2016, and again in 2017-2019 especially among children < 5 years with meningitis (penicillin, 53.9%; ceftriaxone, 28.0%); multidrug-resistance reached 25% in 2017-2019. Serotypes 19A, 6C and 23A were most associated with antimicrobial non-susceptibility. CONCLUSIONS: Antimicrobial non-susceptible Spn decreased in the three-years after vaccination but subsequently increased and was associated with non-PCV10-types. Antimicrobial susceptibility surveillance is fundamental for guiding antibiotic therapy policies.

Asunto(s)

Infecciones Neumocócicas , Streptococcus pneumoniae , Antibacterianos/farmacología , Brasil , Niño , Farmacorresistencia Bacteriana , Humanos , Lactante , Pruebas de Sensibilidad Microbiana , Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas , Serogrupo

RESUMEN

Objective: Pneumococcal diseases including invasive pneumococcal disease (IPD), pneumonia, and acute otitis media (AOM) impose a substantial public health burden. This study performed a budget impact analysis of the use of pneumococcal conjugate vaccines (PCVs) in the National Immunization Program (NIP) in Colombia.Methods: We compared the direct medical cost of the scenario without and with PCV vaccination using either pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) or 13-valent pneumococcal conjugate vaccine (PCV-13) over 5 years (2020-2024) from the health-care system perspective. Vaccine efficacy estimates were obtained from published sources and vaccine prices were taken from the Pan-American Health Organization Revolving Fund. Vaccine coverage was assumed to be 90% based on Colombia data.Results: Using PHiD-CV in the NIP in Colombia would reduce the estimated cost for treating pneumococcal disease by US$46.1 m over the 2020-2024 period (US$40.2 m using PCV-13), with a budget impact of US$100.1 m for PHiD-CV (US$121.4 m for PCV-13), and would cost US$3.1 m less per year on vaccine doses than using PCV-13.Conclusion: These findings are potentially valuable for the selection of vaccines for their national immunization programs under conditions of budgetary constraint.

Asunto(s)

Programas de Inmunización/economía , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/administración & dosificación , Presupuestos , Colombia , Costo de Enfermedad , Humanos , Infecciones Neumocócicas/economía , Vacunas Neumococicas/economía , Vacunación/economía , Vacunación/métodos

RESUMEN

The World Health Organization (WHO) recommends that pneumococcal conjugate vaccines (PCVs) be included in immunization programs worldwide. In China, the 7-valent pneumococcal conjugate vaccine (PREVNAR 7®) was authorized in 2008 but was not included in the national immunization programs. In 2016, PREVNAR 13®, a 13-valent pneumococcal conjugate vaccine (PCV13), was licensed for optional use in China. We will conduct a scoping review of the distribution of serotypes and antimicrobial resistance of Streptococcus pneumoniae in children aged under 5 years in China since the introduction of PCV13. We will obtain data from PubMed, the China National Knowledge Infrastructure (CNKI), and Wanfang Med Online. We will also review epidemiological data from WHO and the China Antimicrobial Surveillance Network (CHINET). Our analysis will include the condition of interest, the intervention, and the geographical region. All types of studies will be eligible for inclusion in the study database if they meet the inclusion criteria. This scoping review is intended to outline how S. pneumoniae serotypes are distributed, and it will map their antimicrobial resistance in children aged under 5 years in China. The results of this study will provide useful information on the impact of PCV13 in China.

Asunto(s)

Antiinfecciosos , Farmacorresistencia Bacteriana , Infecciones Neumocócicas/microbiología , Antibacterianos , Preescolar , China/epidemiología , Humanos , Lactante , Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/administración & dosificación , Proyectos de Investigación , Literatura de Revisión como Asunto , Serogrupo , Streptococcus pneumoniae/clasificación , Streptococcus pneumoniae/efectos de los fármacos

RESUMEN

OBJECTIVES: To evaluate the cost-effectiveness of introducing a domestic pneumococcal conjugate vaccine (PCV7-TT) into the Cuban National Immunization Program (NIP). METHODS: We compared PCV7-TT given at two, four and six months of age to a scenario without PCV7-TT, over a ten-year period (2020-2029). We calculated the cost (Cuban pesos - CUP) per Disability Adjusted Life Year (DALY) averted from a Government perspective. We compared results from a static cohort model and a parsimonious prediction model informed by the serotype distribution among pneumococcal carriers and cases. We ran probabilistic and deterministic uncertainty analyses. RESULTS: PCV7-TT could prevent 6897 (95% uncertainty interval, 4344-8750) hospitalizations and 189 (115-253) deaths in children <5 years of age, over the period 2020-2029. This could cost around 25 million (20-31) discounted CUP but would be offset by treatment cost savings of around 23 million (14-31). A parsimonious model predicted less favourable impact and cost-effectiveness but the cost per DALY averted was still less than 0.4 times the current GDP per capita. CONCLUSIONS: PCV7-TT is likely to be cost-effective in Cuba. The impact of the vaccine would need to be carefully monitored following its introduction into the NIP.

Asunto(s)

Programas de Inmunización/economía , Infecciones Neumocócicas/economía , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/administración & dosificación , Vacunas Neumococicas/economía , Algoritmos , Preescolar , Estudios de Cohortes , Análisis Costo-Beneficio , Cuba , Femenino , Costos de la Atención en Salud , Hospitalización/economía , Humanos , Lactante , Masculino , Infecciones Neumocócicas/inmunología , Infecciones Neumocócicas/microbiología , Vacunas Neumococicas/inmunología , Años de Vida Ajustados por Calidad de Vida , Streptococcus pneumoniae/inmunología , Vacunas Conjugadas/administración & dosificación , Vacunas Conjugadas/economía , Vacunas Conjugadas/inmunología