Although there have been no cases of serotype 2 wild poliovirus for more than 20 years, transmission of serotype 2 vaccine-derived poliovirus (VDPV2) and associated paralytic cases in several ...continents represent a threat to eradication. The withdrawal of the serotype 2 component of oral poliovirus vaccine (OPV2) was implemented in April 2016 to stop VDPV2 emergence and secure eradication of all serotype 2 poliovirus. Globally, children born after this date have limited immunity to prevent transmission. Using a statistical model, we estimated the emergence date and source of VDPV2s detected between May 2016 and November 2019. Outbreak response campaigns with monovalent OPV2 are the only available method to induce immunity to prevent transmission. Yet our analysis shows that using monovalent OPV2 is generating more paralytic VDPV2 outbreaks with the potential for establishing endemic transmission. A novel OPV2, for which two candidates are currently in clinical trials, is urgently required, together with a contingency strategy if this vaccine does not materialize or perform as anticipated.
Abstract A live-attenuated vaccine against herpes zoster (HZ) has been approved for use, on the basis of a large-scale clinical trial that suggests that the vaccine is safe and efficacious. This ...study uses a Markov cohort model to estimate whether routine vaccination of the elderly (60+) would be cost-effective, when compared with other uses of health care resources. Vaccine efficacy parameters are estimated by fitting a model to clinical trial data. Estimates of QALY losses due to acute HZ and post-herpetic neuralgia were derived by fitting models to data on the duration of pain by severity and the QoL detriment associated with different severity categories, as reported in a number of different studies. Other parameters (such as cost and incidence estimates) were based on the literature, or UK data sources. The results suggest that vaccination of 65 year olds is likely to be cost-effective (base-case ICER = £20,400 per QALY gained). If the vaccine does offer additional protection against either the severity of disease or the likelihood of developing PHN (as suggested by the clinical trial), then vaccination of all elderly age groups is highly likely to be deemed cost-effective. Vaccination at either 65 or 70 years (depending on assumptions of the vaccine action) is most cost-effective. Including a booster dose at a later age is unlikely to be cost-effective.
Quantification of human interactions relevant to infectious disease transmission through social contact is central to predict disease dynamics, yet data from low-resource settings remain scarce.
We ...undertook a social contact survey in rural Uganda, whereby participants were asked to recall details about the frequency, type, and socio-demographic characteristics of any conversational encounter that lasted for ≥5 min (henceforth defined as 'contacts') during the previous day. An estimate of the number of 'casual contacts' (i.e. < 5 min) was also obtained.
In total, 566 individuals were included in the study. On average participants reported having routine contact with 7.2 individuals (range 1-25). Children aged 5-14 years had the highest frequency of contacts and the elderly (≥65 years) the fewest (P < 0.001). A strong age-assortative pattern was seen, particularly outside the household and increasingly so for contacts occurring further away from home. Adults aged 25-64 years tended to travel more often and further than others, and males travelled more frequently than females.
Our study provides detailed information on contact patterns and their spatial characteristics in an African setting. It therefore fills an important knowledge gap that will help more accurately predict transmission dynamics and the impact of control strategies in such areas.
Assessments of vaccine efficacy and safety capture only the minimum information needed for regulatory approval, rather than the full public health value of vaccines. Vaccine efficacy provides a ...measure of proportionate disease reduction, is usually limited to etiologically confirmed disease, and focuses on the direct protection of the vaccinated individual. Herein, we propose a broader scope of methods, measures and outcomes to evaluate the effectiveness and public health impact to be considered for evidence-informed policymaking in both pre- and post-licensure stages.
Pre-licensure: Regulatory concerns dictate an individually randomised clinical trial. However, some circumstances (such as the West African Ebola epidemic) may require novel designs that could be considered valid for licensure by regulatory agencies. In addition, protocol-defined analytic plans for these studies should include clinical as well as etiologically confirmed endpoints (e.g. all cause hospitalisations, pneumonias, acute gastroenteritis and others as appropriate to the vaccine target), and should include vaccine-preventable disease incidence and 'number needed to vaccinate' as outcomes. Post-licensure: There is a central role for phase IV cluster randomised clinical trials that allows for estimation of population-level vaccine impact, including indirect, total and overall effects. Dynamic models should be prioritised over static models as the constant force of infection assumed in static models will usually underestimate the effectiveness and cost-effectiveness of the immunisation programme by underestimating indirect effects. The economic impact of vaccinations should incorporate health and non-health benefits of vaccination in both the vaccinated and unvaccinated populations, thus allowing for estimation of the net social value of vaccination.
The full benefits of vaccination reach beyond direct prevention of etiologically confirmed disease and often extend across the life course of a vaccinated person, prevent outcomes in the wider community, stabilise health systems, promote health equity, and benefit local and national economies. The degree to which vaccinations provide broad public health benefits is stronger than for other preventive and curative interventions.
: To establish whether universal vaccination of infants with the pneumococcal conjugate vaccine is likely to be cost-effective from the perspective of the health care provider (NHS).
: Two ...hypothetical cohorts – one vaccinated and one unvaccinated – were followed over their lifetime, and the expected net costs and benefits (measured in terms of life-years and quality adjusted life years (QALY) gained) were compared in the two cohorts. The impact of indirect effects of the vaccine, such as herd immunity and serotype replacement, were investigated and their relative importance was assessed by performing univariate sensitivity analysis and multivariate Monte Carlo simulations.
: Under base-case assumptions (no herd immunity and no serotype replacement) the programme is not expected to be cost-effective from the NHS perspective at the current price of the vaccine (assumed £30 per dose, three-dose programme). A reduction of the cost of the vaccine to half of its current level could bring the cost per QALY gained within normally acceptable ranges. If the burden of disease is significantly underestimated by current surveillance systems, then the cost per QALY gained approaches acceptable levels at the current vaccine price. Herd immunity may substantially reduce the burden of pneumococcal disease, particularly of pneumonia among the elderly, leading to a significant improvement in the cost per life year and QALY gained. Serotype replacement would partly offset these benefits, although only with a complete substitution of vaccine types with non-vaccine types and a low level of herd immunity, would pneumococcal vaccination programme would not be cost-effective.
: Conclusions on the cost-effectiveness of pneumococcal conjugate vaccine are sensitive to assumptions regarding the current burden of pneumococcal disease and the future impact that vaccination will have in the unvaccinated and on the future serotype distribution. This study quantifies, for the first time, how these indirect effects may change the cost-effectiveness of pneumococcal vaccination.
Rotavirus is the leading cause of acute gastroenteritis in children. Two rotavirus vaccines (RotaTeq and Rotarix) have recently completed clinical trials. We investigated whether routine infant ...immunisation with either vaccine can be cost effective.
We compared costs and outcomes of vaccination using a cohort model, following children over the first 5 years of life. We estimated health provider costs, economic costs and quality adjusted life years (QALYs) lost due to rotavirus-related deaths, hospital admissions, nosocomial infections, accident and emergency attendances, general practice consultations and calls to NHS Direct.
Under base case assumptions, a programme using RotaTeq (priced at pound 25 a dose) would cost the health provider pound 79,900 per QALY gained. Using Rotarix (priced at pound 35 a dose) would cost pound 61,000 per QALY gained. Univariate and multivariate sensitivity analysis indicate that at these prices an immunisation programme would be unlikely to be cost-effective for any realistic value of the key parameters.
Rotavirus immunisation could reduce the substantial short-term morbidity burden due to rotavirus, but is unlikely to be deemed cost effective unless the vaccine is competitively priced.
Measles is a highly infectious and potentially dangerous disease. Before mass vaccination was started in the UK, measles caused an average of 100 deaths per year. Since the introduction of ...vaccination, vaccine uptake has risen from around 50% in 1968 to 76% in 1988. After the introduction of the combined measles, mumps, and rubella vaccine in 1988, vaccine uptake rose rapidly to a national average of 91% by 1998.
Cervical cancer, the most common cancer affecting women in developing countries, is caused by persistent infection with "high-risk" genotypes of human papillomaviruses (HPV). The most common ...oncogenic HPV genotypes are 16 and 18, causing approximately 70% of all cervical cancers. Types 6 and 11 do not contribute to the incidence of high-grade dysplasias (precancerous lesions) or cervical cancer, but do cause laryngeal papillomas and most genital warts. HPV is highly transmissible, with peak incidence soon after the onset of sexual activity. A quadrivalent (types 6, 11, 16 and 18) HPV vaccine has recently been licensed in several countries following the determination that it has an acceptable benefit/risk profile. In large phase III trials, the vaccine prevented 100% of moderate and severe precancerous cervical lesions associated with types 16 or 18 among women with no previous infection with these types. A bivalent (types 16 and 18) vaccine has also undergone extensive evaluation and been licensed in at least one country. Both vaccines are prepared from non-infectious, DNA-free virus-like particles produced by recombinant technology and combined with an adjuvant. With three doses administered, they induce high levels of serum antibodies in virtually all vaccinated individuals. In women who have no evidence of past or current infection with the HPV genotypes in the vaccine, both vaccines show > 90% protection against persistent HPV infection for up to 5 years after vaccination, which is the longest reported follow-up so far. Vaccinating at an age before females are exposed to HPV would have the greatest impact. Since HPV vaccines do not eliminate the risk of cervical cancer, cervical screening will still be required to minimize cancer incidence. Tiered pricing for HPV vaccines, innovative financing mechanisms and multidisciplinary partnerships will be essential in order for the vaccines to reach populations in greatest need.
Highlights • Phase 3 vaccine trials are challenging to design in epidemics, such as Ebola. • A mechanistic transmission model allowed more accurate estimation of declining incidence. • Mechanistic ...models can include change in incidence caused by the use of an effective vaccine. • Changes in likely trial feasibility were updated in real time as the epidemic progressed.
A central tenet of close-contact or respiratory infection epidemiology is that infection patterns within human populations are related to underlying patterns of social interaction. Until recently, ...few researchers had attempted to quantify potentially infectious encounters made between people. Now, however, several studies have quantified social mixing behaviour, using a variety of methods. Here, we review the methodologies employed, suggest other appropriate methods and technologies, and outline future research challenges for this rapidly advancing field of research.
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