Mycobacterium tuberculosis is the causative agent of pulmonary tuberculosis which has infected one third of the mankind and causes 2–3 million deaths worldwide each year. The persistence of the infection ensues from the ability of M. tuberculosis to subvert host immune responses in favor of survival and growth of mycobacteria in macrophages. The mechanisms by which M. tuberculosis manipulates the host immune system have only recently come to light. These activities are attributed to lipoarabinomannans (LAM) and their precursors (...) lipomannans (LM), two predominant glycolipids of M. tuberculosis cell wall. LM are able to skew anti‐mycobacterial immune responses into un‐protective ones, while LAM evoke immunosupression upon binding to macrophage and dendritic cell receptors specialized in binding to “self” host components. A newly emerging idea implicates plasma membrane rafts in LM and LAM signaling. Depending on acylation patterns, the glycolipids may either directly incorporate into the raft membrane via mannosylphosphatidylinositol anchors or interact with raft‐associated proteins to affect the assembly of receptor signaling complexes. BioEssays 30:943–954, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Rifamycin is a clinically useful macrolide antibiotic produced by the gram positive bacterium. Amycolatopsis mediterranei. This antibiotic is primarily used against Mycobacterium tuberculosis and Mycobacterium leprae, causative agents of tuberculosis and leprosy, respectively. In these bacteria, rifamycin treatment specifically inhibits the initiation of RNA synthesis by binding to β‐subunit of RNA polymerase. Apart from its activity against the bacteria, rifamycin has also been reported to inhibit reverse transcriptase (RT) of certain RNA viruses. Recently, rifamycin derivatives have been dis‐covered (...) that are effective against Mycobacterium avium, which is associated with the AIDS complex. Consequently, the importance of and demand for rifamycin has increased tremendously, the world over. In this article, recent trends in rifamycin research and accessability of recombinant DNA techniques to increase rifamycin production are reviewed. (shrink)

The Mycobacterium Tuberculosis complex is a group of species of Mycobacteria involved in a serious bacterial disease which infects the respiratory system and organs. Multi-drug resistant (MDR) strains have been produced as a result of the fast emergence of resistance against first-line anti-tuberculosis medicines in recent years worldwide. The objective of this study is to determine alternatives to anti-mycobacterial antibiotics, such as Manuka honey and Indian costus. MTB isolates (???? = 15) were evaluated for their susceptibility to Manuka honey (...) graded as +15 and Indian costus by using different concentrations. Among the TB isolates (???? = 15) tested, four (27%) isolates were resistant at 15% v/v honey, while, at 18% v/v of Manuka honey, two (13%) isolates were found to be resistant. Resistance was not seen at honey concentrations of 20% v/v. On the other hand, Indian costus had a slight effectiveness at concentrations of 20% and 25%, affecting only two and five isolates of Mycobacteria, respectively; however, all isolates were inhibited at a concentration of 33% v/v of Indian costus. The present study clearly demonstrates that supposed alternatives (Manuka honey graded as +15 and Indian costus) possess significant anti-mycobacterial activity in vitro; however, further clinical trials should be performed to corroborate our initial findings. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Sick with PassionAlfred LouchOpera: Desire, Disease, Death, by Linda and Michael Hutcheon; xvi & 294 pp. Lincoln: University of Nebraska Press, 1996, $40.00.IDriving east from the Auvergne you may chance upon La Chaise-Dieu, a charming village where a very acceptable cafe confronts the fortress-like Abbatiale de St Robert across the village square. The church itself is an imposing monument to the ephemeral glory of the Avignon Pope Clement VI, (...) but its most extraordinary feature is a fresco in the aisle to the left of the choir. Called the Danse Macabre, it depicts death as a sequence of skeletons, each of which beckons, pleads with, consoles, or compels its many victims—young and old, rich and poor, exalted or mean—toward their inevitable end. At times the skeleton’s posture is sinister and threatening, at others, as with children, it seems to turn away, as if to shield them from its fearful aspect. The skeletons seem to catch the movement of a single dancer as they select one partner after another, taking the life of each in a graceful though ghastly movement.The fresco depicts the Black Death—art inspired by disease and contagion. But even if you were as innocent of history as the typical American tourists you would confront in the fresco the undeniable image of death, and the caprice of its visitation, a thought contrasting strangely with the enduring granite of the church. Your experience may be enriched by history and lead you to moralize on the contrast [End Page 155] between the pomp and grandeur of the papal builder and the fresco’s depiction of the vanity of human wishes. But it would be a jarring note if some know-it-all in the company of viewers were to lecture for all to hear on the transmission and symptoms of pasteurella pestis. That is another story, and an interesting one, but not here and now.And so it is, if not so abrasively, with a recent book by Linda and Michael Hutcheon on desire, disease, and death in opera. They hope to shed new light, by combining literary analysis and the medical theory of disease and contagion, on the themes and purposes of opera, or certain operas anyway. Somehow the passages on mycobacterium tuberculosis, treponema pallidum, and vibrio cholerae, together with graphic descriptions of the symptoms caused by these micro-organisms, and an accompanying photograph of syphilitic gummæ seem intrusive, just as talk about the etiology and the pathology of the plague strikes a discordant note as we look upon the Danse Macabre in wonder and fear. The Hutcheons, a husband and wife team who practice, respectively, medicine and literary criticism, tell the reader they are opera lovers. I hope their affection is not prompted only by infection.But why shouldn’t medicine and its history be relevant to literary, artistic, or musical creation? Think here of a question Wittgenstein asks in Zettel (paragraph 610): “Why should there not be a psychological regularity to which no physiological regularity corresponds? If this upsets our concept of causality then it is high time it was upset.” He did not mean to say that it would not be surprising if someone talked and acted and looked like a person but turned out to have an empty skull. But he did mean surely that talk about human projects and emotions is complete as it stands; what is going on in the neurons and what busy microbes are doing are other stories. Literature is about human projects, the skill or clumsiness with which they are pursued, the responses to success and failure, achievement and frustration. Opera, which, ever since someone had the idea of putting story to song, raided literary invention for its subject matter, is the same. Heroes and villains may of course be expected to be vulnerable to the various vicissitudes of life. Diseases may lay them low, as well as passing trains. But disease enters their stories to delay or frustrate or put period to their projects, not as new characters on the stage. If you read about the death of Ivan Illych and come away dissatisfied because Tolstoy failed to identify the... (shrink)

Indoleamine 2,3‐dioxygenase (IDO) is the rate‐limiting enzyme in conversion of tryptophan to kynurenines, feeding de novo nicotinamide synthesis. IDO orchestrates materno‐foetal tolerance, increasing human reproductive fitness. IDO mediates immune suppression through depletion of tryptophan required by T lymphocytes and other mechanisms. IDO is expressed by alternatively activated macrophages, suspected to play a key role in tuberculosis (TB) pathogenesis. Unlike its human host, Mycobacterium tuberculosis can synthesize tryptophan, suggesting possible benefit to the host from infection with the microbe. Intriguingly, (...) nicotinamide analogues are used to treat TB. In reviewing this field, it is postulated that flux through the nicotinamide synthesis pathway reflects switching between aerobic glycolysis and oxidative phosphorylation in M. tuberculosis‐infected macrophages. The evolutionary cause of such shifts may be ancient mitochondrial behavior related to reproductive fitness. Evolutionary perspectives on the IDO pathway may elucidate why, after centuries of co‐existence with the Tubercle bacillus, humans still remain susceptible to TB disease. (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)

Epidemiological data suggest that previous infections can alter an individual's susceptibility to unrelated diseases. Nevertheless, the underlying mechanisms are not completely understood. Substantial research efforts have expanded the classical concept of immune memory to also include long‐lasting changes in innate immunity and antigen‐independent reactivation of adaptive immunity. Collectively, these processes provide possible explanations on how acute infections might induce long‐term changes that also affect immunity to unrelated diseases. Here, we review lasting changes the immune compartment undergoes upon infection and (...) how infection experience alters the responsiveness of immune cells towards universal signals. This heightened state of alert enhances the ability of the immune system to combat even unrelated infections but may also increase susceptibility to autoimmunity. At the same time, infection‐induced changes in the regulatory compartment may dampen subsequent immune responses and promote pathogen persistence. The concepts presented here outline how infection‐induced changes in the immune system may affect human health. (shrink)

The practice of HIV‐infected physicians who perform seriously invasive procedures calls for professional guidance to protect patient safety and the privacy of infected physicians.

Stuttering is one of the most well-known speech disorders, but the underlying neurological mechanisms are debated. In addition to genetic factors there are also major non-genetic contributions. It is here proposed that infection with group A beta-hemolytic streptococcus (GAS) was a major underlying cause of stuttering until the mid 1900s, when penicillin was introduced for the treatment of streptococcal infections about 1946. The main mechanism proposed is an autoimmune reaction from tonsillitis, targeting specific molecules, for example within the basal (...) ganglia. It is here also proposed that GAS infections may have continued to cause stuttering to some extent, to the present date, though more rarely. If so, early diagnosis of such cases would be of importance. Childhood cases with sudden onset of stuttering after throat infection may be particularly important to assess for possible GAS infection. The support for this hypothesis primarily comes from three lines of argument. First, medical record data from the 1930s strongly indicates that there was one type of medical event in particular that preceded the onset of childhood stuttering with unexpected frequency: diseases related to GAS throat infections. In particular, this included tonsillitis and scarlet fever, but also rheumatic fever. Rheumatic fever is a childhood autoimmune sequela of GAS infection, which was a relatively widespread medical problem until the early 1960s. Secondly, available reports of changes of the childhood prevalence of stuttering indicates striking parallels between stuttering and the incidence of rheumatic fever, with (1) decline from the early 1900s, (2) marked decline from the introduction of penicillin about 1946, and (3) reaching a more stable level in the 1960s. The correlations between the data for stuttering and for rheumatic fever after introduction of penicillin are very high, at about 0.95. Thirdly, there are established biological mechanisms linking GAS tonsillitis to immunological effects on the brain. In addition, a small number of more recent case reports have provided further support for the hypothesis linking stuttering to GAS infection. Overall, it is proposed that the available data provides strong evidence for the hypothesis that GAS infection was a major cause of stuttering until the mid 1900s. (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.

An additional compartment of vaccinated individuals is considered in a SIS stochastic epidemic model with infection reintroduction. The quantification of the spread of the disease is modeled by a continuous time Markov chain. A well-known measure of the initial transmission potential is the basic reproduction number $$R_0$$, which determines the herd immunity threshold or the critical proportion of immune individuals required to stop the spread of a disease when a vaccine offers a complete protection. Due to repeated contacts between (...) the typical infective and previously infected individuals, $$R_0$$ overestimates the average number of secondary infections and leads to, perhaps unnecessary, high immunization coverage. Assuming that the vaccine is imperfect, alternative measures to $$R_0$$ are defined in order to study the influence of the initial coverage and vaccine efficacy on the transmission of the epidemic. (shrink)

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)

Human infection challenge studies (HCS) involve intentionally infecting research participants with pathogens (or other micro-organisms). There have been recent calls for more HCS to be conducted in low-income and middle-income countries (LMICs), where many relevant diseases are endemic. HCS in general, and HCS in LMICs in particular, raise numerous ethical issues. This paper summarises the findings of a project that explored ethical and regulatory issues related to LMIC HCS via (i) a review of relevant literature and (ii) 45 qualitative (...) interviews with scientists and ethicists. Among other areas of consensus, we found that there was widespread agreement that LMIC HCS can be ethically acceptable, provided that they have a sound scientific rationale, are accepted by local communities and meet usual research ethics requirements. Unresolved issues include those related to (i) acceptable approaches to trade-offs between the scientific aim to produce generalisable results and the protection of participants, (iii) the sharing of benefits with LMIC populations, (iii) the acceptable limits to risks and burdens for participants, (iv) the potential for third-party risk and whether the degree of acceptable third-party risk is different in endemic settings, (v) the conditions under which (if any) it would be appropriate to recruit children for disease-causing HCS, (v) appropriate levels of payment to participants and (vi) appropriate governance of (LMIC) HCS. This paper provides preliminary analyses of these ethical considerations in order to (i) inform scientists and policymakers involved in the planning, conduct and/or governance of LMIC HCS and (ii) highlight areas warranting future research. Insofar as this article focuses on HCS in (endemic) settings where diseases are present and/or widespread, much of the analysis provided is relevant to HCS (in HICs or LMICs) involving pandemic diseases including COVID19. (shrink)

Clear guidelines addressing the ethically appropriate use of anti-infectives in the setting of hospice care do not exist. There is lack of understanding about key treatment decisions related to infection treatment for patients who are eligible for hospice care. Ethical concerns about anti-infective use at the end of life include: (1) delaying transition to hospice, (2) prolonging a dying process, (3) prescribing regimens incongruent with a short life expectancy and goals of care, (4) increasing the reservoir of potential resistant (...) pathogens, (5) placing unreasonable costs on a capitated hospice system. Although anti-infectives are thought to be relatively safe, they can place a burden on patients and be inconsistent to particular care plans. The current complex, and at times fragmented, medical care often fails to address these issues in decision-making. In many ways, the ethics governing the end of life decisions related to dialysis, hydration/nutrition, and hypercalcemia parallel those of anti-infectives. In this article we articulate important elements in ethical decision-making in the application of anti-infectives for patients who are eligible for hospice care, and we point to the need for prospective studies to help refine particular guidelines in these cases. (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)

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)

The AIDS epidemic calls for an ethical analysis of conflicting obligations surrounding HIV-infected psychiatric patients and confidentiality, as well as issues that go beyond confidentiality. Although laws pertaining to HIV infection have been enacted in a number of states, these statutes leave much discretion to health professionals. The ethical principle known as "the harm principle" can permit disclosure of confidential information and detention or isolation of psychiatric patients who pose a threat of infecting other patients. From an ethical point (...) of view, however, the circumstances under which traditional protections may be weakened or abandoned remain limited. (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)

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)

Ford, Norman There has been some confusion in the media over what Pope Benedict XVI meant by his comments on the use of condoms. He was discussing acts of sexual intercourse performed by male prostitutes in relation to HIV (human immune deficiency virus) infection in reply to a question put to him during an interview with Peter Seewald. The Vatican spokesman Fr Lombardi SJ said the Pope 'had confirmed to him that the example was valid in the case of (...) all prostitutes. The point of the example, he said, "was not the sex of the prostitute but the process of growing awareness of the risk [to] the life of the other person".' He was not referring to married couples nor contraception but the prevention of HIV infection from acts of prostitution. (shrink)

In this paper I argue that there is good reason to believe that we can be influenced by fictions in ways that matter morally, and some of the time we will be unaware that we have been so influenced. These arguments fall short of proving a clear causal link between fictions and specific changes in the audience, but they do reveal rather interesting and complex features of the moral psychology of fiction. In particular, they reveal that some Platonic worries about (...) the dangers of art cannot be dismissed lightly. (shrink)

Recent findings regarding the cellular biology and immunology of BST‐2 (also known as tetherin) indicate that its function could be exploited as a universal replication inhibitor of enveloped respiratory viruses (e.g., influenza, respiratory syncytial virus, etc.). BST‐2 inhibits viral replication by preventing virus budding from the plasma membrane and by inducing an antiviral state in cells adjacent to infection via unique inflammatory signaling mechanisms. This review presents the first comprehensive summary of what is currently known about BST‐2 anti‐viral function (...) against respiratory viruses, how these viruses construct countermeasures to antagonize BST‐2, and how BST‐2 function might be targeted to develop therapies to treat respiratory virus infections. The authors address the current gaps in knowledge, including the need for mechanistic understanding of BST‐2 antagonism by respiratory viruses, that should be bridged to achieve that goal. (shrink)

Here we identify approximately 40,000 healthy human volunteers who were intentionally exposed to infectious pathogens in clinical research studies dating from late World War II to the early 2000s. Microbial challenge experiments continue today under contemporary human subject research requirements. In fact, we estimated 4,000 additional volunteers who were experimentally infected between 2010 and the present day. We examine the risks and benefits of these experiments and present areas for improvement in protections of participants with respect to safety. These are (...) the absence of maximum limits to risk and the potential for institutional review boards to include questionable benefits to subjects and society when weighing the risks and benefits of research protocols. The lack of a duty of medical care by physician–investigators to research subjects is likewise of concern. The transparency of microbial challenge experiments and the safety concerns raised in this work may stimulate further dialogue on the risks to participants of human experimentation. (shrink)

An Institute of Medical Ethics working party argues that an ethically desirable relationship of mutual empowerment between patient and clinician is more likely to be achieved if patients understand the ground rules of medical confidentiality. It identifies and illustrates ambiguities in the General Medical Council's guidance on AIDS and confidentiality, and relates this to the practice of different doctors and specialties. Matters might be clarified, it suggests, by identifying moral factors which tend to recur in medical decisions about maintaining or (...) breaching confidentiality. The working party argues that two such factors are particularly important: the patient's need to exercise informed choice and the doctor's primary responsibility to his or her own patients. (shrink)

ABSTRACT If we have a duty not to infect others, how far does it go? This question is often discussed with respect to HIV transmission, but reflection on other diseases like influenza raises a number of interesting theoretical issues. I argue that a duty to avoid infection not only yields requirements for persons who know they carry a disease, but also for persons who know they are at increased risk, and even for those who definitely know they are completely (...) healthy. Given the numerous ways in which human interaction facilitates the spread of communicable diseases, a maximum level of precaution would be very demanding – possibly unreasonably demanding. The ‘over‐demandingness problem’ is mostly invoked as a criticism of utilitarianism, as this theory requires moral agents to always maximise general welfare, even at significant cost for themselves. However, I argue that, with respect to precautions against infectious diseases like influenza, utilitarianism is able to avoid the over‐demandingness problem. A contractualist account, on the other hand, whilst able to explain how one's obligations to avoid infection can be limited, given that other persons have opportunities and responsibilities to protect themselves, in the end requires precautions that raise the over‐demandingness problem. (shrink)

Prior research has demonstrated that the adverse consequences of the coronavirus disease 2019 pandemic may go beyond its economic hardships and physical health concerns, having a significant influence on psychological distress for individuals under quarantine. Nevertheless, relatively little attention has been paid to exploring the risk and protective factors in the link between COVID-19 infection risk and psychological distress among young adults. Following a socioecological framework, the current study examines the moderating role of grit and social support in the (...) association between COVID-19 infection risk and depressive symptoms. A sample of 1,251 young adults under home quarantine was involved in this study, and they were asked to complete a set of self-reported questionnaires online. Results of a linear regression analysis exhibited that COVID-19 infection risk was positively associated with depressive symptoms in young adults in quarantine. Moreover, moderation analyses showed that this association was moderated by perseverance and social support. To be specific, for those reporting higher levels of social support, this linkage was not significantly positive; in contrast, for those reporting lower levels of social support, perseverance was a significant protective factor for depressive symptoms when young adults were exposed to a high infection risk of COVID-19. The current study suggests that greater social support is essential to helping young adults deal with possible negative emotions in the context of the COVID-19 pandemic. Moreover, university-based counseling services should pay specific attention to those young adults with relatively insufficient social support resources and low levels of perseverance. (shrink)

ABSTRACT Clear guidelines addressing the ethically appropriate use of anti‐infectives in the setting of hospice care do not exist. There is lack of understanding about key treatment decisions related to infection treatment for patients who are eligible for hospice care. Ethical concerns about anti‐infective use at the end of life include: (1) delaying transition to hospice, (2) prolonging a dying process, (3) prescribing regimens incongruent with a short life expectancy and goals of care, (4) increasing the reservoir of potential (...) resistant pathogens, (5) placing unreasonable costs on a capitated hospice system. Although anti‐infectives are thought to be relatively safe, they can place a burden on patients and be inconsistent to particular care plans. The current complex, and at times fragmented, medical care often fails to address these issues in decision‐making. In many ways, the ethics governing the end of life decisions related to dialysis, hydration/nutrition, and hypercalcemia parallel those of anti‐infectives. In this article we articulate important elements in ethical decision‐making in the application of anti‐infectives for patients who are eligible for hospice care, and we point to the need for prospective studies to help refine particular guidelines in these cases. (shrink)

Leishmania major infection of inbred mice leads to a major dichotomous response—death or survival—that depends on the strain of mice. This finding has motivated efforts to locate genetic determinants of disease susceptibility. Genotyping studies have confirmed a complex multilocus trait, but studies directed at the biology of the response suggest identifiable components of susceptibility that may direct the genetic investigations. A confluence of parasite variables—residence in macrophages, class II-dependent immunity, and avoidance of early IL-12 induction—with host factors—a prominent helper (...) T-cell precursor frequency to a dominant parasite epitope and a bias in IL-4 gene activation—conspires to drive an aberrant immune response in animals that suffer fatal disease. These insights may lead to an understanding of factors that focus responses on dominant antigens and that mold the naive T-cell repertoire. Collectively, such factors might contribute to the pathogenesis of other infectious and autoimmune diseases. BioEssays 21:510–518, 1999. © 1999 John Wiley & Sons, Inc. (shrink)

Doctors and dentists have traditionally used antibiotic prophylaxis in certain patient groups in order to prevent infective endocarditis (IE). New guidelines, however, suggest that the risk to patients from using antibiotics is higher than the risk from IE. This paper analyses the relative risks of prescribing and not prescribing antibiotic prophylaxis against the background of Pascal’s Wager, the infamous assertion that it is better to believe in God regardless of evidence, because of the prospective benefits should He exist. Many doctors (...) seem to believe the parallel proposition that it is better to prescribe antibiotics, regardless of evidence, because of the prospective benefit conferred upon the patient. This has been called the “no lose philosophy” in medicine: better safe than sorry, even if the evidence inconveniently suggests that following this mantra is potentially more likely to result in sorry than safe. It transpires that, just as Pascal’s Wager fails to convince because of a lack of evidence to support it and the costs incurred by trying to believe, so the “belts and braces” approach of prescribing antibiotic prophylaxis is unjustifiable given the actual evidence of potential risk and benefit to the patient. Ultimately, there is no no-lose if your clinical decisions, like Pascal’s Wager, are based on faith rather than evidence. (shrink)

COVID-19 has been studied extensively for its direct effects on healthcare workers. Despite this, very little is known about the effect of COVID-19 fear on future orientation. Studying medical social workers’ fear of being infected with COVID-19 and their future orientation was the primary method used to examine this relationship. 204 Turkish medical social workers on the pandemic’s front lines were included in the total sample. Social workers were found to be extremely concerned about contracting COVID-19. Although only gender is (...) a significant predictor of the fear of contracting COVID-19 infection, the study also found that female social workers have a higher fear of infection than males. Also, no correlation exists between social workers’ vaccination status and their fear of contracting COVID-19. There was a weak negative correlation between social workers’ fear of contracting COVID-19 and their future orientation, but in general, social workers had a positive future orientation. Medical social workers and front-line health care providers can use these findings to develop effective and culturally appropriate intervention programs to reduce COVID-19 concerns and foster a forward-looking outlook. (shrink)

Despite huge efforts towards understanding the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pathogenesis, little is known about the long‐term consequences of the disease. Here, we critically review existing literature about oncogenesis as a potential long‐term effect of SARS‐CoV‐2 infection. Like other viral infections, SARS‐CoV‐2 may promote cancer onset by inhibiting tumor suppressor genes. We conclude that, although unlikely, such hypothesis cannot be excluded a priori and we delineate an experimental approach to address it. Also see the video abstract (...) here: https://youtu.be/TBUTDSLR7vY. (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)

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)

The diagnosis of HIV infection is the point of entry for treatment and prevention services, yet many infected persons in both developed and developing countries remain undiagnosed. To reduce the number of undiagnosed infections, a variety of expanded testing policies have been recommended, including opt-out testing. This testing model assumes that in populations of increased HIV prevalence, voluntary testing should be offered to all patients seen in healthcare settings and performed unless patients specifically decline. While this approach raises ethical (...) issues concerning “voluntariness”, access to care, and stigma, the potential benefits of opt-out testing far outweigh its potential adverse effects. (shrink)

Human infection challenge studies (HCS) have been proposed as a means to accelerate SARS-CoV2 vaccine development and thereby help to mitigate a prolonged global public health crisis. A key criterion for the ethical acceptability of SARS-CoV2 HCS is that potential benefits outweigh risks. Although the assessment of risks and benefits is meant to be a standard part of research ethics review, systematic comparisons are particularly important in the context of SARS-CoV2 HCS in light of the significant potential benefits and (...) harms at stake as well as the need to preserve public trust in research and vaccines. In this paper we explore several considerations that should inform systematic assessment of SARS-CoV-2 HCS. First, we detail key potential benefits of SARS-CoV-2 HCS including, but not limited to, those related to the acceleration of vaccine development. Second, we identify where modelling is needed to inform risk-benefit (and thus ethical) assessments. Modelling will be particularly useful in (i) comparing potential benefits and risks of HCS with those of vaccine field trials under different epidemiological conditions and (ii) estimating marginal risks to HCS participants in light of the background probabilities of infection in their local community. We highlight interactions between public health policy and research priorities, including situations in which research ethics assessments may need to strike a balance between competing considerations. (shrink)

Using theories in medical anthropology, especially the ideas inspired by Hector Avalos and George Foster, the study explains three activities associated with the early Christian healthcare system: (1) touching infectious people, (2) hospitality towards possibly infectious people and (3) the practice of itinerary evangelism as an activity that earned Christianity the dubious role of being a carrier of infectious diseases. Discussed alongside the issues associated with the advent of COVID-19, the study aims at (1) reflecting that early Christian healthcare system, (...) which was an offshoot of Jewish healthcare systems, had practices that were perceived to exacerbate infection. In addition, (2) in view of the advent of COVID-19 pandemic, although of lesser catastrophe to ancient plagues, the study proposes that such epidemics call upon the collective actions of mercy and kindness, as Jesus did towards the infected. Theoretically, Victor Turner’s concepts of liminality and communitas assist in imagining the discursive ideas concerning labelling and marginalisation of the Jesus movement, with comparative implication towards those suspected to have contracted the deadly COVID-19 virus. The study concludes with a warning against Christian practices that may further inflame infection by suggesting alternative practices for love and empathy towards others. Contribution: Using ideas concerning infectious diseases in antiquity, the study reinterprets the Jesus movement as a movement that was perceived as carriers of infectious disease. Due to fear of infectious diseases, the rituals associated with hospitality towards the outsiders, the touch and laying of hands and iternary lifestyle were seen as promoting infection. Taking this perspective, the Jesus movement whose modus operandi is mostly associated with the periphery of the villages and cities created alternative rituals for the outcast. In view of the spread of COVID19, such stance by the Jesus movement provides lessons for the church and society to reach out to people who are considered infectious and burden to main society. (shrink)

Population-based research is enhanced by biological measures, but biological sampling raises complex ethical issues. The third British National Survey of Sexual Attitudes and Lifestyles (Natsal-3) will estimate the population prevalence of five sexually transmitted infections (STIs) (Chlamydia trachomatis, Neisseria gonorrhoeae, human papillomavirus (HPV), HIV and Mycoplasma genitalium) in a probability sample aged 16–44 years. The present work describes the development of an ethical approach to urine testing for STIs, including the process of reaching consensus on whether to return results. The (...) following issues were considered: (1) testing for some STIs that are treatable and for which appropriate settings to obtain free testing and advice are widely available (Natsal-3 provides all respondents with STI and healthcare access information), (2) limits on test accuracy and timeliness imposed by survey conditions and sample type, (3) testing for some STIs with unknown clinical and public health implications, (4) how a uniform approach is easier to explain and understand, (5) practical difficulties in returning results and cost efficiency, such as enabling wider STI testing by not returning results. The agreed approach, to perform voluntary anonymous testing with specific consent for five STIs without returning results, was approved by stakeholders and a research ethics committee. Overall, this was acceptable to respondents in developmental piloting; 61% (68 of 111) of respondents agreed to provide a sample. The experiences reported here may inform the ethical decision making of researchers, research ethics committees and funders considering population-based biological sampling. (shrink)