The immunogenicity and safety of respiratory syncytial virus vaccines in development: A systematic review

BackgroundRespiratory syncytial virus (RSV) is a leading cause of acute lower respiratory infection globally. There are vaccine candidates in development, but a systematic review on immunogenicity and safety of vaccine is lacking.MethodsThis systematic review of RSV vaccine clinical trials was undertaken using four databases. Searches were conducted using both controlled vocabulary terms such as “Respiratory Syncytial Virus, Human,” “Respiratory Syncytial Virus Infections,” “Respiratory Syncytial Virus Vaccines,” “Immunization,” “Immunization Programs” and “Vaccines” and corresponding text word terms. The included studies were limited to clinical trials published from January 2000 to 31 December 2020. RSV infection case was defined as RSV‐associated medically attended acute respiratory illness (MAARI) or RSV infection by serologically confirmed test (Western blot) during the RSV surveillance period. We calculated the relative risk of each vaccine trial with RSV infection case.ResultsOf 6306 publications, 38 were included and data were extracted covering four major types of RSV vaccine candidates, these being live‐attenuated/chimeric (n = 14), recombinant‐vector (n = 6), subunit (n = 12) and nanoparticle vaccines (n = 6). For RSV infection cases, nine trials were involved and none of them showed a vaccine‐related increased MAARI during RSV surveillance season.ConclusionLID ∆M2‐2, MEDI M2‐2, RSVcps2 and LID/∆M2‐2 /1030s (live‐attenuated) were considered the most promising vaccine candidates in infant and children. In the elderly, a nanoparticle F vaccine candidate and Ad26.RSV.preF were considered as two potential effective vaccines. A promising maternal vaccine candidate is still lacking.     

Plant-Based Vaccines: The Way Ahead?

Severe virus outbreaks are occurring more often and spreading faster and further than ever. Preparedness plans based on lessons learned from past epidemics can guide behavioral and pharmacological interventions to contain and treat emergent diseases. Although conventional biologics production systems can meet the pharmaceutical needs of a community at homeostasis, the COVID-19 pandemic has created an abrupt rise in demand for vaccines and therapeutics that highlight the gaps in this supply chain’s ability to quickly develop and produce biologics in emergency situations given a short lead time. Considering the projected requirements for COVID-19 vaccines and the necessity for expedited large scale manufacture the capabilities of current biologics production systems should be surveyed to determine their applicability to pandemic preparedness. Plant-based biologics production systems have progressed to a state of commercial viability in the past 30 years with the capacity for production of complex, glycosylated, “mammalian compatible” molecules in a system with comparatively low production costs, high scalability, and production flexibility. Continued research drives the expansion of plant virus-based tools for harnessing the full production capacity from the plant biomass in transient systems. Here, we present an overview of vaccine production systems with a focus on plant-based production systems and their potential role as “first responders” in emergency pandemic situations.     

Prospects for development of a transmission blocking vaccine against Schistosoma japonicum

Despite intensive long-term control programmes, schistosomiasis japonica remains a serious public health problem in China and the Philippines. The termination of mass praziquantel-treatment has seen a dramatic recent rebound in both its prevalence and associated morbidity. Schistosomiasis japonica is a zoonosis but, despite complicating control efforts, this feature provides a practical method for attacking Schistosoma japonicum through development and deployment of a transmission blocking veterinary vaccine. A recently completed bovine drug intervention trial and mathematical modelling of the transmission of S. japonicum underpin the concept that such a vaccine, targeting water buffalo, would have major implications for future integrated schistosomiasis control in China. A major block to success is the low ceiling efficacy achieved with current vaccine molecules. To solve this challenge, an antigen discovery pipeline needs to be established for identification of new vaccine targets that induce greater potency than the current anti-S. japonicum candidate vaccines. Excretory-secretory products and molecules exposed on epithelial surfaces (including receptors) which interact directly with the host immune system warrant especial attention. Extensive schistosome genomics programmes currently underway coupled with new advances in proteomics and microarray technology provide an unparalleled opportunity to identify new molecules exploitable as vaccine targets. These will then need to be produced in quantity and rigorously tested first in the laboratory and then the field. If a transmission blocking veterinary vaccine developed for bovines can be put into practice in combination with other control strategies such as human chemotherapy, elimination of S. japonicum from China may be achievable.     

Serological,Molecular and Culture-Based Diagnosis of Lentiviral Infections in Small Ruminants

Small ruminant lentiviruses (SRLVs) infections lead to chronic diseases and remarkable economic losses undermining health and welfare of animals and the sustainability of farms. Early and definite diagnosis of SRLVs infections is the cornerstone for any control and eradication efforts; however, a “gold standard” test and/or diagnostic protocols with extensive applicability have yet to be developed. The main challenges preventing the development of a universally accepted diagnostic tool with sufficient sensitivity, specificity, and accuracy to be integrated in SRLVs control programs are the genetic variability of SRLVs associated with mutations, recombination, and cross-species transmission and the peculiarities of small ruminants’ humoral immune response regarding late seroconversion, as well as intermittent and epitope-specific antibody production. The objectives of this review paper were to summarize the available serological and molecular assays for the diagnosis of SRLVs, to highlight their diagnostic performance emphasizing on advantages and drawbacks of their application, and to discuss current and future perspectives, challenges, limitations and impacts regarding the development of reliable and efficient tools for the diagnosis of SRLVs infections.     

An Improved αvβ6-Receptor-Expressing Suspension Cell Line for Foot-and-Mouth Disease Vaccine Production

Foot-and-mouth disease (FMD) is endemic in large parts of sub-Saharan Africa, Asia and South America, where outbreaks in cloven-hooved livestock threaten food security and have severe economic impacts. Vaccination in endemic regions remains the most effective control strategy. Current FMD vaccines are produced from chemically inactivated foot-and-mouth disease virus (FMDV) grown in suspension cultures of baby hamster kidney 21 cells (BHK-21). Strain diversity means vaccines produced from one subtype may not fully protect against circulating disparate subtypes, necessitating the development of new vaccine strains that “antigenically match”. However, some viruses have proven difficult to adapt to cell culture, slowing the manufacturing process, reducing vaccine yield and limiting the availability of effective vaccines, as well as potentiating the selection of undesired antigenic changes. To circumvent the need to cell culture adapt FMDV, we have used a systematic approach to develop recombinant suspension BHK-21 that stably express the key FMDV receptor integrin αvβ6. We show that αvβ6 expression is retained at consistently high levels as a mixed cell population and as a clonal cell line. Following exposure to field strains of FMDV, these recombinant BHK-21 facilitated higher virus yields compared to both parental and control BHK-21, whilst demonstrating comparable growth kinetics. The presented data supports the application of these recombinant αvβ6-expressing BHK-21 in future FMD vaccine production.     

湖北省血吸虫病消除工作面临的主要挑战

本文总结了湖北省血吸虫病防治的主要经验、分析了消除血吸虫病面临的挑战,并提出了下一步工作的相关建议,以期对加快湖区血吸虫病消除工作进程、推动《“十三五”全国血吸虫病防治规划》目标的实现有所助益。     

From the Cover: Impact and cost-effectiveness of new tuberculosis vaccines in low- and middle-income countries

To help reach the target of tuberculosis (TB) disease elimination by 2050, vaccine development needs to occur now. We estimated the impact and cost-effectiveness of potential TB vaccines in low- and middle-income countries using an age-structured transmission model. New vaccines were assumed to be available in 2024, to prevent active TB in all individuals, to have a 5-y to lifetime duration of protection, to have 40–80% efficacy, and to be targeted at “infants” or “adolescents/adults.” Vaccine prices were tiered by income group (US $1.50–$10 per dose), and cost-effectiveness was assessed using incremental cost per disability adjusted life year (DALY) averted compared against gross national income per capita. Our results suggest that over 2024–2050, a vaccine targeted to adolescents/adults could have a greater impact than one targeted at infants. In low-income countries, a vaccine with a 10-y duration and 60% efficacy targeted at adolescents/adults could prevent 17 (95% range: 11–24) million TB cases by 2050 and could be considered cost-effective at $149 (cost saving to $387) per DALY averted. If targeted at infants, 0.89 (0.42–1.58) million TB cases could be prevented at $1,692 ($634–$4,603) per DALY averted. This profile targeted at adolescents/adults could be cost-effective at $4, $9, and $20 per dose in low-, lower-middle–, and upper-middle–income countries, respectively. Increased investments in adult-targeted TB vaccines may be warranted, even if only short duration and low efficacy vaccines are likely to be feasible, and trials among adults should be powered to detect low efficacies.The bacterium Mycobacterium tuberculosis was responsible for ∼8.6 million cases of tuberculosis (TB) disease and ∼1.3 million deaths in 2012 (1), of which over 80% were in low-income countries (LICs) and middle-income countries. This burden remains despite the widespread use of the infant TB vaccine, bacille Calmette–Guérin (bacillus Calmette–Guérin) (2). Dramatic levels of control are required to reach the World Health Organization (WHO) targets of TB elimination as a public health problem by 2050 (3). Previous mathematical modeling has suggested elimination can only be achieved through the use of new vaccines (4–7).In 2013, there were more than a dozen new TB vaccines in clinical trials, using a large range of antigens and adjuvants (8). A variety of modes of action and target populations are being researched (9, 10). The most recent TB vaccine tested in a large-scale phase II trial reported a nonsignificant impact on TB disease of 17.3% [95% confidence interval (CI): −31.9 to 48.2] (11). However, such an undertaking highlights the progress that has been made in TB vaccine clinical trials, as well as the need for a reevaluation of the potential impact and need for increased investment in new TB vaccines (12).Estimates of the likely impact and cost-effectiveness of new products before and during development are useful for informing target product profiles and guiding product prioritization. Such analyses of future vaccines have been undertaken for several other diseases (13–17) but have been limited to exploring the cost-effectiveness of infant vaccination in Asia and Sub-Saharan Africa for TB (18–20). To inform the products and targeting that will be most useful for achieving the 2050 elimination target (3), there is a need to systematically estimate the impact in a wide range of settings of a variety of potential TB vaccine profiles defined by efficacy, duration of protection, and potential target groups (e.g., by age). The aim of this study was to estimate this potential impact and cost-effectiveness for prospective TB vaccine profiles in LICs and middle-income countries over the time horizon 2024–2050.We used an age-structured M. tuberculosis transmission model. To be conservative in vaccine impact, we model an aggressive scale-up of existing technologies before the introduction of the new vaccine, in line with the recently approved post-2015 WHO global TB strategy (21). New TB vaccines were assumed to be available in 2024, to prevent active TB in infected and uninfected individuals, to have a 5-y to lifetime duration of protection and 40–80% efficacy, and to be targeted at “infants” or “adolescents/adults.” The former involved vaccination at birth, and the latter involved vaccination at the age of 10 y in schools supplemented with mass campaigns directed to those individuals aged 11 y and older at a frequency corresponding to the duration of protection or every 10 y (whichever was longer). These age groups were chosen to reflect the feasibility of vaccine delivery. Infant vaccination would be alongside the routine schedule, and 10-y-olds could be reached in schools, where immunization is becoming increasingly common. Mass campaigns were included as a scenario in which all people at risk from TB could be targeted. Vaccine prices were tiered by country income group, as measured in US dollars ($1.50–$10 per dose), and cost-effectiveness was defined as a cost per disability adjusted life year (DALY) averted of less than the gross national income (GNI) per capita.We carried out two main analyses. The first estimated the impact and cost-effectiveness of a broad range of prespecified potential vaccine characteristics when targeted at infants or adolescents/adults. The second analysis estimated the maximum price per vaccine dose at which the vaccine could still be deemed cost-effective. Full details are provided in Materials and Methods and SI Appendix.     

Old vaccines for new infections: Exploiting innate immunity to control COVID-19 and prevent future pandemics

The COVID-19 pandemic triggered an unparalleled pursuit of vaccines to induce specific adaptive immunity, based on virus-neutralizing antibodies and T cell responses. Although several vaccines have been developed just a year after SARS-CoV-2 emerged in late 2019, global deployment will take months or even years. Meanwhile, the virus continues to take a severe toll on human life and exact substantial economic costs. Innate immunity is fundamental to mammalian host defense capacity to combat infections. Innate immune responses, triggered by a family of pattern recognition receptors, induce interferons and other cytokines and activate both myeloid and lymphoid immune cells to provide protection against a wide range of pathogens. Epidemiological and biological evidence suggests that the live-attenuated vaccines (LAV) targeting tuberculosis, measles, and polio induce protective innate immunity by a newly described form of immunological memory termed “trained immunity.” An LAV designed to induce adaptive immunity targeting a particular pathogen may also induce innate immunity that mitigates other infectious diseases, including COVID-19, as well as future pandemic threats. Deployment of existing LAVs early in pandemics could complement the development of specific vaccines, bridging the protection gap until specific vaccines arrive. The broad protection induced by LAVs would not be compromised by potential antigenic drift (immune escape) that can render viruses resistant to specific vaccines. LAVs might offer an essential tool to “bend the pandemic curve,” averting the exhaustion of public health resources and preventing needless deaths and may also have therapeutic benefits if used for postexposure prophylaxis of disease.     

Pandemic influenza vaccines: meeting the supply,distribution and deployment challenges

An influenza pandemic will place an enormous strain on the world’s vaccine production, distribution and administration systems. Following a pandemic declaration, industry’s priority will be to deliver as much vaccine in as short a timeframe as possible. In respect to this challenge, manufacturers have successfully developed antigen‐sparing strategies and significantly increased production capacity, with further growth planned assuming ongoing rising demand for seasonal vaccines. The combination of these factors has the potential to closer meet global needs for vaccine supply than ever before through increased availability of pandemic and pre‐pandemic vaccines. The demonstration of cross‐clade reactivity with H5N1 viruses makes the concept of pre‐pandemic stockpiling and vaccination a reality for this subtype. Ensuring these vaccines are made available in a timely fashion to those who need them will present significant challenges. For local authorities, national governments and international organisations this means defining vaccine allocation and procurement processes as well as strengthening, and where necessary establishing, the critical health systems and infrastructure required for vaccine deployment. For vaccine producers this means addressing the technical and logistical issues associated with supply. This includes working with regulators to streamline key procedures, including generic labelling and batch release, while establishing flexibility in supply formats, including bulk and finished products, to maximise the speed of delivery. Similarly, the deployment of large quantities of vaccines in an emergency situation requires appropriate transport infrastructure and the distribution of associated medical supplies. As well as addressing these issues, specific consideration must be given to the logistics and storage aspects associated with stockpiling pre‐pandemic vaccines. Finally, mutually agreed contractual arrangements between manufacturers and governments or international institutions represent the best approach toward addressing supply challenges and assisting vaccine producers meet national and international demand. To be effective, these contracts should be based on accurate forecasts, clearly defined vaccination strategies and the capabilities of public health infrastructure.     

阻断血吸虫病传播策略与措施专家共识

2015年全国达到血吸虫病传播控制标准后,进入以全面阻断血吸虫病传播为新目标、开展监测预警为主要干预措施的新时期.“十三五”时期,四川、江苏、云南、湖北等4个血吸虫病防治重点省份先后达到血吸虫病传播阻断标准或通过国家血吸虫病传播阻断技术评估,我国血吸虫病疫情处于历史最低水平,流行程度进一步降低,《“十三五”全国血吸虫病...     

Transparent communication about negative features of COVID-19 vaccines decreases acceptance but increases trust

During the rapid development and rolling out of vaccines against COVID-19, researchers have called for an approach of “radical transparency,” in which vaccine information is transparently disclosed to the public, even if negative information can decrease vaccine uptake. Consistent with theories about the psychology of conspiracy beliefs, these calls predict that a lack of transparency may reduce trust in health authorities and may facilitate the spread of conspiracy theories, which may limit the long-term capabilities of health authorities during and after the pandemic. On the basis of preregistered experiments conducted on large, representative samples of Americans and Danes (N > 13,000), the current study contrasts the effects of vague vaccine communication with transparent communication, which discloses either positive or negative vaccine features. The evidence demonstrates that transparent negative communication may indeed harm vaccine acceptance here and now but that it increases trust in health authorities. Furthermore, the alternative of vague, reassuring communication does not increase vaccine acceptance either and leads to both lower trust and higher endorsement of conspiracy theories.

The World Health Organization (WHO) has emphasized that a vaccine against COVID-19 is a “vital tool” to counter the current pandemic (1) and, accordingly, unprecedented amounts of resources have been invested in the race toward the development and distribution of vaccines. Yet, the challenges of a vaccine-based solution to the COVID-19 pandemic does not end with the development of an effective and safe vaccine. A rapidly developed vaccine will have no effect if citizens across the world are not willing to get vaccinated. Given the emergence of more contagious and potentially vaccine-resistant coronavirus variants, a significant proportion of the public will need to get vaccinated to reach herd immunity (2) and may need to be revaccinated. As a number of international studies have demonstrated significant public vaccine hesitancy (3–6), a key challenge is to ensure sufficient vaccine acceptance both now and in the future.Over the course of the pandemic, the importance of ensuring sufficient compliance with health recommendations has placed health communication at the center of pandemic management and, accordingly, there has been a pressing need for research on the factors underlying effective health communication. In the initial phases of the pandemic, as uncertainties about the COVID-19 disease and its cures abounded, a necessary focus was on how health authorities and researchers could transparently disclose what is not yet known (7) and the evidence documented that such uncertainties can be disclosed without harming public trust (8, 9). Yet, as knowledge is accumulating, discussions are increasingly shifting toward whether and how to transparently disclose what is known by authorities but which may constitute a barrier to public compliance with health recommendations.Not disclosing health-relevant information transparently is a frequent problem in relationships between patients and health practitioners and a source of distrust (10). While practitioners sometimes worry that full transparency will cause emotional distress in patients (11, 12), the incentives toward lack of transparency during the COVID-19 pandemic relates more to the massive pressure of ending the pandemic as quickly as possible and, hence, to incentives to not disclose information that may jeopardize vaccine acceptance. These incentives may be larger because health communication during the pandemic is strongly influenced and often conducted by politicians. As evidenced by a rich history of political science research, politicians are motivated by myopic goals (13) and may prioritize short-term successes compared with building trust for the next health crisis.In the domain of COVID-19 vaccines, negative information may relate to the fact that distribution and production difficulties require the use of vaccines with lower effectiveness and more side effects than other vaccines; unwelcome news may emerge about long-term side effects; the duration of immunity following vaccination may be lower than expected; and effectiveness may drop against new and emerging variants. Studies suggest that such negative information (e.g., information about lower effectiveness and side effects) may lower acceptance of vaccines in general (14) and COVID-19 vaccines specifically (15). This has been a real concern for health authorities in both Europe and United States where discussions about the presumed lower effectiveness and potential side effects of some COVID-19 vaccines have been argued to spur hesitancy and implies that millions of doses of those vaccines remain unused (16, 17). Also, several countries worldwide—including Western democracies—have started vaccination campaigns without or prior to the publication of phase III trial results (18).Against such developments, research communities have called for the transparent disclosing of information about the development, approval processes, and features of COVID-19 vaccines. The Royal Society DELVE Initiative (19) calls for “clear, transparent communication,” a Nature editorial (20) for “radical transparency,” and Mahase (21) for “real transparency” (see also ref. 22). As discussed by the Royal Society DELVE Initiative (19) this entails a commitment to “not hide the potential limitations of vaccines, including possible limited availability, incomplete protection requiring boosting and reactogenicity,” even if “such negative or complicating factors might lower uptake” as “their discovery post-rollout is likely to have a far greater negative impact on uptake.” Importantly, these current calls resonate with a number of critiques of the lack of transparency in prior but smaller-scale immunization campaigns (23–25).While transparency is normatively important in itself, calls for transparent communication also resonate with psychological research on vaccine skepticism both during and prior to the COVID-19 pandemic. Disregarding outright disinformation, the often used alternative to transparently disclosing distressing information in communication between doctors and patients is the use of vague communication (11). Such communication has been demonstrated to have the potential to elicit feelings of uncertainty (26), a psychological state linked to triggers of vaccine skepticism (27, 28). In particular, feelings of uncertainty have been found to be fertile ground for distrust and conspiracy beliefs, which are major predictors of skepticism toward vaccines both in general and in relation to the COVID-19 pandemic (6, 29–31). Hence, while transparently disclosing negative vaccine information may elicit rationally grounded vaccine hesitancy (19), the alternative of vague communication may elicit hesitancy grounded in conspiratorial beliefs. Indeed, prior work on the communication of uncertainty suggests that uncertainty communicated in vague rather than specific terms may decrease trust in the communication (8). As noted in several of the calls for transparency, this emergence of conspiratorial beliefs may not just create a short-term obstacle in the coming months but may also create long-term obstacles by inducing general conspiracy-based distrust toward authorities. This may impede not just reimmunization campaigns during the pandemic but also the handling of future health crises.Despite these hopes for the benefits of transparent health communication, even when disclosing negative information, other researchers remain skeptical. In particular, the effectiveness of any communication strategy may hinge on the prior existence of trust in the communicator (32). In the words of O’Neill (33), “unless the individuals and institutions who sort, process, and assess information are themselves already trusted, there is little reason to think that transparency and openness are going to increase trust.” This challenge is exacerbated by the fact that the transparent disclosing of negative information may trigger the very psychological state that transparency was intended to guard against, namely uncertainty. In particular, there is substantial evidence that concerns about side effects, even if well grounded, can elicit anxiety and uncertainty (34).On this basis, there is a pressing need to understand the role of transparency in health communication in the context of the COVID-19 pandemic and beyond. The core purpose of the present set of studies is to add to this understanding by examining how vague health communication and transparent health communication—both when disclosing negative and positive information—influence short- and long-term factors associated with acceptance of a COVID-19 vaccine.     

剖析新版WHO指南内容与特点 加速推进中国消除血吸虫病步伐

2022年2月,WHO基于循证医学框架发布了《WHO控制和消除人体血吸虫病指南》(以下简称WHO新指南）,以指导血吸虫病流行国家和地区控制和消除这一公共卫生问题、促进阻断血吸虫病传播。WHO新指南以全健康理念为基础,提出了6项核心建议。本文旨在分析WHO新指南中的关键内容对我国血吸虫病防控工作的适用性,阐释其对我国血吸虫病防治工作后续发展的指导意义。目前,我国血吸虫病防控体系在实施层面上已基本体现全健康理念及其组成部分。基于WHO新指南,针对我国血吸虫病防治工作提出如下建议：加强系统性框架建设,推动跨部门共识的形成,建立高级别领导小组;优化现阶段我国血吸虫病防治策略中的人畜治疗措施;开发高敏感度和高特异度的检测工具和消除验证框架;通过整合其他寄生虫病防治项目,进一步推动血吸虫病和其他寄生虫病防控工作。     

Replicating Viral Vector-Based Vaccines for COVID-19: Potential Avenue in Vaccination Arena

The “severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)” is the third member of human coronavirus (CoV) that is held accountable for the current “coronavirus disease 2019 (COVID-19)” pandemic. In the past two decades, the world has witnessed the emergence of two other similar CoVs, namely SARS-CoV in 2002 and MERS-CoV in 2013. The extent of spread of these earlier versions was relatively low in comparison to SARS-CoV-2. Despite having numerous reports inclined towards the zoonotic origin of the virus, one cannot simply sideline the fact that no animal originated CoV is thus far identified that is considered similar to the initial edition of SARS-CoV-2; however, under-sampling of the diverse variety of coronaviruses remains a concern. Vaccines are proved to be an effective tool for bringing the end to such a devastating pandemic. Many vaccine platforms are explored for the same but in this review paper, we will discuss the potential of replicating viral vectors as vaccine carriers for SARS-CoV-2.     

我国血吸虫疫苗研究进展及应用前景

血吸虫病疫苗研究一直是WHO/TDR热带病防治和我国血防研究的热点内容,近年来我国有关血吸虫病疫苗的研究取得了重要进展。随着蛋白质组学和分子生物学技术的发展,我国血吸虫病疫苗研究已发展到基因工程疫苗研制阶段。其中DNA疫苗已成为当前我国血吸虫病疫苗研究的主流方向。同时,新的有效疫苗抗原分子的筛选鉴定及其配伍与优化,混合疫苗、多价疫苗的构建及其与佐剂的联用,为提高疫苗免疫保护效果提供了新的途径。     

老挝消除血吸虫病的SWOT分析

［摘要］　目的　对老挝消除血吸虫病具备的优势与劣势、面临的机遇与挑战等进行分析,提出相应的卫生政策和建议。方法　采用 SWOT 分析法,从老挝消除血吸虫病工作所具备的优势与劣势、面临的机遇与威胁4个方面,对老挝消除血吸虫病防治工作进行全面分析,并提出相应的对策建议。结果　老挝消除血吸虫病工作得到了政府高度重视和大力支持,积极开展了以群体化疗为主的防治工作,并建立起基于哨点的监测系统。但老挝仍面临血防经费与专业能力不足、社区防病意识薄弱、媒介控制困难等挑战。结论　继续发挥政府主导作用、加大资金投入、加强专业人才队伍建设、提升社区人群防病意识,有利于推动老挝血吸虫病消除进程。     

Overcoming COVID-19 vaccination resistance when alternative policies affect the dynamics of conformism,social norms,and crowding out

What is an effective vaccination policy to end the COVID-19 pandemic? We address this question in a model of the dynamics of policy effectiveness drawing upon the results of a large panel survey implemented in Germany during the first and second waves of the pandemic. We observe increased opposition to vaccinations were they to be legally required. In contrast, for voluntary vaccinations, there was higher and undiminished support. We find that public distrust undermines vaccine acceptance, and is associated with a belief that the vaccine is ineffective and, if enforced, compromises individual freedom. We model how the willingness to be vaccinated may vary over time in response to the fraction of the population already vaccinated and whether vaccination has occurred voluntarily or not. A negative effect of enforcement on vaccine acceptance (of the magnitude observed in our panel or even considerably smaller) could result in a large increase in the numbers that would have to be vaccinated unwillingly in order to reach a herd-immunity target. Costly errors may be avoided if policy makers understand that citizens’ preferences are not fixed but will be affected both by the crowding-out effect of enforcement and by conformism. Our findings have broad policy applicability beyond COVID-19 to cases in which voluntary citizen compliance is essential because state capacities are limited and because effectiveness may depend on the ways that the policies themselves alter citizens’ beliefs and preferences.

Legally required vaccination against measles and other diseases is an essential part of public health policies around the world. But opposition to even voluntary COVID-19 vaccination has emerged in many countries. During the initial rollout of vaccinations in the United States, for example, an antivaccine demonstration temporarily closed down one of the country’s largest vaccination sites (1).In early March 2021, among Americans not already vaccinated, 38% said that they would not willingly do so (2). In late March, among rural Americans who were not yet vaccinated, only a quarter were willing to be “as soon as possible” (3). In mid-February, a Wall Street Journal opinion piece authored by two former heads of the US Food and Drug Administration warned of a “vaccine glut.” By April, “[t]he challenge won’t be how to ration a scarce resource, but how to reach patients reluctant to get vaccinated” (4).Perhaps in response to concerns that voluntary vaccine take-up would be insufficient to end the pandemic, in all but 3 of the 14 countries surveyed, majorities of those expressing an opinion supported mandatory vaccination policies (this was in late January, prior to the discovery of rare adverse effects of the AstraZeneca vaccine) (5). In March, the government of Galicia in Spain announced that vaccinations would be mandatory with violations subject to substantial fines (6). In April, Italy made vaccinations mandatory for health care workers (7). At the same time, the Chinese government ordered local authorities to cease mandatory vaccines, fearing adverse public reaction (8). In the United States, 41% of those surveyed in March said they were “very concerned” that they “might be required to get the COVID-19 vaccine even if [they] don’t want to,” and another 21% were “somewhat concerned” (9).An important fact motivating our evaluation of policies to overcome resistance to vaccination is that those hesitating appear to be taking their cues from others. In late February, 27% of Americans not already vaccinated said they would “wait […] to see how it is working for other people.” A total of 69% of those in households in which someone had already been vaccinated also wanted to be vaccinated “as soon as possible,” while this was true of only 37% of those who do not know anyone vaccinated (10).Our panel data set from Germany allows us to ask how vaccine resistance is changing and to identify some of the determinants of these changes, including changes in public trust and whether vaccination is voluntary or legally mandated. To apply our findings to anti–COVID-19 policy making, we develop a model of the dynamics of vaccine resistance. This model illustrates how the willingness to be vaccinated may vary over time in response to the fraction of the population already vaccinated and whether this has occurred voluntarily or not.     

Detection of Onchocerca volvulus in Skin Snips by Microscopy and Real-Time Polymerase Chain Reaction: Implications for Monitoring and Evaluation Activities

Microscopic evaluation of skin biopsies is the monitoring and evaluation (M and E) method currently used by multiple onchocerciasis elimination programs in Africa. However, as repeated mass drug administration suppresses microfilarial loads, the sensitivity and programmatic utility of skin snip microscopy is expected to decrease. Using a pan-filarial real-time polymerase chain reaction with melt curve analysis (qPCR-MCA), we evaluated 1) the use of a single-step molecular assay for detecting and identifying Onchocerca volvulus microfilariae in residual skin snips and 2) the sensitivity of skin snip microscopy relative to qPCR-MCA. Skin snips were collected and examined with routine microscopy in hyperendemic regions of Uganda and Ethiopia (N = 500 each) and “residual” skin snips (tissue remaining after induced microfilarial emergence) were tested with qPCR-MCA. qPCR-MCA detected Onchocerca DNA in 223 residual snips: 139 of 147 microscopy(+) and 84 among microscopy(−) snips, suggesting overall sensitivity of microscopy was 62.3% (139/223) relative to qPCR-MCA (75.6% in Uganda and 28.6% in Ethiopia). These findings demonstrate the insufficient sensitivity of skin snip microscopy for reliable programmatic monitoring. Molecular tools such as qPCR-MCA can augment sensitivity and provide diagnostic confirmation of skin biopsies and will be useful for evaluation or validation of new onchocerciasis M and E tools.     

血吸虫病疫苗联合免疫的研究进展

血吸虫病疫苗是减轻血吸虫感染、控制血吸虫病传播的重要措施。为提高血吸虫病疫苗的免疫效果,国内外通过不同抗原基因的连接、不同疫苗抗原的组合或从噬菌体肽库中筛选到若干个不同抗原表位的混合等途径来实现复合疫苗或多种单一疫苗的联合免疫,并取得较好的成果。