The holidays seem to have cast their pall over my productivity, so this post is emerging three weeks late. Hopefully January’s will be a little prompter. As ever, do let me know if I’ve missed/misinterpreted anything important.
Epidemic dynamics
First up, Jean-Paul Chretien and colleagues take on the monumental task of reviewing all 66 Ebola modelling studies from the past 18 months. Chapeau! They highlight variability in methods and approaches and call for best practice guidelines for future outbreaks.
At the national level, Jason T. Ladner and colleagues use genomic analysis of 140 Liberian genomes to show that almost all cases of Ebola in Liberia most-likely all came from a single introduction – probably from Sierra Leone. Given the importance of intense personal contact, models reflecting network structure are often informative. Anca Radulescu and Joanna Herron investigate the implications of community structures (internal and external, static and dynamic) for key quarantine choices (e.g. focus on breaking local or global ties), and in turn of these choices on epidemic spread. Also at the community level, Mosoka Fallah and colleagues use a stochastic model framework populated with individual-level data on cases in Montserrado county, Liberia – including contact tracing information on a subset – to suggest that the poorest communities were not only the most affected areas, but also most likely to spread infection elsewhere. Moving down to the household level, Ben Adams builds a household-structured model of a population, and shows the importance of larger household sizes in increasing initial growth rates, the basic reproduction number and the household reproduction number (how many within-household infections the average infectious person causes). If, as seems likely, poorer households are larger households, then the Adams and Fallah papers may be approaching the same issue from different angles.
Patient-level epidemiology
Several papers in December reported on the clinical profile of the epidemic, and how this affected patient outcomes. Oumar Faye and colleagues reviewed viremia data at hospital entry for 699 patients around Conakry up to February 2015, showing that a one-log higher baseline viremia was associated with a 14% reduction in survival probability. Samuel Crowe and colleagues showed that amongst patients in Bo District, Sierra Leone, time from symptoms to hospital admission was not associated with mortality risk, but viral load at first testing was. JY Wong and several colleagues reviewed line-list data on all confirmed, probable and suspected Ebola cases in Sierra Leone up to the end of January 2015. In addition to the typical inverted-u mortality curve associated with age, the authors found no increased mortality risk for women, or for healthcare workers. Finally, Stefano Petti and colleagues noted, based on a systematic review, that the West African Ebola outbreak showed very different haemorrhagic symptoms to earlier outbreaks – notably a two-thirds drop in bleeding from gums and a tenfold drop in bleeding from the eyes and nose. It is unclear if these changes reflect host, agent or environment (e.g. healthcare) differences.
On the paediatric front, and linked to an earlier suggestion by Benjamin Black and colleagues to focus on maternal health for pregnant women with Ebola ), JM Nelson and colleagues review all published data on live births to Ebola-infected mothers since 1976, showing that all 15 known neonates died with 19 days of birth (although I believe that there is now one longer infant survivor – the last Guinean survivor in the initial outbreak). On a similar topic, Séverine Caluwaerts and colleagues report two cases of pregnant women who recovered from Ebola, but delivered stillborn babies approximately one month post-recovery with EVD in the amniotic fluid. As well as having obstetric implications, these cases suggest yet another reservoir for Ebola post-recovery.
On an operational note, F Vogt and colleagues review MSF’s triage system for admitting suspected Ebola cases in Kailahun to suspect or highly suspect wards in advance of confirmatory tests, based on positive contact history and one other relevant sign/symptom. They find PPV, NPV, sensitivity and specificity for confirmed cases were all below 76%. Given the high risk of nosocomial infection, the authors recommend single compartments where possible, and the swift implementation of any point-of-care rapid test available. Similarly, Cristina Carias and colleagues evaluated the cost-effectiveness of providing malaria prophylaxis to Ebola case contacts, to avoid malaria and thus false-positive admissions of these contacts to ETUs. Their analysis showed cost savings based just in terms of the cost of admission/bed-stay at the ETUs, although there is also potential benefit of avoiding infection with Ebola, and of sending those with malaria (especially children) to ETUs unable to manage malaria treatment (as highlighted by an article by Gillian McKay on the ethical dilemmas of field triage for malaria/Ebola).
Vaccine and treatment trials
A common message as the West Africa epidemic wanes is that we do not know all that much more about what works in terms of products than we did two years ago. Jon Cohen and Martin Enserink provide two succinct summaries [online article, Magazine version] of the 13 clinical treatment and vaccine trials run to date, noting that only the Guinea Ebola, ca suffit! Ring vaccination trial has shown a clear benefit and had been published by the end of 2015. Anton Camacho and colleagues provide a model that shows one reason for this dearth of evidence, showing that trials begun in the context of a waning epidemic – in this case Forécariah prefecture in Guinea, beginning in mid-2015 and enrolling 100,000 – are often doomed to failure. One reason for the delay in rolling out trials was uncertainty about the correct way to balance various ethical criteria. Francis Kombe and colleagues discuss the ethical considerations and deliberations that arose in planning a convalescent plasma trial, highlighting the need to provide access even to those typically considered vulnerable and excluded from trials (children; pregnant women), and to provide supportive services to both donors and recipients.
Diagnostics
In contrast to treatments, there appears to have been some progress in developing rapid, point-of-care Ebola tests. Pierre Nouvellet and colleagues review rapid tests for Ebola already available and under development, and use mathematical models to suggest that the earlier isolation they might have allowed could have reduced case numbers by a substantial amount. Meanwhile, Petrus Jansen van Vuren and colleagues, and Benjamin Pinsky and colleagues provide lab evidence of Cepheid’s GeneXpert Ebola PCR test working within 90 minutes. At a conference in late October 2015, Amanda Semper and colleagues showed 100% sensitivity/specificity for the same test in field laboratory setting in West Africa.
Prevention
Less this month on behavioural interventions. Umberto Pellecchia and colleagues used qualitative interviews and discussions to flag the importance of local engagement in epidemic management. Their work highlighted tensions within communities in Liberia as they negotiated the Ebola outbreak, notably the economic strains of forced quarantines and (bribable) cremation teams, and the effectiveness of local ownership over behavioural interventions and enforcement. On a different tack, Jillian Sacks and colleagues described the process of developing, rolling out and troubleshooting an mHealth solution for electronic data collection by contact tracers in Guinea.
Survivors
As the epidemic splutters out, increasing focus is turning to the health sequelae of infection. In an important piece for planning for possible future outbreaks, Rosalind Eggo and colleagues combined temporal EVD survivor data with evidence that virus can remain in semen for up to nine months for some men, to estimate how the number of potentially-infectious men might evolve over the next few months. The authors show that the numbers are low and likely to have fallen to a handful by the end of 2015. Malcolm Hugo and colleagues highlighted the need for ongoing psychological assessment and support for Ebola survivors. Amongst 74 discharged individuals, experiences of death, family member loss and arousal reactions were common; one-third faced stigma in their communities and one-fifth pre-PTSD-type reactions one month post-discharge. John Mattia and colleagues reviewed early data (March/April 2015) from the Port Loko Ebola survivors clinic, finding joint pain (76%) and novel eye symptoms (60%) to be very common; the latter were highly associated with acute Ebola viral load.
Constrained Optimization 