Elizabeth Smout

Temporal Changes in Ebola Transmission in Sierra Leone and Implications for Control Requirements: a Real-time Modelling Study

Background: Between August and November 2014, the incidence of Ebola virus disease (EVD) rose dramatically in several districts of Sierra Leone. As a result, the number of cases exceeded the capacity of Ebola holding and treatment centres. During December, additional beds were introduced, and incidence declined in many areas. We aimed to measure patterns of transmission in different regions, and evaluate whether bed capacity is now sufficient to meet future demand. Methods: We used a mathematical model of EVD infection to estimate how the extent of transmission in the nine worst affected districts of Sierra Leone changed between 10th August 2014 and 18th January 2015. Using the model, we forecast the number of cases that could occur until the end of March 2015, and compared bed requirements with expected future capacity. Results: We found that the reproduction number, R, defined as the average number of secondary cases generated by a typical infectious individual, declined between August and December in all districts. We estimated that R was near the crucial control threshold value of 1 in December. We further estimated that bed capacity has lagged behind demand between August and December for most districts, but as a consequence of the decline in transmission, control measures caught up with the epidemic in early 2015. Conclusions: EVD incidence has exhibited substantial temporal and geographical variation in Sierra Leone, but our results suggest that the epidemic may have now peaked in Sierra Leone, and that current bed capacity appears to be sufficient to keep the epidemic under-control in most districts.

Development and validation of a tool incorporating cervical length and quantitative fetal fibronectin to predict spontaneous preterm birth in asymptomatic high‐risk women

To develop a predictive tool for spontaneous preterm birth (sPTB) in asymptomatic high‐risk women that includes quantification of fetal fibronectin (fFN) along with cervical length (CL) measurement and other clinical factors.

Development and validation of a predictive tool for spontaneous preterm birth incorporating cervical length and quantitative fetal fibronectin in asymptomatic high‐risk women

To develop a predictive tool for spontaneous preterm birth (sPTB) in asymptomatic high‐risk women that includes quantification of fetal fibronectin (fFN) along with cervical length (CL) measurement and other clinical factors.

Power, fairness and trust: understanding and engaging with vaccine trial participants and communities in the setting up the EBOVAC-Salone vaccine trial in Sierra Leone.

BackgroundThis paper discusses the establishment of a clinical trial of an Ebola vaccine candidate in Kambia District, Northern Sierra Leone during the epidemic, and analyses the role of social science research in ensuring that lessons from the socio-political context, the recent experience of the Ebola outbreak, and learning from previous clinical trials were incorporated in the development of community engagement strategies. The paper aims to provide a case study of an integrated social science and communications system in the start-up phase of the clinical trial.MethodsThe paper is based on qualitative research methods including ethnographic observation, interviews with trial participants and key stakeholder interviews.ResultsThrough the case study of EBOVAC Salone, the paper suggests ways in which research can be used to inform communication strategies before and during the setting up of the trial. It explores notions of power, fairness and trust emerging from analysis of the Sierra Leonean context and through ethnographic research, to reflect on three situations in which social scientists and community liaison officers worked together to ensure successful community engagement. Firstly, a section on “power” considers the pitfalls of considering communities as homogeneous and shows the importance of understanding intra-community power dynamics when engaging communities. Secondly, a section on “fairness” shows how local understandings of what is fair can help inform the design of volunteer recruitment strategies. Finally, a section on “trust” highlights how historically rooted rumours can be effectively addressed through active dialogue rather than through an approach focused on correcting misinformation.ConclusionThe paper firstly emphasises the value of social science in the setting up of clinical trials, in terms of providing an in depth understanding of context and social dynamics. Secondly, the paper suggests the importance of a close collaboration between research and community engagement to effectively confront political and social dynamics, especially in the context of an epidemic.

Deaths, late deaths, and role of infecting dose in Ebola virus disease in Sierra Leone: retrospective cohort study

Objectives To assess the frequency of fatal recrudescence from Ebola virus disease after discharge from treatment centres, and explore the influence of infecting dose on case fatality rates. Design Retrospective cohort study. Setting Western Area, Sierra Leone. Participants 151 survivors treated for Ebola virus disease at the Kerry Town treatment centre and discharged. Survivors were followed up for a vital status check at four to nine months after discharge, and again at six to 13 months after discharge. Verbal autopsies were conducted for four survivors who had died since discharge (that is, late deaths). Survivors still living in Western Area were interviewed together with their household members. Exposure level to Ebola virus disease was ascertained as a proxy of infecting dose, including for those who died. Main outcome measures Risks and causes of late death; case fatality rates; odds ratios of death from Ebola virus disease by age, sex, exposure level, date, occupation, and household risk factors. Results Follow-up information was obtained on all 151 survivors of Ebola virus disease, a mean of 10 months after discharge. Four deaths occurred after discharge, all within six weeks: two probably due to late complications, one to prior tuberculosis, and only one after apparent full recovery, giving a maximum estimate of recrudescence leading to death of 0.7%. In these households, 395 people were reported to have had Ebola virus disease, of whom 227 died. A further 53 people fulfilled the case definition for probable disease, of whom 11 died. Therefore, the case fatality rate was 57.5% (227/395) for reported Ebola virus disease, or 53.1% (238/448) including probable disease. Case fatality rates were higher in children aged under 2 years and adults older than 30 years, in larger households, and in infections occurring earlier in the epidemic in Sierra Leone. There was no consistent trend of case fatality rate with exposure level, although increasing exposure increased the risk of Ebola virus disease. Conclusions In this study of survivors in Western Area, Sierra Leone, late recrudescence of severe Ebola virus disease appears to be rare. There was no evidence for an effect of infecting dose (as measured by exposure level) on the severity of disease.

The use and accuracy of manual and electronic gestational age calculators

The accuracy of gestational age (GA) wheels has been shown to be poor, yet they remain commonly used. We surveyed their use within our institution and determined the inter‐observer and inter‐device variability of a range of devices. We have devised a procedure for validating device accuracy.

EBOVAC-Salone: Lessons learned from implementing an Ebola vaccine trial in an Ebola-affected country:

Background/aims During the 2014–2016 West African Ebola epidemic, clinical trials were fast-tracked in order to identify prophylactic vaccines and experimental treatments that might be useful in preventing or treating Ebola. These trials included the ongoing EBOVAC-Salone study, which was established and implemented in Sierra Leone to assess the safety and immunogenicity of the Ad26.ZEBOV/MVA-BN-Filo prime-boost Ebola vaccine regimen. Methods This article describes the experiences of the EBOVAC-Salone research team in setting up and implementing the trial, and provides recommendations for research teams aiming to conduct clinical trials in future outbreak situations. Results Establishing a clinical trial during an outbreak brought some unique challenges, including those related to trial design and the regulatory environment, operational issues, and community engagement. The situation was further complicated by the weak infrastructure and limited experience of clinical trials in Sierra Leone. However, operating in an outbreak context also brought some benefits to the research team, including strong stakeholder support. The EBOVAC-Salone study recruited participants both during and after the outbreak, leading to additional challenges to trial implementation during the post-outbreak transition. Conclusion Many lessons have been learned about setting up and implementing a clinical trial during a devastating Ebola epidemic, and some of the experiences of the EBOVAC-Salone team were mirrored by those of other researchers operating in the region. Common to several of these research groups is a recommendation that research should be more closely incorporated into outbreak response planning, which could expedite the establishment of timely and appropriate research projects. We recommend that the lessons learned by researchers during the West African Ebola epidemic are built into programmes and strategies to improve the responses to future epidemics, wherever they occur.

The use of fetal fibronectin in primiparous women with cervical surgery

Background Fetal fibronectin (fFN) is an excellent predictor of preterm birth (PTB). However its use in primiparous women is limited, including those with previous cervical surgery, who are at increased risk of PTB. Methods The authors evaluated the use of fFN in all women referred to a Preterm Clinic over 12 months, comparing primiparous women with cervical surgery, to those tested for previous preterm delivery. 30 primiparous women with either a LLETZ or Cone biopsy and 306 with a previous delivery between 16 and 37 weeks were compared. χ2 or Fishers exact test were used to compare proportions as appropriate. Results Table shows similar proportion of women with a +ve test, and similar outcome in both groups. (NS using χ2) False negative rates for delivery <34/40 were 9% (22/243) in the previous PTB group, compared to 0/22 for the primip group. Conclusions fFN can be used to screen for PTB risk in women with previous cervical surgery. Positive rates have similar prediction to screening high risk women based on previous early delivery. Negative prediction may be better in primiparous women than those with a previous adverse event. +ve fFN PPV for Del <34/40 PPV for Del <37/40 Primips Cone Bx/LLETZ (n=30) 27% 25% 50% Previous 16–37/40 delivery (n=306) 21%* 32%* 49%* * p=NS

The use of fetal fibronectin testing in the management of a triplet pregnancy with a short cervix

Following in vitro fertilisation treatment, a 40-year-old woman was expecting trichorionic, triamniotic triplets. Her cervix shortened from 34 mm at 16+5 weeks to 16 mm at 20+5 weeks, a risk reported with 100% delivery before 28 weeks gestation. She was admitted to hospital and at 24+1 weeks was given corticosteroids. From 21+5 weeks her cervical length remained below 16 mm. However, weekly fetal fibronectin (fFN) tests were negative from 22+5 weeks to delivery at 35+5 weeks. This, along with an absence of symptoms, gave her doctors confidence to manage her as an outpatient from 28 weeks. At 33+5 weeks she was diagnosed as having pre-eclampsia and three live births were delivered by prelabour caesarean section. Prior to delivery her cervical length was 10 mm and fFN test remained negative. There are no reports of outcome following a negative fFN with a short cervix in triplet pregnancies but fFN could be a useful tool, in conjunction with cervical length measurement, in the management of triplets.

Interobserver and interdevice variability of manual and electronic gestational age calculators

Background The accuracy of gestational age (GA) calculators has been demonstrated to be poor but they remain commonly used. The authors surveyed the use of GA calculators in our institution and determined interobserver and interdevice variability of different models, including new electronic methods. The authors devised a protocol for validating device accuracy. Methods All clinicians in obstetrics were asked their most recent method of calculating GA and whether they felt this was accurate to within 1 day. 10 clinicians then assessed 16 available devices: 14 manual and 2 electronic. Five dates arbitrarily spread across the year were used as the last menstrual period. Individuals had to calculate the estimated date of delivery (EDD) of the five dates for each device. Analysis of variance (ANOVA) was used to statistically analyse variability. Results 97 staff responded. 73% last used a manual device. 72% believed their method was accurate. There were significant differences (ANOVA, p<0.0001) between device-calculated and control EDD for all manual devices except one, with differences of up to 4 days; electronic devices were consistently accurate with perfect agreement at all gestations and observers. The degree of variability altered throughout the year and was consistent between observers. Interobserver variability was insignificant. Conclusion Clinicians should be aware of the inaccuracy of manual GA calculators. Electronic devices are perfect and recommended. Manual devices should be validated before use by comparing device-calculated EDD with a 280 day control at five points throughout the year, as errors are scale dependent and related to time of year.