scholarly journals Exploring the role of competition induced by non-vaccine serotypes for herd protection

2017 ◽  
Author(s):  
G. L. Masala ◽  
M. Lipsitch ◽  
C. Bottomley ◽  
S. Flasche
Keyword(s):  
Disease Burden ◽  
Vaccine Coverage ◽  
Conjugate Vaccines ◽  
Effective Coverage ◽  
Vaccine Serotypes ◽  
Herd Protection ◽  
Vaccine Type ◽  
Vaccine Impact ◽  
Indirect Protection

AbstractThe competitive pressure from non-vaccine serotypes may have helped pneumococcal conjugate vaccines (PCVs) to limit vaccine serotype (VT) prevalence. We aim to investigate if, consequently, the indirect protection of higher valency vaccines could fall short of the profound effects of current formulations.We compare three previously described pneumococcal models harmonized to simulate 20 serotypes with a combined pre-vaccination prevalence in <5y old children of 40%. We simulate vaccines of increasing valency by adding serotypes in order of their competitiveness and explore their ability to reduce VT carriage by 95% within 10 years after introduction.All models predict that additional valency will reduce indirect vaccine effects and hence the overall vaccine impact on carriage both in children and adults. Consequently, the minimal effective coverage (efficacy against carriage * vaccine coverage) needed to eliminate vaccine type carriage increases with increasing valency. One model predicts this effect to be modest while the other two predict that high-valency vaccines may struggle to eliminate VT pneumococci unless vaccine efficacy against carriage can be substantially improved. Similar results were obtained when settings of higher transmission intensity and different PCV formulations were explored.Failure to eliminate carriage as a result of increased valency could lead to overall decreased impact of vaccination if the disease burden caused by the added serotypes is low. Hence a comparison of vaccine formulations of varying valency, and pan-valent formulations in particular, should consider the invasiveness of targeted serotypes, as well as efficacy against carriage.

scholarly journals Exploring the role of competition induced by non-vaccine serotypes for herd protection following pneumococcal vaccination

2017 ◽  
Vol 14 (136) ◽  
pp. 20170620 ◽  
Author(s):  
G. L. Masala ◽  
M. Lipsitch ◽  
C. Bottomley ◽  
S. Flasche
Keyword(s):  
Disease Burden ◽  
Vaccine Coverage ◽  
Pneumococcal Vaccination ◽  
Effective Coverage ◽  
Vaccine Serotypes ◽  
Herd Protection ◽  
Vaccine Type ◽  
Vaccine Impact ◽  
Indirect Protection

The competitive pressure from non-vaccine serotypes may have helped pneumococcal conjugate vaccines (PCVs) to limit vaccine-type (VT) serotype prevalence. We aimed to investigate if, consequently, the indirect protection of vaccines targeting most pneumococcal serotypes could fall short of the profound effects of current formulations. We compared three previously described pneumococcal models harmonized to simulate 20 serotypes with a combined pre-vaccination prevalence in children younger than 5-years-old of 40%. We simulated vaccines of increasing valency by adding serotypes in order of their competitiveness and explored their ability to reduce VT carriage by 95% within 10 years after introduction. All models predicted that additional valency will reduce indirect vaccine effects and hence the overall vaccine impact on carriage both in children and adults. Consequently, the minimal effective coverage (efficacy against carriage×vaccine coverage) needed to eliminate VT carriage increased with increasing valency. One model predicted this effect to be modest, while the other two predicted that high-valency vaccines may struggle to eliminate VT pneumococci unless vaccine efficacy against carriage can be substantially improved. Similar results were obtained when settings of higher transmission intensity and different PCV formulations were explored. Failure to eliminate carriage as a result of increased valency could lead to overall decreased impact of vaccination if the disease burden caused by the added serotypes is low. Hence, a comparison of vaccine formulations of varying valency, and pan-valent formulations in particular, should consider the invasiveness of targeted serotypes, as well as efficacy against carriage.

scholarly journals Herd Protection against Meningococcal Disease through Vaccination

2020 ◽  
Vol 8 (11) ◽  
pp. 1675
Author(s):  
Stephen A. Clark ◽  
Ray Borrow
Keyword(s):  
Capsular Polysaccharide ◽  
High Weight ◽  
Age Groups ◽  
Invasive Disease ◽  
Current Data ◽  
Conjugate Vaccines ◽  
Herd Protection ◽  
Cast Doubt ◽  
Group B ◽  
Indirect Protection

Reduction in the transmission of Neisseria meningitidis within a population results in fewer invasive disease cases. Vaccination with meningococcal vaccines composed of high weight capsular polysaccharide without carrier proteins has minimal effect against carriage or the acquisition of carriage. Conjugate vaccines, however, elicit an enhanced immune response which serves to reduce carriage acquisition and hinder onwards transmission. Since the 1990s, several meningococcal conjugate vaccines have been developed and, when used in age groups associated with higher carriage, they have been shown to provide indirect protection to unvaccinated cohorts. This herd protective effect is important in enhancing the efficiency and impact of vaccination. Studies are ongoing to assess the effect of protein-based group B vaccines on carriage; however, current data cast doubt on their ability to reduce transmission.

scholarly journals Association of Pneumococcal Conjugate Vaccine Coverage With Pneumococcal Meningitis: An Analysis of French Administrative Areas, 2001–2016

2019 ◽  
Vol 188 (8) ◽  
pp. 1466-1474
Author(s):  
Anna Alari ◽  
Félix Cheysson ◽  
Lénaig Le Fouler ◽  
Philippe Lanotte ◽  
Emmanuelle Varon ◽  
...  
Keyword(s):  
Conjugate Vaccine ◽  
Invasive Pneumococcal Disease ◽  
Pneumococcal Conjugate Vaccine ◽  
Pneumococcal Disease ◽  
Pneumococcal Meningitis ◽  
Vaccine Coverage ◽  
Mixed Effect ◽  
Cumulative Impact ◽  
Vaccine Serotypes ◽  
Vaccine Impact

Abstract Geographic variations of invasive pneumococcal disease incidence and serotype distributions were observed after pneumococcal conjugate vaccine introduction at regional levels and among French administrative areas. The variations could be related to regional vaccine coverage (VC) variations that might have direct consequences for vaccination-policy impact on invasive pneumococcal disease, particularly pneumococcal meningitis (PM) incidence. We assessed vaccine impact from 2001 to 2016 in France by estimating the contribution of regional VC differences to variations of annual local PM incidence. Using a mixed-effect Poisson model, we showed that, despite some variations of VC among administrative areas, vaccine impact on vaccine-serotype PM was homogeneously confirmed among administrative areas. Compared with the prevaccine era, the cumulative VC impact on vaccine serotypes led, in 2016, to PM reductions ranging among regions from 87% (25th percentile) to 91% (75th percentile) for 7-valent pneumococcal conjugate vaccine serotypes and from 58% to 63% for the 6 additional 13-valent pneumococcal conjugate vaccine serotypes. Nonvaccine-serotype PM increases from the prevaccine era ranged among areas from 98% to 127%. By taking into account the cumulative impact of growing VC and VC differences, our analyses confirmed high vaccine impact on vaccine-serotype PM case rates and suggest that VC variations cannot explain PM administrative area differences.

scholarly journals Levels of pneumococcal conjugate vaccine coverage and indirect protection against invasive pneumococcal disease and pneumonia hospitalisations in Australia: An observational study

PLoS Medicine ◽  
2021 ◽  
Vol 18 (8) ◽  
pp. e1003733
Author(s):  
Jocelyn Chan ◽  
Heather F. Gidding ◽  
Christopher C. Blyth ◽  
Parveen Fathima ◽  
Sanjay Jayasinghe ◽  
...  
Keyword(s):  
Invasive Pneumococcal Disease ◽  
Pneumococcal Disease ◽  
Vaccine Coverage ◽  
A Priori ◽  
Indigenous Populations ◽  
South Wales ◽  
Vaccine Type ◽  
Urban Rural ◽  
Program Costs ◽  
Indirect Protection

Background There is limited empiric evidence on the coverage of pneumococcal conjugate vaccines (PCVs) required to generate substantial indirect protection. We investigate the association between population PCV coverage and indirect protection against invasive pneumococcal disease (IPD) and pneumonia hospitalisations among undervaccinated Australian children. Methods and findings Birth and vaccination records, IPD notifications, and hospitalisations were individually linked for children aged <5 years, born between 2001 and 2012 in 2 Australian states (New South Wales and Western Australia; 1.37 million children). Using Poisson regression models, we examined the association between PCV coverage, in small geographical units, and the incidence of (1) 7-valent PCV (PCV7)-type IPD; (2) all-cause pneumonia; and (3) pneumococcal and lobar pneumonia hospitalisation in undervaccinated children. Undervaccinated children received <2 doses of PCV at <12 months of age and no doses at ≥12 months of age. Potential confounding variables were selected for adjustment a priori with the assistance of a directed acyclic graph. There were strong inverse associations between PCV coverage and the incidence of PCV7-type IPD (adjusted incidence rate ratio [aIRR] 0.967, 95% confidence interval [CI] 0.958 to 0.975, p-value < 0.001), and pneumonia hospitalisations (all-cause pneumonia: aIRR 0.991 95% CI 0.990 to 0.994, p-value < 0.001) among undervaccinated children. Subgroup analyses for children <4 months old, urban, rural, and Indigenous populations showed similar trends, although effects were smaller for rural and Indigenous populations. Approximately 50% coverage of PCV7 among children <5 years of age was estimated to prevent up to 72.5% (95% CI 51.6 to 84.4) of PCV7-type IPD among undervaccinated children, while 90% coverage was estimated to prevent 95.2% (95% CI 89.4 to 97.8). The main limitations of this study include the potential for differential loss to follow-up, geographical misclassification of children (based on residential address at birth only), and unmeasured confounders. Conclusions In this study, we observed substantial indirect protection at lower levels of PCV coverage than previously described—challenging assumptions that high levels of PCV coverage (i.e., greater than 90%) are required. Understanding the association between PCV coverage and indirect protection is a priority since the control of vaccine-type pneumococcal disease is a prerequisite for reducing the number of PCV doses (from 3 to 2). Reduced dose schedules have the potential to substantially reduce program costs while maintaining vaccine impact.

scholarly journals Distribution and Severity of Placental Lesions Caused by the Chlamydia abortus 1B Vaccine Strain in Vaccinated Ewes

Pathogens ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 543
Author(s):  
Sergio Gastón Caspe ◽  
Javier Palarea-Albaladejo ◽  
Clare Underwood ◽  
Morag Livingstone ◽  
Sean Ranjan Wattegedera ◽  
...  
Keyword(s):  
Disease Outbreaks ◽  
Principal Component ◽  
Placental Pathology ◽  
Wild Type ◽  
Cell Infiltrate ◽  
Chlamydia Abortus ◽  
Vaccine Type ◽  
The Difference ◽  
Enzootic Abortion Of Ewes

Chlamydia abortus infects livestock species worldwide and is the cause of enzootic abortion of ewes (EAE). In Europe, control of the disease is achieved using a live vaccine based on C. abortus 1B strain. Although the vaccine has been useful for controlling disease outbreaks, abortion events due to the vaccine have been reported. Recently, placental pathology resulting from a vaccine type strain (vt) infection has been reported and shown to be similar to that resulting from a natural wild-type (wt) infection. The aim of this study was to extend these observations by comparing the distribution and severity of the lesions, the composition of the predominating cell infiltrate, the amount of bacteria present and the role of the blood supply in infection. A novel system for grading the histological and pathological features present was developed and the resulting multi-parameter data were statistically transformed for exploration and visualisation through a tailored principal component analysis (PCA) to evaluate the difference between them. The analysis provided no evidence of meaningful differences between vt and wt strains in terms of the measured pathological parameters. The study also contributes a novel methodology for analysing the progression of infection in the placenta for other abortifacient pathogens.

scholarly journals Therapy for myeloproliferative neoplasms: when, which agent, and how?

Hematology ◽  
2014 ◽  
Vol 2014 (1) ◽  
pp. 277-286 ◽  
Author(s):  
Holly L. Geyer ◽  
Ruben A. Mesa
Keyword(s):  
Quality Of Life ◽  
Disease Burden ◽  
Myeloproliferative Neoplasms ◽  
Jak Inhibitors ◽  
Symptom Profiles ◽  
Risk Of Progression ◽  
Life Threatening ◽  
Jak2 Inhibition

Abstract Myeloproliferative neoplasms, including polycythemia vera (PV), essential thrombocythemia, and myelofibrosis (MF) (both primary and secondary), are recognized for their burdensome symptom profiles, life-threatening complications, and risk of progression to acute leukemia. Recent advancements in our ability to diagnose and prognosticate these clonal malignancies have paralleled the development of MPN-targeted therapies that have had a significant impact on disease burden and quality of life. Ruxolitinib has shown success in alleviating the symptomatic burden, reducing splenomegaly and improving quality of life in patients with MF. The role and clinical expectations of JAK2 inhibition continues to expand to a variety of investigational arenas. Clinical trials for patients with MF focus on new JAK inhibitors with potentially less myelosuppression (pacritinib) or even activity for anemia (momelotinib). Further efforts focus on combination trials (including a JAK inhibitor base) or targeting new pathways (ie, telomerase). Similarly, therapy for PV continues to evolve with phase 3 trials investigating optimal frontline therapy (hydroxyurea or IFN) and second-line therapy for hydroxyurea-refractory or intolerant PV with JAK inhibitors. In this chapter, we review the evolving data and role of JAK inhibition (alone or in combination) in the management of patients with MPNs.

scholarly journals Vaccines for older adults

BMJ ◽  
2021 ◽  
pp. n188
Author(s):  
Anthony L Cunningham ◽  
Peter McIntyre ◽  
Kanta Subbarao ◽  
Robert Booy ◽  
Myron J Levin
Keyword(s):  
Older Adults ◽  
Older People ◽  
Vaccine Coverage ◽  
Relative Effectiveness ◽  
Similar Efficacy ◽  
Influenza Vaccines ◽  
Public Confidence ◽  
Zoster Vaccine ◽  
Vaccine Serotypes ◽  
Recombinant Zoster Vaccine

Abstract The proportion of the global population aged 65 and older is rapidly increasing. Infections in this age group, most recently with SARS-CoV-2, cause substantial morbidity and mortality. Major improvements have been made in vaccines for older people, either through the addition of novel adjuvants—as in the new recombinant zoster vaccine and an adjuvanted influenza vaccine—or by increasing antigen concentration, as in influenza vaccines. In this article we review improvements in immunization for the three most important vaccine preventable diseases of aging. The recombinant zoster vaccine has an efficacy of 90% that is minimally affected by the age of the person being vaccinated and persists for more than four years. Increasing antigen dose or inclusion of adjuvant has improved the immunogenicity of influenza vaccines in older adults, although the relative effectiveness of the enhanced influenza vaccines and the durability of the immune response are the focus of ongoing clinical trials. Conjugate and polysaccharide pneumococcal vaccines have similar efficacy against invasive pneumococcal disease and pneumococcal pneumonia caused by vaccine serotypes in older adults. Their relative value varies by setting, depending on the prevalence of vaccine serotypes, largely related to conjugate vaccine coverage in children. Improved efficacy will increase public confidence and uptake of these vaccines. Co-administration of these vaccines is feasible and important for maximal uptake in older people. Development of new vaccine platforms has accelerated following the arrival of SARS-CoV-2, and will likely result in new vaccines against other pathogens in the future.

scholarly journals Dynamic transmission modelling to address infant pneumococcal conjugate vaccine schedule modifications in the UK

2018 ◽  
Vol 146 (14) ◽  
pp. 1797-1806 ◽  
Author(s):  
M. Wasserman ◽  
A. Lucas ◽  
D. Jones ◽  
M. Wilson ◽  
B. Hilton ◽  
...  
Keyword(s):  
Conjugate Vaccine ◽  
Pneumococcal Conjugate Vaccine ◽  
Disease Burden ◽  
Invasive Disease ◽  
Transmission Model ◽  
Routine Immunisation ◽  
Scenario Analyses ◽  
Vaccine Schedule ◽  
Vaccine Type ◽  
The Uk

AbstractThe 13-valent pneumococcal conjugate vaccine (PCV) has been part of routine immunisation in a 2 + 1 schedule (two primary infant doses and one booster during the second year of life) in the UK since 2010. Recently, the UK's Joint Committee on Vaccination and Immunisation recommended changing to a 1 + 1 schedule while conceding that this will increase disease burden; however, uncertainty remains on how much pneumococcal burden – including invasive pneumococcal disease (IPD) and non-invasive disease – will increase. We built a dynamic transmission model to investigate this question. The model predicted that a 1 + 1 schedule would incur 8777–27 807 additional cases of disease and 241–743 more deaths over 5 years. Serotype 19A caused 55–71% of incremental IPD cases. Scenario analyses showed that booster dose adherence, effectiveness against carriage and waning in a 1 + 1 schedule had the most influence on resurgence of disease. Based on the model assumptions, switching to a 1 + 1 schedule will substantially increase disease burden. The results likely are conservative since they are based on relatively low vaccine-type pneumococcal transmission, a paradigm that has been called into question by data demonstrating an increase of IPD due to several vaccine serotypes during the last surveillance year available.

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