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

BACKGROUND: 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. OBJECTIVES: 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). METHODS: 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. RESULTS: 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%, 18 months 21.7%, and 5 years 15.2%. Risk factors significantly associated with pneumococcal colonisation included young age (9 - 18 months (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%). CONCLUSIONS: 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.

Assessing Pneumococcal Vaccination Availability in Under-Vaccinated Rural Counties: A Pharmacy Perspective.

OBJECTIVE: Vaccines are a low-cost, high-impact interventions that effectively and efficiently reduce the burden of infectious diseases. Many rural populations have vaccination rates well below nationally recommended levels. Community pharmacies may offer a solution to this problem. Under a collaborative drug therapy agreement (CDTA), pharmacists can prescribe and administer immunizations. The purpose of this study was to examine pneumococcal vaccine access in rural pharmacies in Eastern Washington state. DESIGN: A qualitative descriptive design was utilized in this study. The sample included all pharmacies located in two rural Washington state counties. Interviews were conducted with pharmacy staff. Every pharmacy in the two counties was surveyed over the telephone. Data analysis included directed content analysis and descriptive statistics. FINDINGS: Each of the 10 pharmacies identified participated. Pharmacy volume varied (weekly prescription counts of 300 to 2,500). Sixty percent of pharmacies currently provide vaccines. Quoted prices of the PCV13 varied between $65 and $228. Quoted prices of the PPSV23 varied between $64 and $120. Pharmacies that vaccinated made it convenient with "walk-in" scheduling practices. Some pharmacies required a prescription from a separate provider while others could prescribe on-site through CDTA. Pharmacies that chose not to vaccinate did so for a variety of reasons. CONCLUSIONS: Access to pneumococcal vaccines will be enhanced by pharmacist administration, resulting in improved availability, accessibility, accommodation, affordability, and acceptability for patients in rural Washington.

Beyond new vaccine introduction: the uptake of pneumococcal conjugate vaccine in the African Region.

The number of vaccines available to low-income countries has increased dramatically over the last decade. Overall infant immunization coverage in the WHO African region has stagnated in the past few years while countries' ability to maintain high immunization coverage rates following introduction of new vaccines has been uneven. This case study examines post-introduction coverage among African countries that introduced PCV between 2008 and 2013 and the factors affecting Pneumococcal Conjugate Vaccine (PCV) introduction. Nearly one-third of countries did not achieve 80% infant PCV3 coverage by two years post-introduction and 58% of countries experienced a decline in coverage between post introduction years two and four. Major factors affecting coverage rates included introduction without adequate preparation, insufficient supply chain capacity and management, poor communication between organizations and with the public, and data collection systems that were insufficient to meet information needs. Deliberately addressing these issues as well as longstanding weaknesses during new vaccine introduction can strengthen the immunization and broader health system. Further study is required to identify and address factors that affect maintenance of high coverage following introduction of new vaccines in the African region. Immunization with PCV is one of the most important interventions protecting against pneumonia, the second leading cause of death for children under five globally.

Minimum incidence of adult invasive pneumococcal disease in Blantyre, Malawi an urban african setting: a hospital based prospective cohort study.

Invasive pneumococcal disease causes substantial morbidity and mortality in Africa. Evaluating population level indirect impact on adult disease of pneumococcal conjugate vaccine (PCV) programmes in infants requires baseline population incidence rates but these are often lacking in areas with limited disease surveillance. We used hospital based blood culture and cerebrospinal fluid surveillance to calculate minimal incidence of invasive pneumococcal disease in the adult (≥15 years old) population of Blantyre, a rapidly growing urban centre in southern Malawi, in the period preceding vaccine introduction. Invasive pneumococcal disease incidence in Blantyre district was high, mean 58.1 (95% confidence interval (CI): 53.7, 62.7) per 100,000 person years and peaking among 35 to 40 year olds at 108.8 (95%CI: 89.0, 131.7) mirroring the population age prevalence of HIV infection. For pneumococcal bacteraemia in urban Blantyre, mean incidence was 60.6 (95% CI: 55.2, 66.5) per 100,000 person years, peaking among 35 to 40 year olds at 114.8 (95%CI: 90.3, 143.9). We suspected that our surveillance may under-ascertain the true burden of disease, so we used location data from bacteraemic subjects and projected population estimates to calculate local sub-district incidence, then examined the impact of community level socio-demographic covariates as possible predictors of local sub-district incidence of pneumococcal and non-pneumococcal pathogenic bacteraemia. Geographic heterogeneity in incidence was marked with localised hotspots but ward level covariates apart from prison were not associated with pneumococcal bacteraemia incidence. Modelling suggests that the current sentinel surveillance system under-ascertains the true burden of disease. We outline a number of challenges to surveillance for pneumococcal disease in our low-resource setting. Subsequent surveillance in the vaccine era will have to account for geographic heterogeneity when evaluating population level indirect impact of PCV13 introduction to the childhood immunisation program.

Serotype distribution and antimicrobial resistance of invasive and noninvasive pneumococcal isolates in Tunisia.

Pneumococcal conjugate vaccines have not yet been introduced into the national program for childhood vaccination in Tunisia. The aim of this 7-year study was to obtain local data about serotype distribution and antimicrobial resistance of Streptococcus pneumoniae. A total of 203 isolates of culture confirmed that S. pneumoniae was evaluated. Invasive (n=108) and noninvasive (n=95) pneumococcal isolates were obtained from patients aged from 1 month to 85 years old. Considering all age groups, vaccine coverage was 40%, 62%, and 68% for PCV7, PCV10, and PCV13 serotypes, respectively. Overall, 31% of these isolates were penicillin G nonsusceptible. The most prevalent serotypes identified were those found in currently available pneumococcal conjugate vaccines, emphasizing the importance of implementing the vaccine in the routine immunization schedule at the national level.

Systems and spread.

This is the fifth in a series of papers about the science of quality improvement. In this paper, we explore the issue of healthcare as a system and how this contributes to our understanding of how to spread improvement.

Nasopharyngeal carriage and transmission of Streptococcus pneumoniae in American Indian households after a decade of pneumococcal conjugate vaccine use.

BACKGROUND: Young children played a major role in pneumococcal nasopharyngeal carriage, acquisition, and transmission in the era before pneumococcal conjugate vaccine (PCV) use. Few studies document pneumococcal household dynamics in the routine-PCV7 era. METHODS: We investigated age-specific acquisition, household introduction, carriage clearance, and intra-household transmission in a prospective, longitudinal, observational cohort study of pneumococcal nasopharyngeal carriage in 300 American Indian households comprising 1,072 participants between March 2006 and March 2008. RESULTS: Pneumococcal acquisition rates were 2-6 times higher in children than adults. More household introductions of new pneumococcal strains were attributable to children <9 years than adults ≥17 years (p<0.001), and older children (2-8 years) than younger children (<2 years) (p<0.008). Compared to children <2 years, carriage clearance was more rapid in older children (2-4 years, HRclearance 1.53 [95% CI: 1.22, 1.91]; 5-8 years, HRclearance 1.71 [1.36, 2.15]) and adults (HRclearance 1.75 [1.16, 2.64]). Exposure to serotype-specific carriage in older children (2-8 years) most consistently increased the odds of subsequently acquiring that serotype for other household members. CONCLUSIONS: In this community with a high burden of pneumococcal colonization and disease and routine PCV7 use, children (particularly older children 2-8 years) drive intra-household pneumococcal transmission: first, by acquiring, introducing, and harboring pneumococcus within the household, and then by transmitting acquired serotypes more efficiently than household members of other ages.

Cincinnati pediatricians' measured and reported immunizing behavior for children during the national shortages of pneumococcal conjugate vaccine.

BACKGROUND: The United States has experienced two shortages of heptavalent pneumococcal conjugate vaccine (PCV7). National guidelines called for deferring the third and fourth PCV7 doses from healthy children during these shortages. However, recommendations were not the same during the first and second shortages, and recommendations changed over time during each of the shortages as shortages worsened. OBJECTIVES: To measure PCV7 immunizing behavior for healthy children during shortage and non-shortage periods and assess the accuracy of the physicians' reported immunizing behavior when compared to their actual immunizing behavior. METHODS: We reviewed medical records in 14 randomly selected practices to measure actual immunizing behavior during shortage and non-shortage periods. We surveyed pediatricians in the Greater Cincinnati area to ascertain reported immunizing behavior. Actual and reported immunizing behaviors were compared. RESULTS: 2888 medical records were reviewed; surveys were obtained from 51 pediatricians (65% response rate). During periods of non-shortage, 74% of healthy children received their first two doses of PCV7 on time, whereas during periods of shortage, only 66% of healthy children received their first two doses of PCV7 on time. Compared with measured immunizing behavior from chart reviews, 54-76% of the pediatricians overestimated their compliance with guidelines to defer the fourth PCV7 dose while only 5-20% underestimated their compliance. CONCLUSIONS: Physicians often overestimated the percentage of children whose vaccine doses they deferred during vaccine shortages. Despite these findings, physicians were able to maintain high coverage with the first two PCV7 doses among healthy children.

New trends in the prevention and management of community-acquired pneumonia.

Community-acquired pneumonia (CAP) is an important cause of morbidity and mortality worldwide. This review summarises current trends and knowledge gaps in CAP management and prevention. Although Streptococcus pneumoniae is the most frequent cause of CAP, identification of the microbial cause of infection remains unsuccessful in most episodes, and little is known about the aetiology of CAP in immunocompromised patients. Urinary antigen testing has become standard care for diagnosing Legionella infection, and pneumococcal urinary antigen testing is now recommended in the Dutch guidelines to streamline antibiotic therapy in patients hospitalised with CAP. In primary care C-reactive protein determination is recommended to improve antibiotic prescription for lower respiratory tract infections. In patients hospitalised with CAP, three strategies are considered equally effective for choosing empirical antibiotic treatment. Yet, more (and better designed) studies are needed to determine the best strategy, as well as to determine optimal (which usually means the minimum) duration of antibiotic therapy and the role of adjuvant treatment with corticosteroids. The effectiveness of the 23-valent pneumococcal polysaccharide vaccine in preventing invasive pneumococcal disease and pneumococcal CAP remains debated, and whether the newer conjugate vaccines are more effective remains to be determined. Many of these questions are currently being addressed in large-scaled trials in the Netherlands, and their results may allow evidence-based decisions in CAP management and prevention.

Demand for pneumococcal vaccination under subsidy program for the elderly in Japan.

BACKGROUND: Vaccination programs often organize subsidies and public relations in order to obtain high uptake rates and coverage. However, effects of subsidies and public relations have not been studied well in the literature. In this study, the demand function of pneumococcal vaccination among the elderly in Japan is estimated, incorporating effects of public relations and subsidy. METHODS: Using a data from a questionnaire survey sent to municipalities, the varying and constant elasticity models were applied to estimate the demand function. The response variable is the uptake rate. Explanatory variables are: subsidy supported shot price, operating years of the program, target population size for vaccination, shot location intensity, income and various public relations tools. The best model is selected by c-AIC, and varying and constant price elasticities are calculated from estimation results. RESULTS: The vaccine uptake rate and the shot price have a negative relation. From the results of varying price elasticity, the demand for vaccination is elastic at municipalities with a shot price higher than 3,708 JPY (35.7 USD). Effects of public relations on the uptake rate are not found. CONCLUSIONS: It can be suggested that municipalities with a shot price higher than 3,708 JPY (35.7 USD) could subsidize more and reduce price to increase the demand for vaccination. Effects of public relations are not confirmed in this study, probably due to measurement errors of variables used for public relations, and studies at micro level exploring individual's response to public relations would be required.

Is the pneumococcal vaccine Advance Market Commitment motivating innovation and increasing manufacturing capacity? Some preliminary answers.

This paper seeks to give some preliminary evidence on the potential outcome of the pneumococcal vaccine Advance Market Commitment (AMC), with a focus on its impact on innovation in 'emerging' vaccine manufacturers in developing countries. The evidence is derived from a series of interviews with executives at industrial vaccine developing organizations with pneumococcal vaccines in their R&D portfolio, including both multinational pharmaceutical companies and 'emerging' manufacturers. The main findings are that so far there is no evidence to support any claim that the AMC is speeding innovation of pneumococcal vaccines, or that it is contributing to productive capacity expansion. Representatives of emerging manufacturers consistently state that the AMC is either irrelevant or inappropriate for supporting their innovative activities on pneumococcal vaccines.

Cost-effectiveness of introducing the 10-valent pneumococcal conjugate vaccine into the universal immunisation of infants in Brazil.

BACKGROUND: Cost-effectiveness studies have been increasingly part of decision processes for incorporating new vaccines into the Brazilian National Immunisation Program. This study aimed to evaluate the cost-effectiveness of 10-valent pneumococcal conjugate vaccine (PCV10) in the universal childhood immunisation programme in Brazil. METHODS: A decision-tree analytical model based on the ProVac Initiative pneumococcus model was used, following 25 successive cohorts from birth until 5 years of age. Two strategies were compared: (1) status quo and (2) universal childhood immunisation programme with PCV10. Epidemiological and cost estimates for pneumococcal disease were based on National Health Information Systems and literature. A 'top-down' costing approach was employed. Costs are reported in 2004 Brazilian reals. Costs and benefits were discounted at 3%. RESULTS: 25 years after implementing the PCV10 immunisation programme, 10 226 deaths, 360 657 disability-adjusted life years (DALYs), 433 808 hospitalisations and 5 117 109 outpatient visits would be avoided. The cost of the immunisation programme would be R$10 674 478 765, and the expected savings on direct medical costs and family costs would be R$1 036 958 639 and R$209 919 404, respectively. This resulted in an incremental cost-effectiveness ratio of R$778 145/death avoided and R$22 066/DALY avoided from the society perspective. CONCLUSION: The PCV10 universal infant immunisation programme is a cost-effective intervention (1-3 GDP per capita/DALY avoided). Owing to the uncertain burden of disease data, as well as unclear long-term vaccine effects, surveillance systems to monitor the long-term effects of this programme will be essential.

[Conjugate pneumococcal vaccines and influence on the ear, nose and throat area]. / Konjuge pnömokok asilari ve kulak burun bogaz alanindaki etkileri.

The importance of anti-pneumococcal vaccines has increased due to the gradually increasing incidence rate of pneumococcal infections and their antibiotic resistance. Conjugate pneumococcal vaccine began to be used routinely in the USA in 2000. An important property of this conjugate vaccine is the ability to create immunity in infants after two months. Thus, conjugate vaccines allow us to protect children below the age of two years against to invasive and mortal pneumococcal infections. The first pneumococcal conjugate vaccine (PCV7) contains the seven most common pneumococcal serotypes in the USA. Pneumococci are also the most important bacterial agents in acute otitis media (AOM) and recurrent acute otitis media. Acute otitis media is the most common infectious disease in childhood and resistance to treatment has rapidly increased over the last decade. The incidence of AOM and applications of tympanostomy tubes saw statistically significant decreases in the USA after implementation of PCV7 in national immunization programs. PCV7 was implemented in the national immunization program in Turkey in 2008. For this reason, reductions in the incidence of upper respiratory tract infectious diseases and especially AOM should be expected in our country.

[Public health service prescriptions of vaccines not included in systematic vaccination programs in Valencian community, Spain, during the period 2004-2009]. / Prescripción de vacunas no incluidas en el calendario vacunal en la Comunitat Valenciana durante el período 2004-2009.

BACKGROUND: In the context of the policies of rational use of medicine, and in order to achieve an efficient management of the vaccinations programs, we expect to know the number of packings and cost of prescribed vaccines not included in the vaccination programs of Valencian Community and its departments during 2009 and to analyze its evolution since 2004, focusing on an analysis of Heptavalent pneumococcal conjugate vaccine in children under two years old. METHODS: Retrospective descriptive study to analyze the prescriptions of vaccines in Valencian Community during 2009 and its evolution since 2004. VARIABLES: vaccine availability, number of packings, group of beneficiary (actives/pensioners), department, and cost of prescriptions. DATA SOURCES: Gestor de Prestación Farmacéutica (GAIA) and Sistema Información Poblacional (SIP). RESULTS: In 2009 prescribed vaccines on official national health system prescription forms that are not included in vaccination programs, supposed a cost of 683.445,71 € corresponding to 17.353 packings (87% of the total prescribed vaccines). Heptavalent pneumococcal conjugate vaccine generated 72% of the total cost of vaccines not included in the vaccination programs. The trend from 2004 to 2009 shows an increase in expenditure of 735.334 € (24,66%) in 2005 from which there takes place a marked and gradual decrease that reaches 1.562.650,67 € (-228.64%). The cost by departments of prescriptions per 1000 children under two years old of pneumococcal conjugate vaccine ranges between 17.377 and 324 €. CONCLUSIONS: The declining trend of prescriptions, mainly of pneumococcal conjugate vaccines, continues during 2009. A great interdepartmental variability is observed, nevertheless, in rates of prescription that should be corrected.

Economic perspectives on the advance market commitment for pneumococcal vaccines.

Pharmaceutical companies have long been reluctant to invest in producing new vaccines for the developing world because they have little prospect of earning an attractive return. One way to stimulate such investment is the use of an advance market commitment, an innovative financing program that guarantees manufacturers a long-term market. Under this arrangement, international donors pay a premium for initial doses sold to developing countries. In exchange, companies agree to continue supplying the vaccine over the longer term at more sustainable prices. This article provides a preliminary economic analysis of a pilot advance market commitment program for pneumococcal vaccines, explaining the principles behind the program's design and assessing its early performance. Spurred by the advance market commitment--and other contemporaneous initiatives that also increased resources to vaccine suppliers--new, second-generation pneumococcal vaccines have experienced a much more rapid rollout in developing countries than older first-generation vaccines.