Background

Higher-valency pneumococcal conjugate vaccines (PCV) are under development; their potential cost-effectiveness in older adults (≥65 years) is unknown.

Methods

A Markov model estimated the cost-effectiveness of current US recommendations and sole pneumococcal polysaccharide vaccine (PPSV23) use compared to: in-development PCV15 and PCV20, and a hypothetical vaccine (HypoPCV20) adding the 7 commonest non-PCV13 serotypes in older adults (all with/without PPSV23). Sensitivity analyses and alternative scenarios were examined.

Results

In analyses considering only existing and in-development vaccines, sole PCV20 use cost $176,500 per quality-adjusted life-year (QALY) gained compared to current US recommendations, while dual PCV20/PPSV23 use cost $4,050,000/QALY when equal serotype effectiveness and no childhood vaccination indirect effects on added serotypes were assumed. PCV15 strategies were dominated. When PCV13/PCV20 were assumed ineffective against serotype 3 and PCV15 was fully effective, PCV15 cost $209,000/QALY and PCV15/PPSV23 cost $1,403,000/QALY. Adding childhood vaccination indirect effects or alternative serotype effectiveness assumptions decreased PCV15/PCV20 cost-effectiveness. When HypoPCV20 was considered, HypoPCV20 cost $152,700/QALY gained, and HypoPCV20/PPSV23 cost $2,480,000/QALY; other strategies were dominated.

Conclusions

In exploratory analyses, PCV15/PCV20 may not be economically reasonable in older adults, regardless of serotype effectiveness assumptions, particularly when potential indirect effects were considered. Adult vaccines containing higher-risk serotypes not contained in childhood vaccines may be more promising.

Background

In Canada, higher-valence pneumococcal conjugate vaccines (PCV10, PCV13) were introduced into the routine pediatric programs in 2009/2010. Despite their impact, there remains substantial disease burden. PCVs inclusive of up to 20 serotypes (PCV20), currently in development, are expected to considerably expand pneumococcal disease coverage. Our objective was to estimate the clinical and economic burden caused by PCV20 serotypes among Canadian children under five years.

Methods

Epidemiologic, clinical, and cost data were derived or estimated from published sources (Table 1). Cases (invasive pneumococcal disease (IPD), pneumonia, acute otitis media (AOM)), mortality, and direct costs caused by PCV20 serotypes were calculated for children under 5 based on 2017 population figures and assuming IPD serotype distribution for all clinical entities.

Results

Results are summarized in Table 1. Based on our assumptions, PCV20 serotypes were estimated to cover 52% of pneumococcal disease, or a total of 102,036 annual cases. Of these, IPD represented an estimated 0.13%. Total direct attributable costs were 27 million CAD.

Conclusions

Substantial amount of morbidity from pneumococcal disease, of which IPD represents only a small proportion, could be potentially addressed by the next generation PCVs currently in development.

Background

Brazil has a 10-valent pneumococcal conjugate vaccine (PCV10) pediatric national immunization program (NIP), even though a 13-valent (PCV13) is available and protects against three additional serotypes, 3, 6A, and 19A. Inadvertently, there has been emergence of PCV10 non-vaccine serotypes, notably 19A. We sought to evaluate the cost-effectiveness and budget impact of switching from PCV10 to PCV13 in 2019.

Methods

The analysis estimated future costs ($BRL), quality-adjusted life years (QALYs), and health outcomes for PCV10 and PCV13 NIPs over five years. The adapted model uses local Brazil serotype and Latin America incidence data from 2009-2018. Input parameters are from Brazilian sources. Future serotype dynamics is predicted using Brazilian and global historical trends (Figure 1).

Results

Over five years, switching from PCV10 to PCV13 prevents 176 thousand disease cases and 20 thousand deaths, gains 29 thousand QALYs, and saves 135 million direct and 3 million indirect costs. After one year, 16 million direct healthcare costs are saved by implementing a PCV13 NIP in Brazil.

Conclusions

Despite a higher PCV13 vaccine cost, a PCV13 NIP is cost-saving compared with PCV10, from both societal and payer perspectives. Brazil should consider switching to prevent disease burden, improve population health, and save immediate healthcare costs.

Background

Pneumococcal conjugate vaccine (PCV) national immunization programs (NIPs) have effectively reduced vaccine serotype pneumococcal disease (PD) morbidity and mortality across Latin America (LatAm). In 2010, the 10-valent and 13-valen PCVs were introduced in routine alimentation. Given PCV13’s broader use and serotype coverage, we quantified its impact across LatAm.

Methods

We calculated the 10-year impact of pediatric PCV13 NIPs in LatAm by estimating PD cases averted and mortality prevented. A model was used to conduct the analysis for ages <5 in 14 LatAm countries that implemented PCV13 NIPs. Data were from reports by the United Nations, World Health Organization, and World Bank for parameters where available. Results are presented by country and aggregately.

Results

Approximately 39.4 million children have been vaccinated. Pediatric PCV13 vaccination translated into 13.7 million total pneumococcal disease cases averted (Table 1). Of the cases averted, 334 thousand were invasive pneumococcal disease, 2.2 million were pneumonia, and 11.2 million were otitis media. Moreover, 49.5 thousand estimated deaths were prevented.

Conclusions

The 10-year history of pediatric PCV13 NIPs in LatAm prevented millions of pneumococcal disease cases and thousands of deaths. However, the true public health impact is underestimated, as herd effects for non-vaccinated groups are not included in the calculations.

Background

An investigational 20-valent pneumococcal conjugate vaccine (PCV20) is in development and contains the 13 serotypes in PCV13, with 7 additional serotypes 22F,33F,8,10A,11A,12F and 15B. We estimated the epidemiologic and economic burden of pneumococcal disease attributable to serotypes contained in PCV13 and PCV20 for US adults.

Methods

The burden of disease was estimated using published and unpublished data on incidence rates, serotype coverage, mortality, and costs for invasive pneumococcal disease (IPD) and pneumonia. Active Bacterial Core surveillance data from 2017 was used for IPD data. Data was extrapolated to the total US adult population, stratified by age and risk group.

Results

Results are summarized in Table. An additional 9,900 cases of IPD, 44,000 cases of inpatient pneumonia, 52,000 cases of outpatient pneumonia, and 4,300 death are estimated to be caused by the seven new serotypes in PCV20. The new serotypes account for approximately 40% of all cases, deaths, and costs. Direct costs attributed to all PCV20 serotypes are estimated at $4.2 billion.

Conclusions

Pneumococcal disease remains an unmet need in US adults despite increasing uptake with PCV13 and 23-valent polysaccharide vaccine. The seven new serotypes contribute substantially to the clinical and economic burden of pneumococcal disease in adults.

Background

The 13-valent PCV (PCV13) has reduced vaccine preventable pneumococcal disease caused by serotypes 4,6B,9V,14,18C,19F,23F1,5,7F,3,6A,19A, with cross-protection against 6C. However, non-vaccine type burden remains in the United States (US). Higher-valent PCVs in development will contain additional serotypes 22F,33F,8,10A,11A,12F, and 15B (PCV20). We estimated the remaining clinical and economic burden attributed to current and future vaccine serotypes in US children under five.

Methods

The burden of invasive pneumococcal disease (IPD), pneumonia, and acute otitis media (AOM) was estimated by extrapolating the IPD serotype distribution from 2017 CDC Active Bacterial Core (ABC) surveillance data for PCV13 serotypes (25.0%) and PCV20 serotypes (58.1%) to current population statistics for all clinical entities. Clinical, epidemiologic, and costs data were sourced or estimated from published evidence.

Results

The estimated burden associated with PCV13 and PCV20 serotypes are in Table 1. Based on assumptions, the incremental burden is 700,000 disease cases and 69 deaths annually caused by additional serotypes contained in PCV20. This represented $445 million incremental annual direct costs in 2019 dollars.

Conclusions

Future PCV serotypes encompass a considerable amount of the disease burden. US infant pneumococcal disease and healthcare expenditure may be reduced if future PCVs provide comparable levels of protection as PCV13 serotypes.

Background

The burden of disease for pneumonia in older adults has a major impact on health systems.

The aim of the study is to carry out an economic evaluation of the vaccination strategy against S. pneumoniae using the 13 valent pneumococcal conjugate vaccine (PCV13) in adults over 65 years

Methods

A simulated economic model has been developed in the form of a decision tree to evaluate the cost of the vaccination strategy in the population over 65 years of the health Area of Valladolid-East, versus non-vaccination, using a Monte Carlo probabilistic analysis.

Results

Streptococcus pneumoniae annually generates 557.24 cases of pneumococcal disease in the Valladolid-Este Health Area, 506.60 episodes are pneumonic. Vaccination to the age cohort over 65 years is an efficient measure from the third year, with a cost per quality-adjusted life years (QALY) of 20,496.20 euros. The number of QALYs gained in a decade is 86.07 and the expense of 216.252.89 euros with this vaccination strategy would be avoided.

Conclusions

The evaluation of the different incremental costs (QALY,euros) in the years of follow-up the program of vaccination against pneumococcus in people over 65 in Castilla y León with PCV13 is cost‐effective.

Background

Population-based epidemiological studies provide opportunities for innovation and collaboration among global-health researchers. ClinEpiDB (https://clinepidb.org) is an open-access online resource that enables investigators to maximize the utility and reach of their research and make optimal use of data from others.

Methods

ClinEpiDB was built on EuPathDB infrastructure - a collection of databases covering eukaryotic pathogens, related species, and hosts. Data is integrated via a unified semantic web framework. An intuitive web interface overlays SQL queries with results visualized via interactive applications in the ClinEpiDB browser, providing insight into data distributions and covariate associations.

Results

ClinEpiDB, first released in 2018, contains datasets from the MAL-ED and GEMS enteric disease projects, SCORE schistosomiasis project, and ICEMR malaria studies. Integration of the Pneumonia Etiology Research for Child Health (PERCH) study, with ~1000 variables for >9500 children from 9 sites, will provide a rich source of information for the pneumonia research community. Once public (expected 2020-2021), investigators will be able to explore all PERCH data through the ClinEpiDB browser before deciding whether to request download access.

Conclusions

The ClinEpiDB resource provides an intuitive interface to view data and will continue to grow with integration of new datasets, enhanced tool development, and user outreach and education.

Background

Accumulating—albeit limited—evidence indicates that PCV13 is effective against serotype 3 (ST3), which causes a disproportionate share of pneumococcal disease in US adults. Estimates of protection employed in economic evaluations have varied widely; we thus examined the importance of vaccine effectiveness (VE) against ST3 in determining the cost-effectiveness of PCV13.

Methods

A probabilistic cohort model depicting risks and costs of pneumococcal disease was employed to evaluate the cost per QALY gained with PCV13->PPSV23 versus PPSV23 alone in immunocompetent US adults aged 65 years under alternative assumptions regarding VE-PCV13 versus ST3. VE-PCV13 (excl. ST3) was based on data from the Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA); VE-PPSV23 against IPD was based on published literature, and against CAP, was zero.

Results

Cost per QALY gained with PCV13->PPSV23 (vs. PPSV23) ranged from $449,304 to $184,807 when varying VE-PCV13 versus ST3 from 0% to 125% of point-estimates from published literature.

Conclusions

Cost-effectiveness of PCV13 in immunocompetent US adults aged 65 years varies considerably under alternative assumptions regarding VE-PCV13 versus ST3. When assuming a reasonable value for VE-PCV13 versus ST3, results suggest that PCV13 provides acceptable value for money in this patient population.

Background

We describe factors associated with pneumococcal nasopharyngeal carriage in Fiji, using data from annual (2012-2015) cross-sectional surveys, pre- and post-introduction of ten-valent pneumococcal conjugate vaccine (PCV10).

Methods

Infants (5-8 weeks), toddlers (12-23 months), children (2-6 years), and their caregivers participated. Pneumococci were detected using lytA qPCR, with molecular serotyping by microarray. We used logistic regression to determine predictors of pneumococcal carriage.

Results

There were 8,109 participants. Pneumococcal carriage was associated with: years post-PCV10 introduction (global P<0.001), indigenous iTaukei ethnicity (aOR 2.74 [95% CI 2.17-3.45] P<0.001); young age (global P<0.001); urban residence (aOR 1.45 [95% CI 1.30-2.57] P<0.001); living with >2 children <5 years (aOR 1.42 [95% CI 1.27-1.59] P<0.001); poverty (aOR 1.44 [95% CI 1.28-1.62] P<0.001); and upper respiratory tract infection symptoms (aOR 1.77 [95% CI 1.57-2.01] P<0.001). Factors associated with PCV10 and non-PCV10 carriage were similar to those associated with overall carriage. Additionally, PCV10 carriage was associated with PCV10 vaccination (0.58 [95% CI 0.41-0.82] P=0.002) and cigarette smoke exposure (aOR 1.21 [95% CI 1.02-1.43] P=0.031, while non-PCV10 carriage was not associated with years post-PCV10 introduction.

Conclusions

Introduction of PCV10 reduced the odds of overall and PCV10 pneumococcal carriage in Fiji. Indigenous iTaukei ethnicity was positively associated with carriage after adjustment for PCV10.

Background

The cost-effectiveness studies of adult pneumococcal vaccinations have shown discordant results. We evaluated the cost-effectiveness of pneumococcal vaccinations for high-risk groups in 18–84-year-olds under the PCV13 childhood vaccination programme.

Methods

A multi-cohort model with 15 year time-horizon was applied to estimate the cost-effectiveness of PCV13 and PPV23 vaccinations for various age and risk groups. Risk groups (diabetes, asthma or chronic obstructive pulmonary disease (COPD), renal failure or chronic heart failure) were defined using the Register for Special Reimbursements of medical expenses. The pneumococcal disease incidence in the risk groups were estimated by linking individual’s events within and between individual-level national registries.

Results

The disease incidence was highest among the renal failure risk group and both PCV13 and PPV23 vaccinations were cost-saving in 18–74-year-olds. In ≥65-year-olds PPV23 vaccinations were more cost-effective than PCV13 vaccinations. In all risk groups both vaccinations were most cost-effective in 65–74-year-olds. The results were sensitive to the changes in effectiveness and price of both vaccines and assumed mortality impact of vaccinations and life expectancy estimates.

Conclusions

Life expectancy affects significantly the cost-effectiveness results among the elderly. When evaluating the cost-effectiveness of pneumococcal risk group vaccinations it’s important to consider the high all-cause mortality among the elderly at-risk population.

Background

While much is known about the cost of community-acquired pneumonia (CAP) during the acute phase, little is known about the potential attributable cost of CAP thereafter.

Methods

A retrospective matched-cohort design and data from a US private healthcare claims repository were employed. In each month of accrual (01/2013 – 07/2017), adults who were hospitalized for CAP in that month (“CAP patients”) were matched (1:1, without replacement) on demographic and clinical profiles to adults who did not develop CAP in that month (“comparison patients”). All-cause healthcare utilization and expenditures (2018 US$) were tallied during the acute phase (i.e., from date of CAP hospitalization through 30 days post-discharge) as well as from the end of the acute phase to the end of the three-year follow-up period.

Results

Expenditures during the acute phase of the CAP hospitalization averaged $32,064 (vs. $1,556 for comparison patients). By the end of the 3-year follow-up period, all-cause expenditures averaged $124,035 for CAP patients versus $63,652 for comparison patients, and thus attributable costs totaled $60,383.

Conclusions

Our findings provide additional evidence that the cost of CAP requiring hospitalization is high, and that the impact of CAP extends beyond the expected time for resolution of acute inflammatory signs.

Background

Streptococcus pneumoniae is a leading cause of bacterial pneumonia in children. This analysis assessed pneumonia incidence rates (IRs) and expenditures following PCV13 introduction in 2010 in Veneto.

Methods

Outpatient pneumococcal and unspecified pneumonia episodes in children <15 years in the Veneto Region were identified in the Pedianet database from 2010-2017. IRs were numbers of episodes/1,000 person-years. Interrupted time series (ITS) analysis were conducted to assess trends in annual IRs in the early and late PCV13 (2010-2013, 2014-2017) periods.

Results

Incidence was higher in children 2-4 years, compared to children <2 and 5-14 years. IRs declined from 14/1,000 person-years in 2010 to 5/1,000 person-years in 2017 in the total cohort.

In ITS analysis, a significant downward trend was detected in the late PCV13 period (p =0.0027) with rates declining by 2.8% annually in children under 15 years. Mann-Kendall test showed a significant negative correlation over the analysis period (coef=-0.64, p=0.026). Similar results were found for children 2-4 and 5-14 years but not in children < 2 years.

Total regional expenditures declined from €472,573 in 2010 to €157,865 in 2017.

Conclusions

Results demonstrate a decrease in outpatient pneumonia incidence and regional expenditures in children <15 years after PCV13 introduction with greater benefits in older children.

Background

Invasive pneumococcal disease (IPD) is associated with high mortality and healthcare utilization. This analysis assessed IPD and unspecified invasive disease incidence rates (IRs) following PCV13 introduction in 2010 in Veneto.

Methods

IPD and unspecified invasive disease episodes in children <15 years in the Veneto region were identified in the Pedianet database from 2010-2017. IPD and unspecified invasive disease included pneumococcal and unspecified bacteremia, meningitis and septicemia. IRs were numbers of episodes/100,000 person-years. Interrupted time series (ITS) analyses assessed trends in annual IRs in the early and late PCV13 (2010-2013, 2014-2017) periods.

Results

We identified 81 episodes of IPD and unspecified invasive disease over the analysis period of which 94% were associated with non-specific codes.

IPD and unspecified invasive disease incidence decreased from 40/100,000 person-years (95% CI: 17-63/100,000 person-years) in 2010 to 31/100,000 person-years (95% CI: 6-56/100,000 person-years) in 2017 in children <15 years. While incidence was numerically lower in 2017 than in 2010, ITS analysis did not detect a significant trend in the early (coef=1.97; p=0.63) or late PCV13 (coef=0.50; p=0.90) periods.

Conclusions

Results did not show a significant decrease in IPD and unspecified invasive disease incidence in children <15 years after PCV13 introduction in Veneto.

Background

China is one of few countries yet to introduce PCV. We aimed to estimate the long-term impact of a PCV13 programme on childhood IPD in mainland China, accounting for provincial heterogeneity.

Methods

A Bayesian hierarchical model was fit to systematic review data on the proportion of vaccine-type IPD and carriage in each province. A mechanistic model was then used to predict the relative reduction in IPD incidence of a PCV13 programme, assuming VT circulation is eventually interrupted and replaced by NVTs.

Results

Across China, we estimate that a median 75% (95% HDI: 53 – 90%) of carriage and 88% (95% HDI: 76 - 94%) of IPD is caused by vaccine serotypes. A mature PCV programme would lead to a median 51% (95% HDI: -40 – 81%) reduction in the incidence of IPD, ranging from 33% in Hubei (95% HDI: -34 – 76%) to a median 76% in Beijing (95% HDI: 44 – 92%). All 95% credible intervals for province-level covariate effects contain zero for VT carriage and IPD, and as such the impact estimates in provinces with little or no serotype distribution data remain uncertain.

Conclusions

PCV13 has the potential to substantially reduce the pneumococcal disease burden in China, but data to underpin the estimates is sparse in Western China.

Background

The United States experienced a substantial reduction in the incidence of invasive pneumococcal disease (IPD) following the introduction of pneumococcal conjugate vaccines (PCVs), PCV7 in 2000 and PCV13 in 2010, yet, disease remains. Expanded valency PCVs, PCV15 and PCV20 that contain two and seven additional serotypes compared to PCV13, are in advanced development.

Methods

We used the CDC Active Bacterial Core surveillance (ABCs) data from 2017 to quantify the incidence and to assess PCV coverage of IPD. ABC is an active laboratory and population-based surveillance system in 10 geographically diverse sites in the United States. Analyses were limited to the serotypes covered by PCV13 (1,3,4,5,6A,6B, 7F,9V,14,18C,19A,19F,23F, plus 6C, which is highly-related to 6A), PCV15 (PCV13-types, 22F,33F), and PCV20 (PCV15-types, 8,10A,11A,12F, plus 15C, which is highly-related to 15B).

Results

In 2017, non-PCV13 and PCV13 serotypes accounted for 63.1-75.0% and 25.0-36.9% of IPD cases across different age groups. The additional two serotypes in PCV15 and the seven serotypes in PCV20 accounted for 8.3-17.0% and 23.8-37.1% of the remaining IPD cases, respectively (Table).

Conclusions

PCV20 could address a substantial remaining burden of IPD, covering an estimated 55.1-66.1% of cases across all age groups.

Background

The indigenous Bajau people (Sea Nomads) have lived an entirely marine-dependent existence and renowned for their extraordinary breath-holding abilities. Kotabaru in South Kalimantan is one of the island inhabited by Bajau people. We investigated nasopharyngeal carriage of S. pneumoniae in healthy Bajau children <5 in Kotabaru, South Kalimantan, Indonesia.

Methods

Serotyping was performed using Conventional multiplex PCR. Antimicrobial susceptbility test using disk diffusion and microdulution were employed to all pneumococcal and MDR isolates, respectively.

Results

We found 45% (180/399) of S. pneumoniae. Cigarette exposure contributed to colonization of S. pneumoniae (OR = 1,87). The most common serotypes were 6A/6B (18%), 15B/15C (17%) and 19F (16%). We identified 46% (86/185) was vaccine-type and 40% as non-vaccine type (74/185). The majority of 18% (34/185) defined as Multidrug Resistant pneumococcus were 19F serotype (74%), followed by 6A/6B (9%), 19A (9%), 14 (6%), and 23F (3%). Tetracycline (89%), trimethoprim/sulfamethoxazole (79%), cefuroxime (76%), azithromycin (76%) and erythromycin (76%) showed high prevalence of resistance among MDR isolates with MICs90 were 8, 4/76, >4, and >2 μg/mL, respectively.

Conclusions

Almost half of the identified serotype were vaccine type. All of the multidrug resistant isolates were vaccine type and dominated by 19F. Serotype 15B/15C was the second most common serotype.

Background

Streptococcus pneumoniae is one of the pathogens causing respiratory invasive diseases in children worldwide. Pneumococcus often resides as normal flora in nasopharynx but the balance of pathogens and host usually diminished due to viral infections. We investigated the prevalence of pneumococcal carriage and antimicrobial resistance profile of upper respiratory infections outpatients presenting at Tabanan General Hospital, Bali in 2017.

Methods

We collected 200 nasopharyngeal (NP) swabs from all ages outpatients with upper respiratory infections symptoms. Pneumococcus colonization was evaluated using direct culture. Serotyping was performed by conventional multiplex PCR. Antimicrobial susceptibilities were determined using disk diffusion.

Results

We found 18,5% (37/200) patients were colonized with pneumococcus. The most common serotypes found were PCV-13 vaccine types (54%), including 6A/6B and 19F (18%), 14 (8%), sg18 and 3 (3%). Most pneumococci isolates found were susceptible to Chloramphenicol (87%), followed by Clindamycin (74%) and Macrolides (72%), whereas resistance were mostly found in Cotrimoxazole (59%) and Tetracycline (44%). Multidrug resistance (MDR) were found in 11 isolates (28%), dominated by serotype 19F (18%).

Conclusions

The pneumococcus colonization rate in upper respiratory infection outpatients were less than 20% and still dominated by PCV-13 serotypes. Resistance were shown to most common antibiotics used in Indonesia.

Background

Streptococcus pneumoniae causes substantial morbidity and mortality globally, with serotype-specific disease burden varying geographically. Currently there are two widely used pneumococcal conjugate vaccines (PCV). Evidence is limited regarding their comparative serotype-specific immunogenicity and efficacy.

Methods

We conducted a systematic-review and network meta-analysis of studies in which the immunogenicity of PCVs was directly compared in head-to-head randomised trials. Network meta-analysis incorporates both direct pair-wise comparisons and indirect comparisons (e.g. PCV10 vs PCV7, and PCV13 vs PCV7) thereby increasing overall statistical precision for the main comparison of interest (PCV10 vs PCV13). The difference in immunogenicity, as measured by geometric mean ratio (GMR), was examined by serotype.

Results

27 trials were included in the network meta-analysis, 4 directly comparing PCV10 and PCV13, 7 comparing PCV7 and PCV10, and 16 comparing PCV7 and PCV13. For the 10 common serotypes, immunogenicity at 1 month after the primary vaccination series was higher for PCV13 for 7 serotypes, with GMRs ranging from 1.18 to 2.50. In contrast, serotype 5, 18C and 19F favoured PCV10. Similar results were observed post-booster dose except for serotype 5 and 7F.

Conclusions

Variation in serotype-specific immunogenicity exists between PCV10 and PCV13, indicating that further investigation into whether this translates to heterogeneity in protection is needed.

Background

The serotype distribution of invasive pneumococcal disease (IPD) informs the coverage of next generation pneumococcal conjugate vaccines (PCVs). This analysis describes IPD coverage by the current PCVs (PCV10/PCV13) and next generation, PCV15 and PCV20.

Methods

Serotype counts for children <5 years were obtained from national or regionally-representative IPD surveillance systems from high-income countries. Up to the three most recent years of data were included. Excluded countries reported <20 cases overall or only reported data prior to pediatric PCV introduction into the National Immunization Program (NIP). Coverage was calculated for PCV10 (1,4,5,6B,7F,9V,14,18C,19F,23F), PCV13 (PCV10-types, 3,6A,19A, plus 6C, which is highly-related to 6A), PCV15 (PCV13-types, 22F,33F), and PCV20 (PCV15-types, 8,10A,11A,12F,15B, plus 15C, which is highly-related to 15B) as the number of cases in PCVs divided by the total number of cases (excluding missing and non-typeable cases) reported for each country.

Results

Twenty-seven of 80 (34%) high-income countries met inclusion criteria, reporting >5,000 cases that were included in the analysis. Coverage by current and next generation PCVs varied by country and World Health Organization (WHO) region (Table).

Conclusions

PCV20 offers substantial coverage above current PCVs and next generation PCV15 and could address the considerable remaining IPD burden among children in high-income countries globally.

Background

Despite the indirect effects of routine pediatric pneumococcal conjugate vaccine (PCV) use, invasive pneumococcal disease (IPD) persists in older adults. This analysis describes IPD coverage of current PCVs (PCV10/PCV13) and next generation, PCV15 and PCV20.

Methods

Serotype counts for adults ≥60/≥65 years were obtained from national or regionally-representative IPD surveillance systems in high-income countries. Up to the three most recent years of data were included. Excluded countries reported <20 cases overall or only reported data prior to pediatric PCV introduction into the National Immunization Program (NIP). Coverage was calculated for PCV10 (1,4,5,6B,7F,9V,14,18C,19F,23F), PCV13 (PCV10-types,3,6A,19A, plus 6C, which is highly-related to 6A), PCV15 (PCV13-types, 22F,33F), and PCV20 (PCV13-types, 8,10A,11A,12F,15B, plus 15C, which is highly-related to 15B) as the number of cases in PCVs divided by total number of cases (excluding missing and non-typeable) reported for each country.

Results

Twenty-eight of 80 (35%) high-income countries met inclusion criteria, reporting >25,000 cases that were included in the analysis. Coverage by current and next generation PCVs varied by country and World Health Organization (WHO) region (Table).

Conclusions

PCV20 offers substantial coverage above current PCVs and next generation PCV15 and could address the considerable remaining IPD burden among older adults in high-income countries globally.

Background

A 15-valent pneumococcal conjugate vaccine (V114) containing PCV13 serotypes and 22F/33F is under development. This study quantifies the health and economic burden of V114-type pneumococcal disease in Canadian children.

Methods

V114-type invasive pneumococcal disease (IPD) and acute otitis media (AOM) cases were simulated in a single, unvaccinated cohort from birth to 20 years with a Markov model. In the pre-PCV scenario, pre-PCV7 epidemiological inputs were used. In the post-PCV scenario, pre-PCV7, pre-PCV13 and current-day inputs were used to estimate PCV7, PCV13 not PCV7 (PCV13-PCV7), and 22F/33F disease, respectively. Costs were estimated from a societal perspective and discounted at 1.5%.

Results

In the pre-PCV scenario, 600 V114-type IPD cases were attributable to PCV7 serotypes (n=535, 89%), PCV13-PCV7 serotypes (n=56, 9%), and 22F/33F (n=9, 2%); 715,642 V114-type AOM outpatient visits were attributable to PCV7 serotypes (n=519,286, 73%), PCV13-PCV7 serotypes (n=189,864, 27%), and 22F/33F (n=6,491, 1%). Total costs for V114-type IPD and AOM were CA$274 million. In the post-PCV scenario, PCV13-PCV7 serotypes increased, specifically serotypes 3, 19A and 7F for IPD, and 19A for AOM.

Conclusions

PCV7 serotypes cause most pneumococcal morbidity and are important to retain in PCVs. Select PCV13-PCV7 serotypes also contribute to the disease burden. Including non-vaccine serotypes can prevent additional disease burden.

Background

The study objective was to determine the prevalence of serotypes and coverage provided by currently licensed and next generation pneumococcal conjugate vaccines (PCVs) in adults hospitalized with community-acquired pneumonia (CAP) in the United States.

Methods

Hospitalized adults aged ≥18 years with radiologically-confirmed (CXR+) CAP were enrolled from 10 U.S. cities between October 2013 and September 2016. S. pneumoniae isolates cultured from normally-sterile standard-of-care specimens were serotyped by Quellung. Urine was tested using BinaxNOW® and a serotype-specific urine antigen detection (UAD) assay that detects serotypes contained in PCV13 plus 6C (highly-related to 6A), PCV15 (PCV13 serotypes, 22F, and 33F), PCV20 (PCV15 serotypes, 8, 10A, 11A, 12F, and 15B plus 15C (highly-related to 15B)), and non-PCV serotypes 2, 9N, 17F, and 20. Coverage was calculated as the percent of CXR+CAP participants positive for a serotype in PCV13, PCV15, and PCV20.

Results

Of 15,572 enrolled participants, 12,055 with CXR+CAP were included in the analysis; 52.7% (n=6347) were ≥65 years. Coverage of CXR+CAP varied by PCV formulation (Table). About 1% of CXR+CAP was due to serotypes 2, 9N, 17F, and 20 combined.

Conclusions

Compared to PCV13, PCV20 increased coverage of CXR+CAP due to PCV serotypes by 71% (18-64 years) and 64% (≥65 years).

Background

Pneumococcal nasopharyngeal carriage (SP-NPC) in children aged <5 years is well-described. Less is known about SP-NPC in adolescents. SP-NPC studies in Atlanta documented carriage rates of ~30% in children aged <5 years. We evaluated SP-NPC in adolescents.

Methods

NP swabs collected from children aged 11-17 years in an Atlanta emergency department from December 2017-December 2018 were broth-enriched, cultured for SP, and serotyped. Demographics and medical and immunization records were collected.

Results

Of 260 adolescents enrolled, 8 (3.1%) had SP-NPC. Mean age of enrollees was 13.5 years (12.9 years for carriers); 58% were female (63% for carriers). 72% had no documented underlying conditions (50% for carriers). 50% of carriers reported having asthma. Among enrollees with immunization records available, 132/219 (60%) overall and 5/6 (83%) carriers were fully immunized for SP with PCV7. 2 carried vaccine serotypes (VT): S3 (PCV13 VT), S19F (PCV7/13 VT) but were immunized with PCV7 only. 6 carried non-VT: S6C, S15C, S21, S23A, S23B, S37.

Conclusions

Adolescent SP-NPC was low compared to children aged <5 years in Atlanta, GA USA, illustrating adolescents’ limited role in SP-NPC. Adolescent SP-NPC of mostly non-VT, despite lack of PCV13 immunization, supports successes of routine pediatric vaccination and herd immunity.

Background

S. pneumoniae isolation from indigenous population prior to pneumococcal vaccine introduction is critically important to provide baseline and ensure data representativeness across different regions in Indonesia for vaccine impact evaluation in the future.

Methods

We collected nasopharyngeal swabs from children <5 in Wakatobi, Sulawesi and Kotabaru, Kalimantan from October 2018 – April 2019. S. pneumoniae was identified by optochin-susceptibility and bile-solubility test and serotyped using multiplex PCR.

Results

We isolated 305/499 (61%) of S. pneumoniae in Wakatobi and 180/399 (45%) in Kotabaru. 65% of pneumococcus in Wakatobi were PCV13-types. The rate was lower in Kotabaru with 46%. Most common serotypes in Kotabaru were 6A/B, 15B/C and 19F with 18%, 17% and 16%. 6A/B, 23F and 19F were the most common in Wakatobi with 29%, 16% and 9% respectively. Cigarette smoke exposure was associated to colonization in Kotabaru with OR 1.87. Rhinorrhoea and use of kerosene and wood as fuel for cooking were associated to colonization in Wakatobi with OR 2.0 (95%CI 1.3 – 3.0), 3.6 (95%CI 1.4 – 9.0) and 4.3 (95%CI 1.7 – 10.9) respectively.

Conclusions

Different serotype distribution and risk factors were shown despite both communities were the same tribe (Bajau). This result provides baseline data representing indigenous population in Indonesia.

Background

Pneumococc vaccine is effective and safe but vaccine immunogenicity is a challenging matter in renal transplantation and accessible guidelines suggest pneumococcal revaccination every 3–5 year intervals .This study judge guideline based on reality .

Methods

Articles related to pneumococc vaccine in renal transplant was evaluated from 1996 -2019 .

Results

Most accessible studies followed small selective healthier cases for short period time ,they showed persistence of immunogenicity with PPSV23 vaccination in hemodiyalisis and renal transplant after 1 year is same (43%) ,the vaccnes cover half of pneumococc serotypes , not same for all types (6B type :12% , 19F :27% ), while the revaccination with the newer vaccine (PPSV23) was less effective than the first immunization that produce a significant immune response followed by rapid decline of immunity, there is not also difference in immunogenicity of PCV7 versus PPV23 at 8th week postvaccination

Conclusions

Pneumococcal vaccine immunogenicity appearance and duration in renal transplantation is not compatible with guidelines recommendations , immunogenicity decrease after first year dramatically in spite of using newer generation and booster doses ,we are face to questions such as the best time of installation,how can enhance immunogenicity and the best vaccine type that we can use .

Background

Routine pneumococcal vaccination of adults in Russia is recommended in immunization schedule for recruits, adults 60 years and older, with chronic lung disease. We conducted all-national study on the coverage of adult pneumococcal vaccination for the period 2014-2018.

Methods

Information was provided by the departments of health of each region and republic of RF, using special forms.

Results

In four years, 1.9 million of adults have been vaccinated against pneumococcus. The highest coverage was achieved among recruits - 92.5%. The coverage of patients with chronic lung diseases, including COPD was 15.1%. In addition, pneumococcal vaccination was carried out among other groups of immunocompetent adults with chronic diseases. However, the absolute number of vaccinated was not large. Coverage rate was 3.8% among patients with chronic heart disease, 2.8% in patients with diabetes mellitus and lower in other groups. In some regions of Russia pneumococcal vaccination of adults with immunocompromising сonditions and people with occupational risk factors was carried out.

Conclusions

Routine pneumococcal vaccination of adults in Russia was include in immunizations schedule in 2014. The highest coverage was achieved among recruits. Besides, pneumococcal vaccination is carried out in other risk groups, but coverage is not high so far.

Background

Herd protection has contributed greatly to PCV impact and may enable use of reduced dose schedules. We estimated which population age groups contribute most to VT pneumococcal transmission and hence herd effects

Methods

We used transmission models to mirror pre PCV epidemiology in England & Wales, Finland, Kilifi in Kenya and Nha Trang in Vietnam and extracted the per capita and population based contribution of different age groups to VT transmission.

Results

<1y old infants cause frequent secondary vaccine type infections per capita. However, 1-5y olds have the much higher contribution to the force of infection at 51%(28-73), 40%(27-59), 37%(28-48) and 67%(41-86) of the total infection pressure in E&W, Finland, Kilifi and Nha Trang, respectively. Unlike the other settings, school age children in Kilifi were the dominant source for VT infections with 42% (29-54) of all infections caused. Similarly, the main source of VT infections in infants are pre-school children and in Kilifi 39%(28-51) of VT infant infections stem from school age children, whereas this was below 15% in the other settings.

Conclusions

Pre-school children are key PCV targets for achieving herd immunity. In highly endemic settings school children may substantially contribute to transmission and may have little PCV protection with current schedules.

Background

Human development index (HDI) is the most frequently indicator used of socioeconomic level in a nation. However, few studies have analyzed the role of HDI in the epidemiology of community-acquired pneumonia (CAP) in Costa Rica and worldwide.

Methods

A descriptive study analyzes the relationship between HDI and the incidence of CAP by county between the years 2005 to 2014 in Costa Rica.

Results

The incidence of CAP and HDI had an inversely proportional relationship. Over this period of time, HDI increased progressively (0.729 to 0.766); this was correlated with decrease of incidence in CAP (164.9 to 138.1 per 100.000 persons) (p = 0.005). When this index exceeded 0.75, the incidence showed significant decrease from 155.0 to 127.1 cases per 100,000 persons. Prior to this change, the average annual variation rate was -1.2% and turned to -2.9% after it. Counties with very high and / or high HDI had a significantly lower incidence of CAP compared to those with a medium HDI (OR = 0.62; CI95% 0.46 - 0.83 vs OR = 0.43; CI95% 0.30 - 0.61).

Conclusions

HDI is a good predictor of CAP incidence in Costa Rica; the higher the HDI the lower incidence of CAP.

Background

Quantification of Streptococcus pneumoniae (Sp) carriage density and identification of serotypes in contacts contribute to understanding Sp transmission and thus evaluating pneumococcal conjugate vaccine impact.

Methods

266 lytA-positive nasopharyngeal samples (NPS) taken during season 1 (of 2, October-December 2017) of the Transmission of Pneumococcus (TOP) study (see abstract 715) were analysed by microarray. NPS were collected from 120 families, 2-weekly over 2 months.

Results

83/120 index children (2-year-olds) were lytA positive at baseline (visit 1): the three most common serotypes were 11A, 15B and 35F (n=83) (Graph 1).

In 17/28 families (28 index children, 45 contacts: 26 <16-year-olds and 19), index children shared ≥1 strain/serotype with ≥1 household contact.

40% (107/266) of lytA-positive NPS analysed had multiple serotypes/strains.

Sp was not detected in some lytA-positive samples but rather related streptococcal species, particularly from participants aged ≥5 years (Table 1).

Conclusions

NP carriage of the same Sp serotypes by multiple household members suggests that household Sp transmission occurs.

Multiple serotype carriage was observed in a significant proportion of participants.

Among young children, the age group most likely to transmit Sp, lytA was more predictive of true Sp infection than it was among older persons.

Background

Anti-pneumococcal vaccines are the most effective strategy to prevent pneumococcal disease. However, the pneumococcal burden continues to be a remarkable problem worldwide. Thus, new conjugated vaccines are under development. Through the analysis of the prevalence of pneumococcal serotypes between 2005-2019, we aim to determine the theorical effect of these vaccines in Bogotá, Colombia.

Methods

This is a retrospective analysis of patients reported to a surveillance program due to invasive pneumococcal disease, between 2005 and 2019. We compared the potential serotype coverage of PCV10, PCV13, PCV15, PCV20 by age groups to determine the possible role of these vaccines in Bogotá, Colombia.

Results

A total of 2605 patients were included. In the group of children ˂5 years, PCV10 had serotype coverage of 9%, PCV13 of 27.8%, PCV15 of 28.2%, and PCV20 of 30%. In Adults ˃18 years, PCV10 covered was 11.8%, PCV13 of 26.6%, PCV15 of 27.7%, and PCV20 of 32.7% (Figure-1). Additionally, in adults ˃65 years, PCV10 covered was 10.2%, PCV13 of 26%, PCV15 of 27.4%, and PCV20 of 34%.

Conclusions

According to the most prevalent serotypes in our city, the usage of new vaccines may prevent some episodes of IPD in Bogotá, Colombia. However, further clinical, epidemiological and pharmacoeconomical studies should be performed

Background

The study assessed the incidence rate of all-cause pneumonia (ACP) and invasive pneumococcal disease (IPD) and associated direct medical costs among individuals aged 16 years and older in Germany.

Methods

ACP and IPD were identified using ICD-10-GM codes in the InGef database from 2014 to 2017. Incidence rate was expressed as the number of episodes per 100,000 person-years. Direct medical costs were estimated as the total cost of all inpatient and outpatient visits, divided by the total number of episodes.

Results

The annual incidence of IPD per 100,000 person-years were as follows: 16 to 49 years: 7.2; 50 to 59 years: 29.4; 60 to 69 years: 69.1; and >=70 years: 207.1. The annual incidence of ACP per 100,000 person-years were as follows: 16 to 49 years: 438.8; 50 to 59 years: 809.6; 60 to 69 years: 1199.5; and >=70 years: 2770.9. The mean direct medical costs for IPD and ACP per episode were estimated to be €4551 and €993 respectively. The aggregate direct medical costs for IPD and ACP were estimated to be €28.5 million and €117.7 million respectively.

Conclusions

The clinical and economic burden of IPD and ACP among German adults is substantial regardless of age.

Background

Almost 20% of CAP cases require hospitalization. This study aimed to assess the cost of hospitalization due to CAP to inform delivery of preventative strategies such as vaccination programs.

Methods

The SOS Network study has collected data from 40 tertiary care sites across Canada regarding the clinical characteristics, outcomes information, and resource use of CAP cases from 2010 to 2015. The cost per case was calculated by linking resource costs to resource use frequency for each case. Resource costs included direct and overhead costs.

Results

8,802 CAP admissions were enrolled, and 17.5% were admitted to ICU. The mean age of patients was 69.6 years. The overall length of hospitalization was 10.9 days (95% CI: 10.6, 11.2) and length of ICU stay was 9.0 days (95% CI: 8.4, 9.5). The average cost per case was $138 (95% CI: $129, $147) prior to admission, $14,354 (95% CI: $13,966, $14,743) during admission, and $455 (95% CI: $393, $516) 30-days following admission. The total cost per case was $14,947 (95% CI: $14,553, $15,341).

Conclusions

The cost of CAP hospitalization was higher than previous estimates, and driven mostly by the length of stay. Such data is important for accurate cost effectiveness estimates of prevention programs.

Background

Streptococcus pneumoniae is a major cause of morbidity and mortality worldwide, being the most common etiological pathogen of pneumonia, meningitis and bacteremia. This study assessed the healthcare resource utilization and costs associated with inpatient admissions for pneumonia and invasive pneumococcal disease (IPD) in individuals aged 15 years and older in Spain during 2015.

Methods

A retrospective, descriptive study was conducted using Conjunto Mínimo de Datos-Hospitalización (CMBD-H), a publicly available database provided by the Spanish Ministry of Health capturing approximately 90% of hospitalization episodes.

The economic burden of pneumococcal disease was calculated by multiplying the average cost associated with an inpatient admission for pneumonia or IPD by the number of each type of episode. Additionally, the length of stay (days of hospitalization) due to pneumococcal disease was estimated

Results

The aggregated annual economic burden of pneumococcal disease was 54.1 million euros ($60.1 million) These represented over 97,390 hospitalization days, 80% of which were associated with pneumococcal pneumonia. Pneumococcal meningitis has the highest average cost per episode, 10,706 euros ($11,904) followed by the average cost of a septicemia episode, 9,338 euros ($10,382).

Conclusions

These results demonstrate the substantial economic impact of pneumococcal disease on the Spanish National Health System.

Background

Serotypes 22F and 33F have been added to a new 15-valent pneumococcal-conjugate vaccine (V114, Merck) because of their prevalence causing IPD. An effectiveness study to prove disease prevention for pneumococcal strains expressing 22F and/or 33F capsule would be challenging due to sample size required. A possible solution may be to demonstrate a serologic correlate of protection (COP) based on natural disease responses.

Methods

We evaluated anti-polysaccharide 22F and 33F antibody levels in 6-36 month old children before and after AOM infections caused by pneumococcal strains expressing 22F or 33F capsule. COP levels were inferred using generalized-linear models. To validate our approach testing of anti-19A and 6A antibody levels as comparators is underway.

Results

The contribution of antibody level to AOM risk was statistically significant for 22F (p=0.014) and 33F (p=0.006). We derived that a level of antibody=0.25µg/ml is a COP threshold for prevention of pneumococcal AOM infections caused by 22F and 33F strains. Among unvaccinated children 18-months olds, 62.5% had titers that exceeded this threshold for 22F.

Conclusions

We conclude that a level of antibody of 0.25μg/ml for 22F and 33F will be effective for preventing AOM in children if such levels are produced in response to V114.

Background

In mid-2018, the Australian infant 13vPCV schedule changed from three primary doses (3+0) to two primary doses and a 12 month booster (2+1) to address increasing breakthrough cases of invasive pneumococcal disease (IPD), predominantly in children >12 months. We assess the impact of this schedule change on breakthrough IPD.

Methods

All cases of breakthrough IPD following 13vPCV (2012-2018) reported to the national notifiable diseases surveillance system were analysed by age, serotype and clinical syndrome. In addition, cases in the first 3 quarters post-schedule change were compared to corresponding period pre-change.

Results

Annual 13vPCV breakthrough case counts in children aged <5yrs (figure) increased progressively from 2012(n=3) to 2017(n=73) but declined in 2018 (n=65). Of 306 total cases, 297 were caused by serotypes 3(41%),19A(38%) and 19F(19%). Those aged 12-24 months accounted for 41% (n=125) of cases. Over two thirds of cases (n=211) were pneumonia and 12 were meningitis. Breakthrough cases in children aged >12 months post-schedule change were still more than that in the comparison pre-change period (41 versus 31).

Conclusions

The change to administer the third scheduled PCV dose as a booster (2+1)is expected to reduce breakthrough IPD by improving both direct and indirect protection from 13vPCV but discernible impact is not yet observed.

Background

The incidence of invasive pneumococcal disease (IPD) due to serotypes covered by pneumococcal conjugate vaccines (PCVs) has declined since PCVs introduction. Whether the risk profile of IPD cases have changed following PCVs introduction is unclear.

Methods

We examined the comorbidity profile of all laboratory-confirmed IPD cases identified in Tennessee through active population and laboratory-based surveillance (1998-2017). Comorbidities were identified through chart review, and classified as high-risk and at-risk, as previously described (Figure). We examined changes in the proportion of patients with relevant comorbidities over time, and stratified estimates according to serotype information.

Results

The proportion of IPD cases with high-risk and at-risk comorbidities increased over time from 9% (1998-1999) to 26% (2016-2017) and from 22% to 59%, respectively. For IPD caused by vaccine-covered serotypes (PCV7 or those only covered by PCV13), increases in comorbidities prevalence were attenuated during recent years, but estimates’ precision was limited. For IPD caused by serotypes not in PCV13, the prevalence of comorbidities increased continuously (Figure).

Conclusions

After widespread use of PCVs, patients with residual IPD in Tennessee have a higher prevalence of relevant comorbidities than in previous years. These risk profile changes need to be considered in future prevention plans.