This is an appendix to the article "Wie effizient sollten Altruisten handeln?" ("How Efficient Should Altruists Act?") The appendix provides detailed moral efficiency calculations for two charitable projects: a children's home in Guatemala for neglected children versus malaria prevention by distributing mosquito nets in malaria areas in sub-Saharan Africa. The exact method of efficiency calculation is explained and applied. At least prima facie, the malaria prophylaxis project is clearly more efficient.

The article develops a general theory of the goals of free moral commitment. The theoretical hook is the discussion of the strict efficiency striving as demanded by the movement and theory of effective altruism. A detailed example shows prima facie counterintuitive consequences of this efficiency striving, the analysis of which reveals various problems such as: merely point-like but not structural commitment; radical universalism; violation of established moral standards and institutions. The article takes these problems as an occasion to develop a (...) general theory of moral investment with moral guidelines and planning instruments of its implementation such as: efficiency; preservation of existing moral standards and obligations, especially also towards those close to one; rooted universalism with adequate consideration of all beneficiaries of one's moral concern through allocation of separate budgets; real efficiency also through inclusion of strategic and organic investments. (shrink)

Definitive diagnosis of malaria requires the demonstration through laboratory tests of the presence within the patient of malaria parasites or their components. Since malaria parasites can be present even in the absence of malaria manifestations, and since symptoms of malaria can be manifested even in the absence of malaria parasites, malaria diagnosis raises important issues for the adequate understanding of disease, etiology and diagnosis. One approach to the resolution of these issues adopts a (...) realist view, according to which the needed clarifications will be derived from a careful representation of the entities on the side of the patient which form the ultimate truthmakers for clinical statements. We here address a challenge to this realist approach relating to the diagnosis of malaria, and show how this challenge can be resolved by appeal to Basic Formal Ontology (BFO) and to the Ontology for General Medical Science (OGMS) constructed in its terms. (shrink)

Between 1906 and 1909 the biologist Ronald Ross and the classicist W.H.S. Jones pioneered interdisciplinary research in biology and history in advancing the claim that malaria had been crucial in the decline of golden-age Greece. The idea had originated with Ross, winner of the Nobel Prize for demonstrating the importance of mosquitoes in the spread of the disease. Jones assembled what, today, we would call an interdisciplinary network of collaborators in the sciences and humanities. But early negative reviews of (...) Jones’s Malaria and Greek History by classicists and historians ended the project, despite a positive reception among malariologists. Today, the “Jones hypothesis” is often used to exemplify the naïvete of past scholarship, and few examine Jones’s evidence and reasoning. In this age of renewed interdisciplinarity, a review of what went wrong is timely. Jones and Ross knew they were opening new methodological territory and struggled with the challenges of multiple ways of knowing. Over 100 years later, malaria remains an important site of historical-biological research, yet integration is elusive. After reviewing the Jones-Ross relationship, Jones’s interdisciplinary campaign, and the reception of the hypothesis among classicists/ancient historians and in malariology, we conclude by highlighting some of the specific challenges faced by those exploring the interface of biology and history. (shrink)

Opinion about neonatal male circumcision is deeply divided. Some take it to be a prophylactic measure with unequivocal and significant health benefits, while others consider it a form of child abuse. We argue against both these polar views. In doing so, we discuss whether circumcision constitutes bodily mutilation, whether the absence of the child's informed consent makes it wrong, the nature and strength of the evidence regarding medical harms and benefits, and what moral weight cultural considerations have. We conclude that (...) nontherapeutic circumcision of infant boys is a suitable matter for parental discretion. (shrink)

This review of Professor Marcos Cueto's Cold War Deadly Fevers: Malaria Eradication in Mexico, 1955–1975 discusses some of the historical, sociological, political and parasitological topics included in Dr. Cueto's superbly well-informed volume. The reviewer, a parasitologist, follows the trail illuminated by Dr. Cueto through the foundations of the malaria eradication campaign; the release in Mexico of the first postage stamp in the world dedicated to malaria control; epidemiological facts on malarial morbidity and mortality in Mexico when the (...) campaign began; the emergence of problem areas that impeded eradication; considerations on mosquitoes and malaria transmission in Mexico; the role of business and society in malaria eradication; the results of the campaign; the relationship between malaria and poverty; and the parasitological lessons to be learned from the history of malaria eradication campaigns. Dr. Cueto's excellent and well-informed exploration of malaria – not merely as a disease but as a social, economic and human problem – makes this book required reading. (shrink)

The term “hypnozoite” is derived from the Greek words hypnos and zoon. Hypnozoites are dormant forms in the life cycles of certain parasitic protozoa that belong to the Phylum Apicomplexa and are best known for their probable association with latency and relapse in human malarial infections caused by Plasmodium ovale and P. vivax. Consequently, the hypnozoite is of great biological and medical significance. This, in turn, makes the origin of the name “hypnozoite” a subject of interest. Some “missing” history that (...) is now placed on record shows that Miles B. Markus coined the term “hypnozoite”. While a PhD student at Imperial College London, he carried out research that led to the identification of an apparently dormant form of Cystoisospora. In 1976, he speculated: “If sporozoites of Isospora can behave in this fashion, then those of related Sporozoa, like malaria parasites, may have the ability to survive in the tissues in a similar way.” He adopted the term “hypnozoite” for malaria in 1978 when he wrote in a little-known journal that this name would “… describe any dormant sporozoites or dormant, sporozoite-like stages in the life cycles of Plasmodium or other Haemosporina.” At that time, the existence of a hypnozoite form in the life cycle of Plasmodium was still a hypothetical notion. In 1980, however, Wojciech A. Krotoski published details concerning his actual discovery of malarial hypnozoites, an event of considerable importance. (shrink)

Fast and effective detection of the causative agent of malaria in humans, protozoan Plasmodium parasites, is of crucial importance for increasing the effectiveness of treatment and to control a devastating disease that affects millions of people living in endemic areas. The microscopic examination of Giemsa‐stained blood films still remains the gold‐standard in Plasmodium detection today. However, there is a high demand for alternative diagnostic methods that are simple, fast, highly sensitive, ideally do not rely on blood‐drawing and can potentially (...) be conducted by the patients themselves. Here, the history of Plasmodium detection is discussed, and advantages and disadvantages of diagnostic methods that are currently being applied are assessed. (shrink)

This article examines whether a policy of mandatory neonatal eye prophylaxis is ethically justified within the Canadian context. An existing framework for public health ethics is used to examine criteria that would justify state intervention in parental decision-making authority in order to protect public health. The benefits, harms, and utility of mandatory neonatal eye prophylaxis are described. Established criteria for the infringement of basic individual liberties in the interests of public health, including effectiveness, proportionality, necessity, least infringement and (...) public justification, are considered. The extent and limits of parental decision-making authority are then discussed, and conditions that warrant state intervention in parental decision-making based on the harm principle are reviewed. Ultimately, infringement of parental authority is not deemed to be necessary to protect public health or to protect the newborn in this case and existing circumstances do not meet any criteria that would justify such an infringement. Mandatory eye prophylaxis is found not to be ethically justified in the current Canadian context. (shrink)

Cas9/guide RNA (gRNA)‐based gene drive systems are expected to play a transformative role in malaria elimination efforts., whether through population modification, in which the drive system contains parasite‐refractory genes, or population suppression, in which the drive system induces a severe fitness load resulting in population decline or extinction. DNA sequence polymorphisms representing alternate alleles at gRNA target sites may confer a drive‐resistant phenotype in individuals carrying them. Modeling predicts that, for observed levels of SGV at potential target sites and (...) observed rates of de novo DRA formation, population modification strategies are uniquely resilient to DRAs. We conclude that gene drives can succeed when fitness costs incurred by drive‐carrying mosquitoes are low enough to prevent strong positive selection for DRAs produced de novo or as part of the SGV and that population modification strategies are less prone to failure due to drive resistance. (shrink)

Malaria is a disease of developing countries whose local health services do not have the time, resources or personnel to mount studies of drugs or vaccines without the collaboration and technology of western investigators. This investigative collaboration requires a unique bridging of cultural differences with respect to human investigation. The following debate, sponsored by The Institute of Medicine and The American Society of Tropical Medicine and Hygiene, raises questions concerning the conduct of trans-cultural clinical malaria research. Specific questions (...) are raised about the difficulties of informed consent in different cultural settings and whether there is any role for community involvement. Discussants debate whether drug and vaccine trials not approved in an industrialised country are ever defensible if performed in a third-world setting. Potential conflicting priorities between investigators are discussed and ideas regarding conflict resolution are offered. (shrink)

Post-exposure prophylaxis in the form of combination drug therapy is now recommended for healthcare workers following occupational HIV exposure. The expansion of this form of preventive medicine to include other types of HIV transmission, notably through sexual activity, raises a number of ethical concerns.

The term "hypnozoite" is derived from the Greek words hypnos (sleep) and zoon (animal). Hypnozoites are dormant forms in the life cycles of certain parasitic protozoa that belong to the Phylum Apicomplexa (Sporozoa) and are best known for their probable association with latency and relapse in human malarial infections caused by Plasmodium ovale and P. vivax. Consequently, the hypnozoite is of great biological and medical significance. This, in turn, makes the origin of the name "hypnozoite" a subject of interest. Some (...) "missing" history that is now placed on record (including a letter written by P. C. C. Garnham, FRS) shows that Miles B. Markus coined the term "hypnozoite". While a PhD student at Imperial College London, he carried out research that led to the identification of an apparently dormant form of Cystoisospora (synonym: Isospora). In 1976, he speculated: "If sporozoites of Isospora can behave in this fashion, then those of related Sporozoa, like malaria parasites, may have the ability to survive in the tissues in a similar way." He adopted the term "hypnozoite" for malaria in 1978 when he wrote in a little-known journal that this name would "... describe any dormant sporozoites or dormant, sporozoite-like stages in the life cycles of Plasmodium or other Haemosporina." At that time, the existence of a hypnozoite form in the life cycle of Plasmodium was still a hypothetical notion. In 1980, however, Wojciech A. Krotoski published (together with several co-workers) details concerning his actual discovery of malarial hypnozoites, an event of considerable importance. (shrink)

The last few years have seen dramatic progress in the development of HIV pre-exposure prophylaxis (PrEP). These developments have been met by ethical concerns. HIV interventions are often thought to be ethically difficult. In a context which includes disagreements over human rights, controversies over testing policies, and questions about sexual morality and individual responsibility, PrEP has been seen as an ethically complex intervention. We argue that this is mistaken, and that in fact, PrEP does not raise new ethical concerns. (...) Some of the questions posed by PrEP are not specific to HIV prophylaxis, but simply standard public health considerations about resource allocation and striking a balance between individual benefit and public good. We consider sexual disinhibition in the context of private prescriptions, and conclude that only unjustified AIDS-exceptionalism or inappropriate moralism about sex supports thinking that PrEP raises new ethical problems. This negative conclusion is significant in a context where supposed ethical concerns about PrEP have been raised, and in the context of HIV exceptionalism. (shrink)

Gene drive technologies (GDTs) have been proposed as a potential new way to alleviate the burden of malaria, yet have also raised ethical questions. A central ethical question regarding GDTs relates to whether it is morally permissible to intentionally modify or eradicate mosquitoes in this way and how the inherent worth of humans and non-human organisms should be factored into determining this. Existing analyses of this matter have thus far generally relied on anthropocentric and zoocentric perspectives and rejected an (...) individualist biocentric outlook in which all living organisms are taken to matter morally for their own sake. In this paper, we reconsider the implications of taking a biocentric approach and highlight nuances that may not be evident at first glance. First, we shortly discuss biocentric perspectives in general, and then outline Paul Taylor’s biocentric theory of respect for nature. Second, we explore how conflicting claims towards different organisms should be prioritised from this perspective and subsequently apply this to the context of malaria control using GDTs. Our ethical analysis shows that this context invokes the principle of self-defence, which could override the pro tanto concerns that a biocentrist would have against modifying malaria mosquitoes in this way if certain conditions are met. At the same time, the case study of GDTs underlines the relevance of previously posed questions and criticism regarding the internal consistency of Taylor’s egalitarian biocentrism. (shrink)

The impending implementation of pre-exposure prophylaxis has prompted complicated bioethical and public health ethics concerns regarding the moral distribution of antiretroviral medications to ostensibly healthy populations as a form of HIV prevention when millions of HIV-positive people still lack access to ARVs globally. This manuscript argues that these questions are, in part, concerns over the ethics of the knowledge production practices of epidemiology. Questions of distribution, and their attendant cost-benefit calculations, will rely on a number of presupposed, and therefore, (...) normatively cultural assumptions within the science of epidemiology specifically regarding the ability of epidemiologic surveillance to produce accurate maps of HIV throughout national populations. Specifically, ethical questions around PrEP will focus on who should receive ARVs given the fact that global demand will far exceed supply. Given that sexual transmission is one of the main modes of HIV transmission, these questions of ‘who’ are inextricably linked to knowledge about sexual personhood. As a result, the ethics of epidemiology, and how the epidemiology of HIV in particular conceives, classifies and constructs sexual populations will become a critical point of reflection and contestation for bioethicists, health activists, physicians, nurses, and researchers in the multi-disciplinary field of global health. This paper examines how cultural conundrums within the fields of bioethics and public health ethics are directly implicated within the ethics of PrEP, by analyzing the problems of population inaugurated by the construction of the men who have sex with men epidemiologic category in the specific national context of South Africa. (shrink)

In this paper, we present a probabilistic-based method to predict malaria disease at an early stage. Malaria is a very dangerous disease that creates a lot of health problems. Therefore, there is a need for a system that helps us to recognize this disease at early stages through the visual symptoms and from the environmental data. In this paper, we proposed a Bayesian network model to predict the occurrences of malaria disease. The proposed BN model is built (...) on different attributes of the patient’s symptoms and environmental data which are divided into training and testing parts. Our proposed BN model when evaluated on the collected dataset found promising results with an accuracy of 81%. One the other hand, F1 score is also a good evaluation of these probabilistic models because there is a huge variation in class data. The complexity of these models is very high due to the increase of parent nodes in the given influence diagram, and the conditional probability table also becomes more complex. (shrink)

This chapter analyzes the ‘hard sell’ of genetically engineered (GE) mosquitoes with gene drives as the solution to mosquito-borne diseases. A defining characteristic of the aggressive sell of the bio-technology is the ‘biologization’ of the significant prevalence of mosquito-borne diseases in certain socio-economically marginalized regions of the global South. Specifically, hard sell narratives either minimize or ignore the structural, systemic factors that are partially responsible for the public health problem that the GE mosquitoes are intended to bio-solve. The biologization of (...) a public health problem that disproportionately affects low-income, marginalized populations in certain global South regions has epistemic, epidemiological, and gendered ethico-political costs. The primary focus of this chapter is two scientific papers by researchers with ties to Target Malaria, a research organization developing GE mosquitoes with gene drives as the solution to malaria in the global South. In the interest of a contextualized analysis of the hard sell of GE mosquitoes with gene drives in those scientific papers, this chapter examines the normative commitments of Target Malaria’s key backer, the Bill and Melinda Gates Foundation, a powerful private organization that currently dominates the global health governance stage. (shrink)

A geographically stratified cross-sectional survey was conducted in 2002 to investigate household-level factors associated with use of mosquito control measures and self-reported malaria in Malindi, Kenya. A total of 629 households were surveyed. Logistic regressions were used to analyse the data. Half of all households (51%) reported all occupants using an insecticide-treated bed net and at least one additional mosquito control measure such as insecticides or removal of standing water. Forty-nine per cent reported a history of malaria in (...) the household. Of the thirteen household factors analysed, low (OR=0·23, CI 0·11, 0·48) and medium (OR=0·50, CI 0·29, 0·86) education, mudcoral (OR=0·0·39, CI 0·24, 0·66) and mud block–plaster (OR=0·47, CI 0·25, 0·87) wall types, farming (OR=1·38, CI 1·01, 1·90) and travel to rural areas (OR=0·48, CI 0·26, 0·91) were significantly associated with the use of mosquito control, while controlling for other covariates in the model. History of reported malaria was not associated with the use of mosquito control (OR=1·22, CI 0·79, 1·88). Of the thirteen covariates analysed in the second model, only two household factors were associated with history of malaria: being located in the well-drained stratum (OR=0·49, CI 0·26, 0·96) and being bitten while in the house (OR=1·22, CI 0·19, 0·49). These results suggest that high socioeconomic status is associated with increased household-level mosquito control use, although household-level control may not be enough, as many people are exposed to biting mosquitoes while away from the house and in areas that are more likely to harbour mosquitoes. (shrink)

Antiretroviral pre-exposure prophylaxis (PrEP) is protective against HIV. Low utilization rates amongst HIV vulnerable populations are due in part to the high cost of PrEP. Generic PrEP offers the potential to improve health at significantly reduced costs. In this study, we examine early utilization patterns and prices for generic PrEP. We discuss the opportunities and challenges for generic PrEP to improve health among HIV vulnerable populations.

In a military-sponsored research project begun during the Second World War, inmates of the Stateville Penitentiary in Illinois were infected with malaria and treated with experimental drugs that sometimes had vicious side effects. They were made into reservoirs for the disease and they provided a food supply for the mosquito cultures. They acted as secretaries and technicians, recording data on one another, administering malarious mosquito bites and experimental drugs to one another, and helping decide who was admitted to the (...) project and who became eligible for early parole as a result of his participation. Thus, the prisoners were not simply research subjects; they were deeply constitutive of the research project. Because a prisoners time on the project was counted as part of his sentence, and because serving on the project could shorten ones sentence, the project must be seen as simultaneously serving the functions of research and punishment. Michel Foucault wrote about such mixed mechanisms in his Discipline and punish. His shining example of such a transparent and subtle style of punishment was the panopticon, Jeremy Benthams architectural invention of prison cellblocks arrayed around a central guard tower. Stateville prison was designed on Benthams model; Foucault featured it in his own discussion. This paper, then, explores the power relations in this highly idiosyncratic experimental system, in which the various roles of model organism, reagent, and technician are all occupied by sentient beings who move among them fluidly. This, I argue, created an environment in the Stateville hospital wing more panoptic than that in the cellblocks. Research and punishment were completely interpenetrating, and mutually reinforcing. (shrink)

Over the past decade AIDS research has turned toward the use of pharmacology in HIV prevention, including pre-exposure prophylaxis (PrEP): the use of HIV medication as a means of preventing HIV acquisition in those who do not have it. This paper explores the contradictory reasons offered in support of PrEP—to empower women, to provide another risk-reduction option for gay men—as the context for understanding the social meaning of the experimental trials that appear to show that PrEP works in gay (...) men and heterosexual couples but not single women. The PrEP debates reveal the different ideas about “demedicalization” in the earlier gay health and women’s health movements and highlight the relationship between health activism and critique of research ethics in the context of a global pharmaceutical market. (shrink)

Le recueil de prophylaxie contre les agressions des animaux venimeux du Musée de Brooklyn: Papyrus Wilbour 47.218.138. By Jean-Clauce Goyon. Studien zur spätägyptischen Religion, vol. 5. Wiesbaden: Harrassowitz Verlag, 2012. Pp. xi + 192, 18 plts. €78.

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)

Plasmodium falciparum is the most deadly human malarial parasite, responsible for an estimated 207 million cases of disease and 627,000 deaths in 2012. Recent studies reveal that the parasite actively regulates a large fraction of its genes throughout its replicative cycle inside human red blood cells and that epigenetics plays an important role in this precise gene regulation. Here, we discuss recent advances in our understanding of three aspects of epigenetic regulation in P. falciparum: changes in histone modifications, nucleosome occupancy (...) and the three‐dimensional genome structure. We compare these three aspects of the P. falciparum epigenome to those of other eukaryotes, and show that large‐scale compartmentalization is particularly important in determining histone decomposition and gene regulation in P. falciparum. We conclude by presenting a gene regulation model for P. falciparum that combines the described epigenetic factors, and by discussing the implications of this model for the future of malaria research. (shrink)

Advances in medical capability should be accompanied by discussion of their ethical implications. In the military medical context there is a growing interest in developing prophylactic interventions that will mitigate the effects of trauma and improve survival. The ethics of this novel capability are currently unexplored. This paper describes the concept of trauma prophylaxis and outlines some of the ethical issues that need to be considered, including within concept development, research and implementation. Trauma prophylaxis can be divided into (...) interventions that do not and those that do have medical enhancement as an unintended side effect of their prophylactic action. We conclude that type 1 interventions have much in common with established military medical prophylaxis, and the potentially enhancing qualities of type 2 interventions raise different issues. We welcome further debate on both interventions. (shrink)

Thanks to the extensive use of recombinant DNA technology and immunological methods, much insight into cellular functions of the human malaria parasite Plasmodium falciparum has been gained since it was learnt ten years ago how to grow this organism in culture. The amino acid sequence of over a dozen surface proteins of the parasite and of several proteins the parasite excretes into its most important host cell, the erythrocyte, have been determined. Interestingly many of these proteins show blocks of (...) repeated amino acids. Several proteins have been shown to be involved in specific aspects of the complex hostparasite interaction, such as penetration of host cells or increased stickiness of infected red blood cells in the blood vessels. Some of the proteins described here may be protective antigens and may become important in vaccine development. (shrink)

Approximately a quarter of a billion people around the world suffer from malaria each year. Most cases are located in sub-Saharan Africa where Anopheles gambiae mosquitoes are the principal vectors of this public health problem. With the use of CRISPR-based gene drives, the population of mosquitoes can be modified, eventually causing their extinction. First, we discuss the moral status of the organism and argue that using genetically modified mosquitoes to combat malaria should not be abandoned based on some (...) moral value of A. gambiae. Secondly, we argue that environmental impact studies should be performed to obtain an accurate account of the possible effects of a potential eradication of the organism. However, the risks from the purposeful extinction of A. gambiae should not overtake the benefits of eradicating malaria and risk assessments should be used to determine acceptable risks. Thirdly, we argue that the eventual release of the genetically modified mosquitoes will depend on transparency, community involvement, and cooperation between different nations. (shrink)

Initial responses to questionnaires used to assess participants' understanding of informed consent for malaria vaccine trials conducted in the United States and Mali were tallied. Total scores were analyzed by age, sex, literacy (if known), and location. Ninety-two percent (92%) of answers by United States participants and 85% of answers by Malian participants were correct. Questions more likely to be answered incorrectly in Mali related to risk, and to the type of vaccine. For adult participants, independent predictors of higher (...) scores were younger age and female sex in the United States, and male sex in Mali. Scores in the United States were higher than in Mali (P = 0.005). Despite this difference participants at both sites were well informed overall. Although interpretation must be qualified because questionnaires were not intended as research tools and were not standardized among sites, these results do not support concerns about systematic low understanding among research participants in developing versus developed countries. (shrink)