This article considers what can be learned regarding the ethical acceptability of intrusive interventions intended to halt the spread of infectious disease (‘Infection Control’ measures) from existing ethical discussion of intrusive interventions used to prevent criminal conduct (‘Crime Control’ measures). The main body of the article identifies and briefly describes six objections that have been advanced against Crime Control, and considers how these might apply to Infection Control. The final section then draws out some (...) more general lessons from the foregoing analysis for the ethical acceptability of different kinds of Infection Control. (shrink)

On March 16, 2020, the Director-General of the World Health Organization said: “We have a simple message to all countries—test, test, test.” This seems like sound advice, but what if limiting the number of tests has a positive effect on infection control? Although this may rarely be the case, the possibility raises an important ethical question that is closely related to a central tension between deontological and consequentialist approaches to ethics. In this paper, we first argue that early (...) during the COVID-19 pandemic, Japan offers an interesting case because it experienced few deaths due to COVID while the number of tests was limited, suggesting that there may be cases in which low testing contributes to infection control indeed. After that, we examine deontological constraints on such a “low-testing” policy, focusing on issues related to a supposed “right to know,” which is a central issue in medical ethics in general. (shrink)

Control measures directed at carriers of multidrug-resistant organisms are traditionally approached as a trade-off between public interests on the one hand and individual autonomy on the other. We propose to reframe the ethical issue and consider control measures directed at carriers an issue of solidarity. Rather than asking “whether it is justified to impose strict measures”, we propose asking “how to best care for a person’s carriership and well-being in ways that do not imply an unacceptable risk for (...) others?”. A solidarity approach could include elevating baseline levels of precaution measures and accepting certain risks in cases where there is exceptionally much at stake. A generous national compensation policy that also covers for costs related to dedicated care is essential in a solidarity approach. An additional benefit of reframing the questions is that it helps to better acknowledge that being subjected to control measures is a highly personal matter. (shrink)

Many countries have implemented infection control measures directed at carriers of multidrug-resistant organisms. To explore the ethical implications of these measures, we analyzed 227 consultations about multidrug resistance and compared them with the literature on communicable disease in general. We found that control measures aimed at carriers have a range of negative implications. Although moral dilemmas seem similar to those encountered while implementing control measures for other infectious diseases, 4 distinct features stand out for carriage of (...) multidrug-resistant organisms: carriage presents itself as a state of being; carriage has limited relevance for the health of the carrier; carriage has little relevance outside healthcare settings; and antimicrobial resistance is a slowly evolving threat on which individual carriers have limited effect. These features are of ethical relevance because they influence the way we traditionally think about infectious disease control and urge us to pay more attention to the personal experience of the individual carrier. (shrink)

Duty of candour legislation was introduced in Scotland in 2018. However, literature and experience of duty of candour when applied to infection control incidents/outbreaks is scarce. We describe clinician and parental perspectives with regard to duty of candour and communication during a significant infection control incident in a haemato-oncology ward of a children’s hospital. Based on the learning from this incident, we make recommendations for duty of candour and communication to patients and families during future (...) class='Hi'>infection control incidents. These include the need to consider a crisis management approach, the importance of not underestimating psychological harm in incidents of a prolonged duration and embedding the existing legislation pertaining to the rights of the child. (shrink)

Keeping the lid on infection: infection control practices of a regional Queensland hospital 1930–50 Nurses have played an important role in infection control practices throughout the past century. However, the desire for minimisation of cross infection has not always been the basis for many of the activities undertaken by nurses within the general ward. This paper is a historical analysis of those practices that formed the basis of infection control within the medical (...) and surgical wards of the Rockhampton Hospital between 1930 and 1950. In particular, those activities dealing with the disposal of body fluids, ward cleaning, aseptic techniques and associated sterilisation of instruments and articles, the nurses’ personal cleanliness and isolation nursing have been addressed. This study has identified economic factors, professional image and local traditions as being influential in the origins and persistence of many activities which may be loosely grouped as infection control measures. (shrink)

The proposed framework by Lynch et al. (2021) for promoting ethical forms of payment in Human Infection Controlled Studies (HICS) in general and SARS-Cov-2 HICS in particular is an important contri...

This study investigated the relationship between hospital nurses’ professional care obligation, their attitudes towards SARS infection control measures, whether they had ever cared for SARS patients, their current health status, selected demographic characteristics, and the time frame of the data collection (from May 6 to May 12 2003 during the SARS epidemic, and from June 17 to June 24 2003 after the SARS epidemic). The study defines 172 nurses’ willingness to provide care for SARS patients as a professional (...) obligation regardless of the nature of the disease. A conceptual model was developed and tested using ordinal logistic regression modelling. The findings showed that nurses’ levels of agreement with general SARS infection control measures and the lack of necessity for quarantining health care workers who provided care for SARS patients were statistically significant predicators of the nurses’ fulfilling of their professional care obligation. Suggestions and study limitations are discussed. (shrink)

Disparities in maternal morbidity and mortality for Latinx populations are a paradigmatic example of the now widely acknowledged structural racism in U.S. health care that predisposed minorities to...

A number of papers have appeared recently arguing for the conclusion that it is ethically acceptable to infect healthy volunteers with severe acute respiratory syndrome coronavirus 2 as part of research projects aimed at developing COVID-19 vaccines or treatments. This position has also been endorsed in a statement by a working group for the WHO. The papers generally argue that controlled human infection is ethically acceptable if the risks to participants are low and therefore acceptable, the scientific quality of (...) the research is high, the research has high social value, participants give full informed consent, and there is fair selection of participants. All five conditions are necessary premises in the overall argument that such research is ethically acceptable. The arguments concerning risk and informed consent have already been critically discussed in the literature. This paper therefore looks specifically at the arguments relating to condition 3 ‘high social value’ and condition 5 ‘fair selection of participants’ and shows that whereas they may be valid, they are not sound. It is highly unlikely that the conditions that are necessary for ethical CHI trials to take place will be fulfilled. Most, if not all, CHI trials will thus be well intentioned but unethical. (shrink)

Controlled human infection challenge studies (CHIs) involve intentionally exposing research participants to, and/or thereby infecting them with, micro‐organisms. There have been increased calls for more CHIs to be conducted in low‐ and middle‐income countries (LMICs) where many relevant diseases are endemic. This article is based on a research project that identified and analyzed ethical and regulatory issues related to endemic LMIC CHIs via (a) a review of relevant literature and (b) qualitative interviews involving 45 scientists and ethicists with relevant (...) expertise. In this article we argue that though there is an especially strong case for conducting CHIs in endemic (LMIC) settings, certain ethical issues related to the design and conduct of such studies (in such settings) nonetheless warrant particularly careful attention. We focus on ethical implications of endemic LMIC CHIs regarding (a) potential direct benefits for participants, (b) risks to participants, (c) third‐party risks, (d) informed consent, (e) payment of participants, and (f) community engagement. We conclude that there is a strong ethical rationale to conduct (well‐designed) CHIs in endemic LMICs, that certain ethical issues warrant particularly careful consideration, and that ethical analyses of endemic LMIC CHIs can inform current debates in research ethics more broadly. (shrink)

Controlled human infection (CHI) studies involve the deliberate exposure of healthy research participants to infectious agents to study early disease processes and evaluate interventions under controlled conditions with high efficiency. Although CHI studies expose participants to the risk of infection, they are designed to offer investigators unique advantages for studying the pathogenesis of infectious diseases and testing potential vaccines or treatments in humans. One of the central challenges facing investigators involves the fair selection of research subjects to participate (...) in CHI studies. While there is widespread agreement that investigators have a duty to select research participants fairly, this principle also yields conflicting ethical imperatives, for example requiring investigators to both exclude potential participants with co‐morbidities since they face increased risks, but also to include them in order to ensure generalizability. In this paper we defend an account of fair subject selection that is tailored to the context of CHI studies. We identify the considerations of fairness that bear directly on selecting participants for CHI studies and provide investigators and members of IRBs and RECs with a principled way to navigate the conflicting imperatives to which these considerations give rise. (shrink)

In this work, a co-infection model for human papillomavirus and Chlamydia trachomatis with cost-effectiveness optimal control analysis is developed and analyzed. The disease-free equilibrium of the co-infection model is shown not to be globally asymptotically stable, when the associated reproduction number is less unity. It is proven that the model undergoes the phenomenon of backward bifurcation when the associated reproduction number is less than unity. It is also shown that HPV re-infection induced the phenomenon of backward (...) bifurcation. Numerical simulations of the optimal control model showed that: focusing on HPV intervention strategy alone, in the absence of C. trachomatis control, leads to a positive population level impact on the total number of individuals singly infected with C. trachomatis, Concentrating on C. trachomatis intervention controls alone, in the absence of HPV intervention strategies, a positive population level impact is observed on the total number of individuals singly infected with HPV. Moreover, the strategy that combines and implements HPV and C. trachomatis prevention controls is the most cost-effective of all the control strategies in combating the co-infections of HPV and C. trachomatis. (shrink)

In controlled human infection studies (CHIs), participants are deliberately exposed to infectious agents in order to better understand the mechanism of infection or disease and test therapies or vaccines. While most CHIs have been conducted in high‐income countries, CHIs have recently been expanding into low‐ and middle‐income countries (LMICs). One potential ethical concern about this expansion is the challenge of obtaining the voluntary informed consent of participants, especially those who may not be literate or have limited education. In (...) some CHIs in LMICs, researchers have attempted to address this potential concern by limiting access to literate or educated populations. In this paper, we argue that this practice is unjustified, as it does not increase the chances of obtaining valid informed consent and therefore unfairly excludes illiterate populations and populations with lower education. Instead, we recommend that investigators improve the informed consent process by drawing on existing data on obtaining informed consent in these populations and interventions aimed at improving their understanding. Based on a literature review, we provide concrete suggestions for how to follow this recommendation and ensure that populations with lower literacy or education are given a fair opportunity to protect their rights and interests in the informed consent process. (shrink)

In spring, summer and autumn 2020, one abiding argument against controlled human infection studies of SARS-CoV-2 vaccines has been their impact on local communities. Leading scientists and bioethicists expressed concern about undue usage of local residents’ direly needed scarce resources at a time of great need and even about their unintended infection. They recommended either avoiding CHI trials or engaging local communities before conducting any CHIs. Similar recommendations were not made for the alternative—standard phase III field trials of (...) these same vaccines. We argue that the health effects of CHI studies on local residents not participating in the study tend to be smaller and more positive than those of field trials. That is all the more so now that tested vaccines are being rolled out. Whether or not local community engagement is necessary for urgent vaccine studies in the pandemic, the case for its engagement is stronger prior to field trials than prior to CHI studies. (shrink)

In controlled human infection (CHI) studies, investigators deliberately infect healthy individuals with pathogens in order to study mechanisms of disease or obtain preliminary efficacy data on investigational vaccines and medicines. CHI studies offer a fast and cost‐effective way of generating new scientific insights, prioritizing investigational products for clinical testing, and reducing the risk that large numbers of people are exposed to ineffective or harmful substances in research or in practice. Yet depending on the pathogen, CHI studies can involve significant (...) risks or burdens for participants, pose risks to individuals or communities not involved in the research, and lead to public controversy. It is therefore essential to ensure that the risks of CHI studies are justified by their social value—that is, their potential to generate benefits for society—and that public trust can be maintained. In this paper, we aim to clarify how research sponsors, research ethics committees and other reviewers should judge the social value of CHI studies. We develop a list of relevant considerations for making social value judgments based on the standard view of social value. We then use this list to discuss the example of potentially conducting dengue virus CHI studies in endemic settings. We argue that dengue virus CHI studies in endemic settings would fall on the higher end of the spectrum of social value, mostly because of their potential to redirect all fields of future dengue research. Drawing on this discussion, we derive several general recommendations for how reviewers should judge the social value of CHI studies. (shrink)

The maternal‐fetal HIV transmission trials, conducted in developing countries in the 1990s, undoubtedly generated one of the most intense, high profile controversies in international research ethics. They sparked off a prolonged acrimonious and public debate and deeply divided the scientific community. They also provided an impetus for the revision of the Declaration of Helsinki – the most widely known guideline for international research. In this paper, I provide a brief summary of the context, outline the arguments for and against the (...) controversial use of placebo controls, and focus on particular areas that I believe merit further discussion or clarification. On balance, I argue that the researchers failed in their duties to protect the best interests of their research subjects, and to promote distributive justice. I discuss the difficulties of obtaining valid consent in this research context, and argue that it is unethical to inform women of their HIV status without at least offering them prophylactic treatment for their unborn children. A global view of justice, which endorses international equity, cannot be squared with international research guidelines that allow ‘local conditions’ to define the scope of duty to the control group. Finally, I suggest that the heated debate reflects a tension, if not an outright war, between two conflicting meta‐ethical systems, or incommensurable paradigms, that underpin scientific research involving human subjects. (shrink)

Research using Controlled Human Infection Models is yet to be attempted in India. This study was conducted to understand the perceptions of the lay public and key opinion makers prior to the possible introduction of such studies in the country. 110 respondents from urban and rural Bangalore district were interviewed using qualitative research methods of Focus Group Discussions and In-depth Interviews. The data was analyzed using grounded theory. Safety was a key concern of the lay public, expressed in terms (...) of fear of death. The notion of infecting a healthy volunteer, the possibility of continued effects beyond the study duration and the likelihood of vulnerable populations volunteering solely for monetary benefit, were ethical concerns. Public good outcomes such as effective treatments, targeted vaccines and prevention of diseases was necessary justification for such studies. However, the comprehension of this benefit was not clear among non-medical, non-technical respondents and suggestions to seek alternatives to CHIMs repeatedly arose. There was a great deal of deflection—with each constituency feeling that people other than themselves may be ideally suited as participants. Risk takers, those without dependents, the more health and research literate, financially sound and those with an altruistic bent of mind emerged as possible CHIM volunteers. While widespread awareness and advocacy about CHIM is essential, listening to plural voices is the first step in public engagement in ethically contentious areas. Continued engagement and inclusive deliberative processes are required to redeem the mistrust of the public in research and rebuild faith in regulatory systems. (shrink)

ABSTRACT Controlled human infection (CHI) models have been developed for numerous pathogens in order to better understand disease processes and accelerate drug and vaccine testing. In the past, some researchers conducted highly controversial CHIs with vulnerable populations, including children. Ethical frameworks for CHIs now recommend vulnerable populations be excluded because they cannot consent to high risk research. In this paper we argue that CHI studies span a wide spectrum of benefit and risk, and that some CHI studies may involve (...) minimal risk. The categorical exclusion of children from CHIs therefore departs from the standard approach to evaluating research risks, as international regulations and ethical guidance for pediatric research generally permit non‐beneficial research with low risks. The paradigm in research ethics has also shifted from focusing on protecting vulnerable participants to recognizing that inclusion can be important as a matter of justice, providing new reasons to question this default exclusion of children from CHIs. Recognizing that pediatric CHIs can raise complex ethical issues and are easy to sensationalize in ways that may threaten the public’s trust in research and sponsor institutions, we conclude by describing additional complexities that must be addressed before pediatric CHIs beyond licensed vaccine studies might be ethically acceptable. (shrink)

Controlled human infection model (CHIM) studies involve the intentional exposure of healthy research volunteers to infectious agents. These studies contribute to knowledge about the cause or development of disease and to the advancement of vaccine research. But they also raise ethical questions about the kinds of risks that should be permissible and whether limits should be imposed on research risks in CHIM studies. Two possible risk thresholds have been considered for CHIM studies. The first suggests constraining ethically permissible risks (...) according to a minimal risk threshold and the second endorses a higher risk threshold that excludes irreversible or fatal infections. I argue that neither of these thresholds is persuasive and situate questions about risk thresholds in CHIM studies within a broader debate about permissible risks in research. I argue that risks in CHIM studies should be constrained according to limits on research risks that do not offer corresponding benefits in all studies rather than developing a unique risk threshold for CHIM studies. I then propose five recommendations for the ethical assessment of risk in CHIM studies. (shrink)

Risks and benefit evaluation for controlled human infection studies, where healthy volunteers are deliberately exposed to infectious agents to evaluate vaccine efficacy, should be explicit, systematic, thorough, and non‐arbitrary. Decision analysis promotes these qualities using four steps: (1) determining explicit criteria and measures for evaluation, (2) identifying alternatives to the study, (3) defining the models used to estimate the measures for each alternative, and (4) running the models to produce the estimates and compare the alternatives. In this paper, we (...) describe how decision analysis might be applied by funders and regulators, as well as by others contemplating the use of novel controlled human infection studies for vaccine development and evaluation. (shrink)

The right to withdraw from research without penalty is well established around the world. However, it has been challenged in some corners of bioethics based on concerns about various harms—to participants, to scientific integrity, and to research bystanders—that may stem from withdrawal. These concerns have become particularly salient in emerging debates about the ethics of controlled human infection (CHI) studies in which participants are intentionally infected with pathogens, often in inpatient settings with extensive follow‐up. In this article, I provide (...) support for preserving the right to withdraw from research without penalty and demonstrate that it is also typically justified in the specific context of CHI studies. The right is well aligned with individual freedoms outside the research setting, where autonomous individuals are permitted to engage in behaviors that will foreseeably cause them harm; where they cannot be compelled to satisfy contracts for their services, nor penalized for failure to do so; and where their behavior is not constrained by public health authorities except in extreme circumstances. These freedoms are supported by U.S. law, as well as by ethical analysis that is more globally relevant. The problems associated with the right to withdraw, however, remain. The best approach to addressing them is not to restrict the right but rather to avoid initiating research when withdrawal would be especially problematic. If research proceeds, steps can still be taken to minimize participant withdrawal without infringing the right. Investigators can avoid participant surprise through informed consent focused on a study’s most burdensome aspects and promote study completion through financial incentives. Should participants nonetheless seek to withdraw, investigators may attempt to persuade them not to do so by encouraging consideration of the range of potential harms that may result. Researchers conducting CHI studies and other research from which withdrawal might be especially problematic should prepare for the possibility of participant withdrawal, respect participant requests to withdraw without penalty, and incorporate various measures to avoid such requests. (shrink)

(No abstract is available for this citation).

In response to the COVID‐19 pandemic, some authors have advocated a program of controlled voluntary infection (CVI) with SARS‐CoV‐2. Under CVI, during periods where the medical system is under capacity, volunteers from low‐risk groups would be intentionally infected after giving informed consent, and then quarantined until they have developed immunity. Proponents claim that this could have benefits for society, such as building herd immunity and ensuring that critical workers won’t be incapacitated during the peak of the infection. They (...) also claim that this could have benefits for individuals, such as being safely exempted from lockdown measures and (for individuals who are likely to be infected anyway) ensuring that the infection happens under relatively less dangerous conditions. Some respond that CVI would unethical. Here, I argue that, while CVI may or may not be ill‐advised for empirical reasons, there are no in‐principle ethical objections to it (i.e., if CVI would work as well as its proponents think, it would be ethical to implement it). I present three arguments for this conclusion. The first is an argument from informed consent: informed consent to relevantly similar medical procedures renders performing these procedures permissible, so informed consent to CVI would render it permissible. The second is an argument from reasonable beneficence: it draws on recent work by Caspar Hare on relevantly similar choices to argue that CVI is permissible. The third is an argument from precedent: smallpox variolation was permissible, and CVI is relevantly similar to that, so CVI is permissible. (shrink)

Controlled human malaria infection (CHMI) studies involve the deliberate infection of healthy volunteers with malaria parasites under controlled conditions to study immune responses and/or test drug or vaccine efficacy. An empirical ethics study was embedded in a CHMI study at a Kenyan research programme to explore stakeholders’ perceptions and experiences of deliberate infection and moral implications of these. Data for this qualitative study were collected through focus group discussions, in‐depth interviews and non‐participant observation. Sixty‐nine participants were involved, (...) including CHMI study volunteers, community representatives and research staff. Data were managed using QSR Nvivo 10 and analysed using an inductive‐deductive approach, guided by ethics literature. CHMI volunteers had reasonable understanding of the study procedures. Decisions to join were influenced by study incentives, trust in the research institution, their assessment of associated burdens and motivation to support malaria vaccine development. However, deliberate malaria infection was a highly unusual research strategy for volunteers, community representatives and some study staff. Volunteers’ experiences of physical, emotional and social burdens or harms were often greater than anticipated initially, and fluctuated over time, related to specific procedures and events. Although unlikely to deter volunteers' participation in similar studies in furture, we argue that the dissonance between level of understanding of the burdens involved and actual experiences are morally relevant in relation to community engagement, informed consent processes, and ongoing support for volunteers and research staff. We further argue that ethics oversight of CHMI studies should take account of these issues in deciding whether consent, engagement and the balance of benefits and harms are reasonable in a given context. (shrink)

Issues related to controlled human infection studies using Schistosoma mansoni (CHI-S) were explored to ensure the ethical and voluntary participation of potential CHI-S volunteers in an endemic setting in Uganda. We invited volunteers from a fishing community and a tertiary education community to guide the development of informed consent procedures. Consultative group discussions were held to modify educational materials on schistosomiasis, vaccines and the CHI-S model and similar discussions were held with a test group. With both groups, a mock (...) consent process was conducted. Fourteen in-depth key informant interviews and three group discussions were held to explore perceptions towards participating in a CHI-S. Most of the participants had not heard of the CHI-S. Willingness to take part depended on understanding the study procedures and the consenting process. Close social networks were key in deciding to take part. The worry of adverse effects was cited as a possible hindrance to taking part. Volunteer time compensation was unclear for a CHI-S. Potential volunteers in these communities are willing to take part in a CHI-S. Community engagement is needed to build trust and time must be taken to share study procedures and ensure understanding of key messages. (shrink)

Upon separation of the protein from the nucleic acid component of tobacco mosaic virus by phenol, using a fast and gentle procedure, the nucleic acid is infective in assays on tobacco leaves. A series of qualitative and quantitative control experiments demonstrates that the biological activity cannot depend on residual proteins in the preparation, but is a property of isolated nucleic acid which is thus the genetic material of the virus.

Meat is a multi-billion-dollar industry that relies on people performing risky physical work inside meat-processing facilities over long shifts in close proximity. These workers are socially disempowered, and many are members of groups beset by historic and ongoing structural discrimination. The combination of working conditions and worker characteristics facilitate the spread of SARS-CoV-2, the virus that causes COVID-19. Workers have been expected to put their health and lives at risk during the pandemic because of government and industry pressures to keep (...) this “essential industry” producing. Numerous interventions can significantly reduce the risks to workers and their communities; however, the industry’s implementation has been sporadic and inconsistent. With a focus on the U.S. context, this paper offers an ethical framework for infection prevention and control recommendations grounded in public health values of health and safety, interdependence and solidarity, and health equity and justice, with particular attention to considerations of reciprocity, equitable burden sharing, harm reduction, and health promotion. Meat-processing workers are owed an approach that protects their health relative to the risks of harms to them, their families, and their communities. Sacrifices from businesses benefitting financially from essential industry status are ethically warranted and should acknowledge the risks assumed by workers in the context of existing structural inequities. (shrink)

A new multi-stage deterministic model for the transmission dynamics of syphilis, which incorporates disease transmission by individuals in the early latent stage of syphilis infection and the reversions of early latent syphilis to the primary and secondary stages, is formulated and rigorously analysed. The model is used to assess the population-level impact of preventive and therapeutic measures against the spread of the disease in a community. It is shown that the disease-free equilibrium of the model is globally-asymptotically stable whenever (...) the associated control reproduction number is less than unity. A special case of the model is shown to have a unique and globally-asymptotically stable endemic equilibrium whenever the associated reproduction number exceeds unity. Uncertainty and sensitivity analysis of the model, using parameter values and ranges relevant to syphilis transmission dynamics in Nigeria, show that the top three parameters that drive the syphilis infection are the disease transmission rate, compliance in condom use and efficacy of condom. Numerical simulations of the model show that the targeted treatment of secondary syphilis cases is more effective than the targeted treatment of individuals in the primary or early latent stage of syphilis infection. (shrink)

Neospora caninum infection, one of the major causes of abortions in dairy cattle, has brought a huge loss to farmers worldwide. In this study, we develop a six-compartment susceptible-infected model of N. caninum transmission which is later reduced to a two-equation system. Potential controls including medication, test-and-cull, and vaccination are proposed and analyzed, and the corresponding reproduction numbers are derived. The conditions for the global stabilities of disease-free and endemic equilibria are investigated with analytical solutions and geometric approach. Furthermore, (...) uncertainty and sensitivity analysis shows that three control strategies are effective towards the varied environment, whereas the effectiveness of each measure highly depends on parameters related to control actions. Dynamics of reproduction numbers illustrate that disease elimination can be achieved by three types of controls: adopting medication with medicine efficacy higher than 0.4 to prevent vertical transmission, implementing test-and-cull with culling coverage larger than 0.3, and taking vaccine with coverage larger than 0.1. Numerical results suggest that preventive measures should at least include the prevention of access of other hosts, such as dogs, to cattle; otherwise, these control measures will lose effectiveness. Our presented study provides guidance for decision-making on N. caninum infected farm management. (shrink)

There is limited guidance on how to assess the ethical acceptability of research risks that extend beyond research participants to third parties (or “research bystanders”). Community or stakeholder engagement has been proposed as one way to address potential harms to community members, including bystanders. Despite widespread agreement on the importance of community engagement in biomedical research, this umbrella term includes many different goals and approaches, agreement on which is ethically required or recommended for a particular context. We analyse the case (...) of a potential Zika virus human challenge trial to assess whether and how community engagement can help promote the ethical acceptability of research posing risks to bystanders. We conclude that, in addition to having intrinsic value, community engagement can improve the identification of bystander risks, effective approaches to minimizing them, and transparency about bystander risks for host communities. (shrink)

ObjectiveTo investigate the association of pre-existing migraine in patients hospitalised and who recovered from severe acute respiratory syndrome coronavirus 2 infection with the presence of post-coronavirus disease symptoms.BackgroundNo study has investigated the role of migraine as a risk factor for development of post-COVID symptoms.MethodsA case-control study including individuals hospitalised during the first wave of the pandemic was conducted. Patients with confirmed previous diagnosis of migraine were considered cases. Two age- and sex-matched individuals without a history of headache per (...) case were also recruited as controls. Hospitalisation/clinical data were collected from hospital medical records. Patients were scheduled for a telephone interview. A list of post-COVID symptoms was systematically evaluated, but participants were invited to freely report any symptom. The Hospital Anxiety and Depression Scale and the Pittsburgh Sleep Quality Index were used to assess anxiety/depressive symptoms and sleep quality. Multivariable conditional logistic regression models were constructed.ResultsOverall, 57 patients with confirmed diagnosis of migraine and 144 non-migraine controls who had recovered from COVID-19 were assessed at 7.3 months after hospital discharge. The number of post-COVID symptoms in the migraine group was significantly greater than in the non-migraine group. Fatigue was significantly more prevalent in the migraine group. However, no between-groups difference in the prevalence of headache as a post-COVID symptom was detected.ConclusionPatients with a history of migraine who recovered from COVID-19 exhibited more long-term fatigue as post-COVID sequelae than those without migraine. Some of the pathophysiological changes associated with migraine could predispose to the occurrence of post-COVID symptoms. (shrink)

The pandemic of SARS-CoV-2 has led to unprecedented changes to society, causing unique problems that call for extraordinary solutions. We consider one such extraordinary proposal: ‘safer infection sites’ that would offer individuals the opportunity to be intentionally infected with SARS-CoV-2, isolate, and receive medical care until they are no longer infectious. Safer infection could have value for various groups of workers and students. Health professionals place themselves at risk of infection daily and extend this risk to their (...) family members and community. Similarly, other essential workers who face workplace exposure must continue their work, even if have high-risk household members and live in fear of infecting. When schools are kept closed because of the fear that they will be sites of significant transmission, children and their families are harmed in multiple ways and college students who are living on campus, whether or not they are attending classes in person, are contributing to high rates of transmission and experiencing high rates of exposure. We consider whether offering safer infection sites to these groups could be ethically defensible and identify the empirical unknowns that would need to resolve before reaching definitive conclusions. This article is not an endorsement of intentional infection with the coronavirus, but rather is meant to spark conversation on the ethics of out-of-the-box proposals. Perhaps most meaningfully, our paper explores the value of control and peace of mind for those among us most impacted by the pandemic: those essential workers risking the most to keep us safe. (shrink)

‘Zero tolerance’ of avoidable infection events is explicit in UK and international policy documents describing strategies for the control of healthcare-associated infection. I consider what principles governing avoidable infections acquired in healthcare institutions might be reasonably rejected from the contractualist perspective of Thomas Scanlon. Many hospital infections can be cost-effectively avoided. There would seem to be additional reasons to take the prevention of avoidable infection acquired in hospitals seriously in addition to optimizing the cost-effectiveness of healthcare. (...) These include the irretrievable nature of the harm of some of the infections; the reasonable rejection of avoidable harm when the patient could not rationally consent to the risk of harm and the social consequences such as loss of trust in healthcare providers. Despite these reasons, a principle of ‘zero tolerance’ has implausible implications, promotes unrealistic patient expectations and can be reasonably rejected from the perspective of those who will suffer unacceptable opportunity costs. However, the contractualist perspective would also seem to reject a principle of tolerance of harm when there is a feasible reconfiguration of institutional arrangements that reduces the risk of harm without a redistribution of a proportionate or greater burden to others. (shrink)

A mathematical model of the dynamics of the immune system is considered to illustrate the effect of its response to HIV infection, i.e. on viral growth and on T-cell dynamics. The specific immune response is measured by the levels of cytotoxic lymphocytes in a human body. The existence and stability analyses are performed for infected steady state and uninfected steady state. In order to keep infection under control, roles of drug therapies are analyzed in the presence of (...) efficient immune response. Numerical simulations are computed and exhibited to illustrate the support of the immune system to drug therapies, so as to ensure the decay of infection and to maintain the level of healthy cells. (shrink)

Active surveillance cultures and contact precautions is a strategy to control the transmission of methicillin-resistant Staphylococcus aureus (MRSA) within healthcare facilities. Whether to implement this strategy to routinely screen and isolate inpatients with MRSA in non-outbreak (endemic) settings, or to remove it and use standard infection control precautions only is scientifically and ethically controversial, in view of the potential adverse effects of contact precautions on patients. To support the use of standard precautions only, it has been argued (...) that active surveillance to identify patients who are asymptomatically colonised with MRSA to place them in contact precautions is unjust or unfair to these patients in various ways. This paper will unpack and examine four distinct arguments, which are advanced from a medical ethics or quality improvement ethical framework, for why this is so. Our analysis shows that while these arguments highlight the injustice of current practices, they do not provide strong ethical reasons for justifying the removal of active surveillance and contact precautions to control MRSA transmission and infection. An implication of our arguments is that the ethical frame for evaluating prevention and control strategies for MRSA, a multi-drug resistant bacteria, should shift from healthcare to primarily public health. From a public health ethics perspective, whether a strategy is unjust, or how ethically significant its lack of fairness is, depends on assessing the evidence for its public health effectiveness and necessity in a given setting, and the extent of the harms and burdens patients with MRSA bear when they are on contact precautions, which remain matters of scientific debate or uncertainty. As an ethical consideration in the debate, the chief normative implication of justice is to provide us further reasons to revise current active surveillance-contact precautions practices, and for the need for research and interventions to minimise their potential adverse effects on patients. (shrink)

Background In the context of limited health care budgets in countries where Neglected Tropical Diseases are endemic, scaling up disease control interventions entails the setting of priorities. However, solutions based solely on cost-effectiveness analyses may lead to biased and insufficiently justified priorities. Objectives The objectives of this paper are to 1) demonstrate how a range of equity concerns can be used to identify feasible priority setting criteria, 2) show how these criteria can be fed into a multi-criteria decision-making matrix, (...) and 3) discuss the conditions under which this decision-making procedure should be carried out in a real-world decision-making context. Methods This paper draws on elements from theories of decision analysis and ethical theories of fair resource allocation. We explore six typical NTD interventions by employing a modified multi-criteria decision analysis model with predefined criteria, drawn from a priority setting guide under development by the WHO. To identify relevant evidence for the six chosen interventions, we searched the PubMed and Cochrane databases. Discussion Our in vitro multi-criteria decision analysis suggested that case management for visceral leishmaniasis should be given a higher priority than mass campaigns to prevent soil-transmitted helminthic infections. This seems to contradict current health care priorities and recommendations in the literature. We also consider procedural conditions that should be met in a contextualised decision-making process and we stress the limitations of this study exercise. Conclusion By exploring how several criteria relevant to the multi-facetted characteristics of NTDs can be taken into account simultaneously, we are able to suggest how improved priority settings among NTDs can be realised. (shrink)

BackgroundIn the context of limited health care budgets in countries where Neglected Tropical Diseases (NTDs) are endemic, scaling up disease control interventions entails the setting of priorities. However, solutions based solely on cost‐effectiveness analyses may lead to biased and insufficiently justified priorities.ObjectivesThe objectives of this paper are to 1) demonstrate how a range of equity concerns can be used to identify feasible priority setting criteria, 2) show how these criteria can be fed into a multi‐criteria decision‐making matrix, and 3) (...) discuss the conditions under which this decision‐making procedure should be carried out in a real‐world decision‐making context.MethodsThis paper draws on elements from theories of decision analysis and ethical theories of fair resource allocation. We explore six typical NTD interventions by employing a modified multi‐criteria decision analysis model with predefined criteria, drawn from a priority setting guide under development by the WHO. To identify relevant evidence for the six chosen interventions, we searched the PubMed and Cochrane databases.DiscussionOur in vitro multi‐criteria decision analysis suggested that case management for visceral leishmaniasis should be given a higher priority than mass campaigns to prevent soil‐transmitted helminthic infections. This seems to contradict current health care priorities and recommendations in the literature. We also consider procedural conditions that should be met in a contextualised decision‐making process and we stress the limitations of this study exercise.ConclusionBy exploring how several criteria relevant to the multi‐facetted characteristics of NTDs can be taken into account simultaneously, we are able to suggest how improved priority settings among NTDs can be realised. (shrink)

The way communicable diseases do spread from one person to another, depending upon the specific disease or causative infectious agent. Out of these diseases, some are incurable and the health care workers during their practice or otherwise acquire such infections and transmit them further to innocent patients who are unaware of about the health status of health care workers. The rights of an infected health care worker and patients are protected by many laws but in case of conflict of interests (...) between the individual right of the health care worker and life of a patient, then obviously by the principle of natural justice, saving the life of a person from such incurable infection gets the privilege. Therefore, there is a lot of ethical and professional dilemma, arising out, in such a type of scenario, irrespective of concealed or disclosed health status and the question mark is raised on whether clinical practice may be allowed in such cases. Some of the studies show the actual but very little risk of transmission from infected health care workers to patients. Therefore, in the current scenario, many western countries such as USA and UK are following different guidelines in this regard but the same is lacking in India. So, this article critically analyses the various issues arising out of it and thereby justifies the need to have a uniform infection control policy in this regard apart from legal and ethical binding on infected health care workers. (shrink)

The versatile clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system has emerged as a promising technology for therapy and molecular diagnosis. It is especially suited for overcoming viral infections outbreaks, since their effective control relies on an efficient treatment, but also on a fast diagnosis to prevent disease dissemination. The CRISPR toolbox offers DNA‐ and RNA‐targeting nucleases that constitute dual weapons against viruses. They allow both the manipulation of viral and host genomes for therapeutic purposes and the detection of (...) viral nucleic acids in “Point of Care” sensor devices. Here, we thoroughly review recent advances in the use of the CRISPR/Cas system for the treatment and diagnosis of viral deleterious infections such as HIV or SARS‐CoV‐2, examining their strengths and limitations. We describe the main points to consider when designing CRISPR antiviral strategies and the scientific efforts to develop more sensitive CRISPR‐based viral detectors. Finally, we discuss future prospects to improve both applications. Also see the video abstract here: https://www.youtube.com/watch?v=C0z1dLpJWl4. (shrink)