Alexandre Delamou

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 Unions 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

Clinical evaluation of convalescent plasma (CP) as Ebola treatment in the current outbreak was prioritized by the World Health Organization. Although no efficacy data are available, current field experience supports the safety, acceptability, and feasibility of CP as Ebola treatment.

Ebola in Africa: beyond epidemics, reproductive health in crisis

According to WHO, more than 5000 people have died from Ebola, including 240 health workers. We are deeply concerned about the devastating effect of Ebola on reproductive health in Guinea, Liberia, and Sierra Leone in the context of continuous deterioration of socioeconomic conditions and general health in aff ected countries. The indirect negative effect of Ebola on reproductive health stems mainly from the desertion of already understaffed health facilities by health-care workers who are fearful of contracting Ebola. This fear is further increased because most reproductive health life-saving interventions include handling blood or bodily fluids from patients whose Ebola status is often unknown and health staff often do not have access to appropriate protection. Most referral maternity wards in the three most affected countries (Guinea, Liberia, and Sierra Leone) do not have equipment to do real-time screening for Ebola (eg, PCR), which could lead to the denial of care for women suspected to be pregnant. Additionally, the absence of providers offering relevant services, the inability to differentiate between Ebola and other febrile diseases, and the fear of contracting Ebola at a health facility can prevent users seeking reproductive health services. Statistics from Matam maternity hospital in Conakry, Guinea, show a substantial drop in attendance between March, 2014, and September, 2014, compared with 2013 (fi gure). A decrease in paediatric or maternal admissions because of fear of contracting Ebola has also been reported by Medecins Sans Frontieres in Sierra Leone. We are concerned that women in need of reproductive health care because of pregnancy, childbirth, and post-partum related complications, including haemorrhage, eclampsia, obstructed labour, and abortion, will not have necessary and even life-saving care and attention. United Nations Population Fund estimates that 15% of the 800 000 women who will give birth in the next 12 months in Guinea, Liberia, and Sierra Leone could die of complications because of inade quate emergency obstetric care, and thousands of others could develop devastating pathological conditions, such as obstetric fistula. Increased support to fight Ebola is needed in Guinea, Liberia, and Sierra Leone coupled, with specific attention to reproductive health services. Adequate measures, including health system strengthening and community mobilisation coupled with an enabling environment for provision of emergency obstetric care, need to be put in place urgently to avoid devastating short-term and long-term effects for thousands of women.

Blood as medicine: social meanings of blood and the success of Ebola trials

The urgent need to contain the Ebola epidemic has led to clinical treatment trials being fast-tracked, including a trial of blood or plasma from Ebola survivors. However, the taking of blood samples is associated with fear and reticence throughout sub-Saharan Africa, including rumours of blood stealing. In the context of the convalescent blood trial (Ebola_Tx trial, to begin Jan 15–21, 2015), blood has an ambiguous meaning; although the blood of people who are ill should be avoided, the transfer of blood from Ebola survivors is a potential treatment. Anecdotal reports from the field that the blood from Ebola survivors is being traded informally, suggest it is already a valuable commodity. Meanwhile, rumours are circulating in some Guinean communities that patients with Ebola in treatment centres are being given infected blood to hasten death. Such perceptions should not be dismissed as superstitions or ignorance because they function as a means to understand the cause of misfortune and manifest as magico-religious beliefs, such as sorcery, the infl uence of ancestors, or the will of God. Furthermore, these perceptions refl ect a historically forged mistrust towards specifi c institutions, reinforced by social inequality, confl ict, and a conviction that some people are rich and infl uential at the cost of the poor. For example, the epicentre of the Ebola epidemic was also the location of epidemics of sleeping sickness that were fought in colonial times with measures including forced internment in treatment camps. The legacy of these campaigns should be recognised when regarding present suspicions about the Ebola response. Additionally, ongoing stigmatisation of Ebola survivors, who are expected to donate blood for the treatment of people with this disease, might be affected by the outcome of a trial. Positive results might foster the re-integration of survivors into their communities or, conversely, if convalescent blood treatment is shown to be ineffective, donors might be suspected of transmitting the disease. The post-trial follow-up of participants is therefore an ethical responsibility. Ebola trials must take into acocunt local perceptions of blood and other contextual factors. Unfortunately, despite anthropological insights, there has been insufficient opportunity for interdisciplinary research to investigate the eff ect of beliefs about blood on clinical trials. As a result, little evidence exists on which to base recommendations for Ebola trials. This approach is essential in the fi ght against Ebola and has broad applicability for other diseases.

Clinical research during the Ebola virus disease outbreak in Guinea: Lessons learned and ways forward

The West African Ebola virus disease epidemic was officially declared on 8 March 2014 in Guinea and has become the worst ever witnessed. The epidemic has primarily affected Guinea, Sierra Leone, and Liberia where health systems were already weak. As of 10 September 2015, 3791 laboratory confirmed cases of Ebola were recorded in 31 health districts (out of 38) in Guinea. Of these confirmed cases, 62% died. Health care workers have been particularly affected. Given the lack of existing effective Ebola-specific treatment and the high mortality rates associated with the disease, the World Health Organization (WHO) convened a meeting on candidate vaccines and therapies in September 2014 and provided a list of potential interventions that had demonstrated promising results in animal models for Ebola prevention and treatment. At the time, there was a debate in the scientific and humanitarian communities as to whether the study designs should include randomization. The Government of Guinea committed itself to providing support and participating in the international efforts to control Ebola and to test vaccines and therapy candidates. In this article, we report on a portfolio of clinical research conducted in Guinea and draw the lessons learned for the future from our perspective as Guinean medical researchers.

Determinants of Maternal Near-Miss in Morocco: Too Late, Too Far, Too Sloppy?

Background In Morocco, there is little information on the circumstances surrounding maternal near misses. This study aimed to determine the incidence, characteristics, and determinants of maternal near misses in Morocco. Method A prospective case-control study was conducted at 3 referral maternity hospitals in the Marrakech region of Morocco between February and July 2012. Near-miss cases included severe hemorrhage, hypertensive disorders, and prolonged obstructed labor. Three unmatched controls were selected for each near-miss case. Three categories of risk factors (sociodemographics, reproductive history, and delays), as well as perinatal outcomes, were assessed, and bivariate and multivariate analyses of the determinants were performed. A sample of 30 near misses and 30 non-near misses was interviewed. Results The incidence of near misses was 12‰ of births. Hypertensive disorders during pregnancy (45%) and severe hemorrhage (39%) were the most frequent direct causes of near miss. The main risk factors were illiteracy [OR = 2.35; 95% CI: (1.07–5.15)], lack of antenatal care [OR = 3.97; 95% CI: (1.42–11.09)], complications during pregnancy [OR = 2.81; 95% CI:(1.26–6.29)], and having experienced a first phase delay [OR = 8.71; 95% CI: (3.97–19.12)] and a first phase of third delay [OR = 4.03; 95% CI: (1.75–9.25)]. The main reasons for the first delay were lack of a family authority figure who could make a decision, lack of sufficient financial resources, lack of a vehicle, and fear of health facilities. The majority of near misses demonstrated a third delay with many referrals. The women’s perceptions of the quality of their care highlighted the importance of information, good communication, and attitude. Conclusion Women and newborns with serious obstetric complications have a greater chance of successful outcomes if they are immediately directed to a functioning referral hospital and if the providers are responsive.

Effect of Ebola virus disease on maternal and child health services in Guinea: a retrospective observational cohort study

Summary Background The 2014 west African epidemic of Ebola virus disease posed a major threat to the health systems of the countries affected. We sought to quantify the consequences of Ebola virus disease on maternal and child health services in the highly-affected Forest region of Guinea. Methods We did a retrospective, observational cohort study of women and children attending public health facilities for antenatal care, institutional delivery, and immunisation services in six of seven health districts in the Forest region (Beyla, Guéckédou, Kissidougou, Lola, Macenta, and N’Zérékoré). We examined monthly service use data for eight maternal and child health services indicators: antenatal care (≥1 antenatal care visit and ≥3 antenatal care visits), institutional delivery, and receipt of five infant vaccines: polio, pentavalent (diphtheria, tetanus, pertussis, hepatitis B virus, and Haemophilus influenzae type b), yellow fever, measles, and tuberculosis. We used interrupted time series models to estimate trends in each indicator across three time periods: pre-Ebola virus disease epidemic (January, 2013, to February, 2014), during-epidemic (March, 2014, to February, 2015) and post-epidemic (March, 2015, to Feb, 2016). We used segmented ordinary least-squares (OLS) regression using Newey-West standard errors to accommodate for serial autocorrelation, and adjusted for any potential effect of birth seasonality on our outcomes. Findings In the months before the Ebola virus disease outbreak, all three maternal indicators showed a significantly positive change in trend, ranging from a monthly average increase of 61 (95% CI 38–84) institutional deliveries to 119 (95% CI 79–158) women achieving at least three antenatal care visits. These increasing trends were reversed during the epidemic: fewer institutional deliveries occurred (–240, 95% CI −293 to −187), and fewer women achieved at least one antenatal care visit (–418, 95% CI −535 to −300) or at least three antenatal care visits (–363, 95% CI −485 to −242) per month (p<0·0001 for all). Compared with the negative trend during the outbreak, the change in trend during the post-outbreak period showed that 173 more women per month (95% CI 51–294; p=0·0074) had at least one antenatal care visit, 257 more (95% CI 117–398; p=0·0010) had at least three antenatal care visits and 149 more (95% CI 91–206; p<0·0001) had institutional deliveries. However, although the numbers for these indicators increased in the post-epidemic period, the trends for all stagnated. Similarly, the increasing trend in child vaccination completion during the pre-epidemic period was followed by significant immediate and trend reductions across most vaccine types. Before the outbreak, the number of children younger than 12 months who had completed each vaccination ranged from 5752 (95% CI 2821–8682) for tuberculosis to 8043 (95% CI 7621–8464) for yellow fever. Immediately after the outbreak, significant reductions occurred in the level of all vaccinations except for yellow fever for which the reduction was marginal. The greatest reductions were noted for polio and tuberculosis at −3594 (95% CI −4811 to −2377; p<0·0001) and −3048 (95% CI −5879 to −216; p=0·0362) fewer vaccines administered, respectively. Compared with pre-Ebola virus disease outbreak trends, significant decreases occurred for all vaccines except polio, with the trend of monthly decreases in the number of children vaccinated ranging from −419 (95% CI −683 to −155; p=0·0034) fewer for BCG to −313 (95% CI–446 to −179; p<0·0001) fewer for pentavalent during the outbreak. In the post-Ebola virus disease outbreak period, vaccination coverage for polio, measles, and yellow fever continued to decrease, whereas the trend in coverage for tuberculosis and pentavalent did not significantly differ from zero. Interpretation Most maternal and child health indicators significantly declined during the Ebola virus disease outbreak in 2014. Despite a reduction in this negative trend in the post-outbreak period, the use of essential maternal and child health services have not recovered to their pre-outbreak levels, nor are they all on a course that suggests that they will recover without targeted interventions.

Family planning in Guinea: a need for better public commitment

To describe the evolution of family planning (FP) in Guinea and to identify strengths, weaknesses, opportunities and threats of the current FP programme.

Good clinical outcomes from a 7‐year holistic programme of fistula repair in Guinea

Female genital fistula remains a public health concern in developing countries. From January 2007 to September 2013, the Fistula Care project, managed by EngenderHealth in partnership with the Ministry of Health and supported by USAID, integrated fistula repair services in the maternity wards of general hospitals in Guinea. The objective of this article was to present and discuss the clinical outcomes of 7 years of work involving 2116 women repaired in three hospitals across the country.

Exploring Maternal Health Care-Seeking Behavior of Married Adolescent Girls in Bangladesh: A Social-Ecological Approach.

Background The huge proportion of child marriage contributes to high rates of pregnancies among adolescent girls in Bangladesh. Despite substantial progress in reducing maternal mortality in the last two decades, the rate of adolescent pregnancy remains high. The use of skilled maternal health services is still low in Bangladesh. Several quantitative studies described the use of skilled maternal health services among adolescent girls. So far, very little qualitative evidence exists about attitudes and practices related to maternal health. To fill this gap, we aimed at exploring maternal health care-seeking behavior of adolescent girls and their experiences related to pregnancy and delivery in Bangladesh. Methods and Findings A prospective qualitative study was conducted among thirty married adolescent girls from three Upazilas (sub-districts) of Rangpur district. They were interviewed in two subsequent phases (2014 and 2015). To triangulate and validate the data collected from these married adolescent girls, key informant interviews (KIIs) and focus group discussions (FGDs) were conducted with different stakeholders. Data analysis was guided by the Social-Ecological Model (SEM) including four levels of factors (individual, interpersonal and family, community and social, and organizational and health systems level) which influenced the maternal health care-seeking behavior of adolescent girls. While adolescent girls showed little decision making-autonomy, interpersonal and family level factors played an important role in their use of skilled maternal health services. In addition, community and social factors and as well as organizational and health systems factors shaped adolescent girls’ maternal health care-seeking behavior. Conclusions In order to improve the maternal health of adolescent girls, all four levels of factors of SEM should be taken into account while developing health interventions targeting adolescent girls.