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)

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)

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 (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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

In this paper, a nonlinear dynamical system is proposed and qualitatively analyzed to study the dynamics and effects of HIV-malaria co-infection in the workplace. Basic reproduction numbers of sub-models are derived and are shown to have LAS disease-free equilibria when their respective basic reproduction numbers are less than unity. Conditions for existence of endemic equilibria of sub-models are also derived. Unlike the HIV-only model, the malaria-only model is shown to exhibit a backward bifurcation under certain conditions. Conditions for (...) optimal control of the co-infection are derived using the Pontryagin’s maximum principle. Numerical experimentation on the resulting optimality system is performed. Using the incremental cost-effectiveness ratio, it is observed that combining preventative measures for both diseases is the best strategy for optimal control of HIV-malaria co-infection at the workplace. (shrink)

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 prisoner’s time on the project was counted as part of his sentence, and because serving on the project could shorten one’s 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 Bentham’s architectural invention of prison cellblocks arrayed around a central guard tower. Stateville prison was designed on Bentham’s 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)

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)

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)

The immunology of falciparum malaria, the lethal type of human malaria, has been transformed by two developments. First, a culture system for the asexual blood stages of Plasmodium falciparum.1 Secondly, the cloning and expression of genes coding for a large number of the protein antigens of this malaria parasite over the past two years. Data on proteins, protein antigens and epitopes of P. falciparum supplied by gene cloning techniques have been supplemented by monoclonal antibody approaches, peptide synthesis, (...) and high‐resolution immunochemistry. (shrink)

Malaria is a Plasmodium parasitic disease transmitted by infected female Anopheles mosquitoes. Climatic factors, such as temperature, humidity, rainfall, and wind, have significant effects on the incidence of most vector-borne diseases, including malaria. The mosquito behavior, life cycle, and overall fitness are affected by these climatic factors. This paper presents the results obtained from investigating the optimal control strategies for malaria in the presence of temperature variation using a temperature-dependent malaria model. The study further identified the (...) temperature ranges in four different geographical regions of sub-Saharan Africa, suitable for mosquitoes. The optimal control strategies in the temperature suitable ranges suggest, on average, a high usage of both larvicides and adulticides followed by a moderate usage of personal protection such as bednet. The average optimal bednet usage mimics the solution profile of the mosquitoes as the mosquitoes respond to changes in temperature. Following the results from the optimal control, this study also investigates using a temperature-dependent model with insecticide-sensitive and insecticide-resistant mosquitoes the impact of insecticide-resistant mosquitoes on disease burden when temperature varies. The results obtained indicate that optimal bednet usage on average is higher when insecticide-resistant mosquitoes are present. Besides, the average bednet usage increases as temperature increases to the optimal temperature suitable for mosquitoes, and it decreases after that, a pattern similar to earlier results involving insecticide-sensitive mosquitoes. Thus, personal protection, particularly the use of bednets, should be encouraged not only at low temperatures but particularly at high temperatures when individuals avoid the use of bednets. Furthermore, control and reduction of malaria may be possible even when mosquitoes develop resistance to insecticides. (shrink)

In 1960, American parasitologist Don Eyles was unexpectedly infected with a malariaparasite isolated from a macaque. He and his supervisor, G. Robert Coatney of the National Institutes of Health, had started this series of experiments with the assumption that humans were not susceptible to “monkey malaria.” The revelation that a mosquito carrying a macaque parasite could infect a human raised a whole range of public health and biological questions. This paper follows Coatney’s team of parasitologists and their subjects: from (...) the human to the nonhuman; from the American laboratory to the forests of Malaysia; and between the domains of medical research and natural history. In the course of this research, Coatney and his colleagues inverted Koch’s postulate, by which animal subjects are used to identify and understand human parasites. In contrast, Coatney’s experimental protocol used human subjects to identify and understand monkey parasites. In so doing, the team repeatedly followed malaria parasites across the purported boundary separating monkeys and humans, a practical experience that created a sense of biological symmetry between these separate species. Ultimately, this led Coatney and his colleagues make evolutionary inferences, concluding “that monkeys and man are more closely related than some of us wish to admit.” In following monkeys, men, and malaria across biological, geographical, and disciplinary boundaries, this paper offers a new historical narrative, demonstrating that the pursuit of public health agendas can fuel the expansion of evolutionary knowledge. (shrink)

Human Infection Studies have emerged as an important research approach with the potential to fast track the global development of vaccines and treatments for infectious diseases, including in low resource settings. Given the high level of burdens involved in many HIS, particularly prolonged residency and biological sampling requirements, it can be challenging to identify levels of study payments that provide adequate compensation but avoid ‘undue’ levels of inducement to participate. Through this embedded ethics study, involving 97 healthy volunteers and other (...) research stakeholders in a malaria HIS programme in Kenya, and using in-depth interviews, focus group discussions and observations during and after a malaria HIS, we give a grounded account of ethical issues emerging in relation to study payments in this setting. While careful community, national, international scientific and ethics review processes meant that risks of serious harm were highly unlikely, the levels of motivation to join HIS seen could raise concerns about study payments being too high. Particular value was placed on the reliability, rather than level, of study payment in this setting, where subsistence livelihoods are common. Study volunteers were generally clear about the study aims at the point of recruitment, and this knowledge was retained over a year later, although most reported experiencing more burdens than anticipated at enrolment. Strict study screening procedures, regular clinical and laboratory monitoring of volunteers, with prompt treatment with antimalarial at predetermined endpoints suggested that the risks of serious harm were highly unlikely. Ethical concerns emerged in relation to volunteers’ attempts to conceal symptoms, hoping to prolong residency periods and increase study payments; and volunteers making decisions that compromised important family relationships and personal values. Our findings support an interpretation that, although study volunteers were keen to join the study to access cash payments, they also paid attention to other features of the study and the general clinical research landscape, including levels of risk associated with study participation. Overall, our analysis shows that the ethical concerns emerging from the study payments can be addressed through practical measures, hinged on reducing burdens and strengthening communication, raising important issues for research policy and planning. (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)

BackgroundAfrica continues to bear a disproportionate share of the global HIV/AIDS, tuberculosis (TB) and malaria burden. The development and distribution of safe, effective and affordable vaccines is critical to reduce these epidemics. However, conducting HIV/AIDS, TB, and/or malaria vaccine trials simultaneously in developing countries, or in populations affected by all three diseases, is likely to result in numerous ethical challenges.MethodsIn order to explore convergent ethical issues in HIV/AIDS, TB and malaria vaccine trials in Africa, the Ethics, Law (...) and Human Rights Collaborating Centre of the WHO/UNAIDS African AIDS Vaccine Programme hosted a consultation on the Convergent Ethical Issues in HIV/AIDS, TB and Malaria Vaccine Trials in Africa in Durban, South Africa on the 10-11 February 2009.ResultsKey cross cutting ethical issues were prioritized during the consultation as community engagement; ancillary care obligations; care and treatment; informed consent; and resource sharing.ConclusionThe consultation revealed that while there have been few attempts to find convergence on ethical issues between HIV/AIDS, TB and malaria vaccine trial fields to date, there is much common ground and scope for convergence work between stakeholders in the three fields. (shrink)

The classical models of epidemics dynamics by Ross and McKendrick have to be revisited in order to incorporate elements coming from the demography (fecundity, mortality and migration) both of host and vector populations and from the diffusion and mutation of infectious agents. The classical approach is indeed dealing with populations supposed to be constant during the epidemic wave, but the presently observed pandemics show duration of their spread during years imposing to take into account the host and vector population changes (...) as well as the transient or permanent migration and diffusion of hosts (susceptible or infected), as well as vectors and infectious agents. Two examples are presented, one concerning the malaria in Mali and the other the plague at the middle-age. (shrink)

This article explores the question of how malaria “ends” in Myanmar, since malaria has been categorized both as an epidemic and as being endemic on seemingly countless occasions. The example of malaria reveals some of the limitations of understanding a disease within a single category of experience, such as an “epidemic.” In the case of malaria, epidemic is a shifting term that is best understood as being the point at which health authorities decide to intervene in (...) the disease, rather than as a clear and absolute measure of the scale or intensity of the threat. The identification of malaria as epidemic may thus be better understood as a political choice rather than as a precisely defined medical category. This article thus discusses what it means to end malaria in Myanmar, what kind of ending has been envisaged, and by whom. As this article demonstrates, policy makers have at various points aimed for the “elimination,” “eradication,” and “control” of malaria. Unlike the local population, who seem to have a rather nonchalant attitude toward malaria since malaria has long been familiar to them, international partners and the government have been shaping the narrative toward elimination with the aim of obtaining the World Health Organization's malaria-free certificate. Despite a number of political, social, and environmental obstacles, they believe that elimination can be achieved by 2030. However, unexpected political events such as the military coup in 2021, as well as the emergence of another pandemic, demonstrates that the “end” of malaria is a fragile concept. (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)

Placebo-controlled trials are controversial when individuals might be denied existing beneficial medical interventions. In the case of malaria, most patients die in rural villages without healthcare facilities. An artesunate suppository that can be given by minimally skilled persons might be of value when patients suddenly become too ill for oral treatment but are several hours from a facility that can give injectable treatment for severe disease. In such situations, by default, no treatment is (or can be) given until the (...) patient reaches a facility, making the placebo control design clinically relevant; alternative bioequivalence designs at the facility would misrepresent reality and risk incorrect conclusions. We describe the ethical issues underpinning a placebo-controlled trial in severe malaria. To protect patients and minimise risk, all patients were referred immediately to hospital so that each had a higher chance of prompt treatment through participation. There was no difference between artesunate and placebo in patients who reached clinic rapidly; among those who could not, a single artesunate suppository significantly reduced death or permanent disability, a finding of direct and indirect benefit to patients in participating villages and elsewhere. (shrink)

Internationally, calls for feedback of findings to be made an ‘ethical imperative’ or mandatory have been met with both strong support and opposition. Challenges include differences in issues by type of study and context, disentangling between aggregate and individual study results, and inadequate empirical evidence on which to draw. In this paper we present data from observations and interviews with key stakeholders involved in feeding back aggregate study findings for two Phase II malaria vaccine trials among children under the (...) age of 5 years old on the Kenyan Coast. In our setting, feeding back of aggregate findings was an appreciated set of activities. The inclusion of individual results was important from the point of view of both participants and researchers, to reassure participants of trial safety, and to ensure that positive results were not over-interpreted and that individual level issues around blinding and control were clarified. Feedback sessions also offered an opportunity to re-evaluate and re-negotiate trial relationships and benefits, with potentially important implications for perceptions of and involvement in follow-up work for the trials and in future research. We found that feedback of findings is a complex but key step in a continuing set of social interactions between community members and research staff (particularly field staff who work at the interface with communities), and among community members themselves; a step which needs careful planning from the outset. We agree with others that individual and aggregate results need to be considered separately, and that for individual results, both the nature and value of the information, and the context, including social relationships, need to be taken into account. (shrink)