Pneumococcal Conjugate Vaccine Vaccination Research Articles

Non-vaccine serotype pneumococcal carriage in healthy infants in South Africa following introduction of the 13-valent pneumococcal conjugate vaccine.

Pneumococcal carriage studies provide a baseline for measuring the impact of pneumococcal conjugate vaccines (PCVs). The advent of conjugate vaccines has led to reductions in vaccine serotypes (VTs) in pneumococcal carriage. However, increasing non-vaccine serotypes (NVTs) remain a significant concern, necessitating continued surveillance of serotypes in the 13-valent PCV vaccine (PCV13) era. To investigate pneumococcal carriage, serotype distribution and risk factors for pneumococcal colonisation among children presenting for routine immunisation at two clinics in Gauteng Province, South Africa (SA), 10 years after PCV introduction into the SA Expanded Programme on Immunisation (EPI-SA). Nasopharyngeal swabs were collected from 322 healthy children aged between 6 weeks and 5 years at two clinic centres in 2014 and 2016. Demographic data, risk factors for colonisation and vaccination details were recorded. The pneumococcal isolates were serotyped and tested for antimicrobial susceptibility. Pneumococci were isolated from 138/316 healthy children (43.7%) presenting for routine immunisation at two clinics. The median age was 8.3 months and the age range 1.4 months - 5 years. Carriage varied across the age groups: 6 - 14 weeks 35.5%, 9 months 27.5%, 18months 21.7%, and 5 years 15.2%. Risk factors significantly associated with pneumococcal colonisation included young age (9 - 18months (odds ratio OR 3.5; 95% confidence interval (CI) 1.9 - 5.9), type of dwelling (single room (OR 8.1; 95% CI 1.3 - 52.3) or informal dwelling (OR 2.4; 95% CI 1.2 - 4.5)) and Haemophilus influenzae carriage (OR 5.6; 95% CI 0.6 - 2.5). Of the 26 serotypes detected, 19F (10/121; 8.3%) was the most frequent. The most frequent NVTs were 23B (16/121; 13.2%), 15B/C (14/121; 11.6 %) and 35B (11/121; 8.2%). Children aged 9 months carried the highest proportion of NVTs (33/101; 32.7%). Penicillin non-susceptibility was observed in 20 NVT isolates (20/36; 55.6%) and 2 VT isolates (2/36; 5.6%). The pneumococcal carriage prevalence described in our study varied across the age groups and was lower compared with other African studies that looked at pneumococcal carriage post PCV. The study gave insight into the common NVTs encountered at two immunisation clinics in Gauteng. Given that pneumococcal carriage precedes disease, common colonisers such as 15B/C and 35B may be sufficiently prevalent in carriage for expansion to result in significant disease replacement.

Subcutaneous abscess caused by Streptococcus pneumoniae serotype 28F in an infant: a case report

BackgroundInvasive pneumococcal disease (IPD) is defined by the detection of Streptococcus pneumoniae on culture from samples obtained from a normally sterile site. Pneumococcal conjugate vaccines (PCV) have been developed for the prevention of IPD that is caused by highly virulent serotypes. Despite the effective reduction of IPD caused by vaccine serotypes after the introduction of PCV, there has been a rapid increase in the incidence of IPD caused by non-vaccine serotypes, and serotype replacement has become a global issue.Case presentationWe report a previously healthy 4-month-old girl presenting with a large subcutaneous abscess caused by S. pneumoniae, identified as non-vaccine serotype 28F. The patient had received routine vaccination, including PCV vaccination. After the incision and drainage of the subcutaneous abscess, the patient was treated with antibiotics. She was discharged on Day 7 of hospitalization without any residual sequelae.ConclusionsSubcutaneous abscess is a common pediatric skin and soft tissue infection, whereas pneumococcal subcutaneous abscesses are quite rare. As the pneumococcal serotype 28F caused a subcutaneous abscess, this serotype possibly has a high virulence. The incidence of IPD caused by non-vaccine serotypes, such as 28F, is expected to increase in the future. The consolidation of international data on pneumococcal serotypes is important for the development of novel PCV.

Budget impact analysis of pneumococcal conjugate vaccines in Colombia

ABSTRACT 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.

Serotypes and Vaccine Coverage of Streptococcus Pneumoniae Colonization in the Nasopharynx of Thai Children in Congested Areas in Chiang Mai.

Streptococcus pneumoniae causes around 10% of all deaths in children younger than five years of age. This study aimed to examine the serogroups/serotypes of S. pneumoniae colonization and vaccine serotype coverage of this organism among Thai children. Nasopharyngeal swabs of children less than or equal to 15 years of age were obtained in congested areas in Chiang Mai from 1 February 2013 to 1 August 2013. The serotyping of S. pneumoniae isolates was performed using the ImmuLex™ kit and the vaccine serotype coverage for this organism was evaluated. A total of 292 children were enrolled. One hundred and thirty children (44.5%) had nasopharyngeal colonization with Streptococcus pneumoniae. Eighty-seven (66.9%) isolates were from children younger than five years of age, seventeen (13.1%) were from children aged 6–10 years, and twenty-six (20%) were from children aged 11–15 years. The five most common serogroups/serotypes isolated were 6 (6A, 6B, 6C) (46.1%), 23 (23F, 23A, 23B) (14.6%), 19 (19F, 19A, 19B, 19C) (8.5%), 15 (15F, 15A, 15B, 15C) (6.9%), and 14 (6.1%). Vaccine serotype coverages in pneumococcal conjugate vaccines (PCV):PCV7, PCV10, and PCV13 were 79.1%, 83.6%, and 85.9%, respectively. There were significant increases in coverage between PCV7 and PCV10 (from 79.1% to 83.6%, p < 0.001), PCV7 and PCV13 (from 79.1% to 85.9%, p < 0.001), and PCV10 and PCV13 (from 83.6% to 85.9%, p < 0.001). The majority of pneumococcal serogroup/serotype colonization in the nasopharynx of Thai children in the studied areas was included in the current licensed pneumococcal conjugated vaccines (PCVs). PCV vaccination should be considered for high-risk children to reduce the incidence of invasive pneumococcal disease among Thai children.

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

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

Pneumococcal conjugate vaccines for preventing acute otitis media in children.

Pneumococcal conjugate vaccines for preventing acute otitis media in children.

Enabling Lyophilized Pneumococcal Conjugate Vaccines Through Formulation Design and Excipient Selection Suitable for A Multivalent Adjuvanted Vaccine

Despite a consistent benefit of existing pneumococcal conjugate vaccine (PCV) on invasive pneumococcal disease and pneumonia across different epidemiological settings a tremendous gap exists towards global PCV coverage. Currently, no lyophilized dosage form exists in the PCV global vaccine marketplace and currently licensed vaccines target some, but not all relevant serotypes of Streptococcus pneumoniae. The development of lyophilized presentations of an adjuvanted multivalent vaccine formulation that aligns with the evolving epidemiological assessment of the pneumococcal disease offers broader coverage with distinct cold chain and thermostability advantages. To make progress towards this goal, we evaluated the feasibility of developing new formulation to enable a lyophilized adjuvanted PCV vaccine containing 15 different serotypes. Our findings successfully demonstrate a formulation design space that enables enhanced physical stability which controls vaccine agglomeration, preserves in-vitro vaccine potency, maintains PCV antigen adsorption, and yields elegant lyophilized cakes with acceptable clinically relevant reconstitution times. This research also demonstrates the benefit of utilizing specific vaccine formulation excipients and the effectiveness of excipient combinations that may be beneficial for other multivalent adjuvant containing vaccines to enable novel lyophilized formulations necessary for improved global vaccine access.

The direct effect of pneumococcal conjugate vaccines on invasive pneumococcal disease in children in the Latin American and Caribbean region (SIREVA 2006–17): a multicentre, retrospective observational study

Streptococcus pneumoniae isolated from patients with invasive pneumococcal disease has been subjected to laboratory-based surveillance in Latin American and Caribbean countries since 1993. Invasive pneumococcal diseases remain a major cause of death and disability worldwide, particularly in children. We therefore aimed to assess the direct effect of pneumococcal conjugate vaccines (PCVs) on the distribution of pneumococcal serotypes causing invasive pneumococcal disease in children younger than 5 years before and after PCV introduction. We did a multicentre, retrospective observational study in eight countries that had introduced PCV (ie, PCV countries) in the Latin American and Caribbean region: Argentina, Brazil, Chile, Colombia, Dominican Republic, Mexico, Paraguay, and Uruguay. Cuba and Venezuela were also included as non-PCV countries. Isolate data for Streptococcus pneumoniae were obtained between 2006 and 2017 from children younger than 5 years with an invasive pneumococcal disease from local laboratories or hospitals. Species' confirmation and capsular serotyping were done by the respective national reference laboratories. Databases from the Sistema Regional de Vacunas (SIREVA) participating countries were managed and cleaned in a unified database using Microsoft Excel 2016 and the program R (version 3.6.1). Analysis involved percentage change in vaccine serotypes between pre-PCV and post-PCV periods and the annual reporting rate of invasive pneumococcal diseases per 100 000 children younger than 5 years, which was used as a population reference to calculate percentage vaccine type reduction. Between 2006 and 2017, 12 269 isolates of invasive pneumococcal disease were collected from children younger than 5 years in the ten Latin American and Caribbean countries. The ten serotypes included in ten-valent pneumococcal conjugate vaccine (PCV10) decreased significantly (p<0·0001) after any PCV introduction, except for the Dominican Republic. The percentage change for the ten vaccine serotypes in PCV10 countries was -91·6% in Brazil (530 [72·9%] of 727 before, 27 [6·1%] of 441 after); -85·0% in Chile (613 [72·6%] of 844 before, 44 [10·9%] of 404] after); -84·7% in Colombia (231 [63·1%] of 366 before, 34 [9·7%] of 352 after); and -73·8% in Paraguay (127 [77·0%] of 165 before, 22 [20·2%] of 109 after). In the 13-valent pneumococcal conjugate vaccine (PCV13) countries, the percentage change for the 13 vaccine serotypes was -59·6% in Argentina (853 [85·0%] of 1003 before, 149 [34·3%] of 434 after); -16·5% in the Dominican Republic (95 [80·5%] of 118 before, 39 [67·2%] of 58 after); -43·7% in Mexico (202 [73·2%] of 276 before, 63 [41·2%] of 153 after); and -45·9% in Uruguay (138 [80·7%] of 171 before, 38 [43·7%] of 87 after). Annual reporting rates showed a reduction from -82·5% (6·21 before vs 1·09 after per 100 000, 95% CI -61·6 to -92·0) to -94·7% (1·15 vs 0·06 per 100 000, -89·7 to -97·3) for PCV10 countries, and -58·8% (2·98 vs 1·23 per 100 000, -21·4 to -78·4) to -82·9% (7·80 vs 1·33 per 100 000, -76·9 to -87·4) for PCV13 countries. An increase in the amount of non-vaccine types was observed in the eight countries after PCV introduction together with an increase in their percentage in relation to total invasive strains in the post-PCV period. SIREVA laboratory surveillance was able to confirm the effect of PCV vaccine on serotypes causing invasive pneumococcal disease in the eight PCV countries. Improved monitoring of the effect and trends in vaccine type as well as in non-vaccine type isolates is needed, as this information will be relevant for future decisions associated with new PCVs. None. For the Portuguese and Spanish translations of the abstract see Supplementary Materials section.

Pneumococcal Vaccination for Children in Asian Countries: A Systematic Review of Economic Evaluation Studies.

Background: Evidence on costs and health benefits of pneumococcal conjugate vaccine (PCV) for children in Asian countries is limited but growing. As a region with a considerably high burden of pneumococcal disease, it is prominent to have a comprehensive overview on the cost-effectiveness of implementing and adopting a PCV vaccination program. Methods: We conducted a systematic review from Pubmed and Embase to identify economic evaluation studies of PCV for children in Asian countries up to May 2020. Data extraction included specific characteristics of the study, input parameters, cost elements, cost-effectiveness results, and key drivers of uncertainty. The Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) statement was followed for this systematic review. The reporting quality of the included studies was evaluated using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement. Results: After the screening process on both the title and abstract and full text of 518 records, a total of 25 studies fulfilled the inclusion criteria, and were included in the review. The majority of included studies demonstrates that PCV for children is cost-effective in most of the Asian region, and even cost-saving in some countries. Most of the included studies implemented cost utility analysis (CUA) using either quality-adjusted life years (QALYs) or disability-adjusted life years (DALYs). Overall, the main drivers affecting the cost effectiveness were vaccine price, burden regarding pneumonia-related parameters, and the inclusion of herd effects. Conclusion: The children pneumococcal vaccination program appears to be a cost-effective intervention in Asia, and even cost-saving in certain conditions. Vaccine price, pneumonia-related disease burden, and the inclusion of the herd effect are observed as important key drivers in estimating cost-effectiveness in this region. Incorporating PCV in vaccination programs in this region was found to be highly favorable.

A health benefit and cost-effectiveness analysis of pneumococcal conjugate vaccination program in Nigeria

Background: Nigeria ranks third just behind India and China in the global disease burden of pneumococcal disease. The current sustainability approach for an affordable pneumococcal conjugate vaccine (PCV) for the national immunization program from 2014 till 2025 involves a cost sharing plan funded with a 75% financial support from GAVI and a subsidy from Pfizer pharmaceuticals. There is a strong need to generate evidence on the cost-effectiveness of the national PCV program in Nigeria from 2014-2025 and beyond 2025.Methods: The following parameters (demography, disease burden, health services utilization and costs, vaccination coverage, vaccine efficacy, and vaccination costs) were used in a static cohort model to estimate the total cost, health and economic benefit, and cost-effectiveness of the implementation of PCV vaccination program, compared with no PCV vaccination among under-five children in Nigeria from 2014-2025 and from 2026-2033. A sensitivity analysis was conducted to evaluate the robustness of the data used.Results: The national PCV vaccination program would have an approximated 31.4% and 30% reduction of the total burden of pneumococcal diseases over the period of 2014-2025 and 2026-2033 respectively. One-way sensitivity analysis reveals vaccine efficacy as most sensitive parameter followed by disease incidence rate and treatment cost. Removal and addition of DTP3 and 3+1 (measles vaccine) dose respectively resulted to a similar ICER from both.Conclusions: The estimated ICER suggests that the national PCV program in Nigeria will be cost-effective post 2025 era. In addition, it is recommended for policy-makers adoption considering the budget and equity impact of the intervention in Nigeria.

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

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

Routine infant vaccination of pneumococcal conjugate vaccines has decreased pneumonia across all age groups in Northern Spain

ABSTRACT Since the early 2000s, pneumococcal conjugate vaccines (PCVs) have been shown to be effective in the prevention of pneumonia and invasive pneumococcal diseases. In 2011, the Galician region incorporated PCV in the routine infant immunization, the very first stable program in Spain. We aim to assess direct and indirect benefits of PCV vaccination on all-cause pneumonia in the region across different age groups using an ecological study design. For this, we calculated the annual hospitalization rates using a hospital-based disease registry. We identified all-cause pneumonia, pneumococcal pneumonia and pneumococcal invasive diseases within the registry. Hospitalization rates were computed and compared across three study periods: pre-vaccination (1998–2003), early-vaccination (2005–2009) and routine-vaccination (2011–2015). Across Northern Spain, we identified 114,873 all-cause pneumonia hospitalizations, of which 24,808 were further diagnosed with pneumococcal pneumonia. The majority were elderly > 64 years (67.3%). Hospitalizations from all-cause pneumonia had a net increase from 20.6 (pre-PCV) and 21.4/10,000 (early) to 28.4/10,000 (routine) (+32.7%, p < .0001), this is attributed to the huge number of cases in the elderly age group. In contrast, a net reduction of incidence of hospitalized pneumococcal pneumonia was observed from 6.3/10,000 (pre-PCV) and 5.7/10,000 (early) to 2.4/10,000 (routine) cases (−57.9%, p < .0001). Thus, routine infant vaccination may have resulted to an overall decline of pneumococcal pneumonia in infants, as well as in elderly age groups. However, a paradoxical increase on all-cause pneumonia was observed in Galicia, mostly attributed to the growing number of cases in the elderly population.

Awareness Among Parents About Pneumococcal Conjugate Vaccine in Routine Immunization Program to Prevent Pneumococcal Pneumonia in Bangladesh.

IntroductionThis study was conducted in two purposively selected slums of Dhaka to assess parents’ awareness of pneumococcal conjugate vaccine (PCV) in reducing the occurrence of death due to pneumococcal pneumonia.MethodsUsing a semi-structured questionnaire, face-to-face interviews were conducted with 150 parents. Data were analyzed using Statistical Package for the Social Sciences (SPSS), version 20 (IBM Corp., Armonk, NY) and Chi-square (χ2) test performed to determine associations.ResultsAbout 35% of parents were found to be aware of PCV; of them, 92.5% were informed by health service providers, and 81.1% mentioned benefits of PCV. Most parents were unaware of the PCV vaccination status of children, and no significant association was found between vaccination status and parents’ socioeconomic status. Aware parents vaccinated their children, and the association of awareness with vaccination status was statistically significant for PCV-1 (P = 0.04) and PCV-2 (P < 0.001). Although 7.4% of parents did not vaccinate their child with PCV-3 due to a child’s sickness or other priorities in household work, the association was significant (P = 0.01).ConclusionStrengthened efforts by health service providers, prioritizing dissemination of key messages on PCV, its benefits, and side-effects, can motivate parents and reduce dropout rates.

2699. Pneumococcal Vaccination During Chemotherapy in Children Treated for Acute Lymphoblastic Leukemia

BackgroundChildren undergoing therapy for acute lymphoblastic leukemia (ALL) are at high risk of invasive pneumococcal disease (IPD). Immunization with conjugated vaccines following chemotherapy is recommended for pediatric patients. In an attempt to provide an earlier protection against invasive pneumococcal infection, we aimed to assess immunity to S. pneumoniae among children vaccinated during chemotherapy for ALL.MethodsWe retrospectively analyzed the rate of seroprotection among ALL children treated in our institution in accordance with the DFCI ALL Consortium protocol between 2007 and 2014. A pneumococcal conjugate vaccine (PCV) booster was given to all subjects after the end of chemotherapy (groups 1 and 2). In group 2, a PCV dose was also administered during the maintenance phase. Clinical characteristics as well as individual immunization records were collected from our local immunization database. All children were up to date with their vaccination schedule at diagnosis. Serum samples were obtained on a routine follow-up visit, after the end of chemotherapy and after the PCV vaccine booster to measure serotype-specific IgG pneumococcal antibodies. Antibody level ≥0.35µg/mL was considered protective. Patients with seroprotective antibodies level for ≥ 50% of serotypes contained in vaccines were defined as seroprotected.Results62 children [34 girls (54.8%)] were included in the analysis. Median age at diagnosis was 45 months (range:12–160). At the end of chemotherapy, 34.2% of children in group 1 (13/38) and 79.2% in group 2 (19/24) were seroprotected (P < 0.01). Median interval of time between the end of chemotherapy and the PCV booster vaccination was 6 months (range: 2–64 months). After PCV-13 booster, the rate of seroprotection raised to 100% (38/38) in group 1 and 91.7% in group 2 (22/24).ConclusionRates of pneumococcal seroprotected children treated for ALL are low at the end of chemotherapy. However, PCV booster during chemotherapy could be useful to increase the level of seroprotection and shorten the period of susceptibility to IPD. After chemotherapy for ALL, children benefit from a PCV booster to enhance seroprotection. Disclosures All authors: No reported disclosures.

Monitoring of community-acquired pneumonia hospitalisations before the introduction of pneumococcal conjugate vaccine into Polish National Immunisation Programme (2009–2016): A nationwide retrospective database analysis

PurposeCommunity-acquired pneumonia (CAP) is a common infection with significant morbidity and mortality. In January 2017, Poland introduced pneumococcal conjugate vaccine (PCV) into their national immunisation programme to protect children against invasive pneumococcal disease. This study was designed to investigate pneumonia-related hospitalisation rates and trends from 2009 to 2016 prior to the introduction of nationally funded PCV vaccination. MethodsUsing national public statistic data available from the National Institute of Public Health – National Institute of Hygiene, annual hospitalisation rates for pneumonia were analysed, categorised by aetiology and age (<2, 2–3, 4–5, 6–19, 20–59, 60+ years). Trends over time were assessed, as well as in-hospital mortality. ResultsThe overall hospitalisation rate due to pneumonia varied between 325.9 and 372.2/100,000 population. Higher rates of hospitalisation were seen in older adults and children ≤5 years. Trends were observed when analysing hospitalisations by pneumonia aetiology within age groups: between 2009 and 2016, Streptococcus pneumoniae hospitalisations significantly increased for children aged <2, 2–3, and 4–5 years, from 5.3 to 12.4, 5.2 to 8.2, and 1.9 to 4.6/100,000 population respectively. Whereas hospitalisations due to Haemophilus influenzae pneumonia decreased significantly from 7.8 to 1.8 and 4.8 to 1.9/100,000 children aged <2 and 2–3 years respectively. The numbers of in-hospital deaths increased from 5578 in 2009 to 8149 in 2016, with >85% of deaths in the 60+ age group. ConclusionsThis is the first national study of pneumonia hospitalisations in Poland, providing the baseline data from which to investigate the impact of the change in vaccination policy on pneumonia hospitalisations in Poland.

Estimating the economic impact of pneumococcal conjugate, Haemophilus influenzae type b and rotavirus vaccines in India: National and state-level analyses

Background: To support vaccine decision-making we estimated from the societal perspective the potential health impact and costs averted through immunization with three vaccines – Haemophilus influenzae type b (Hib), pneumococcal conjugate vaccine (PCV) and rotavirus vaccine (RVV). Methods: Based on variability in disease burden, strength of health system and economic status, we selected four states in India: Bihar, New Delhi, Maharashtra and Tamil Nadu. We used secondary data sources to estimate the number of under-5 deaths averted from Hib, pneumococcus and rotavirus in each state and back-calculated the total cases averted. We synthesized available data to estimate the disease burden, treatment cost, caretaker productivity loss and vaccine coverage in each state. A Delphi Survey and roundtable among Indian experts was conducted to reach consensus on model inputs. Results: By scaling up coverage of Hib, PCV and RVV, India could save over US$1 billion (uncertainty range: US$0.9–US$2.4 billion) in economic benefits and avert more than 90,000 needless child deaths each year. An estimated US$1 billion (US$0.9–US$2 billion) or 88% of the total amount of cost savings would be attributable to lost productivity due to premature pneumococcal death. Another US$112.8 million (US$105–297 million), or 10% of the total cost would be accounted by costs related to loss of productivity due to disability as a result of these diseases. Treatment costs of Hib, pneumococcal disease and rotavirus gastroenteritis, would account for US$8.4 million (US$4–12 million) or <1% of the total costs of these diseases. Finally, caretaker productivity loss from seeking care would represent US$1.5 million (US$ 1–4.9 million). Cost savings varied by vaccine, coverage scenarios and states. Conclusions: Hib, PCV and RVV vaccine introduction in India can result in immediate benefits to the government and households in terms of savings.

Effectiveness of pneumococcal conjugate vaccine against hospital admissions for pneumonia in Australian children: a retrospective, population-based, record-linked cohort study

Reductions in pneumonia hospitalisations following introduction of pneumococcal conjugate vaccines (PCVs) have been reported from high-incidence and low-incidence settings but long-term data comparing vaccinated with unvaccinated children are sparse. We did a retrospective, population-based, record-linkage cohort study in Australian children using administrative health data from the Western Australian Midwives' Notification System and New South Wales Perinatal Data Collection, and the birth and death registries in both states. PCV vaccination details, pneumonia-coded hospital admissions, and invasive pneumococcal disease notification records were individually linked for children born between 2001 and 2012. The primary outcome was defined as the first hospital admission for all-cause pneumonia. Cox models were used to calculate adjusted hazard ratios (HR) to estimate the effect of PCV doses on pneumonia-coded hospital admissions by Aboriginal status, birth period, remoteness, and pneumonia diagnostic category in children younger than 2 years. Person-time of follow-up time for each child started at birth and was censored at the earliest of first hospital admission for all-cause pneumonia, death, invalid PCV dose, when the child reached age 24 months, or the end date of the study period (Dec 31, 2013) FINDINGS: The study cohort comprised 1 365 893 children liveborn between Jan 1, 2001, and Dec 31, 2012, of whom 66 484 (4·9%) were identified as Aboriginal. The overall rate for all-cause pneumonia hospital admissions for children younger than 2 years over the entire study period was 17·6/1000 child-years in Aboriginal children and 5·5/1000 child-years in non-Aboriginal children. Compared with children born between 2001 and 2004 (ie, the pre-universal PCV period), the incidence of pneumonia-coded hospital admissions decreased in both vaccinated (6·5 vs 5·7 per 1000 child-years [12% reduction, 95% CI 3-21; p=0·01]) and unvaccinated non-Aboriginal children (6·8 vs 3·7 [45% reduction; 41-49]) born 2005-12 (the universal PCV period); among Aboriginal children, declines were significant only among those vaccinated (27·4 vs 14·1 [49% reduction, 40-55]). Among Aboriginal children born 2005-12, the risk of pneumonia-coded hospital admission after three doses of PCV was lower than those unvaccinated (adjusted HR 0·83, 95% CI 0·65-0·99) but, among non-Aboriginal children, the risk was similar (adjusted HR 1·09, 0·98-1·22). Overall, remote-born Aboriginal children had the highest incidence of hospital admission for pneumonia and among children born 2005-12, the adjusted risk was 37% lower (adjusted HR 0·63, 95% CI 0·42-0·96) among those fully vaccinated than those unvaccinated. Reductions in pneumonia-coded hospital admissions in unvaccinated children predominated in non-Aboriginal children with low incidence of pneumonia but were not significant in Aboriginal children with high incidence. These findings have potential implications for measuring PCV effect using a non-specific endpoint such as all-cause pneumonia in high-incidence populations. Commonwealth Government Collaborative Research Infrastructure Strategy and Education Investment Fund Super Science Initiative and the Australian National Health and Medical Research Council.

The 13-Valent Pneumococcal Conjugate Vaccine Is Effective Against Hypoxic Pneumonia in Children in Lao PDR: A Novel Method Using a Hospital-Based Observational Study

Background: Pneumococcal pneumonia is a leading cause of childhood mortality. Pneumococcal conjugate vaccines (PCVs) have been shown to reduce hypoxic pneumonia in children. However, there are no 13-valent PCV (PCV13) vaccine effectiveness (VE) studies on hypoxic pneumonia from Asia. We describe a novel approach to determine the effectiveness of PCV13 against hypoxic pneumonia in children admitted with pneumonia in the Lao People's Democratic Republic, a low-resource setting. Methods: A prospective hospital-based observational study of children up to 59 months old admitted with pneumonia to a single tertiary hospital in Vientiane was undertaken over 54 months. Pneumonia was defined using the 2013 WHO definition. Hypoxia was defined as an oxygen saturation <90% in room air or requiring oxygen supplementation during hospitalisation. PCV13 status was determined by written record. VE was calculated using logistic regression comparing the odds of hypoxia between vaccinated and undervaccinated pneumonia cases. To handle potential confounders a propensity score (PS) analysis using inverse probability of treatment weighting was used; for missing data, multiple imputation (MI) analysis was undertaken. Findings: There were 826 children admitted with pneumonia, 285 had hypoxic pneumonia and 377 were PCV13-vaccinated. The unadjusted, PS adjusted and MI adjusted VE against hypoxic pneumonia were 23% (95% confidence interval [CI]: -9, 46%; p=0·14); 37% ([CI]: 6, 57%; p=0·02) and 35% ([CI]: 7, 55%; p=0·02) respectively. Interpretation: This is the first apparent study to show PCV13 is effective against hypoxic pneumonia in Asia. This single hospital-based approach will enable other similar settings to test for VE. Funding Statement: This study received funding from the Bill & Melinda Gates Foundation (OPP1115490). Declaration of Interests: KM and CN receive grants from Pfizer, outside the submitted work. The Institute of Research for Development (IRD) and Aix-Marseille University funds both ADP and the HRSV testing. PN receives grants from the Wellcome Trust. JL receives funding from Bill and Melinda Gates foundation. All other authors declare no competing interests. The opinion presented in this paper is that of the authors and does not reflect Pfizer. We have not been paid by a pharmaceutical company to write this article. Ethics Approval Statement: This study was conducted according to the study protocol approved by the Oxford Tropical Research Ethics Committee (OxTREC reference:1050-13), Laos Ministry of Health National Ethics Committee for Health Research (No 061NECHR), the Ethics Review Committee of the WHO Regional Office for the Western Pacific Region (WPRO-ERC) (reference ID:2013.30.LAO.2.EPI) and by The Royal Children’s Hospital Human Resources Ethics Committee (HREC) (reference number:33177B).

An updated cost-effectiveness analysis of pneumococcal conjugate vaccine among children in Thailand

BackgroundA previous cost-effectiveness analysis (CEA) showed that Pneumococcal Conjugate Vaccine (PCV) 10 and PCV13 were not cost-effective for universal immunization among children in Thailand. Given recent changes in the evidence of efficacy, herd effects and price, a CEA of PCVs should be revisited. This study aimed to determine the cost-effectiveness of PCV10 and PCV13 compared to no PCV vaccination in Thai children. Material and methodsA Markov model was developed under a societal perspective with a lifetime horizon. Inputs were derived from a comprehensive literature review. Costs were calculated using the Thai National Electronic Database and converted to the year 2017 value. All costs and outcomes were discounted at a rate of 3%. The findings were reported as incremental cost-effectiveness ratios (ICERs) in Thai Baht (THB) per quality-adjusted life year (QALY) gained. Sensitivity analyses were performed. A cost-effectiveness acceptability curve was generated with the cost-effectiveness threshold of 160,000 THB/QALY. ResultsBase-case analysis of 2 + 1 dose schedule and five-year protection, with no consideration of herd effect showed that ICER for PCV10 was 170,437 THB/QALY, while ICER for PCV13 was 73,674 THB/QALY. With consideration of herd effect, both PCV10 and PCV13 had lower costs and higher QALYs compared to no PCV vaccination. Based on our probabilistic sensitivity analysis at willingness-to-pay of 160,000 THB/QALY, PCV13 had 93% of being cost-effective, while 4.7% and 2.3%, for PCV10 and no PCV vaccination, respectively. ConclusionAt current prices, PCV13 is cost-effective, while PCV10 is not cost-effective in Thailand. When considering herd-effect, both PCV10 and PCV13 are cost-effective.

Protective effect of PCV vaccine against experimental pneumococcal challenge in adults is primarily mediated by controlling colonisation density

Widespread use of Pneumococcal Conjugate Vaccines (PCV) has reduced vaccine-type nasopharyngeal colonisation and invasive pneumococcal disease. In a double-blind, randomised controlled trial using the Experimental Human Pneumococcal Challenge (EHPC) model, PCV-13 (Prevenar-13) conferred 78% protection against colonisation acquisition and reduced bacterial intensity (AUC) as measured by classical culture. We used a multiplex qPCR assay targeting lytA and pneumococcal serotype 6A/B cpsA genes to re-assess the colonisation status of the same volunteers. Increase in detection of low-density colonisation resulted in reduced PCV efficacy against colonisation acquisition (29%), compared to classical culture (83%). For experimentally colonised volunteers, PCV had a pronounced effect on decreasing colonisation density. These results obtained in adults suggest that the success of PCV vaccination could primarily be mediated by the control of colonisation density. Studies assessing the impact of pneumococcal vaccines should allow for density measurements in their design.