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1.
Emerg Infect Dis ; 26(1)2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31574242

RESUMO

Vaccines against viral infections have been proposed to reduce prescribing of antibiotics and thereby help control resistant bacterial infections. However, by combining published data sources, we predict that pediatric live attenuated influenza vaccination in England and Wales will not substantially reduce antibiotic consumption or adverse health outcomes associated with antibiotic resistance.

2.
BMC Infect Dis ; 19(1): 1011, 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31783803

RESUMO

BACKGROUND: Antibiotics remain the cornerstone of modern medicine. Yet there exists an inherent dilemma in their use: we are able to prevent harm by administering antibiotic treatment as necessary to both humans and animals, but we must be mindful of limiting the spread of resistance and safeguarding the efficacy of antibiotics for current and future generations. Policies that strike the right balance must be informed by a transparent rationale that relies on a robust evidence base. MAIN TEXT: One way to generate the evidence base needed to inform policies for managing antibiotic resistance is by using mathematical models. These models can distil the key drivers of the dynamics of resistance transmission from complex infection and evolutionary processes, as well as predict likely responses to policy change in silico. Here, we ask whether we know enough about antibiotic resistance for mathematical modelling to robustly and effectively inform policy. We consider in turn the challenges associated with capturing antibiotic resistance evolution using mathematical models, and with translating mathematical modelling evidence into policy. CONCLUSIONS: We suggest that in spite of promising advances, we lack a complete understanding of key principles. From this we advocate for priority areas of future empirical and theoretical research.

3.
Vaccine ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31732326

RESUMO

BACKGROUND: In settings where measles has been eliminated, vaccine-derived immunity may in theory wane more rapidly due to a lack of immune boosting by circulating measles virus. We aimed to assess whether measles vaccine effectiveness (VE) waned over time, and if so, whether differentially in measles-eliminated and measles-endemic settings. METHODS: We performed a systematic literature review of studies that reported VE and time since vaccination with measles-containing vaccine (MCV). We extracted information on case definition (clinical symptoms and/or laboratory diagnosis), method of vaccination status ascertainment (medical record or vaccine registry), as well as any biases which may have arisen from cold chain issues and a lack of an age at first dose of MCV. We then used linear regression to evaluate VE as a function of age at first dose of MCV and time since MCV. RESULTS: After screening 14,782 citations, we identified three full-text articles from measles-eliminated settings and 33 articles from measles-endemic settings. In elimination settings, two-dose VE estimates increased as age at first dose of MCV increased and decreased as time since MCV increased; however, the small number of studies available limited interpretation. In measles-endemic settings, one-dose VE increased by 1.5% (95% CI 0.5, 2.5) for every month increase in age at first dose of MCV. We found no evidence of waning VE in endemic settings. CONCLUSIONS: The paucity of data from measles-eliminated settings indicates that additional studies and approaches (such as studies using proxies including laboratory correlates of protection) are needed to answer the question of whether VE in measles-eliminated settings wanes. Age at first dose of MCV was the most important factor in determining VE. More VE studies need to be conducted in elimination settings, and standards should be developed for information collected and reported in such studies.

4.
Pediatr Infect Dis J ; 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31738319

RESUMO

BACKGROUND: Sepsis and meningitis in neonates and infants are a source of substantial morbidity, mortality and economic loss. The objective of this review is to estimate the acute costs associated with treating sepsis, meningitis and meningococcal septicemia, in neonates and infants, worldwide. METHODS: The electronic databases Medline, Embase and EconLit were searched and exported on November 24, 2018. Studies that reported an average hospitalization cost for confirmed cases of sepsis, meningitis or meningococcal septicemia were eligible for our review. Descriptive data were extracted and reported costs were inflated and converted. A narrative synthesis of the costs was conducted. RESULTS: Our review identified 20 studies reporting costs of sepsis, meningitis and/or meningococcal septicemia. Costs ranged from $55 to $129,632 for sepsis and from $222 to $33,635 for meningitis (in 2017 US dollars). One study estimated the cost of meningococcal septicemia to be $56,286. All reported costs were estimated from the perspective of the healthcare provider or payer. Most studies were from the United States, which also had the highest costs. Only a few studies were identified for low- and middle-income countries, which reported lower costs than high-income countries for both sepsis and meningitis. CONCLUSIONS: Sepsis and meningitis in neonates and infants are associated with substantial costs to the healthcare system and showed a marked difference across global income groups. However, more research is needed to inform costs in low- and middle-income settings and to understand the economic costs borne by families and wider society.

5.
Lancet Glob Health ; 7(11): e1541-e1552, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31607466

RESUMO

BACKGROUND: Infant rotavirus vaccines have led to substantial reductions in hospital admissions and deaths due to gastroenteritis, but some studies have reported an elevated risk of intussusception, a rare bowel disorder. This analysis aimed to provide evidence on the potential mortality reduction benefits and intussusception risks of current rotavirus vaccination schedules, and to explore whether alternative schedules could have advantages. METHODS: All 135 low-income and middle-income countries, defined by gross national income per capita of less than US$12 236 in the 2018 fiscal year, were included in the model. Mortality reduction benefits and intussusception risks of rotavirus vaccination were modelled by use of an Excel-based static cohort model with a finely disaggregated age structure. Numbers of rotavirus gastroenteritis deaths and intussusception deaths in each week of age were calculated for all infants born in the year 2015 between birth and age 5·0 years, with and without restrictions on age at administration. Benefit-risk ratios (rotavirus gastroenteritis deaths prevented per excess intussusception death) and other indicators were calculated for two vaccination schedules currently recommended by WHO and 16 alternative schedules. Of these schedules, it was assumed that between one and three doses would be given; the first dose of the rotavirus vaccine would be co-administered with either BCG or diphtheria-tetanus-pertussis (DTP)1; and the second or third dose would be co-administered with either DTP1, DTP2, DTP3, or measles (Meas)1. FINDINGS: A three-dose schedule co-administered with DTP (without age restrictions) could prevent about 74 000 (95% uncertainty interval 59 000-100 000) rotavirus gastroenteritis deaths (38% reduction) and could lead to 201 (77-550) excess intussusception deaths (1·4% increase) compared with no vaccination, resulting in a benefit-risk ratio of 369:1 (160:1-895:1). The benefit-risk ratio was most favourable when the relative risk of intussusception was assumed to decline with the national under-5 mortality rate (2386:1) and least favourable with pessimistic assumptions about access to hospital for intussusception treatment (168:1). Schedules that involve giving the first dose with BCG and the second with DTP1 had the fewest excess intussusception deaths and most favourable benefit-risk ratios. INTERPRETATION: Rotavirus vaccines have a favourable benefit-risk profile in LMICs. Neonatal schedules have the potential to prevent more rotavirus gastroenteritis deaths and cause fewer excess intussusception deaths than the schedules currently recommended by WHO, but more efficacious rotavirus vaccines would be needed to achieve more substantial mortality reduction benefits. FUNDING: Bill & Melinda Gates Foundation.

6.
Sci Rep ; 9(1): 15141, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31641189

RESUMO

East Asia is as a principal hotspot for emerging zoonotic infections. Understanding the likely pathways for their emergence and spread requires knowledge on human-human and human-animal contacts, but such studies are rare. We used self-completed and interviewer-completed contact diaries to quantify patterns of these contacts for 965 individuals in 2017/2018 in a high-income densely-populated area of China, Shanghai City. Interviewer-completed diaries recorded more social contacts (19.3 vs. 18.0) and longer social contact duration (35.0 vs. 29.1 hours) than self-reporting. Strong age-assortativity was observed in all age groups especially among young participants (aged 7-20) and middle aged participants (25-55 years). 17.7% of participants reported touching animals (15.3% (pets), 0.0% (poultry) and 0.1% (livestock)). Human-human contact was very frequent but contact with animals (especially poultry) was rare although associated with frequent human-human contact. Hence, this densely populated area is more likely to act as an accelerator for human-human spread but less likely to be at the source of a zoonosis outbreak. We also propose that telephone interview at the end of reporting day is a potential improvement of the design of future contact surveys.

7.
BMC Med ; 17(1): 180, 2019 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-31551070

RESUMO

BACKGROUND: Vaccination has reduced the global incidence of measles to the lowest rates in history. However, local interruption of measles virus transmission requires sustained high levels of population immunity that can be challenging to achieve and maintain. The herd immunity threshold for measles is typically stipulated at 90-95%. This figure does not easily translate into age-specific immunity levels required to interrupt transmission. Previous estimates of such levels were based on speculative contact patterns based on historical data from high-income countries. The aim of this study was to determine age-specific immunity levels that would ensure elimination of measles when taking into account empirically observed contact patterns. METHODS: We combined estimated immunity levels from serological data in 17 countries with studies of age-specific mixing patterns to derive contact-adjusted immunity levels. We then compared these to case data from the 10 years following the seroprevalence studies to establish a contact-adjusted immunity threshold for elimination. We lastly combined a range of hypothetical immunity profiles with contact data from a wide range of socioeconomic and demographic settings to determine whether they would be sufficient for elimination. RESULTS: We found that contact-adjusted immunity levels were able to predict whether countries would experience outbreaks in the decade following the serological studies in about 70% of countries. The corresponding threshold level of contact-adjusted immunity was found to be 93%, corresponding to an average basic reproduction number of approximately 14. Testing different scenarios of immunity with this threshold level using contact studies from around the world, we found that 95% immunity would have to be achieved by the age of five and maintained across older age groups to guarantee elimination. This reflects a greater level of immunity required in 5-9-year-olds than established previously. CONCLUSIONS: The immunity levels we found necessary for measles elimination are higher than previous guidance. The importance of achieving high immunity levels in 5-9-year-olds presents both a challenge and an opportunity. While such high levels can be difficult to achieve, school entry provides an opportunity to ensure sufficient vaccination coverage. Combined with observations of contact patterns, further national and sub-national serological studies could serve to highlight key gaps in immunity that need to be filled in order to achieve national and regional measles elimination.

8.
Papillomavirus Res ; 8: 100184, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31505258

RESUMO

Intense research activity in HPV modelling over this decade has prompted the development of additional guidelines to those for general modelling. A specific framework is required to address different policy questions and unique complexities of HPV modelling. HPV-FRAME is an initiative to develop a consensus statement and quality-based framework for epidemiologic and economic HPV models. Its development involved an established process. Reporting standards have been structured according to seven domains reflecting distinct policy questions in HPV and cancer prevention and categorised by relevance to a population or evaluation. Population-relevant domains are: 1) HPV vaccination in pre-adolescent and young adolescent individuals; 2) HPV vaccination in older individuals; 3) targeted vaccination in men who have sex with men; 4) considerations for individuals living with HIV and 5) considerations for low- and middle-income countries. Additional considerations applicable to specific evaluations are: 6) cervical screening or integrated cervical screening and HPV vaccination approaches and 7) alternative vaccine types and alternative dosing schedules. HPV-FRAME aims to promote the development of models in accordance with an explicit framework, to better enable target audiences to understand a model's strength and weaknesses in relation to a specific policy question and ultimately improve the model's contribution to informed decision-making.

9.
Value Health ; 22(9): 1026-1032, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31511179

RESUMO

OBJECTIVES: Within health economic studies, it is often necessary to adjust costs obtained from different time periods for inflation. Nevertheless, many studies do not report the methods used for this in sufficient detail. In this article, we outline the principal methods used to adjust for inflation, with a focus on studies relating to healthcare interventions in low- and middle-income countries. We also discuss issues relating to converting local currencies to international dollars and US$ and adjusting cost data collected from other countries or previous studies. METHODS: We outlined the 3 main methods used to adjust for inflation for studies in these settings: exchanging the local currency to US$ or international dollars and then inflating using US inflation rates (method 1); inflating the local currency using local inflation rates and then exchanging to US$ or international dollars (method 2); splitting the costs into tradable and nontradable resources and using method 1 on the tradable resources and method 2 on the nontradable resources (method 3). RESULTS: In a hypothetical example of adjusting a cost of US$100 incurred in Vietnam from 2006 to 2016 prices, the adjusted cost from the 3 methods were US$116.84, US$172.09, and US$161.04, respectively. CONCLUSIONS: The different methods for adjusting for inflation can yield substantially different results. We make recommendations regarding the most appropriate method for various scenarios. Moving forward, it is vital that studies report the methodology they use to adjust for inflation more transparently.

10.
BMC Med ; 17(1): 163, 2019 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-31422772

RESUMO

BACKGROUND: Despite the increasing popularity of multi-model comparison studies and their ability to inform policy recommendations, clear guidance on how to conduct multi-model comparisons is not available. Herein, we present guidelines to provide a structured approach to comparisons of multiple models of interventions against infectious diseases. The primary target audience for these guidelines are researchers carrying out model comparison studies and policy-makers using model comparison studies to inform policy decisions. METHODS: The consensus process used for the development of the guidelines included a systematic review of existing model comparison studies on effectiveness and cost-effectiveness of vaccination, a 2-day meeting and guideline development workshop during which mathematical modellers from different disease areas critically discussed and debated the guideline content and wording, and several rounds of comments on sequential versions of the guidelines by all authors. RESULTS: The guidelines provide principles for multi-model comparisons, with specific practice statements on what modellers should do for six domains. The guidelines provide explanation and elaboration of the principles and practice statements as well as some examples to illustrate these. The principles are (1) the policy and research question - the model comparison should address a relevant, clearly defined policy question; (2) model identification and selection - the identification and selection of models for inclusion in the model comparison should be transparent and minimise selection bias; (3) harmonisation - standardisation of input data and outputs should be determined by the research question and value of the effort needed for this step; (4) exploring variability - between- and within-model variability and uncertainty should be explored; (5) presenting and pooling results - results should be presented in an appropriate way to support decision-making; and (6) interpretation - results should be interpreted to inform the policy question. CONCLUSION: These guidelines should help researchers plan, conduct and report model comparisons of infectious diseases and related interventions in a systematic and structured manner for the purpose of supporting health policy decisions. Adherence to these guidelines will contribute to greater consistency and objectivity in the approach and methods used in multi-model comparisons, and as such improve the quality of modelled evidence for policy.

11.
Value Health ; 22(8): 942-952, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31426936

RESUMO

BACKGROUND: Many investment cases have recently been published intending to show the value of new health investments, but without consistent methodological approaches. OBJECTIVES: To conduct a scoping review of existing investment cases (using vaccines and immunization programs as an example), identify common characteristics that define these investment cases, and examine their role within the broader context of the vaccine development and introduction. METHODS: A systematic search was conducted from January 1980 to November 2017 to identify investment cases in the area of vaccines and immunization programs from gray literature and electronic bibliographic databases. Investment case outcomes, objectives, key variables, target audiences, and funding sources were extracted and analyzed according to their reporting frequency. RESULTS: We found 24 investment cases, and most of them aim to provide information for decisions (12 cases) or advocate for a specific agenda (9 cases). Outcomes presented fell into 4 broad categories-burden of disease, cost of investment, impact of investment, and other considerations for implementation. Number of deaths averted (70%), incremental cost-effectiveness ratios (67%), and reduction in health and socioeconomic inequalities (54%) were the most frequently reported outcome measures for impact of investment. Health system capacity (79%) and vaccine financing landscape (75%) were the most common considerations for implementation. A sizable proportion (41.4%) of investment cases did not reveal their funding sources. CONCLUSIONS: This review describes information that is critical to decision making about resource mobilization and allocation concerning vaccines. Global efforts to harmonize investment cases more broadly will increase transparency and comparability.

12.
BMC Med ; 17(1): 129, 2019 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-31272431

RESUMO

BACKGROUND: Every year, 90,000 people may die from melioidosis. Vaccine candidates have not proceeded past animal studies, partly due to uncertainty around the potential market size. This study aims to estimate the potential impact, cost-effectiveness and market size for melioidosis vaccines. METHODS: Age-structured decision tree models with country-specific inputs were used to estimate net costs and health benefits of vaccination, with health measured in quality-adjusted life years (QALYs). Four target groups of people living in endemic regions were considered: (i) people aged over 45 years with chronic renal disease, (ii) people aged over 45 years with diabetes, (iii) people aged over 45 years with diabetes and/or chronic renal disease, (iv) everyone aged over 45 years. Melioidosis risk was estimated using Bayesian evidence synthesis of 12 observational studies. In the base case, vaccines were assumed to have 80% efficacy, to have 5-year mean protective duration and to cost USD10.20-338.20 per vaccine. RESULTS: Vaccination could be cost-effective (with incremental cost-effectiveness ratio below GDP per capita) in 61/83 countries/territories with local melioidosis transmission. In these 61 countries/territories, vaccination could avert 68,000 lost QALYs, 8300 cases and 4400 deaths per vaccinated age cohort, at an incremental cost of USD59.6 million. Strategy (ii) was optimal in most regions. The vaccine market may be worth USD268 million per year at its threshold cost-effective price in each country/territory. CONCLUSIONS: There is a viable melioidosis vaccine market, with cost-effective vaccine strategies in most countries/territories with local transmission.


Assuntos
Melioidose/tratamento farmacológico , Vacinação/economia , Análise Custo-Benefício , Feminino , Humanos , Masculino , Melioidose/patologia , Pessoa de Meia-Idade
13.
Lancet Infect Dis ; 19(7): 717-727, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31178289

RESUMO

BACKGROUND: The duration of protection offered by rotavirus vaccines varies across the world, and this variation is important to understanding and predicting the effects of the vaccines. There is now a large body of evidence on the efficacy of live oral rotavirus vaccines in different settings, but these data have never been synthesised to obtain robust estimates of efficacy by duration of follow-up. Our aim is to estimate the efficacy of live oral rotavirus vaccines at each point during follow-up and by mortality stratum. METHODS: In our meta-regression study, we identified all randomised controlled trials of rotavirus vaccines published until April 4, 2018, using the results of a Cochrane systematic review, and cross checked these studies against those identified by another systematic review. We excluded trials that were based on special populations, trials without an infant schedule, and trials without clear reporting of numbers of enrolled infants and events in different periods of follow-up. For all reported periods of follow-up, we extracted the mean duration of follow-up (time since administration of the final dose of rotavirus vaccination), the number of enrolled infants, and case counts for rotavirus-positive severe gastroenteritis in both non-vaccinated and vaccinated groups. We used a Bayesian hierarchical Poisson meta-regression model to estimate the pooled cumulative vaccine efficacy (VE) and its waning with time for three mortality strata. We then converted these VE estimates into instantaneous VE (iVE). FINDINGS: In settings with low mortality (15 observations), iVE pooled for infant schedules of Rotarix and RotaTeq was 98% (95% credibility interval 93-100) 2 weeks following the final dose of vaccination and 94% (87-98) after 12 months. In medium-mortality settings (11 observations), equivalent estimates were 82% (74-92) after 2 weeks and 77% (67-84) after 12 months. In settings with high mortality (24 observations), there were five different vaccines with observation points for infant schedules. The pooled iVE was 66% (48-81) after 2 weeks of follow-up and 44% (27-59) after 12 months. INTERPRETATION: Rotavirus vaccine efficacy is lower and wanes more rapidly in high-mortality settings than in low-mortality settings, but the earlier peak age of disease in high-mortality settings means that live oral rotavirus vaccines are still likely to provide substantial benefit. FUNDING: Bill & Melinda Gates Foundation.

14.
Health Technol Assess ; 23(23): 1-152, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31138395

RESUMO

BACKGROUND: Interferon gamma release assays (IGRAs) are blood tests recommended for the diagnosis of tuberculosis (TB) infection. There is currently uncertainty about the role and clinical utility of IGRAs in the diagnostic workup of suspected active TB in routine NHS clinical practice. OBJECTIVES: To compare the diagnostic accuracy and cost-effectiveness of T-SPOT.TB ® (Oxford Immunotec, Abingdon, UK) and QuantiFERON® TB GOLD In-Tube (Cellestis, Carnegie, VIC, Australia) for diagnosis of suspected active TB and to estimate the diagnostic accuracy of second-generation IGRAs. DESIGN: Prospective within-patient comparative diagnostic accuracy study. SETTING: Secondary care. PARTICIPANTS: Adults (aged ≥ 16 years) presenting as inpatients or outpatients at 12 NHS hospital trusts in London, Slough, Oxford, Leicester and Birmingham with suspected active TB. INTERVENTIONS: The index tests [T-SPOT.TB and QuantiFERON GOLD In-Tube (QFT-GIT)] and new enzyme-linked immunospot assays utilising novel Mycobacterium tuberculosis antigens (Rv3615c, Rv2654, Rv3879c and Rv3873) were verified against a composite reference standard applied by a panel of clinical experts blinded to IGRA results. MAIN OUTCOME MEASURES: Sensitivity, specificity, predictive values and likelihood ratios were calculated to determine diagnostic accuracy. A decision tree model was developed to calculate the incremental costs and incremental health utilities [quality-adjusted life-years (QALYs)] of changing from current practice to using an IGRA as an initial rule-out test. RESULTS: A total of 363 patients had active TB (culture-confirmed and highly probable TB cases), 439 had no active TB and 43 had an indeterminate final diagnosis. Comparing T-SPOT.TB and QFT-GIT, the sensitivities [95% confidence interval (CI)] were 82.3% (95% CI 77.7% to 85.9%) and 67.3% (95% CI 62.1% to 72.2%), respectively, whereas specificities were 82.6% (95% CI 78.6% to 86.1%) and 80.4% (95% CI 76.1% to 84.1%), respectively. T-SPOT.TB was more sensitive than QFT-GIT (relative sensitivity 1.22, 95% CI 1.14 to 1.31; p < 0.001), but the specificities were similar (relative specificity 1.02, 95% CI 0.97 to 1.08; p = 0.3). For both IGRAs the sensitivity was lower and the specificity was higher for human immunodeficiency virus (HIV)-positive than for HIV-negative patients. The most promising novel antigen was Rv3615c. The added value of Rv3615c to T-SPOT.TB was a 9% (95% CI 5% to 12%) relative increase in sensitivity at the expense of specificity, which had a relative decrease of 7% (95% CI 4% to 10%). The use of current IGRA tests for ruling out active TB is unlikely to be considered cost-effective if a QALY was valued at £20,000 or £30,000. For T-SPOT.TB, the probability of being cost-effective for a willingness to pay of £20,000/QALY was 26% and 21%, when patients with indeterminate test results were excluded or included, respectively. In comparison, the QFT-GIT probabilities were 8% and 6%. Although the use of IGRAs is cost saving, the health detriment is large owing to delay in diagnosing active TB, leading to prolonged illness. There was substantial between-patient variation in the tests used in the diagnostic pathway. LIMITATIONS: The recruitment target for the HIV co-infected population was not achieved. CONCLUSIONS: Although T-SPOT.TB was more sensitive than QFT-GIT for the diagnosis of active TB, the tests are insufficiently sensitive for ruling out active TB in routine clinical practice in the UK. Novel assays offer some promise. FUTURE WORK: The novel assays require evaluation in distinct clinical settings and in immunosuppressed patient groups. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and the NIHR Health Protection Research Unit in Respiratory Infections, Imperial College London, London, UK.

15.
Int J Gynecol Cancer ; 2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31018938

RESUMO

OBJECTIVES: In England, human papillomavirus (HPV) testing is to replace cytological screening by 2019-2020. We conducted a model-based economic evaluation to project the long-term clinical impact and cost-effectiveness of routine cytology versus HPV testing. METHODS: An individual-based model of HPV acquisition, natural history, and cervical cancer screening was used to compare cytological screening and HPV testing with cytology triage for women aged 25-64 years (with either 3- or 5-year screening intervals for women aged under 50 years). The model was fitted to data from England's National Health Service Cervical Screening Programme. Both clinical and economic outcomes were projected to inform cost-effectiveness analyses. RESULTS: HPV testing is likely to decrease annual cytology testing (by 2.76 million), cervical cancer incidence (by 290 cases), and health system costs (by £13 million). It may increase the number of colposcopies, although this could be reduced without leading to more cancers compared with primary cytology by increasing the interval between screens to 5 years. The impact in terms of quality-adjusted life-years (QALYs) depends on the quality of life weight given to colposcopies versus cancer. CONCLUSIONS: England's move from cytology to HPV screening may potentially be life-saving and cost-effective. Cost-effectiveness can be improved further by extending the interval between screens or using alternative triage methods such as partial or full genotyping.

16.
Soc Sci Med ; 228: 181-193, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30925392

RESUMO

Vaccination programs generate direct protection, herd protection and, occasionally, side effects, distributed over different age groups. This study elicits the general public's view on how to balance these outcomes in funding decisions for vaccines. We performed an optimal design discrete choice experiment with partial profiles in a representative sample (N = 1499) of the population in the United Kingdom in November 2016. Using a panel mixed logit model, we quantified, for four different types of infectious disease, the importance of a person's age during disease, how disease was prevented-via direct vaccine protection or herd protection-and whether the vaccine induced side effects. Our study shows clear patterns in how the public values vaccination programs. These diverge from the assumptions made in public health and cost-effectiveness models that inform decision-making. We found that side effects and infections in newborns and children were of primary importance to the perceived value of a vaccination program. Averting side effects was, in any age group, weighted three times as important as preventing an identical natural infection in a child whereas the latter was weighted six times as important as preventing the same infection in elderly aged 65-75 years. These findings were independent of the length or severity of the disease, and were robust across respondents' backgrounds. We summarize these patterns in a set of preference weights that can be incorporated into future models. Although the normative significance of these weights remains a matter open for debate, our study can, hopefully, contribute to the evaluation of vaccination programs beyond cost-effectiveness.

17.
Lancet Glob Health ; 7(4): e472-e481, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30797735

RESUMO

BACKGROUND: In the 21st century, increases in immunisation coverage and decreases in under-5 mortality have substantially reduced the global burden of measles mortality. However, the assessment of measles mortality burden is highly dependent on estimates of case-fatality ratios for measles, which can vary according to geography, health systems infrastructure, prevalence of underlying risk factors, and measles endemicity. With imprecise case-fatality ratios, there is continued uncertainty about the burden of measles mortality and the effect of measles vaccination. In this study, we aimed to update the estimations of case-fatality ratios for measles, to develop a prediction model to estimate case-fatality ratios across heterogeneous groupings, and to project future case-fatality ratios for measles up to 2030. METHODS: We did a review of the literature to identify studies examining measles cases and deaths in low-income and middle-income countries in all age groups from 1980 to 2016. We extracted data on case-fatality ratios for measles overall and by age, where possible. We developed and examined several types of generalised linear models and determined the best-fit model according to the Akaike information criterion. We then selected a best-fit model to estimate measles case-fatality ratios from 1990 to 2015 and projected future case-fatality ratios for measles up to 2030. FINDINGS: We selected 124 peer-reviewed journal articles published between Jan 1, 1980, and Dec 31, 2016, for inclusion in the final review-85 community-based studies and 39 hospital-based studies. We selected a log-linear prediction model, resulting in a mean case-fatality ratio of 2·2% (95% CI 0·7-4·5) in 1990-2015. In community-based settings, the mean case-fatality ratio was 1·5% (0·5-3·1) compared with 2·9% (0·9-6·0) in hospital-based settings. The mean projected case-fatality ratio in 2016-2030 was 1·3% (0·4-3·7). INTERPRETATION: Case-fatality ratios for measles have seen substantial declines since the 1990s. Our study provides an updated estimation of case-fatality ratios that could help to refine assessment of the effect on mortality of measles control and elimination programmes. FUNDING: Bill & Melinda Gates Foundation.

18.
JAMA Pediatr ; 173(4): 352-362, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30742207

RESUMO

Importance: The global patterns and distribution of case-fatality rates (CFRs) in pediatric severe sepsis and septic shock remain poorly described. Objective: We performed a systematic review and meta-analysis of studies of children with severe sepsis and septic shock to elucidate the patterns of CFRs in developing and developed countries over time. We also described factors associated with CFRs. Data Sources: We searched PubMed, Web of Science, Excerpta Medica database, Cumulative Index of Nursing and Allied Health Literature (CINAHL), and Cochrane Central systematically for randomized clinical trials and prospective observational studies from earliest publication until January 2017, using the keywords "pediatric," "sepsis," "septic shock," and "mortality." Study Selection: Studies involving children with severe sepsis and septic shock that reported CFRs were included. Retrospective studies and studies including only neonates were excluded. Data Extraction and Synthesis: We conducted our systematic review and meta-analysis in close accordance to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Pooled case-fatality estimates were obtained using random-effects meta-analysis. The associations of study period, study design, sepsis severity, age, and continents in which studies occurred were assessed with meta-regression. Main Outcomes and Measures: Meta-analyses to provide pooled estimates of CFR of pediatric severe sepsis and septic shock over time. Results: Ninety-four studies that included 7561 patients were included. Pooled CFRs were higher in developing countries (31.7% [95% CI, 27.3%-36.4%]) than in developed countries (19.3% [95% CI, 16.4%-22.7%]; P < .001). Meta-analysis of CFRs also showed significant heterogeneity across studies. Continents that include mainly developing countries reported higher CFRs (adjusted odds ratios: Africa, 7.89 [95% CI, 6.02-10.32]; P < .001; Asia, 3.81 [95% CI, 3.60-4.03]; P < .001; South America, 2.91 [95% CI, 2.71-3.12]; P < .001) than North America. Septic shock was associated with higher CFRs than severe sepsis (adjusted odds ratios, 1.47 [95% CI, 1.41-1.54]). Younger age was also a risk factor (adjusted odds ratio, 0.95 [95% CI, 0.94-0.96] per year of increase in age). Earlier study eras were associated with higher CFRs (adjusted odds ratios for 1991-2000, 1.24 [95% CI, 1.13-1.37]; P < .001) compared with 2011 to 2016. Time-trend analysis showed higher CFRs over time in developing countries than developed countries. Conclusions and Relevance: Despite the declining trend of pediatric severe sepsis and septic shock CFRs, the disparity between developing and developed countries persists. Further characterizations of vulnerable populations and collaborations between developed and developing countries are warranted to reduce the burden of pediatric sepsis globally.

19.
Nat Ecol Evol ; 3(3): 440-449, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30742105

RESUMO

The spread of antibiotic resistance, a major threat to human health, is poorly understood. Simple population-level models of bacterial transmission predict that above a certain rate of antibiotic consumption in a population, resistant bacteria should completely eliminate non-resistant strains, while below this threshold they should be unable to persist at all. This prediction stands at odds with empirical evidence showing that resistant and non-resistant strains coexist stably over a wide range of antibiotic consumption rates. Not knowing what drives this long-term coexistence is a barrier to developing evidence-based strategies for managing the spread of resistance. Here, we argue that competition between resistant and sensitive pathogens within individual hosts gives resistant pathogens a relative fitness benefit when they are rare, promoting coexistence between strains at the population level. To test this hypothesis, we embed mechanistically explicit within-host dynamics in a structurally neutral pathogen transmission model. Doing so allows us to reproduce patterns of resistance observed in the opportunistic pathogens Escherichia coli and Streptococcus pneumoniae across European countries and to identify factors that may shape resistance evolution in bacteria by modulating the intensity and outcomes of within-host competition.


Assuntos
Resistência Microbiana a Medicamentos/fisiologia , Escherichia coli/efeitos dos fármacos , Interações Hospedeiro-Patógeno , Interações Microbianas , Streptococcus pneumoniae/efeitos dos fármacos , Antibacterianos/farmacologia , Fenômenos Fisiológicos Bacterianos/efeitos dos fármacos , Evolução Biológica , Escherichia coli/fisiologia , Europa (Continente) , Streptococcus pneumoniae/fisiologia , Simbiose
20.
Sex Transm Infect ; 95(1): 28-35, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30674687

RESUMO

BACKGROUND: Many economic evaluations of human papillomavirus vaccination should ideally consider multiple disease outcomes, including anogenital warts, respiratory papillomatosis and non-cervical cancers (eg, anal, oropharyngeal, penile, vulvar and vaginal cancers). However, published economic evaluations largely relied on estimates from single studies or informal rapid literature reviews. METHODS: We conducted a systematic review of articles up to June 2016 to identify costs and utility estimates admissible for an economic evaluation from a single-payer healthcare provider's perspective. Meta-analyses were performed for studies that used same utility elicitation tools for similar diseases. Costs were adjusted to 2016/2017 US$. RESULTS: Sixty-one papers (35 costs; 24 utilities; 2 costs and utilities) were selected from 10 742 initial records. Cost per case ranges were US$124-US$883 (anogenital warts), US$6912-US$52 579 (head and neck cancers), US$12 936-US$51 571 (anal cancer), US$17 524-34 258 (vaginal cancer), US$14 686-US$28 502 (vulvar cancer) and US$9975-US$27 629 (penile cancer). The total cost for 14 adult patients with recurrent respiratory papillomatosis was US$137 601 (one paper).Utility per warts episode ranged from 0.651 to 1 (12 papers, various utility elicitation methods), with pooled mean EQ-5D and EQ-VAS of 0.86 (95% CI 0.85 to 0.87) and 0.74 (95% CI 0.74 to 0.75), respectively. Fifteen papers reported utilities in head and neck cancers with range 0.29 (95% CI 0.0 to 0.76) to 0.94 (95% CI 0.3 to 1.0). Mean utility reported ranged from 0.5 (95% CI 0.4 to 0.61) to 0.65 (95% CI 0.45 to 0.75) (anal cancer), 0.59 (95% CI 0.54 to 0.64) (vaginal cancer), 0.65 (95% CI 0.60 to 0.70) (vulvar cancer) and 0.79 (95% CI 0.74 to 0.84) (penile cancer). CONCLUSIONS: Differences in values reported from each paper reflect variations in cancer site, disease stages, study population, treatment modality/setting and utility elicitation methods used. As patient management changes over time, corresponding effects on both costs and utility need to be considered to ensure health economic assumptions are up-to-date and closely reflect the case mix of patients.


Assuntos
Neoplasias do Ânus/economia , Condiloma Acuminado/economia , Neoplasias de Cabeça e Pescoço/economia , Infecções por Papillomavirus/economia , Vacinas contra Papillomavirus/economia , Neoplasias Penianas/economia , Infecções Respiratórias/economia , Neoplasias Vaginais/economia , Neoplasias Vulvares/economia , Doenças do Ânus/economia , Doenças do Ânus/prevenção & controle , Neoplasias do Ânus/prevenção & controle , Condiloma Acuminado/prevenção & controle , Análise Custo-Benefício , Feminino , Doenças dos Genitais Femininos/economia , Doenças dos Genitais Femininos/prevenção & controle , Doenças dos Genitais Masculinos/economia , Doenças dos Genitais Masculinos/prevenção & controle , Neoplasias de Cabeça e Pescoço/prevenção & controle , Custos de Cuidados de Saúde , Humanos , Masculino , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/uso terapêutico , Neoplasias Penianas/prevenção & controle , Qualidade de Vida , Infecções Respiratórias/prevenção & controle , Estados Unidos , Neoplasias Vaginais/prevenção & controle , Neoplasias Vulvares/prevenção & controle
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