The Plasma Mobile, 'A gift from heaven': The impact of health technology transfer on trial perceptions and expectations during the Ebola-Tx Trial, Conakry.

During the West African Ebola Virus Disease (EVD) epidemic from 2014 to 2016, a variety of technologies travelled considering the context of the emergency: a highly contagious fast-killing disease outbreak with no known remedy and a rapidly increasing number of cases. The Ebola-Tx clinical trial tested the efficacy of Convalescent Plasma (CP) as a treatment for EVD in Guinea. This paper is based on ethnographic research in the Ebola-Tx trial and focuses on the introduction of a mobile plasma collection centre, referred to as the 'Plasma Mobile', equipped with plasmapheresis and pathogen inactivation technologies, as well as how the transfer itself of this technology entailed complex effects on CP donors as trial participants (i.e. providers of the therapeutic product), directly involved staff and more broadly on the trial implementation as a whole. The transfer led to the emergence of a dimension of hope as CP donors hoped that the plasma would cure and, as providers of the therapeutic, hoped it would decrease their stigmatization and the economic impact of the disease. We conclude that, in light of the intricate effects that the transfer of such health technology can entail-in the localization to the specific context, as well as in the consequences they can have on actors involved in the implementation of such technologies-global health technologies should be put at the services of next epidemic and pandemic (preparedness) on condition that they are accompanied by an understanding of the technologies' own cultural meanings and social understandings.

What motivates Ebola survivors to donate plasma during an emergency clinical trial? The case of Ebola-Tx in Guinea.

INTRODUCTION: During the 2014 Ebola Virus Disease (EVD) epidemic, the Ebola-Tx trial evaluated the use of convalescent plasma (CP) in Guinea. The effectiveness of plasmapheresis trials depends on the recruitment of plasma donors. This paper describes what motivated or deterred EVD survivors to donate CP, providing insights for future plasmapheresis trials and epidemic preparedness. METHODS: This qualitative study, part of Ebola-Tx, researched and addressed emergent trial difficulties through interviewing, participant observation and focus group discussions. Sampling was theoretical and retroductive analysis was done in NVivo 10. RESULTS: Willingness or hesitance to participate in plasma donation depended on factors at the interface of pre-existing social dynamics; the impact of the disease and the consequent emergency response including the trial set-up. For volunteers, motivation to donate was mainly related to the feeling of social responsibility inspired by having survived EVD and to positive perceptions of plasmapheresis technology despite still unknown trial outcomes. Conversely, confidentiality concerns when volunteering due to stigmatization of survivors and perceived decrease in vital strength and in antibodies when donating, leading to fears of loss in protection against EVD, were main deterrents. The dynamic (dis)trust in Ebola Response Actors and in other survivors further determined willingness to participate and lead to the emergence/decline of rumours related to blood stealing and treatment effectiveness. Historic inter-ethnic relations in the health care setting further defined volunteering along socio-economic and ethnic lines. Finally, lack of follow-up and of dedicated care further impacted on motivation to volunteer. CONCLUSIONS: Ebola-Tx was the first trial to solicit and evaluate blood-product donation as an experimental treatment on a large scale in Sub-Saharan Africa. An effective donation system requires directly engaging with emergent social barriers and providing an effective ethical response, including improved and transparent communication, effective follow-up after donation, assuring confidentiality and determining ethical incentives.

Profile and reintegration experience of Ebola survivors in Guinea: a cross-sectional study.

OBJECTIVE: To describe the experience of Guinean Ebola virus disease (EVD) survivors in Guinea, up to ten months after discharge from the Ebola treatment unit. METHODS: Cross-sectional study using a standardised semistructured questionnaire among survivors from Conakry and Coyah districts in 2015 in Guinea. We used proportions, mean (standard deviation) and median (interquartile range) to summarise the variables. The McNemar chi-square test was used to compare proportions. RESULTS: The 121 EVD survivors interviewed had a median reintegration time from discharge of 18 weeks (IQR: 14-32 weeks). Most survivors were aged 15-44 years (87.6%) with secondary to higher level of education (68.6%), and 25.6% were healthcare workers. The majority reported a lower socio-economic status (90%), a less favourable work situation (79%) and psychological status (60%). About 31% reported physical health problems. Most survivors reported lower levels of reintegration with friends and at work place (72%) and lower acceptance by others in general (71%) in the period after the EVD as compared to the period before the EVD. Only 55 survivors (45.5%) were involved in one or more activities of the EVD response: participation in clinical studies on the EVD (44 survivors, 36.4%), community sensitisation (28 survivors, 23.1%) or work in Ebola treatment and/or transit centres (23 survivors, 21.7%). CONCLUSION: There is a need for a long-term follow-up of EVD survivors in Guinea and more efforts to support their social, professional and economic reintegration, especially in rural areas.

Electrolyte and Metabolic Disturbances in Ebola Patients during a Clinical Trial, Guinea, 2015.

By using data from a 2015 clinical trial on Ebola convalescent-phase plasma in Guinea, we assessed the prevalence of electrolyte and metabolic abnormalities at admission and their predictive value to stratify patients into risk groups. Patients underwent testing with a point-of-care device. We used logistic regression to construct a prognostic model and summarized the predictive value with the area under the receiver operating curve. Abnormalities were common among patients, particularly hypokalemia, hypocalcemia, hyponatremia, raised creatinine, high anion gap, and anemia. Besides age and PCR cycle threshold value, renal dysfunction, low calcium levels, and low hemoglobin levels were independently associated with increased risk for death. A prognostic model using all 5 factors was highly discriminatory (area under the receiver operating curve 0.95; 95% CI 0.90-0.99) and enabled the definition of risk criteria to guide targeted care. Most patients had a very low (<5%) or very high (>80%) risk for death.

Organizing the Donation of Convalescent Plasma for a Therapeutic Clinical Trial on Ebola Virus Disease: The Experience in Guinea.

Although convalescent plasma (CP) transfusion was prioritized among potential Ebola treatments by the World Health Organization, there were concerns on the feasibility of its implementation. We report on the successful organization of donor mobilization and plasma collection as part of the Ebola-Tx clinical trial from November 2014 to July 2015 in Conakry, Guinea. Project implementation registers, tools and reports, mission reports, and minutes of research team meetings were used to reconstruct the sequence of events on how donor mobilization was organized, plasmapheresis was set up, and how effective this approach was in collecting CP. An initial needs assessment of the Guinean National Blood Transfusion Center resulted in targeted training of staff on site, resulting in autonomy and independent production of CP within 3 months. The Conakry Ebola Survivors Association played a direct role in donor mobilization and organization of CP donations. A total of 98 Ebola survivors were screened for plasma donation, of which 84 were found eligible for plasmapheresis. Of these, 26 (30.9%) were excluded. The remaining 58 donors made a total of 90 donations, corresponding to 50.9 L of CP. This sufficed to treat the 99 eligible patients enrolled in the trial. Within a poor resource emergency context, transfusion capacity could be rapidly improved through the strengthening of local capacities and gradual transfer of skills coupled with active involvement of Ebola survivors. However, large-scale plasma collection or multisite studies may require further adaptations of both strategy and logistics. The Ebola-Tx trial was funded by the European Union and others.

Evaluation of Convalescent Plasma for Ebola Virus Disease in Guinea.

BACKGROUND: In the wake of the recent outbreak of Ebola virus disease (EVD) in several African countries, the World Health Organization prioritized the evaluation of treatment with convalescent plasma derived from patients who have recovered from the disease. We evaluated the safety and efficacy of convalescent plasma for the treatment of EVD in Guinea. METHODS: In this nonrandomized, comparative study, 99 patients of various ages (including pregnant women) with confirmed EVD received two consecutive transfusions of 200 to 250 ml of ABO-compatible convalescent plasma, with each unit of plasma obtained from a separate convalescent donor. The transfusions were initiated on the day of diagnosis or up to 2 days later. The level of neutralizing antibodies against Ebola virus in the plasma was unknown at the time of administration. The control group was 418 patients who had been treated at the same center during the previous 5 months. The primary outcome was the risk of death during the period from 3 to 16 days after diagnosis with adjustments for age and the baseline cycle-threshold value on polymerase-chain-reaction assay; patients who had died before day 3 were excluded. The clinically important difference was defined as an absolute reduction in mortality of 20 percentage points in the convalescent-plasma group as compared with the control group. RESULTS: A total of 84 patients who were treated with plasma were included in the primary analysis. At baseline, the convalescent-plasma group had slightly higher cycle-threshold values and a shorter duration of symptoms than did the control group, along with a higher frequency of eye redness and difficulty in swallowing. From day 3 to day 16 after diagnosis, the risk of death was 31% in the convalescent-plasma group and 38% in the control group (risk difference, -7 percentage points; 95% confidence interval [CI], -18 to 4). The difference was reduced after adjustment for age and cycle-threshold value (adjusted risk difference, -3 percentage points; 95% CI, -13 to 8). No serious adverse reactions associated with the use of convalescent plasma were observed. CONCLUSIONS: The transfusion of up to 500 ml of convalescent plasma with unknown levels of neutralizing antibodies in 84 patients with confirmed EVD was not associated with a significant improvement in survival. (Funded by the European Union's Horizon 2020 Research and Innovation Program and others; ClinicalTrials.gov number, NCT02342171.).

The Use of Ebola Convalescent Plasma to Treat Ebola Virus Disease in Resource-Constrained Settings: A Perspective From the Field.

The clinical evaluation of convalescent plasma (CP) for the treatment of Ebola virus disease (EVD) in the current outbreak, predominantly affecting Guinea, Sierra Leone, and Liberia, was prioritized by the World Health Organization in September 2014. In each of these countries, nonrandomized comparative clinical trials were initiated. The Ebola-Tx trial in Conakry, Guinea, enrolled 102 patients by 7 July 2015; no severe adverse reactions were noted. The Ebola-CP trial in Sierra Leone and the EVD001 trial in Liberia have included few patients. Although no efficacy data are available yet, current field experience supports the safety, acceptability, and feasibility of CP as EVD treatment. Longer-term follow-up as well as data from nontrial settings and evidence on the scalability of the intervention are required. CP sourced from within the outbreak is the most readily available source of anti-EVD antibodies. Until the advent of effective antivirals or monoclonal antibodies, CP merits further evaluation.

Deletions and recombinations in the core region of hepatitis B virus genotype E strains from asymptomatic blood donors in Guinea, west Africa.

The prevalence of hepatitis B virus (HBV) surface antigen (HBsAg) chronic carriage in west Africa is the highest in the world, but its molecular epidemiology remains relatively poorly investigated. Plasma samples from random asymptomatic carriers of HBsAg in Conakry, Guinea, were studied and the complete genome sequences of 81 strains were obtained. Three additional samples from Kumasi, Ghana, were also included in the analysis. Phylogenetic analyses confirmed the dominance of genotype E (95.1%), including 8.6% of strains (viral load, 5x10(3)-2.6x10(8) IU ml(-1)) comprising dominant variants with large deletions in the core region and minority wild-type variants. The presence of two different patterns of deletions in two and four donors suggested targeted genome fragility between nt 1979 and 2314. The remaining sequences included one subgenotype A3 (1%) and six A/E recombinant forms (4-7%). A/E strains with identical points of recombination in three donors suggested strongly that these recombinant HBV strains are circulating and transmitted in the population. Recombination points were concentrated in the core gene. The detection of similar A/E recombinant strains in Ghana suggested a geographical extension of recombinant HBV to the region. The quasispecies of one additional Ghanaian strain sequenced in the pre-surface/surface region resolved into dominant clones of either the A or E genotype, but also three different patterns of A/E recombinant variants. The observation that both deletions of genotype E strains and A/E recombination points are mostly located in the core gene at specific positions indicates a region of the genome where genetic rearrangements preferentially take place.