Doctors and Vampires in Sub-Saharan Africa: Ethical Challenges in Clinical Trial Research

Collecting blood samples from individuals recruited into clinical research projects in sub-Saharan Africa can be challenging. Strikingly, one of the reasons for participant reticence is the occurrence of local rumors surrounding “blood stealing” or “blood selling.” Such fears can potentially have dire effects on the success of research projects—for example, high dropout rates that would invalidate the trial''s results—and have ethical implications related to cultural sensitivity and informed consent. Though commonly considered as a manifestation of the local population''s ignorance, these rumors represent a social diagnosis and a logical attempt to make sense of sickness and health. Born from historical antecedents, they reflect implicit contemporary structural inequalities and the social distance between communities and public health institutions. We aim at illustrating the underlying logic governing patients'' fear and argue that the management of these beliefs should become an intrinsic component of clinical research.Collecting blood samples from individuals recruited into clinical research projects in sub-Saharan Africa can be challenging. Strikingly, one of the reasons for participant reticence is the occurrence of local rumors surrounding “blood stealing” or “blood selling”^1–5; such fears can potentially have dire effects on the success of research projects—for example, high dropout rates that would invalidate the trial''s results—and ethical implications related to cultural sensitivity and informed consent. Though commonly considered as a manifestation of the local population''s ignorance and/or disconnection from modern society, these rumors often represent an attempt to make sense of sickness and health. As such, the currently adopted solution to address such concerns—namely, including additional information on the medical procedures in the informed consent process—is inadequate to prevent or dispel existing doubts or distrust toward clinical research and fails to circumvent the associated pitfalls for trial implementation and the related ethical hazards. We aim at illustrating the underlying logic governing patients'' fear of providing blood samples in Gabon, while showing its applicability in other settings in sub-Saharan Africa by drawing from ethnographic data collected in Gabon between 2007 and 2009 and a general literature review.The fear of giving blood has been reported across sub-Saharan Africa and has been associated with conceptions of blood as a lifeforce,^4–6 with beliefs that a lack of blood is a sign of diminished strength and inherent disease^7–10 and with notions of blood being a tradable good, requiring remuneration.⁴ In still other settings, such as in Gabon and certain other African countries, these fears are often linked to mystical realms of reality. To understand the logic guiding accusations of blood stealing and selling here we must first understand how and why sudden and unexpected illness/death is frequently attributed to sorcery. In Gabon, disruptions of social order and/or health, such as inexplicable good or bad fortune or sudden illness and death are ascribed to evou, a mystical agent of the invisible world, translated in French as le vampire, though unrelated to the Western concept of the “living-dead.” The vampire is passively available in most people, but is an active force in sorcerers (who use it to inflict illness) and in healers (who with it offer recovery of health).When sorcery is identified as the cause of an inexplicable event, the question of who is responsible soon follows. In various contexts throughout Africa, Gabon included,^11–18 these accusations are frequently directed at those who are “unnaturally” successful. Such people of influence are suspected of having acquired their power through the consumption of the souls of mystically killed innocents (i.e., “eating people,” “drinking their blood”)^19–22; notably, the agent needed to acquire such unnatural wealth is precisely what clinical trials require from their participants: blood. Alleged evou users are believed to acquire power through blood sacrifices, consisting of the mystical forfeit of family members, children, and unknown innocents who, as a result, will become ill and die.^19–21,23 Consequently, institutions where blood is regularly collected—namely hospitals and research centers—are considered highly suspect.In the Gabonese context, it is believed that blood drawn from hospital patients or research participants is sold by medical staff to the Rosicrucian Order,^19–21 a semi-secret society affiliated with the Free Masons of Western Europe and the United States. The Rosicrucian order has been strongly linked to colonial²⁴ and postcolonial governments,²⁵ and boasts numerous highly visible and influential members, reportedly even in government circles. Most importantly, its affiliates are believed to secure their stations through sorcery, whereby members use the acquired blood in sacrificial rites to secure or enhance their positions of influence.²⁶Notably, such perceptions are not a new phenomenon. Rumors of blood theft, including specific references to the medical field, date back to colonial Africa where blood thieves were often described as white people, or their black collaborators, operating at night using European technology, such as medicines and syringes, to extract local people''s blood, which they then either sold or transformed into other commodities, such as medicine.^27–30 Among many examples recorded by historians across sub-Saharan Africa, the following are quite illustrative of populations'' interpretations of the medical field: in the mid-1940s it was said that Medical Department trucks patrolled the streets in Lamu, Kenya, and, were they to come upon a straggler, would draw out all of his blood with a rubber pump, leaving the body in the gutter.²⁹ Over a decade later, “motor vehicles painted red” were said to drain the blood from lone pedestrians captured along the Kisumu highway to Busia; the blood was then reportedly taken to blood banks in hospitals.²⁹Apart from these historical antecedents, various factors continue to foster an association between rumors of blood stealing/selling and medical research in sub-Saharan Africa. Unavoidably, clinical research involves blood sampling from patients. Study participants'' poor understanding of the reasons for blood collection and of general trial goals in general increases the ambiguity required for blood taking to be linked to blood theft and inexplicable illness. Furthermore, limited community participation, the social distance between communities and medical institutions, the association of hospitals—and research centers in particular—with authoritarian and elitist state and foreign institutions, and palpable social class divisions further nurture these suspicions. Pre-existing patients'' fears within any of these domains may be aggravated by poor comprehension during the informed consent process,³⁰ potentially caused, among other factors, by poor communication between the patient and the researcher, power unbalance, lack of time, or by insufficient consideration for the local cultural features in the informed consent process.Blood stealing/selling, however, is not the only rumor associated with clinical research. Rumors of purposive sterilization of women associated with clinical trials have been reported since 1920 throughout Africa. Furthermore, anti-malarials, vaccinations, condoms, micronutrients, vitamins, and other public health interventions continue to be suspected of causing sterility or of containing hidden contraceptives.^30–39 These rumors continue to be reinterpreted or generated in contemporary African societies and are frequently linked to magical realms of power.^13–18 These beliefs paint a grim historical picture on how local populations perceive medical expertise and therapeutic power, with the underlying concerns likely preceding the advent of clinical research. In this context, health education campaigns or consent forms, meant to inform local communities on the use of collected blood may have little impact as perceptions of blood extraction date back to colonialism, to the introduction of western medicine and persist in modern forms of sorcery accusations. Rumors, such as these, are a reflection of social injustice and asymmetric power relations,³² historical threats to the collective survival of particular groups, and a way to interpret society.³¹ As such, though the Gabonese concept of “evou” is local, it is founded upon a universal rational search for causality in the face of inexplicable events such as illness and death. Not very different from attributing the inexplicable to the will of God (in monotheist religions), to transgressions or good deeds in a previous life (reincarnation), to the intervention of ancestors (ancestor worship), to spirits (animism), to good luck, faith, or sorcery,^22,40 such universal beliefs represent a social diagnosis or a rational attempt to make sense of a chaotic, unjust and an often incomprehensible world.Concerns such as these, further present an important bottleneck for the ethical conduct of research and for routine surveillance. The ethical principle of respect for persons, widely recognized as a pillar of medical research,⁴¹ implies the specific duty of being sensitive to other cultural perspectives.⁴² Researchers should, therefore, develop culturally appropriate ways to communicate with research participants^42–44 and address concerns such as those mentioned previously. Being part of the sociocultural context, similar beliefs are also shared to a large extent by local medical staff within international research teams, making the need for cultural sensitivity all the more pressing. Unfortunately, there is a gap between principles and practices as the adequate expertise and resources needed to address culturally based concerns are still largely absent and remain a non-priority in biomedical and clinical research.There have been noteworthy—but anecdotal—efforts of researchers trying to counter blood-selling rumors by increasing the information provided to communities or through some form of community participation (e.g., inviting patients to visit the laboratories) and sensitization or even by avoiding the color red in symbols and products related to the intervention. Additional measures such as community consent and participation aiming at reducing the distance between trial teams and communities could have a positive impact. However, no in-depth research on how to avoid or tackle these rumors has been carried out thus far; therefore, making recommendations at this point remains an exercise in futility.In conclusion, accusations or rumors on blood stealing and blood selling cannot simply be labeled as participants'' ignorance. Born from historical antecedents, reflecting implicit contemporary social and structural inequalities, and the social distance between communities and public health institutions, these rumors or accusations represent a social diagnosis and a logical attempt to make sense of the clinical trial in today''s world. As such, these beliefs should be acknowledged and their management become an intrinsic component of clinical research.     

Hygiene practices and contamination risks of surface waters by schistosome eggs: the case of an infested village in Northern Senegal

The transmission of intestinal schistosomiasis presumes that faecal materials containing viable schistosome eggs reach natural water bodies infested with snail intermediate host. So far there is little knowledge about the contamination dynamics of streams with schistosome eggs. We conducted a pilot study on defecating behaviour and hygienic practices in an Schistosoma mansoni endemic focus in Northern Senegal. Questionnaires were used to obtain quantitative data on hygienic practices and the use of latrines in 59 children. Although the community was well endowed with pit latrines, most of the children declared that they usually defecated somewhere else, in particular near the streams where the vegetation offers hideouts. Observations based on mapping of defecation sites showed that a considerable number of stools were left just a few meters from the riverbank, thus bearing a high risk of being washed off into the water. All these practices can easily lead to contamination of water bodies with schistosomae eggs. In order to improve hygienic practices and reduce fecal pollution of the environment, a health education model respecting local beliefs and customs would be indispensable.     

日本血吸虫卵计量变异的模型建立与参数估计

目的建立虫卵计量变异的随机模型,并估计描述虫卵计量变异特征的参数。方法随机模型把人群中虫卵计量总变异分成两个来源：①虫卵计量在个体间的变异;②个体内虫卵计量的变异。用具有重复虫卵计数的实际资料对模型的参数进行估计。结果参数Ｍ、ｒ值在各年龄组中不同,ｋ值在各年龄组中近于相同;ｒ和Ｍ值的最佳年龄分割点分别为８和１２岁;模型Ｅ中假定ｋ值在各年龄组中相同,ｒ值在２～７岁和８岁以上年龄组间不同,Ｍ值在２～１１岁和１２岁以上年龄组间不同,ＡＩＣ值最小。结论年龄可能为影响Ｍ,ｒ值的重要因素,模型Ｅ为最佳模型     

Phylogenomic Characterization of Lopma Virus and Praja Virus,Two Novel Rodent-Borne Arteriviruses

Recent years have witnessed the discovery of several new viruses belonging to the family Arteriviridae, expanding the known diversity and host range of this group of complex RNA viruses. Although the pathological relevance of these new viruses is not always clear, several well-studied members of the family Arteriviridae are known to be important animal pathogens. Here, we report the complete genome sequences of four new arterivirus variants, belonging to two putative novel species. These new arteriviruses were discovered in African rodents and were given the names Lopma virus and Praja virus. Their genomes follow the characteristic genome organization of all known arteriviruses, even though they are only distantly related to currently known rodent-borne arteriviruses. Phylogenetic analysis shows that Lopma virus clusters in the subfamily Variarterivirinae, while Praja virus clusters near members of the subfamily Heroarterivirinae: the yet undescribed forest pouched giant rat arterivirus and hedgehog arterivirus 1. A co-divergence analysis of rodent-borne arteriviruses confirms that they share similar phylogenetic patterns with their hosts, with only very few cases of host shifting events throughout their evolutionary history. Overall, the genomes described here and their unique clustering with other arteriviruses further illustrate the existence of multiple rodent-borne arterivirus lineages, expanding our knowledge of the evolutionary origin of these viruses.     

A new cytotype of the African pygmy mouse <Emphasis Type="Italic">Mus minutoides</Emphasis> in Eastern Africa. Implications for the evolution of sex-autosome translocations

The African pygmy mice (genus Mus, subgenus Nannomys) are recognized for their highly conserved morphology but extensive chromosomal diversity, particularly involving sex-autosome translocations, one of the rarest chromosomal rearrangements among mammals. It has been shown that in the absence of unambiguous diagnostic morphological traits, sex-autosome translocations offer accurate taxonomic markers. For example, in Mus minutoides, irrespective of the diploid number (which ranges from 2n?=?18 to 34), all specimens possess the sex-autosome translocations (X.1) and (Y.1) that are unique to this species. In this study, we describe a new cytotype that challenges this view. Males are characterized by the translocation (Y.1) only, while females carry no sex-autosome translocation, the X chromosome being acrocentric. Hence, although sex-autosome translocations (X.1) and (Y.1) are still diagnostic when one or both are present, their absence does not rule out M. minutoides. This cytotype has a large distribution, with specimens found in Tanzania and in the eastern part of South Africa. The nonpervasive distribution of Rb(X.1) provides an opportunity to investigate different evolutionary scenarios of sex-autosome translocations using a phylogenetic framework and the distribution of telomeric repeats. The results tend to support a scenario involving a reversal event, i.e., fusion then fission of Rb(X.1), and highlighted the existence of a new X₁X₁X₂X₂/X₁X₂Y sex chromosome system, confirming the remarkable diversity of neo-sex chromosomes and sex determination systems in the African pygmy mice.     

Antibody response to Schistosoma mansoni adult worm cysteine proteinases in infected individuals

Antigens of the Schistosoma mansoni digestive tract are recognized early in the infective process. Two immunogenic components of the excretory/secretory products are proteolytic enzymes that degrade host hemoglobin in the lumen of the parasite gut. These enzymes, CP1 and CP2, belong to the class of cysteine proteinases. In this study, a preparation containing both proteinases has been used to detect proteinase antibodies in the sera of individuals living in Burundi. Of 133 individuals tested, 92% were excreting schistosome eggs. All patients with documented infections had positive anti-proteinase IgG titers (mean = 1:614), while 82% had positive IgM titers (mean = 1:267). Six weeks following praziquantel treatment, patients were assessed for egg excretion and antibody titer. Anti-proteinase IgG titers were significantly lower (mean = 1:259) than pre-treatment titers. Patients who were infected with S. japonicum or S. haematobium typically showed a cross-reactive IgG response. Patients from non-endemic regions yielded negative titers, and those with non-trematode parasites were negative (79%) or weakly positive. S. mansoni cysteine proteinases may be used for the detection of schistosome infections.     

Detection of circulating anodic antigen by ELISA for seroepidemiology of schistosomiasis mansoni

Sera of individuals from Burundi excreting eggs of Schistosoma mansoni (prevalence 35%; 178 subjects) and of similar individuals from Maniema, Zaire (prevalence 95%; 99 subjects), and of 159 Dutch and 81 Zairean non-infected controls, were screened by enzyme-linked immunosorbent assay for the presence of schistosome circulating anodic antigen (CAA). No false positive results were obtained. The sensitivity of the test was 75% in Burundi and 93% in Zaire, a significant difference (P less than 0.05). However, in matched egg output classes the test results did not differ significantly; 60% and 67%, respectively, of those excreting 1-100 eggs per gram of faeces (epg), 86% and 100% of those excreting 101-400 epg, and 100% of those excreting over 400 epg were detected. The efficiency of the assay was 91% in Burundi and 93% in Zaire. The Spearman rank coefficient of correlation between antigen titre and egg output (determined by 3 consecutive Kato egg counts) was 0.61 in Burundi and 0.82 in Zaire. The sensitivity of the test compared well with a single egg count. In addition, preliminary data showed that occasionally CAA was detectable in serum of individuals not excreting schistosome eggs. As CAA is found only in the presence of living worms, such cases reflect active infections.