Links to new research on Ebola: June 2016

The last hurrah. New material from June 2016. From here on, good luck and I look forward to skimming the literature from time-to-time without posting it up here.

Therapeutics and Vaccines

Epidemiology

Epidemic control strategies

There were also a couple of more conceptual modelling papers this month:

Survivors

Health care for Ebola

Ebola epidemic impact

Other items

That’s all folks, thanks.

Links to new research on Ebola: May 2016

Yes, this is late. Sorry. But here’s all the new stuff I saw in May of this year:

Therapeutics and Vaccines

Epidemiology

Epidemic control strategies (mostly models)

Ebola healthcare

Survivors

Impact of Ebola on other things

Other items (mostly trying to understand what went wrong)

One more month of material to come…

Links to new research on Ebola: March 2016

And part II of my attempts to get up-to-date, research that came out in March.

Therapeutics and Vaccines

Epidemiology

Epidemic control strategies

Health care for Ebola

Ebola epidemic impact

Survivors

Other items

Links to new research on Ebola: February 2016

Many apologies for the long radio silence.  I have, unfortunately, not had time to build proper summaries over the past few months.  But rather than leave my initial work to fester, I am putting up these unadorned lists of links, in case others find them to be of use. Starting with materials from February.

Epidemiology

Epidemic control strategies

Health care for Ebola

Ebola epidemic impact

Vaccines

Survivors

Other items

 

 

 

New research on Ebola: December 2015

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.

 

New research on Ebola: November 2015

A summary of research on Ebola newly published in November 2015. I’ve tried to make this round-up flow a little better.  Hopefully the dots are a bit more joined-up.

Patient-level Epidemiology

The association of Ebola infection and mortality with age, viral load and other risk factors.

Several researchers focus on the age structure of this Ebola outbreak. Jin Li and colleagues describe the clinical outcomes of 288 confirmed Ebola patients at Jui hospital from October 2014 to March 2015. The authors again highlight the tight association between viral load and mortality, as well as increasing mortality for those aged over 18 and again over 40.  This pattern was also reported by Marc-Antoine de La Vega and colleaguesAlicia Rosello et al. review all seven past outbreaks of Ebola in the Democratic Republic of the Congo using line-list data. The authors show incident cases are overrepresented amongst those aged 25-65 – perhaps reflecting nosocomial and burial-based transmission routes – with higher mortality amongst the under 5s and over 15s. More severe epidemics appear to have been controlled faster. In a letter, Leslie Libow highlights the relatively low incidence rate of Ebola amongst under 18s in both the 2014 West African and 1976 Zaire outbreaks; Libow focuses on age-specific biological risk factors, however for me this highlights once again the importance of involvement in caregiving as a risk factor for Ebola infection.

Two papers in the same journal delve into the association between EVD viral load and patient outcomes. Marc-Antoine de La Vega and colleagues show that amongst the 632 fully-documented cases of Ebola seen at the MSF hospital in Kailahun between July and November 2014, mean initial viremia of survivors was over 100 times lower than that of non-survivors, and mean viral load fell by a factor of 10 from August onwards, at the same time as Ebola-specific antibodies became more common in the population. Simone Lamini and colleagues provide additional evidence from the Emergency ETC in Freetown, moving beyond initial viral load to show levels decline rapidly 4-5 days after symptom onset in survivors, but remain substantially higher amongst those who subsequently die. Finally, Julii Brainard and colleagues conduct a systematic review of filovirus risk factors, and highlight that that only one-third of those who had direct physical contact with an infected household-member became infected; they show low risks for several other behaviours, reminding us that these diseases are thankfully relatively difficult to transmit in many circumstances.

And in a case study, Angela Dunn and colleagues describe how the admission of two individuals infected with Ebola into general medicine wards led to seven secondary cases due to limited use of PPE – highlighting the importance of careful screening and precautionary use of PPE during Ebola outbreaks.

 

Epidemic dynamics

How disease spreads through populations

There are two new, national-level descriptive studies of the evolution of the epidemic. Adriana Rico and colleagues provided a detailed description of the evolution of the Guinea epidemic in and around Conakry up to March 2015, exploring possible mobility and healthcare-related explanations for the continuation of transmission in this area even after infections had ended in much of the rest of the country. Tolbert Nyenswah et al. provide an overview of the Liberian epidemic, its control and its implications, highlighting the importance of a centralized management system at the national level.

Researchers are increasingly engaging with the networked nature of Ebola spread, both theoretically and empirically. Mark Burch and colleagues built a Bayesian model for the co-evolution of outbreaks and contact networks, and applied it to the 2014 DRC Ebola outbreak. Within Sierra Leone, Wan Yang and colleagues build an adjusted “gravity” model – which assumes closer, denser districts had more movement between one-another – to infer how infections passed between the 14 districts of the country. It will be interesting to see how these results compare to phylogenetic connections once all the samples are in. Marco Ajelli et al. reconstruct the transmission chain for 49 Ebola cases in one Sierra Leone district – Pujehun – by merging field and hospital notes with HCW and community interviews. The authors generate a wealth of empirical epidemiological data and highlight the role of high detection, isolation and rapid burial in controlling the local outbreak.

The effectiveness of interventions

Linked to the work on viremia (above), two more papers address the importance of detecting and isolating cases early – preferably pre-symptoms – to control Ebola epidemics. Diego Chowell and colleagues model the benefits of detecting pre-symptomatic individuals (e.g. systematic PCR testing of case-contacts), while GF Webb and CJ Browne provide similar evidence focused on very early symptomatic cases.

Contact tracers are central to early case identification, and Ashley Greiner and colleagues interviewed Ebola contact tracers in six affected West African nations in late 2014 to understand how they succeeded in following transmission chains. The article highlights many barriers (notably fear, stigma and community mis-perceptions) and some useful strategies for combating them.

Philippe Calain and Marc Poncin consider the ethical dimensions of interventions, exploring the moral basis for quarantine and isolation in the context of Ebola. The authors highlight that, even given evidence of effectiveness, such measures may be morally questionable and potentially counterproductive, if individuals and communities are coerced into compliance.  Umberto Pellicchia and colleagues at MSF provide empirical evidence for exactly such counterproductive effects: showing how top-down quarantine procedures and enforced cremations in Liberia generated stigmatization of – and resistance by – poor Ebola-affected communities, exacerbating existing social inequalities.

Health communication – including messages to induce cooperation – was central to combatting the epidemic. Mauricio Duque-Arrubla outlines in his Masters thesis how messaging in Sierra Leone shifted with phases of the epidemic, moving from top-down to bottom-up as the need shifted from nationwide action to local implementation. The author highlights the need for constant re-evaluation and engagement with community, community leaders and government via a mix of strategies to maximize effectiveness.  Joachim Allgaier and Anna Lydia Svalastog frame the spread of health messages as being in competition with the spread of disease, and of unreliable/harmful information. The authors note that combination prevention efforts include the management of all of these spreading processes.

Within Ebola treatment centres, Adam Potter and colleagues pinpoint how personal protective equipment (PPE) led to heat strain, and provide practical guidance on work/rest timings given specific types of PPE and temperature/humidity.

And finally, Adam Kucharski and colleagues link together networks, interventions and vaccination programmes – in simulating an Ebola outbreak over a network-structured population using observed contact data. The authors show that while ring vaccination can help control an epidemic in concert with other interventions (i.e. behaviour change, active case finding, isolation), such a vaccination method relies on strong knowledge of existing transmission chains. Ebola vaccination strategies therefore need to take account of the epidemic and response context in determining the most efficacious and efficient approach.

 

Miscellanea

No less important than the papers covered above, but my powers of synthesis are insufficient to fit these into another catgegory.

  • Tara Smith outlines the strengths of using the West Africa Ebola outbreak to teach a cohesive and comprehensive course on global health.
  • Marc-Antoine de La Vega et al. review the evolution of the Ebola virus over the past 40 years, noting a relatively stable evolution and a lack rapid change over time.
  • P Loubet and colleagues show how the number of patients attending two HIV clinics in Monrovia dropped – and the level of follow-up delays rose – as the epidemic raged in 2014, highlighting the impact of Ebola on yet-another aspect of the healthcare system.
  • Kai-Lit Phua considers how risk factors acting at many different levels (host, agent, physical , health policy/funding and social/cultural environments) combined to increase the difficulty of turning the epidemic tide, and how a combined approach to addressing such factors might improve the chances of doing so – both now and in future epidemics.
  • A need for WHO and the world health system to reform has been highlighted by many in light of the Ebola epidemic. The Harvard-LSHTM Independent Panel on the Global Response to Ebola reported this month, and provided wide-ranging recommendations on what is needed to ensure a timely, joined-up response to future health crises; the hard part is bringing together those with power to make these changes, and persuading them to do so.   On the research policy front, the WHO and many major journal groups put out a statement on standards for sharing data in health crises – a common concern during the epidemic has been unshared data at the epidemiological and molecular levels.

 

Ebola epidemiology roundup #11

This post a little less thorough than usual on the links; hopefully just as much actual science stuffed inside though.  The material herein covers roughly the period from 6 February to 15 March 2015.

A. Charting the Epidemic

A1. Epidemic trajectory

Past/Present. The great news is that the Liberian epidemic is firmly under control, maybe even closed down for the moment. There hasn’t been a new confirmed case in the country since late February (perhaps the 24th?), and the last patient was released by March 5th. The risk of transmission from hidden infection chains, or from abroad, remains.  But Liberia seems in good shape, and the cautious government has now lifted many of the country’s travel restrictions and its nightly curfew.

Unfortunately the same cannot quite be said for Guinea and Sierra Leone.  In SL the lifting of travel restrictions seems to have led to infection being spread around, and finding all the cases and their contacts is still proving difficult.  The headline news in the past week or so was the outbreak based around the fishing community of Aberdeen close to Freetown.  But there continue to be cases found throughout the north/west of the country. SL has now re-opened some border crossings with Liberia; how that will affect each country remains to be seen.

The situation in Guinea seems a little darker.  Where transmission chains are not being found in SL, perhaps due to passive resistance to tracers, in Guinea there is active mistrust and anger towards public health professionals, leading to (possibly growing levels of) violence.  There are also hidden transmission chains.

The upshot of all this was over 50 new reported cases in Guinea in the last week of February, and over 80 in SL.  These figures are pretty indicative of the month as a whole in these two countries, as can be seen in this figure from the Economist:

Future. Predicting the future trajectory of the epidemic is getting harder as mass-action effects become less important, and variability in individuals’ contact patterns drives case loads. While there remain some “curve fitting” models out there, the shift now has been towards more nuanced modelling efforts. One approach is to look at finer level than the country.  In this article by Anton Camacho and colleagues model each Sierra Leonean district’s epidemic separately.  In a short piece, Gabriel Rainisch and colleagues show that just information on population and distance between districts is enough to predict with some accuracy how infection will spread across the region. Another approach is to explicitly model the contact network in each country; in a recent paper Constantinos Siettos and colleagues did this, successfully predicting the Liberia fade-out in late 2014, and the subsequent SL drop-off in cases in early 2015.  However, such models still appear (understandably) unable to predict rebounds such as those seen in SL in February and March, or Guinea on several occasions.   In order to predict such highly stochastic events, some kind of probabilistic model of divergent epidemic paths (either it dies out, or it blows up) would be needed. Which sounds like several steps forwards in modelling development; I won’t hold my breath on that front.

Modelling. If you have some spare time, and a slightly obsessive interest in modelling Ebola, you probably can’t do better than spend some time watching the presentations from last month’s Ebola modelling workshop organised by LSHTM and WHO in London.  Videos of all the sessions are here.

A2. Epidemic parameters and other epidemiologic findings

First off, there has been a reprise in the academic literature of an idea that seemed to have faded away last year: that Ebola might be spread through the air.  Michael Osterholm and colleagues have published a thorough review of the transmissibility of Ebola that covered many important aspects of the disease. (Osterholm paper). But the headline that ran in the Washington Post was “Limited airborne transmission of Ebola is ‘very likely,’ new analysis says“.  As many researchers, and some news outlets, pointed out, while the study did “hypothesize that Ebola viruses have the potential to be respiratory pathogens with primary respiratory spread”, this didn’t seem to be backed up with any strong evidence, other than the potential for Ebola to infect the respiratory tract.  As virologist Ian Mackay has been pointing out for some time, while this may lead to aerosol spread, it is very unlikely to then evolve into airborne spread.  Read about this here, here and here. Or read the views of a couple of other virologists: Vincent Racaniello, Professor at Columbia University (here) and John Oxford, Emeritus Professor at the University of London (here). TL;DR, Ebola is very very unlikely to go airborne any time soon. For a much more considered read of much of the same literature, please consider another review by Seth Judson and colleagues instead. (Judson paper).

A few groups have been examining the mortality impact of Ebola.  While MSF has been reporting that the fatality rate at their facilities has been dropping over time, now down to ~52%, the Red Cross has noted that they have attended at least 14,000 deaths during the epidemic – some 5,000 more than the total number of cumulative deaths reported by national governments/WHO.  So the overall direct mortality rate is almost certainly higher than official numbers. On a connected note, Stephane Helleringer and Andrew Noymer published a paper showing that Ebola has directly reduced life expectancy by around a year in Guinea and at least 1.5 years (maybe over 5 years) in Sierra Leone and Liberia.  (Helleringer paper).  And that’s without considering all the indirect deaths from non-treatment of other health conditions (malaria; pregnancy; diabetes; etc). The final toll of this epidemic is likely to be very sobering.

Another issue that I have mentioned a couple of times before is post-acute illness.  As well as fatigue and muscle weakness, possibly reflecting the overall impact of Ebola on a human body, it seems that complications of the eye are common.  The establishment of a survivor clinic near Monrovia may help us understand these long-term effects, so long as it doesn’t serve as a focal point for the already considerable stigma associated with recovery. There is also ongoing concern about the potential for sexual transmission  post-recovery; I remain a little skeptical, but as Liberia moves forwards with no reported cases for the past 10 days, any future flare-ups may provide suggestive evidence on this topic.

I will also note this article by Adnan Khan and colleagues looking at R0; they find similar estimates to other papers.

And finally, Joseph Prescott and colleagues have shown that it is possible to find viable virus in swabs of macaques up to seven days postmortem, reinforcing the need for rapid burials or other death rites.

A3. Visualization

Not too much to report here.  However, while most case maps show cases in the past X (usually 7 or 21) days, I liked this alternative approach that may be more relevant as the epidemic winds down: days since last confirmed case:

From a quick piece by Jina Moore at Buzzfeed.

B. Stopping the Epidemic

B1. Containment

Movement: As mentioned above, Liberia has relaxed their travel restrictions as case numbers hit zero last week.  In contrast, Sierra Leone has re-introduced some movement restrictions, notably on boats and trucks. Potentially more importantly, as the next wet season approaches there is concern that movement will be restricted for those trying to find cases – although it should also reduce the virus’ ability to circulate, hopefully.

Case finding: Contact tracing – both from known cases and from secret burials – and subsequent monitoring of said contacts has become the core of the current epidemic-fighting phase.  In this context, a paper by Francis Kateh and colleagues outlining rapid response methods used last year in Liberia is very timely reading. Their “RITE” method emphasizes the technical side of isolating cases, and finding and observing contacts.  Three other papers in the same edition of Mortality and Morbidity Weekly Report [pdf] present case studies of implementing such methods, highlighting the importance of working with existing community structures and chiefs to avoid conflict and further spread.

One technological improvement that might greatly assist contact tracing efforts would be a fast, reliable test for the disease.  On this front, a 15-minute test was approved by the WHO in late February for use in West Africa.  With a sensitivity/specificity of 92%/85%, it remains imperfect, but at a cost of less than $5 a time, it may well be able to act as a first-line method for on-the-ground work. There has also been some progress on a test to differentiate various common sources of fever seen in West Africa – while still in the lab, the test would differentiate yellow fever, dengue and Ebola.  Clearly there would be need to extend this to include other viral haemorrhagic fevers and malaria, but a good start.

Safe burials: The only news I saw on this front was a UN report in early February suggesting that secret burials may be one reason for the uptick in cases in Guinea and SL.  In this context, this paper by Paul Richards and colleagues that I first saw in November remains essential reading: Richards highlights the role of funerals in rural areas in managing the shifts in social relationships that arise from a death (among several other topics).  In related news, Sierra Leone has re-imposed a stringent burial process for all deaths in the country to try and reduce transmission.

There are several new papers using models to look at how various combinations of interventions might have helped with epidemic control. I honestly haven’t read them in depth, but include them here for completeness/interest: LD Valdez and colleagues on the arXiv; Marisa Eisenberg and colleagues on the arXiv; and Glenn Webb and colleagues in PLoS Currents Outbreaks.

B2. Treatment

If you read one piece on drug and vaccine trials, it should probably be this overview in the LA Times. If you read two pieces, I would recommend this back-and-forth in JAMA about the ethics of randomization in an epidemic setting (OK, so officially this is four articles, but they’re all short): Steven JoffeMorenike Oluwatoyin Folayan et al.; Steve Kanters et al.; Steven Joffe again. This is also a good insight into academic debate conducted in a public forum.

Drugs: Things are changing swiftly in the world of Ebola drug trials.  Kai Kupferschmidt and Jon Cohen had a nice overview in mid-February, but things has moved on apace since then. The current roster:

  1. Favipiravir. The first “proof-of-concept” trial of this drug in Guinea is complete.  Early results show that participants who were initially less ill did better on average than similar individuals had at the same hospital prior to the trial (i.e. compared to historic controls).  Debate continues as to whether this finding should be interpreted as evidence for a protective effect.  If favipiravir is seen as effective and then used more widely, it will complicate all future trials of Ebola drugs that were planning to use historic controls, especially favipiravir’s effectiveness is not firmly known.
  2. ZMapp. A randomized trial of ZMapp (the first treatment suggested all the way back in August) finally began in Liberia in late February.  However, given the lack of current cases, it may need to be moved elsewhere.
  3. Survivor-plasma. While a trial of blood plasma from Ebola survivors has been running since December in Liberia, a second one started in Guinea in mid-February.  No word on results yet, but I noticed a modelling paper by Alexander Gutfraind and Lauren Ancel Meyer that highlighted the potential benefits of plasma transfusion if it reduces mortality (essentially, the benefit will be [%hospitalized * %reduction in mortality]).  Nothing groundbreaking, but useful to bear in mind.
  4. TKM-Ebola.  A phase II, non-controlled trial of this drug has recently begun in Port Loko, Sierra Leone (where there are still a steady flow of patients, unfortunately). The drug appears to require considerable staff resources to deliver, which may be feasible in the downswing of an epidemic, but perhaps not when caseloads are rising exponentially?
  5. Tetradine. This herbal extract got quite a lot of media coverage when it was shown effective in mice in an article by Yasuteru Sakuri and colleagues in Science. Next step, large animal and primate studies.
  6. Brincidofivir. This one isn’t quite like the others, since the trial of this drug in Liberia was stopped early by its manufacturers.  I include it hear since there remain questions as to why it was stopped early, with only 10 patients enrolled. Something to watch in the future, perhaps?
  7. VSV-EBOV. And neither is this one, since it is a vaccine candidate.  In fact, this relates to a case study of a healthcare worker who received VSV as post-exposure prophylaxis following a needlestick injury.  While Ebola virus was never detected, a strong virus-specific immune response was seen. (Academic article by Lilin Lai and colleagues.)  Another avenue of potential investigation?

And if you only plan on ever reading one article on drug trials for Ebola, it should probably be this lengthy but comprehensive and highly humanized account from Sarah Boseley the Guardian.

Non-drugs: Perhaps the most long-lived debate in the Ebola treatment world appears to revolve around needles: who gets intravenous treatments, how often, for how long, etc. Partners in Health have recently taken an aggressive stance on this topic, arguing for two intravenous lines for rehydration. Evidence for this approach remains unclear, but one study by Paul Rees and colleagues out this week suggested that in well-controlled environments (specifically, a 12-bed British military treatment unit), early central venous catheterization is feasible and safe.  How well this will translates to general-population ETUs is less clear.

And on the topic of hydration, I will nod to a newly published systematic review of hydration methods, comparing and contrasting needle and non-needle approaches.  (While the press-release pushes the Ebola angle, there are no studies on Ebola contained in the review.)

B3. Vaccination

Quick updates on the three planned phase III trials in West Africa:

  1. Liberia.  With no new cases in almost three weeks, the chances of a significant finding are waning in Liberia.  In addition, there appears to be stigma attached to signing up for the trial, which may further hamper efforts.
  2. Sierra Leone. Still no official start date, with delays currently being ascribed to regulatory approval requirements.  The trial, amongst workers involved with the Ebola response, should start in the next few weeks. This trial will be using the VSV-EBOV, as opposed to the ChAd3, vaccine.
  3. Guinea. The innovative “ring vaccination” trial began in Guinea on March 7th. This trial will also be using the VSV-EBOV vaccine.

While all this vaccine trial-age is important for the long-run battle against Ebola, it is important to note that no decision about mass vaccination is envisaged before August of this year, by which time it will hopefully not be needed for this epidemic.

On the development side, I note that there is a fourth vaccine (Ebola-GP; Novovax) in early-stage trials in Australia.

B4. Behaviour Change

Although I am aware that several behaviour change interventions are taking place, they are not well represented in the news or the academic literature.  Over the past few weeks, though, I’ve seen at least three posts that covered different aspects of the push to prevent infections:

To tie these threads together, listening to communities and understanding the social bonds that hold them together, is crucial to effective interventions.  Which brings us back to the benefits of involving anthropologists in the Ebola response.

C. Social factors/impact

Education: The return of schooling in the three most-affected countries continues to move forwards, slowly:

  1. Guinea. Schools opened in January and remain open. Whether this is the best idea, I’m not so clear.
  2. Liberia.  The good news is that schools are open, as of 16 February, with careful hygeine regulations. The less-good news is that the number of students attending is still inching up from a low initial base, as fears about inter-child contact remain.
  3. Sierra Leone.  The latest plan is to re-open on 30 March 14 April, with concerns about potential disease transmission and the economic burden of schooling for parents. There has now also been an edict that pregnant girls cannot return, for fear of being a “negative influence” on their peers. How unfortunate.

Economics: Another “I haven’t read it in detail, but” note: there’s a new publication out from UNDP highlighting the economic impact of Ebola across the whole West African region due to lower travel, investment and agriculture.

Finances: There has been ongoing concern that funding for the epidemic has not been flowing smoothly. At the international level, the concern is that less money is arriving than promised. Karen Grépin recently showed the gap between promises and deliveries (spoiler: it’s not small) and highlighted the importance of tracking disbursements.  At the country level, the concern is the opposite: less money is officially being spent than is arriving.  Investigations into corruption are flowering.

Health: As has been noted throughout the Ebola outbreak, many of the health concerns raised by the epidemic arise from its secondary effects.  Perhaps the most talked-about effect is on maternal health, especially around childbirth.  While data is sparse to date, there appears to be an expectation that the maternal death rate will double – to as high as 2000 per 100,000 live births in Sierra Leone – as a result of Ebola. Such worrying figures have led to calls from the UN and academics for special attention to be paid to women and children in the recovery phase. There are concerns about mental health for both the infected and the affected, and support plans are being built into recovery efforts. And just this week there has been significant publicity for a modelling study by Saka Takahashi and colleagues led by Justin Lessler at John’s Hopkins, highlighting the troubling fall-off in measles vaccination for young children (in contrast to the mass-prophylaxis efforts against malaria). They estimate that a measles outbreak in West Africa now might cause 2000-16,000 deaths; the same order of magnitude as Ebola itself.  Also well worth reading is Leslie Robert’s commentary on the piece.

Orphanhood: I tend to be wary of claims that an event “has left X thousand children orphaned”, both due to the various meanings of the term orphan – double; single; maternal; paternal – and due to some proportion of even double-orphans having other relatives or community members who still provide them with a home.  However, in the case of Ebola I am more open to calls for concern for at least three reasons: (1) 15-44 year olds are at greater risk of infection than children; (2) infections are highly clustered with families; and (3) stigma follows the family members of the infected strongly, reducing the likelihood of foster care. So the recent suggestion that there may be 12,000 orphans from Ebola  in Sierra Leone is worrying indeed. Especially when considering that Ebola has indirectly taken parents from many other children whose mothers died due to a lack of maternal care, or indeed other health care services.

As ever, if you have seen something I’ve missed (or links are broken), you can reach me @harlingg. And as ever, thank you to all those on whose work this builds on.

There are ten previous posts in this series and a summary of data/research sources.