Impact Of New Vaccines Research Articles

Is neglect of self-clearance biasing TB vaccine impact estimates?

BackgroundMathematical modelling has been used extensively to estimate the potential impact of new tuberculosis vaccines, with the majority of existing models assuming that individuals with Mycobacterium tuberculosis (Mtb) infection remain...

Immunization and Drug Metabolizing Enzymes: Focus on Hepatic Cytochrome P450 3A

ABSTRACT Objective Infectious disease emergencies like the 2013–2016 Ebola epidemic and the 2009 influenza and current SARS-CoV-2 pandemics illustrate that vaccines are now given to diverse populations with preexisting pathologies requiring pharmacological management. Many natural biomolecules (steroid hormones, fatty acids, vitamins) and ~60% of prescribed medications are processed by hepatic cytochrome P450 (CYP) 3A4. The objective of this work was to determine the impact of infection and vaccines on drug metabolism. Methods The impact of an adenovirus-based vaccine expressing Ebola glycoprotein (AdEBO) and H1N1 and H3N2 influenza viruses on hepatic CYP 3A4 and associated nuclear receptors was evaluated in human hepatocytes (HC-04 cells) and in mice. Results CYP3A activity was suppressed by 55% in mice 24 h after administration of mouse-adapted H1N1, while ˂10% activity remained in HC-04 cells after infection with H1N1 and H3N2 due to global suppression of cellular translation capacity, indicated by reduction (70%, H1N1, 56%, H3N2) of phosphorylated eukaryotic translation initiation factor 4e (eIF4E). AdEBO suppressed CYP3A activity in vivo (44%) and in vitro (26%) 24 hours after infection. Conclusion As the clinical evaluation of vaccines for SARS-CoV-2 and other global pathogens rise, studies to evaluate the impact of new vaccines and emerging pathogens on CYP3A4 and other metabolic enzymes are warranted to avoid therapeutic failures that could further compromise the public health during infectious disease emergencies.

Community-acquired Invasive Bacterial Disease in Urban Gambia, 2005-2015: A Hospital-based Surveillance.

Background. Invasive bacterial diseases cause significant disease and death in sub-Saharan Africa. Several are vaccine preventable, although the impact of new vaccines and vaccine policies on disease patterns in these communities is poorly understood owing to limited surveillance data. Methods. We conducted a hospital-based surveillance of invasive bacterial diseases in The Gambia where blood and cerebrospinal fluid (CSF) samples of hospitalized participants were processed. Three surveillance periods were defined in relation to the introduction of pneumococcal conjugate vaccines (PCVs), before (2005- 2009), during (2010–2011) and after (2012–2015) PCV introduction. We determined the prevalences of commonly isolated bacteria and compared them between the different surveillance periods. Results. A total of 14 715 blood and 1103 CSF samples were collected over 11 years; overall, 1045 clinically significant organisms were isolated from 957 patients (972 organisms [6.6%] from blood and 73 [6.6%] from CSF). The most common blood culture isolates were Streptococcus pneumoniae (24.9%), Staphylococcus aureus (22.0%), Escherichia coli (10.9%), and nontyphoidal Salmonella (10.0%). Between the pre-PCV and post-PCV eras, the prevalence of S. pneumoniae bacteremia dropped across all age groups (from 32.4% to 16.5%; odds ratio, 0.41; 95% confidence interval, .29–.58) while S. aureus increased in prevalence, becoming the most prevalent bacteria (from 16.9% to 27.2%; 1.75; 1.26–2.44). Overall, S. pneumoniae (53.4%), Neisseria meningitidis (13.7%), and Haemophilus influenzae (12.3%) were the predominant isolates from CSF. Antimicrobial resistance to common antibiotics was low. Conclusions. Our findings demonstrate that surveillance data on the predominant pathogens associated with invasive disease is necessary to inform vaccine priorities and appropriate management of patients.

Challenges to estimating vaccine impact using hospitalization data

Because the real-world impact of new vaccines cannot be known before they are implemented in national programs, post-implementation studies at the population level are critical. Studies based on analysis of hospitalization rates of vaccine-preventable outcomes are typically used for this purpose. However, estimates of vaccine impact based on hospitalization data are particularly prone to confounding, as hospitalization rates are tightly linked to changes in the quality, access and use of the healthcare system, which often occur simultaneously with introduction of new vaccines. Here we illustrate how changes in healthcare delivery coincident with vaccine introduction can influence estimates of vaccine impact, using as an example reductions in infant pneumonia hospitalizations after introduction of the 10-valent pneumococcal conjugate vaccine (PCV10) in Brazil. To this end, we explore the effect of changes in several metrics of quality and access to public healthcare on trends in hospitalization rates before (2008–09) and after (2011−12) PCV10 introduction in 2010. Changes in infant pneumonia hospitalization rates following vaccine introduction were significantly associated with concomitant changes in hospital capacity and the fraction of the population using public hospitals. Importantly, reduction of pneumonia hospitalization rates after PCV10 were also associated with the expansion of outpatient services in several Brazilian states, falling more sharply where primary care coverage and the number of health units offering basic and emergency care increased more. We show that adjustments for unrelated (non-vaccine) trends commonly employed by impact studies, such as use of single control outcomes, are not always sufficient for accurate impact assessment. We discuss several ways to identify and overcome such biases, including sensitivity analyses using different denominators to calculate hospitalizations rates and methods that track changes in the outpatient setting. Employing these practices can improve the accuracy of vaccine impact estimates, particularly in evolving healthcare settings typical of low- and middle-income countries.

Density Distribution of Pharyngeal Carriage of Meningococcus in Healthy Young Adults: New Approaches to Studying the Epidemiology of Colonization and Vaccine Indirect Effects.

Improved understanding of Neisseria meningitidis (Nm) carriage biology and better methods for detection and quantification would facilitate studies of potential impact of new vaccines on colonization and transmission in adolescents. We performed plate cultures on 107 oropharyngeal swabs stored frozen in skim milk tryptone glucose glycerol (STGG) broth and previously positive for Nm. We compared quantitative polymerase chain reaction (qPCR) detection of Nm in 601 STGG-swabs with culture. Using qPCR (n = 87), a log-phase broth culture standard curve and semiquantitative plate cultures (n = 68), we measured density of carriage. We compared qPCR genogrouping of DNA extracts from STGG-swabs and from plate culture lawns (n = 110) with purified isolates (n = 80). Swab storage resulted in only 10% loss of culture sensitivity. Direct sodC qPCR Nm detection yielded more positives (87/601, 14.5%) than culture (80/601, 13.3%). Most samples (57/110) positive by culture were also positive by qPCR and vice versa, but discrepancies (single positives) were frequent among low-density samples. sodC qPCR was positive in 79/80 isolates but in only 65 by ctrA qPCR. Density both by culture and qPCR varied across 4 orders of magnitude with the majority being low (<50 bacteria-gene copies/mL) and a minority being high (>1000). Genogrouping qPCRs yielded more positive results when performed on DNA extracts from lawn cultures. We provide the first description of the distribution of Nm carriage density. This could be important for understanding transmission dynamics and population-level effectiveness of adolescent vaccine programs. Storage of swabs frozen in STGG for batched laboratory analysis facilitates carriage studies and direct sodC qPCR for Nm combined with qPCR genogrouping of lawn culture extracts provides accurate, detailed description of colonization.

Microbiology of bacteria causing recurrent acute otitis media (AOM) and AOM treatment failure in young children in Spain: Shifting pathogens in the post-pneumococcal conjugate vaccination era

ObjectiveTo prospectively identify the bacterial aetiology and antimicrobial susceptibility of problematic (recurrent and treatment failure) acute otitis media in Spanish children several years after the introduction of 7-valent pneumococcal conjugate vaccine. MethodsTympanocentesis or careful sampling of spontaneous otorrhoea was performed on children aged 3 to <36 months with recurrent acute otitis media, acute otitis media treatment failure or unresolved acute otitis media. Results105 acute otitis media episodes (77 sampled by tympanocentesis, 28 otorrhoea samples) were evaluated: 46 recurrent, 35 treatment failures, 24 unresolved acute otitis media. 74 episodes (70.4%) had at least one bacterium identified on culture: Streptococcus pneumoniae was identified in 21 episodes, Haemophilus influenzae (all non-typeable) in 44, Streptococcus pyogenes in 2, Moraxella catarrhalis in 2. No statistically significant difference in bacterial aetiology by episode type was detected. Non-typeable H. influenzae was the most commonly isolated pathogen in all acute otitis media types and in all age sub-groups. Forty percent of S. pneumoniae isolates were multi-drug resistant. Pneumococcal serotype 19A was the most frequently identified serotype (7/21 episodes). Multi-drug resistance was found in 56% of 19A isolates. Of non-typeable H. influenzae isolates, 15% were ampicillin resistant and 13% were amoxicillin/clavulanate resistant. S. pneumoniae and non-typeable H. influenzae DNA were each detected in 57% of samples culture negative for these pathogens, including 12 co-infections. ConclusionCombining culture and polymerase chain reaction results, H. influenzae and S. pneumoniae may be implicated in 70% and 43% of clinically problematic bacterial acute otitis media episodes, respectively. The impact of new vaccines to prevent both S. pneumoniae and non-typeable H. influenzae acute otitis media may be substantial in this population and is worth investigating.

Health technology assessments on human papillomavirus vaccinations in Europe: a survey from VENICE network

Background: VEnIcE II is a project funded in 2008 by the European centre for disease Preventionand control to collect information on the national vaccination programmes, to increase their knowledgeand to know the impact of new vaccines introduced in member states (MS). In 2006-2007, two vaccinesagainst human papillomavirus (HPV) were authorized in Europe.MEtHodS: an online survey was carried out to investigate the decision-making process undertakenregarding the potential introduction of the HPV vaccinations into MS national immunization pro-grammes as well as to investigate the modalities of implementation of the vaccination programmes.there were specific questions about health technology assessment and reports of the countries that hadcarried them out were reviewed.rESultS: In 21 of the 29 MS, the national advisory body recommended to introduce HPV vaccination intheir national immunization schedule and in 18 countries introduced it. only 6 countries have realizeda health technology assessments (Hta) report, each one with different methodology, but in all of themboth vaccines show positive evaluations.concluSIon: From the available Hta, HPV vaccination is cost-effective under the assumption of a life-long protection. Screening programme for cervical cancer and HPV vaccination programme should bealways complementary. organizational aspects need to be taken into account to improve the vaccina-tion. HPV vaccination should target girls before the debut of their sexual life. Instead HPV vaccinationof boys has not been demonstrated as bringing significant epidemiological benefits and has not beenshown as being cost-effective.

PIH65 What Are We Missing in Meningococcal Disease Modelling to Better Understand the Health and Economic Impact of New Vaccines?

PIH65 What Are We Missing in Meningococcal Disease Modelling to Better Understand the Health and Economic Impact of New Vaccines?

Epidemiology of meningococcal disease in Latin America: current situation and opportunities for prevention

Objective: Meningococcal disease continues to be a serious public health concern, being associated with high morbidity and mortality rates in many countries from Latin America. In addition to discussing recent changes in the epidemiology of meningococcal disease in the region, we also analyse the development and potential impact of new vaccines on the prevention of meningococcal disease.Methods: MEDLINE, SciELO, LILACS and websites of the national Ministries of Health databases were searched using the terms meningococcal disease, meningococcal epidemiology, Neisseria meningitidis, meningococcal vaccines and the name of Latin America countries, from 1998 to 2008, with emphasis on review articles, clinical trials and epidemiological studies.Results: Epidemiology of meningococcal disease in Latin America is characterized by marked differences from country to country. The overall incidence of meningococcal disease per year varied from less than 0·1 cases per 100,000 inhabitants in countries like Mexico to two cases per 100,000 inhabitants in Brazil. The highest age-specific incidence of meningococcal disease occurred in infants less than 1 year of age. Serogroups B and C were responsible for the majority of cases reported, but the emergence of serogroups W135 and Y was reported in some countries. Serogroup A disease is now rare in Latin America.Discussion: Although a few countries have established meningitis surveillance programs, the information is not uniform, and the quality of the reported data is poor in the majority of the region. The availability of new effective meningococcal conjugate vaccines and promising protein-based vaccine candidates against meningococcus B highlights the importance of a better understanding of the true burden of meningococcal disease in Latin America and also the need for cost-effectiveness studies before incorporating the new meningococcal vaccines to national immunization programs.

Discordant immunization schedules can complicate vaccine evaluation for Europe

Background: Most of the world’s vaccines are produced in Europe. Although vaccine licensure can becentralized through the EMEA, immunization recommendations are established at the national levels,reimbursement policies vary widely (ranging from regional to national, from private to public) and the lag timecan be long between licensure and eventual introduction into a national immunization program.Methods: An example of this discordance is the paediatric combination vaccines. Young infants in some EUcountries receive a whole-cell pertussis vaccine, in a three- to five-vaccine combination (“DTPw | IPV | Hib”).Acellular pertussis vaccines have been introduced over the last decade in many other EU countries, with four-to six-vaccine combinations (“DTPa | IPV | HBV | Hib”). Either of these combinations may be administered witha “3 + 1” schedule, with the first dose given between the age of 2 to 3 months, a spacing of 1 to 2 monthsbetween doses, and the final (booster) dose usually given at anywhere between 12 and 24 months of age, butin a handful of countries as late as the age of 3 to 5 years. By contrast, a “2 + 1” schedule is applied in somecountries for the “DTPa | IPV | Hib” or “DTPa | IPV | HBV | Hib” vaccines: first dose, 3 months old; spacing, 2months between doses; final (booster) dose, 11 to 14 months of age.Results: Differing national policies in the EU may have led to delays in the introduction of the newest vaccines(e.g., pneumococcal conjugate, meningococcal conjugate, rotavirus, influenza, varicella-zoster, etc.) thatmust be shown to be compatible with the various infant immunization programs across Europe. This coulddelay the likelihood, in some EU countries, of the public health advancements that these new vaccines canprovide.Conclusions: Sharing of best practices from vaccination schedules might rationalize vaccine development,streamline the introduction of novel vaccines into the national immunization programs, and facilitate theevaluation of the impact of new vaccines in Europe.

The expected impact of new vaccines and vaccination policies

Aim The purpose of this paper is to outline the potential of newly available vaccines and highlight the evolution of tools required for correctly assessing the impact of immunisation policies.

Modelling heterogeneity and the impact of chemotherapy and vaccination against human hookworm

There is a growing emphasis on the development of vaccines against helminths (worms), and mathematical models provide a useful tool to assess the impact of new vaccines under a range of scenarios. The present study describes a stochastic individual-based model to assess the relative impact of chemotherapy and vaccination against human hookworm infection and investigates the implications of potential correlations between risk of infection and vaccine efficacy. Vaccination is simulated as a reduction in susceptibility to infection and the model includes population heterogeneities and dynamical waning of protection. To help identify appropriate measures of vaccine impact, we present a novel framework to quantify the vaccine impact on the infection-associated morbidity and introduce a measure of symmetry to study the correspondence between reduction in intensity and reduction in morbidity. Our modelling shows that, in high-transmission settings, the greatest impact of vaccination will be attained when vaccine efficacy is the greatest among individuals harbouring the heaviest worm burdens, and that the decline of morbidity primarily depends on the level of protection attained in the most at risk 8-12% of the population. We also demonstrate that if risk of infection and vaccine protection are correlated, there is not always a direct correspondence between the reduction in worm burden and in morbidity, with the precise relationship varying according to transmission setting.

The use of health economics to guide drug development decisions: Determining optimal values for an RSV-vaccine in a model-based scenario-analytic approach

Health-economic modelling is useful for assessing the clinical requirements and impact of new vaccines. In this study, we estimate the impact of potential vaccination for respiratory syncytial virus (RSV) of infants in the Netherlands. A decision analysis model was employed using seasonal data from a cohort of children (1996-1997 through 1999-2000) to assess hospitalisation, costs and impact of vaccination. Yearly, an estimated 3670 infants are hospitalised with RSV-infection in the Netherlands, vaccination protecting infants from 3 months of life onwards could prevent approximately 1000-3000 hospitalisations, depending on the effectiveness of the potential vaccine. Additionally, vaccination could prevent a major share of RSV-related costs. Comparison of the calculated break-even prices with the average price of recently introduced vaccines indicates that pricing for a potential RSV-vaccine most likely allows for only a single dose vaccination or several doses at a relatively low price per dose in order to achieve cost savings. However, if evidence on relevant RSV-related mortality would become available, higher pricing would be justified, while still remaining below accepted thresholds for cost-effectiveness.

Automation of MLST Using Third-Generation Liquid-Handling Technology

The molecular characterization of bacterial pathogens of clinical significance is increasingly important. Methods, such as multilocus sequence typing (MLST), allow bacterial strains to be characterized during case clusters, for antibiotic-resistant strains to be monitored, and for the impact of new vaccines to be assessed. Our laboratory performs MLST on Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus. We have developed high-throughput automated methods to allow MLST to be performed in a time scale useful in a clinical setting. Here we describe the automation of MLST on a third-generation liquid-handling robot.

Influenza future: the impact of new vaccines and antivirals

The new vaccines and antivirals may change the way influenza is controlled, but we need first to remember that the current inactivated vaccines are effective and underutilized. A trivalent live-attenuated vaccine has recently been demonstrated to be 93% efficacious in preventing isolation-confirmed influenza and to be 86% efficacious when a drifted strain was circulating. The antivirals zanamivir and oseltamivir shorten the duration of illnesses from 1 to 3 days and prevent complications requiring antibiotics. Both are efficacious in prophylaxis, including postexposure in the family. We can expect to see, in the future, expanded prevention and control of influeza, not only in the traditional groups, but in additional segments of the population, such as working adults and children.

Epidemiology of Invasive &lt;EMPH TYPE="ITAL"&gt;Streptococcus pneumoniae&lt;/EMPH&gt; Infections in the United States, 1995-1998&lt;SUBTITLE&gt;Opportunities for Prevention in the Conjugate Vaccine Era&lt;/SUBTITLE&gt;

Pneumococcal polysaccharide vaccine is recommended for elderly persons and adults with certain chronic illnesses. Additionally, a recently licensed pneumococcal 7-valent conjugate vaccine has been recommended for use in young children and could dramatically change the epidemiology of pneumococcal disease. To assess pneumococcal disease burden in the United States, estimate the potential impact of new vaccines, and identify gaps in vaccine recommendations. Analysis of data from the Active Bacterial Core Surveillance (ABCs)/Emerging Infections Program Network, an active, population-based system in 9 states. A total of 15 860 cases of invasive pneumococcal disease occurring between January 1, 1995, and December 31, 1998. Age- and race-specific pneumoccocal disease incidence rates per 100 000 persons, case-fatality rates, and vaccine preventability. In 1998, overall incidence was 23.2 cases per 100 000, corresponding to an estimated 62 840 cases in the United States. Incidence was highest among children younger than 2 years (166.9) and adults aged 65 years or older (59.7). Incidence among blacks was 2.6 times higher than among whites (95% confidence interval [CI], 2.4-2.8). Overall, 28.6% of case-patients were at least 65 years old and 85.9% of cases in this age group were due to serotypes included in the 23-valent polysaccharide vaccine; 19.3% of case-patients were younger than 2 years and 82.2% of cases in this age group were due to serotypes included in the 7-valent conjugate vaccine. Among patients aged 2 to 64 years, 50.6% had a vaccine indication as defined by the Advisory Committee on Immunization Practices (ACIP). The case-fatality rate among patients aged 18 to 64 years with an ACIP indication was 12.1% compared with 5.4% for those without an indication (relative risk, 2.2; 95% CI, 1.7-2.9). Young children, elderly persons, and black persons of all ages are disproportionately affected by invasive pneumococcal disease. Current ACIP recommendations do not address a subset of persons aged 18 to 64 years but do include those at highest risk for death from invasive pneumococcal disease.

Investigating the epidemiology of heartwater (Cowdria ruminantium infection) by means of a transmission dynamics model.

A mathematical model of the transmission dynamics of Cowdria ruminantium by the ixodid tick Amblyomma hebraeum in the bovine host is developed and used to investigate the epidemiology of heartwater across a range of vector challenge. The processes described are supported by empirical data. The pattern of outcome measures (incidence, case-fatality and proportion of infected hosts) predicted agrees with those described anecdotally from field experience and empirical observation, and demonstrates the concept of endemic stability. The underlying theory is explored and it is shown that endemic stability may be due principally to the protection of calves against disease by either innate or maternally derived factors. The role of vertical infection in the establishment and maintenance of endemic stability is also investigated. Although increasing the vertical infection proportion results in endemic stability occurring at progressively lower levels of tick challenge, the concomitant reduction in incidence and case-fatality predictions across the range of tick challenge means the endemically stable state simultaneously becomes less discernible. Model limitations and future developments are discussed. The essential role of a transmission dynamics model in assessing the impact of new vaccines in conjunction with vector control programmes is highlighted.