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: April 2016

As ever, tempus fugit. I have finally accepted I will not be keeping up with the Ebola literature any time soon. So I am posting three more lists of links, covering April, May and June of 2016, and then leaving you all to run your own PubMed and GoogleScholar alerts (I set mine for delivery weekly and whenever Google wants to send me something respectively). After that, it is back to occasional posts on the social determinants of HIV, TB, etc (i.e. my day job). It has been a privilege learning so much about an awful outbreak and the phenomenal efforts made by so many to fight it. Thank you for dropping by and motivating me to stay focused, and sometimes even up-to-date.

First up, things indexed in April 2016.

Therapeutics and Vaccines

Epidemiology

Epidemic control strategies

Health care for Ebola

Ebola epidemic impact

Survivors

Other items

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: January 2016

A shockingly on-time update, covering all the material on Ebola epidemiology and proximate topics that’s new to me in January.  As ever, please let me know if I’ve missed or mis-interpreted something.

 

A. Clinical epidemiology and health systems

Xudong Gao and colleagues highlight a range of symptoms seen to be predictive of diagnosed Ebola, and of mortality, in 773 suspected cases admitted to Jui hospital in Freetown: vomiting, diarrhoea, weakness, loss of appetite, conjunctivitis, hiccups, and confusion. The authors note that rapid, specific diagnostics would still be preferable.

A couple of papers considered survival predictors. The WHO Ebola Response Team highlight a couple of key gender differences in the >20,000 cases seen in the West African epidemic, based on individual-level data: first, women reached treatment facilities an average of 12 hours earlier following symptom onset; and second they were some 15% less likely to die (63% vs 67%), even after adjusting for various potential confounders. Samuel Crowe and colleagues provide evidence from Bo District in Sierra Leone that symptomatology at facility admission was not associated with survival, but first PCR cycle threshold (a proxy for viral load) was predictive of survival at a cutpoint of 24.

There is also more on Ebola survivors. Abrar Chughtai and colleagues review the 12 published papers (to October 2015) on EBOV in convalescent patients’ body fluids. Viral RNA has been found in urine, aqueous humor, sweat, semen, vaginal secretions, breast milk, faeces and conjunctival fluid up to 9 months post-recovery; EBOV itself has been found in semen, aqueous humor, urine and breast milk. There are also two recent additions to this literature this month. John Chancellor and colleagues provide a detailed case description of a returning US doctor who survived EVD and his subsequent ophthalmologic complications. Helena Nordensted and colleagues report a case of a lactating mother who was admitted to care testing positive for EVD in her breast milk. The authors could neither tell whether virus was transmissible via milk, nor whether it lasted beyond EVD clearance from the woman’s blood, but this will add another way in which Ebola might be spread. Anna Thorson and colleagues review the literature specifically on sexual transmission, highlighting positive RNA tests up to nine months post-recovery in semen, and recommending condom use in the absence of abstinence (although no study of condom effectiveness for EBOV prevention yet exists).

Several other papers present research on healthcare-related topics. Two papers consider treatment protocols during the Ebola outbreak. Emmie de Wit and colleagues examine the feasibility of PCR testing for malaria in parallel with Ebola PCR testing. They note that even though presumptive antimalarial treatment was given for any febrile illness, the marginal resource cost of PCR malaria testing was minimal, and it might help with treatment plans. Indi Trehan and colleagues present the paediatric management protocols for Maforki ETU in Port Loko, Sierra Leone, including how they evolved over three months of use between December 2014 and March 2015.

Jianping You and Qing Mao describe the architecture of the Chinese-built ETC in Monrovia, and its strengths and weakness compared to more temporary structures. Abdoulaye Touré and colleagues report on HCW knowledge, attitudes and practices in Conakry, showing high levels of knowledge about Ebola symptoms and transmission risks, but also a preponderant belief that they did not know enough about the disease. Ibrahim Bundu and colleagues describe the rapid and almost-complete fall-off in surgical activity at Sierra Leone’s main teaching hospital in August 2014 as the Ebola epidemic took off in Freetown, and point to key lessons for surgery in future similar outbreaks. Similarly, Catherine Cooper and colleagues describe the development of infection prevention and control (IPC) guidance in the face of the Ebola epidemic and highlight the importance of sector-wide coordination and in-place national protocols in advance of future epidemics.

 

B. Diagnostics, Therapies and Vaccines

On the diagnostic front, following up from last month’s clutch of papers on the Xpert Ebola assay, Rafael Van den Bergh and colleagues review the field-effectiveness of the test in Guinea. The authors report a halving (from 334 to 165 minutes) of time to results compared to PCR, with no false-negatives amongst 218 tests for the Xpert system; they recommend Xpert as an improvement of current standard of care.

There is also an incredibly rich set of papers up this month, from a special issue of Clinical Trials (Pubmed hack, no direct link yet) curated by Lori Dodd and covering trial designs. I have only scratched the surface of the 19 research and perspective articles, but can already recommend it to the more statistically minded amongst you. Hopefully I will one day have a hard-copy of this on my shelf for dipping into. Several of the Clinical Trials articles touch on the ethics of study designs, and in a separate article Annette Rid and Franklin Miller review the ethical rationale for the Ebola ça Suffit ring vaccination trial, highlighting that although it attempted to avoid leaving participants in a placebo arm, it remained a research study – rather than a vaccine rollout operation.

Emelissa Mendoza and colleagues review the evolution of testing therapeutic candidates during the West Africa outbreak, with detailed descriptions for Amiodarone, Brincidofovir, Favipiravir, convalescent plasma and TKM-Ebola. Mendoza et al. were upbeat about convalescent plasma, however Johan van Griensven and colleagues report no significant impact of such plasma on survival in an 84-person non-randomized trial using historical controls. (van Griensven’s team also has a paper in the Clinical Trials special issue on how this analysis was designed.) Researchers may now focus on more concentrated forms of plasma.  On another tack, Stephen McCarthy and colleagues searched for existing drugs that have antiviral activity against Ebola, identifying Interferon-\beta and combinations of various other drugs as candidates.

 

C. Epidemic dynamics and prevention

There were a grab-bag of modelling and field-methods papers this month:

  • Mosoka Fallah and colleagues http://annals.org/article.aspx?articleid=2480063 detail the setup of a community-based initiative model in Liberia, and its impact in West Point, a low-income, highly affected neighbourhood of Monrovia. This need for community engagement is echoed in a paper by Samuel Cohn and Ruth Kutalek, which shows parallels between community resistance to external control measures for Ebola and that seen for European Cholera outbreaks in the 19th century.
  • Tom Koch provides a detailed overview of various approaches to mapping both human and physical geographies, and suggests how such methods might inform future outbreak responses.
  • Alessandro Rizzo and colleagues present a neat agent-based model of Ebola dynamics that allows for changes in individuals’ contact networks following infection, and more rapid removal via the implementation of behaviour change interventions. The authors reach similar conclusions to previous modelling studies, but with the benefit of added realism that may be crucial for some questions.
  • Eva Santermans and colleagues built an instructive two-part model of the West African epidemic using publically available data: first, a spatio-temporal regression model to understand how infections spread across districts; and second a state-transition model to understand growth within districts. The authors propose such methods for real-time outbreak monitoring and prediction.

 

D. Miscellenea

As ever, there are a few articles that I cannot neatly shoehorn into categories; as ever, this reflects my shortcomings, not the relative importance of the work.

  • First, the Pan-African Medical Journal devoted its October 2015 issue to Ebola in West Africa, with a range of articles covering Nigeria, Senegal and Ghana, in addition to the three most-affected nations.
  • Second, Solomon Benetar outlines three levels of ethical responsibilities in the Ebola outbreak: interpersonal, public health and global.
  • Third, South African clinicians Rosie Burton and Tom Boyles reflect on their experiences working in Liberia and Sierra Leone.
  • And finally, Eugene T. Richardson and colleagues conduct a biosocial analysis based on four interviews with Ebola survivors in Kono District, Sierra Leone, highlighting political, economic, ecological, and cultural factors that led to the distribution of Ebola infection seen globally over the past three years.

 

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 #10

This post covers material published roughly in the month of January 2015.

A. Charting the Epidemic

A1. Epidemic trajectory

Past/Present. The big news in January has been the apparent rapid decline in case numbers in Sierra Leone, following the equally big fall-off in Liberia in December.  Indeed, as of January 23rd, it is being reported that there were only five active, in-care cases of Ebola in Liberia.  Not the end, but maybe the beginning of the endgame? The situation in Guinea remains more murky.  Although there has been a clear decline in reported cases in Guinea throughout January, there are concerns that some areas are still refusing access to case finders and health educators, and indeed that things may be getting worse.  Thus falling reported numbers may not reflect falling actual numbers. Late edit: In the last week of January, case numbers in Guinea ticked up by 10, a 50% increase on the preceding week, and spread to new parts of the country.

While covering the epidemic trajectory, I would be remiss not to mention this WHO overview of the past year.  I won’t pretend to have read it all, but it looks like a strong resource for getting up to speed on the epidemic, if with the standard WHO angle on why things happened the way they did.

And finally, I wanted to take a step back to look at the impact of Ebola on non-human primates (NHP).  A story rolling along this week suggested that up to one-third of all chimpanzees and gorillas worldwide have been killed by Ebola since it was discovered in humans in 1976.  This number appears to have come originally from an unpublished study by Peter Walsh and colleagues. One angle on this was that a vaccine should also be provided to NHPs.  Of course, this is the population on which human vaccines are tested, so we should have a fairly good idea whether or not it will work for them (spoiler: the ones currently in development seem to work excellently on NHPs, maybe because at least one of them is based on a Chimp adenovirus? [this last is pure speculation on my part]).

Future. As uncertainty about the overall impact of this epidemic subsides, concern has turned to new areas.  At the heart of most concerns is that people will get complacent, allowing the epidemic to smoulder and then potentially re-ignite.  Along with the well-publicised fall in interest in the global (social) media interest in Ebola, and concomitant worries about the end of funding for disease control, there already appears to be declining interest and concern within Liberia (see also Containment, Schools below).  One marker for this is the ending of “risk allowances” to healthcare workers in Sierra Leone by the end of March.

Ultimately, much of the concern arises from the possibility that Ebola may become an endemic disease.  As Peter Piot highlighted (in the last link), this is unlikely in strict terms:

We (humans) are a very bad host from the virus’ point of view… A host that’s killed by a virus in a week or so is absolutely useless.

As a result, case numbers will either rise up (if we do nothing) or die down (as has happened in this outbreak) reasonably fast in each epidemic.  However, given ongoing human-bat contact, multiple new outbreaks remains a likely future scenario –  which looks a lot like an endemic situation to many.

Modelling. There isn’t a lot of modelling left to do in real-time on the epidemic curve as it heads slowly downwards.  Which is not to say that there isn’t plenty more modelling to be done.  Both of these points, and the opt-repeated one that modelling is hard, especially about the future, were raised and discussed at the Ebola Modelling Workshop in Atlanta last week.  Helpfully, all the slides from presentations at the meeting, along with a forthcoming curated summary of the discussions, are available on the workshop website.  A must-read for those – like me – who could use some collected wisdom on the topic.

A2. Epidemic parameters

MSF Sierra Leone, under the lead authorship of Silvia Dallatomasinas has published clinical epidemiology data on 489 cases seen in Kailahun between June and October (Dallatomasinas paper). A key finding was that one-third of cases came from outside Kailahun district – largely from Makeni in Bombali district, but also from as far afield as Freetown. For me this emphasizes the importance of mobility for transmission, especially early in the epidemic.

Another interesting insight into transmission dynamics comes from a study by Ousmane Faye and colleagues of transmission chains from March to August in Conakry (Faye paper). The authors show that the great majority of secondary infections were generated in the community – rather than at hospitals or funerals – with over 80% of infections being within families. As Christian Drosten notes in his commentary on the paper, since family sizes vary little by urbanicity, so the reproductive number was no higher in Conakry than in the countryside. Faye et al also show that higher viral loads are associated with greater transmission: hardly shocking, but useful data to accrue.

Concern appears to remain regarding whether ongoing infection could occur via sexual contact with survivors or through breastmilk. While no definitive transmissions have been documented, perceived sexual transmissions are being reported in SL, while concern is being aired that the requirement to abstain from sex for up to six months is not feasible for men.

The issue of potential asymptomatic infection is also rumbling along. Again there are no definitive serological studies of past infections to date, but some small studies suggest that close household contacts test positive without clear symptoms of Ebola. Additionally, one study at Kenema government hospital showed that 22% of suspected Lassa Fever cases presenting from 2001-14 tested IgG/IgM positive for Ebola. Which could beg the question: how specific Ebola tests are?

Another popular topic in the media – for Ebola, but also for almost any other infectious disease, is mutation (on which, please see this great general-audience overview of mutation and infectious disease, in the context of Ebola).  So I appreciated this measured article by Abayomi Olabode and colleagues on the Biological arXiv (so not yet peer-reviewed), which highlights that mutations over the past 40 years have led to no apparent shift in functional mechanism of infection. (Olabode paper). I’m sure that there will be lots more on this topic once we have more sequences from this epidemic, but an interesting first step.

And lastly, a quick dive into the zoonotic.  Raina Plowright and colleagues note that we believe Ebola (and several other viruses) reach humans via bats, but cross the species barrier only rarely, despite common human-bat interactions. (Plowright paper). Plowright’s paper focuses on Hendra virus, but posits two possible reasons for the rarity of zoonotic events: episodic shedding or transient epidemics (such as those typically seen for SIR-type infections in humans, e.g. measles).  I may be far behind the curve on the Ebola-bat literature, but if the world knows as little about Ebola’s cheiropteran lifecycle as I do, this seems to raise some interesting, testable hypotheses.

A3. Visualization

I know that this plot has been around for a bit – since well before Ebola became big news – but it’s a useful benchmark for comparison. Clearly we can quibble about whether 70% is the right CFR, but it gives you an idea of where Ebola sits in the pantheon (or rather the anti-pantheon) of diseases.  As you can see, diseases as virulent as Ebola tend not to be very contagious.  This is good for us, but also good for the disease – if you kill off all your hosts, there’s not much chance of continuing to exist as a species for very long, especially when you do it as fast as Ebola does.

And in case the various visualization sites I have been pointing you to aren’t quite enough, here’s another blog that focuses _only_ on visualizations for Ebola, by John Tigue.  Enjoy.

B. Stopping the Epidemic

B1. Containment

Movement: Speaking as we were of the importance of mobility for transmission, I should quickly update the tale of movement restrictions and associated intensified case-finding in Sierra Leone. At the beginning of January the isolation (quarantine?) of northern districts was extended to ensure that Ebola was under control there. This was followed by “Operation Western Area Surge”, a house-to-house search across several districts, which apparently found well over 200 additional cases. (On a side-note, there is a nice description of the operations of the SL national call centre during September’s “ose-to-ose” campaign in the MMWR). Late in January, the general decline in new cases led to the lifting of inter-district travel restrictions across SL on Thursday 22nd, and a subsequent stream of traffic leaving Freetown. Whether this will lead to an uptick in cases remains to be seen.

Case finding: As the epidemic ebbs, much attention is turning to case finding, the role of contact tracers and other focused prevention activities – in contrast to the earlier focus on broad campaigns. Kai Kupferschmidt has written a nice “day in the life” piece on contact tracers in Bong county, Liberia; while a CommCare app is being used in Guinea to allow real-time reporting and geotagging of potential contacts. Sam Crowe and colleagues have also outlined a system of community-based, event-based surveillance in Bo district, SL. (Crowe paper). The system works through local healthcare workers triggering enhanced monitoring if they hear about clusters of illness, death or traditional burials.

As has been noted, a truly rapid test would be of great benefit to case finders – ensuring false positives can be quickly reassured, and true positives quickly taken into care. Such tests would be even more useful if they could identify infections pre-symptoms: although the feasibility of this remains unclear. Nevertheless, rapid tests appear do appear to be in the pipeline; indeed a “lab-in-a-suitcase” is apparently undergoing testing in West Africa already, using Recombinase Polymerase Amplification (RPA) instead of the standard PCR approach. However, various sources have cautioned that while such an approach would be welcome, complex methods that work in the theory, fail in field-testing, and thus such a lab’s usefulness remains to be proven.

Another important aspect of case-finding is that many cases are found only through reports from community members.  In this context, a letter from Ruth Kutalek and collagues in the Lancet was educational. (Kutalek letter). The Liberian government, WHO and the World Bank had been considering paying $5 per case reported.  A rapid focus-group evaluation of this proposal both rejected the incentive scheme as being disruptive to the community, and highlighted that better case-reporting would require improvements throughout the care continuum that made entering into care a more feasible and acceptable proposition.  Which buttresses other reports highlighting the importance of listening to local communities, to maximize the chances of affecting behaviour change and ending the epidemic.

Isolation: While case finding may be the on-the-ground flavour of the month, there remains a great deal of academic interest in how best to control the epidemic in the healthcare or para-healthcare setting.

One important paper this month was published by Stefano Merler and colleagues (building from the work of Alex Vesgipnani’s lab at Northeastern University). (Merler paper). The team has build a realistic model of the population structure in Liberia at the individual level, and then calibrated epidemic parameters to observed outcomes up to August 2014. They use the model to show the likely impact of various interventions – safer burials, building of ETUs, etc. One key finding of theirs is that local transmission is key to disease propagation – although Gerardo Chowell and colleagues note that long-distance transmission has also been key (and also see Dallatomasinas’ paper above). Chowell and Hiroshi Nishiura also provide both an overview of network models and a plea for spatiotemporal data in reflecting on the publication of John Drake’s work (covered previously when on the arXiv) in PLoS Biology. (Drake paper).

On a side-note, Merler et al find a 40/30/10 split in secondary cases arising from hospitals/home/funerals; this is very different from the numbers seen in Conakry by Faye et al (see above). Whether this is due to different methodologies or truly different dynamics, this seems like a very interesting question that might be crucial to understanding how epidemic dynamics differ by country.

I also appreciated a blogpost by Silvia Munoz-Price, who highlighted the unusual situation in which clinical staff are seeking out Infection Control professionals, in contrast to their usual efforts to avoid all advice on the subject. She doesn’t provide any quick answers on how to sensitize HCWs in other settings – aside from breeding an HCW-preferring strain of C difficile – but the issue is one that has broad resonance for healthcare provision in the age of drug-resistant bugs.

Community-based care continues to be raised as an important part of the care continuum, given its cost and speed benefits over building Ebola Treatment Centres (ETC). Michael Washington and colleagues used a simple SEIR model to estimate the relative benefit of increased ETC and CCC (community care centres) in Montserrado and Lofa counties, Liberia, in September/October last year. (Washington paper). Their models suggested that both were useful individually, and even more so jointly, but that CCCs were likely to have a greater impact if one approach had to be prioritized. In this context, Sharon Salmon and colleagues’ letter highlighting that the Liberian government and NGOs trained up thousands of community volunteers for basic preventative care (and I believe Sierra Leone did similarly) is informative and likely an important component of control efforts.

And finally, a(nother) paper by Nishiura and Chowell compares/contrasts the dynamics of Ebola to that of Influenza, highlighting that the direct-contact mode of transmission of Ebola means that even though the R0 of these two diseases is roughly similar, the speed of epidemic growth is much slower (and the potential for control through social distancing much higher) for EVD. (Nishiura paper).

Safe burials: While safe burials may well have been an important factor in controlling this epidemic, they have not always been appreciated – especially when they were not conducted in a culturally sensitive, or just a sensitive, manner. In this context, it was interesting to me to read Carrie Nielsen and colleagues’ outline of how an SOP for safe and respectful burials was drawn up in Sierra Leone in October, as control efforts were rapidly expanded, and how efforts were then monitored and adjusted as needed. (Nielsen paper). In contrast, Liberia took a crematory approach to safe management of deceased bodies, and as this journalist’s report from Monrovia highlights, this has led to distrust, unhappiness and potentially future social upheaval as families are left without the ability to conduct key social/cultural practices with their deceased relatives. One of these countries looks like it has done a better job on this front.

B2. Treatment

Drugs: Trials of antiviral drugs as Ebola treatments continue in several parts of West Africa through MSF facilities. A trial of favipiravir in Guinea is being run by National Institute of Health and Medical Research (INSERM) – details on dosing being used are here; a trial of brincidofivir is being run by University of Oxford researchers at the MSF ETC in Paynesville, Monrovia (stop press: the brincidofivir trial appears to have been stopped; reasons for this are unclear, maybe due to the low number of patients enrolled). In line with past MSF comments, these are being run without a control group (one assumes using historical outcomes as controls). There will also be a trial of convalescent serum (i.e. part-blood transfusions from recovered patients) in Conakry starting soon (MSF overview here). On this last I would highlight a letter by Melanie Bannister-Tyrrell and colleagues highlighting the potential stigma for both donors and recipients in the context of passing blood between people. The importance of local knowledge, once more.

Also, I would be remiss not to highlight in light of my reporting last month on allegedly unethical testing of amiodarone as a treatment for Ebola at Emergency’s ETC in Freetown. Emergency have responded very firmly to such allegations in a blogpost. As well as contesting many of the facts in the case, the author(s) appear to believe that one reason for opposition to amiodarone’s use is its out-of-patent status and the consequent lack of profits available for its use. I’m not sure which side in this argument holds the greatest validity, but I wanted to make sure I was showing you all the arguments.

B3. Vaccines

Before diving into the practicalities, I noticed that Yazdan Yazdanpanah and colleagues (whom I last saw read while working on HIV cost-effectiveness a decade ago) have put together a brief overview of the intracellular lifecycle of EVD. (Yazdanpanah paper). A wonderful introduction for those of us with little knowledge of at the cellular level.

Now, on to those practicalities. When last we spoke, two vaccines (GSK/NIAID’s ChAd3 and NewLink/Merck/CanGov’s VSV) were in phase II trials, although the VSV trials had been put on hold due to some non-negligible joint pain. The ChAd3 team reported immunogenicity this past week in the NEJM.

The VSV trial resumed in the first week of January after the Christmas/holiday break, at much lower doses. A third product (led by Janssen, a Johnson & Johnson company) has also now begun trials too.

Of course, the real action will happen once trials reach phase III: the search for efficacy. Fortunately, a key challenge to proving the efficacy of any vaccine at the present time: the lack of new infections in the three countries. Clearly this is a good situation to be in from the perspective of the current outbreak; however without evidence for which vaccine(s) work now, planning for future outbreaks will be hampered.

In order to maximize the chances of seeing any true effect (i.e. maximize power) each of three teams putting together phase III trials (one per country) are considering new methods and evolving their plans very rapidly. The first trial will be in Liberiastarting in the first week of February. This will be run in conjunction with the NIH, and will involve three arms – quite probably two treatments (AdCh3 and VSV) and one control involving vaccination for something other than Ebola – with around 9,000 participants in each arm. It will be a classic Randomized Controlled Trial.

The second trial will be run by the CDC in Sierra Leone. The exact methodological details remain sketchy, but the population will be high-risk individuals involved in the Ebola response (ETC workers, burial teams, case finders) and the method will be a cluster randomized trial of some description (it was going to be a Stepped Wedge design; I gather this plan has been changed now). If there prove to be very few cases in Liberia, the SL and Liberia trials may get merged to improve power.

The third trial is decidedly innovative: it will involve “ring vaccination”. In this approach – previously used as a vaccination roll-out strategy, one vaccinates the contacts (approximately 50 local residents here) of each case found, but at different speeds: either immediately, or after 4-8 weeks. This allows a difference in effect to potentially be seen, without denying anyone a chance to get some kind of treatment. It also should help to control the epidemic – something that may be most urgent in Guinea.

And if you thought all that wasn’t complicated enough, CIDRAP at the University of Minnesota and the Wellcome Trust put together a report on potential roadblocks, Bruce Lee and colleagues at the International Vaccine Access Center at John’s Hopkins highlighted seven possible vaccine roll-out issues and two moderators at ProMed added a couple more of their own. Getting to vaccination is a long road that is being heroically shortened for this epidemic, but that doesn’t make it a short path.

B4. Social factors/impact

IMF debateLast month I noted the publication of a commentary by Alex Kentikelenis et al. placing some of the blame for the size of the West Africa outbreak on the IMF’s past policies.  The IMF and Chris Blattman responded on the Monkey Cage blog.  And then things took off. On the Monkey Cage, Adia Benton and Kim Yi Dionne highlighted some key readings on how the IMF affects social spending, Alex responded to Chris, and Chris responded again.  Other notable contributions to the debate included one by Morten Jerven and another by Ken Opalo.

The takeaways are many, and will vary depending on your subjective view of the situation.  As someone who sees everything in shades of grey (no, that link is not to anything EL James related), I can see how the IMF has historically limited the scope for social expenditure in countries it has aided, but can also see how this limitation may have had beneficial knock-on effects on the countries in question, and how existing national political structures might have limited such spending even in the absence of IMF guidelines/strictures. Bottom line: as several commenters have said, the level of evidence in this debate could probably be improved. If, you know, anyone has the spare time and money to get that done…

Education: One impact of this outbreak that I have not been discussing much is the closure of schools. Aside from loss of learning, there have also been concerns within the affected countries about possible increases in teenage pregnancy [refs] All three most-affected countries are now considering re-opening schools, as a very public and visible sign of confidence that the worst is over.

Liberia is planning to reopen in February – although there is concern about children coming to school when sick, potentially because they are not able to understand/communicate their risk, or keep a social distance from classmates (this echoes what I’ve heard about treating young children at ETCs). There are also plenty of logistical problems with enrolling more than six-months’ worth of new pupils. And then of course this has become a political issue, with Senator George Weah (yes, that George Weah) criticizing the move. Upshot: schools are now set to open mid-February.

The minister of Education in Sierra Leone said on Jan 9th that it wouldn’t reopen until the epidemic is over, however by the 21st they have now slated the restart to be in March. Guinea was planning to reopen as early as Feb 2nd, but that now appears likely likely to be pushed back too.

Agriculture: I have seen stories ranging from “everything’s falling apart” to “it’s not really that bad”. In this context, this piece by Lisa Hamilton in The Atlantic provides a nice overview of the current situation: not great, could get worse is the gist I took away.

And finally, couple of things I wanted to include, but haven’t got a clear category for:

  1. A brief insight into a huge future issue: what happens economically after the epidemic ends? It’s not a pretty question, but it is a necessary one.
  2. A symposium on how Ebola looks from the Political Science world.  There is more than one Health/PoliSci person in there worth reading.

C. Journalism

A couple of notable general-consumption longform pieces that caught my eye in the past month:

Finally, I have seen a few more first-person accounts that I would argue are worth a few minutes of your time:

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 intellectual shoulders I am standing.

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

Ebola epidemiology roundup #9

This post covers roughly the month of December.

A. Charting the Epidemic

A1. Epidemic trajectory

Present. There is no doubt that the rapid expansion in case counts seen in September-November 2014 are now beginning to subside. This doesn’t necessarily mean a decline in case numbers – although this does still appear to be the case in Liberia – but does mean that growth is no longer exponential.  This is a good thing, even though there is a long way to go.  Whether this truly represents an improvement is less clear, although I have seen little suggestion that things are still as out of control as they were six weeks ago.

Future. The best estimates I’ve seen for final epidemic size (based on the admittedly imperfect data available), do seem to suggest that things are starting to come under control:

Tuite and Fisman, authors of the above figure, note that this downturn is a function of improvement in their model’s “control parameter”: i.e. the impact of some combination of human interventions appears to be being felt.

Modelling. There’s also an ongoing, rumbling debate about the role of modelling in the epidemic.  There continue to be concerns that projections were intentionally set high, in order to gain funds – either due to need or greed.  Others, for example Ian Mackay, have seen things differently, arguing that in a crisis, we make the best estimates we can and they necessarily come with uncertainty attached. In the end, I think it all comes down to how you view the unviewable – the motives of those making predictions.  And in this context, there were two excellent “explainer” pieces in Science and PNAS this month, laying out how modellers approach problems and how to read their results.  Andy Dobson laid out why this epidemic is hard to predict (no comparable case series for Ebola to compare it to) but that mathematical models present our only option for quantifying our uncertainty (Dobson commentary). Eric Lofgren and colleagues buttressed this argument with a step-by-step walk-through of how modellers think and why their efforts can provide useful structure in an uncertain situation (Lofgren commentary).

However, there is also an important paper out on the arXiv from Aaron King and colleagues, who highlight that fitting deterministic models has the potential to overestimate certainty in predictions (King paper).  By modelling our lack of knowledge arising from the poor quality of Ebola data using stochastic methods (they use a partially observed Markov process), the authors show how we can provide meaningful descriptions of the uncertainty present in model estimates. Which might help reduce the anger towards point predictions that prove incorrect.

A2. Epidemic parameters

At this point in the epidemic, many of Ebola’s natural history parameters are well described.1  However, the parameters that rely on the interaction of infection and response are not.  Primary amongst these is the case fatality rate (CFR), which continues to vary with time and space, and which is promoting a lively debate about what is the minimum level achievable – and how do we achieve it (see Treatment, below).  The WHO sitrep reports a CFR of around 60% at this point for hospitalized patients, but rates of around 35-50% seem to be more common in recent reports.  Indeed, Rachel Ansumana and colleagues at the Hastings ETC in Freetown have seen the mortality rate fall to 24% since early November (Asnumana letter).

The increasing number of cases recorded has also allowed for some interesting investigations of co-factors that reside within the human body.  Michael Lauck and colleagues showed that in a subsample of 49 patients from Gire et al.’s May/June Sierra Leone case series, the 13 that were infected with GB virus C (also known as Pegivirus, and previously as Hepatitis G) and that risk of death was almost halved, even after adjustment for age and sex, in those co-infected. (Lauck paper).  This is very preliminary data, but given previous evidence that GBV-C may be associated with better survival for HIV-infected persons, it’s a line of enquiry that may well be pursued in the future.

On another ongoing topic of interest – undetected Ebola, either at present or prior to this outbreak – I think that I have failed to previously flag a study by Randal Schoepp and colleagues from July 2014. (Schoepp paper).  Studying blood submitted to Kenema hospital between 2006 and 2008 to look for Lassa fever, the authors found that 8.6% of 253 patients tested positive for Ebola.  Since these individuals had a fever, this is a selected sample of the population, but suggests that a substantial proportion of infections previously thought to be other fevers in the area where Ebola emerged in 2014 may in fact have been Ebola.

Which links neatly to a study released this week by

Sam Scarpino and colleagues also used data from the Gire case series to look at clustering of social contacts. (Scarpino paper). The authors show that a best-fit network-structured state transition model requires far greater levels of triadic closure (i.e. the chance that two of my friends are friends with each other) than would be expected at random. This is hardly surprising, since we know such features are typical within close-knit groups such as those who attend funerals or care for one-another.  But a nice addition to the literature that highlights the importance of linking social factors to biological ones.

On the occupational health front, a paper from Peter Kilmarx and colleagues has quantified quite how hard the healthcare professional has been hit by Ebola, but also shows that infection rates probably peaked in August. (Kilmarx paper). The authors note that this fall-off in infection may reflect the closure of many healthcare settings, or improved preventative measures – an important question if efforts to re-open non-Ebola care settings are to proceed.

And finally, a worrying new development in recent weeks has been the emergence of post-recovery health problems for some patients. I wonder if anyone has the resources to track survivors to check on this over the next few months, or even to get at what aspect of the disease/treatment process has led to these conditions.

A3. Visualization

I know the past couple of posts have been light on visual representations, and I really can’t apologize enough about that.  This month, however, I can link you a Qlik Ebola widget that automatically builds from the data available on Datamarket to provide charts and dataviz on the outbreak. Lots to explore in there.  For example, here’s a figure comparing case and mortality rates at the sub-national level in each of the three most-affected countries.

I can also point you towards the sterling efforts of the Centre for the Mathematical Modelling of Infectious Diseases at LSHTM.  They are now putting out weekly sitreps with a wealth of data, and using that data to make epidemic need predictions (see Containment, below). Just to scratch the surface, here’s a figure of county-specific weekly case rates in Sierra Leone by type (suspected, probable, confirmed):

CMMID SL Cases Fig 31Dec2014

B. Stopping the Epidemic

B1. Containment

One topic that arose earlier in the year was the use of Community Containment Centres (CCC) to fill the gap when there was insufficient Ebola Treatment Centre/Unit (ETC, ETU) capacity available.  These CCCs would provide minimal care, but by keeping infectious individuals physically separate from their communities, might help reduce onward transmission.  Concern was raised that this amounted to sub-standard care, but in a limited resource situation in which building ETCs was going to take weeks, CCCs were built. (Notably, CCCs are classically public health orientated – benefiting the population, rather than the infected individual.) They have subsequently been assessed for safety, effectiveness, and operational feasibility (results not publicly available, so far as I know).  A recent modelling exercise by Adam Kucharski and colleagues showed that if individuals accessed CCCs within three days of becoming infectious, and if such facilities effectively isolated infectious patients, CCCs could shift Re below 1 (Kucharski paper). I’m not clear how necessary CCCs are now that ETC provision has been ramped up, but it’s good to know how good they need to be, in order to impact the epidemic.

And another ongoing issue: sexual transmission.  As a short report this month from Karen Rogstad and Anne Tunbridge shows, no case of sexual transmission has yet been seen – although virus may be present for several months post-infection in semen (Rogstad paper).  The authors highlight the need to study this in the future; another reason that following up recovered cases might be worthwhile, if/as/when we have the resources to do so.

Behaviour change. While I am quite sure that there is lots of social mobilization going on at the ground-level in SL, Liberia and Guinea, that isn’t getting much news coverage.  What is getting coverage, is bans on congregating at Christmas (in Sierra Leone and Liberia) and New Year (in Guinea, but not in Liberia).  Although allowances are apparently being made for religious gatherings – which may have led to an outbreak in Monrovia.

There also remains concern that burials are not being performed in a safe manner.  Quite possibly due to the perfectly valid fear that engaging with the Ebola care system is associated with death.  Although of course the alternative of not engaging with the system may be even more strongly associated with death. (Understanding counterfactuals is hard enough in a graduate school classroom, let alone in the midst of an epidemic.)  Sierra Leone has been conducting further lockdowns and house-to-house searches.

Whether this top-down approach will have the same impact as bottom-up change remains to be seen. The bottom-up approach is also coming in for some critical consideration this month too – Clare Chandler and colleagues at the Ebola Anthropology Response Platform highlighted the biomedical, exoticising and one-size-fits-all nature of current behaviour change messages for Ebola (Chandler comment).  The authors point to a more tailored messaging programme for best results.

B2. Treatment

One of the up-sides to outbreaks such as the current one is the spur it provides for “general-purpose” technologies that should carry over to many future epidemics and non-epidemics.  On this front, the more engineering-style Ebola hackathons have been very useful.  Recent examples include a double-layer PPE system involving magnets to remove the highest-risk outside layer and another PPE system with battery-powered cooling systems to allow for longer workperiods.  Hopefully, some of these designs will be cost- and build-feasible in the near future.

Another key aspect of treating the epidemic is identifying cases.  As of last week we have a faster test available, however as Laurie Garrett noted, a three-hour waiting time and the need for a lab make it a pretty poor step forwards.  The need for an accurate, rapid, field-ready test remains.

And yet another key factor is how we treat patients once they are in care.  A recent articles in the New York Times played up the level of debate amongst physicians about how aggressively to hydrate patients. My impression of the discussion of this article is that there is more heat than light to this, but there are certainly differing opinions over who/when to treat intravenously, with peripherally inserted central catheters or even intraosseous insertions.  Given the range of medical settings in place in Guinea/SL/Liberia, I expect to see continued variation in care and in opinion in the future.

Drugs. Turning to trials of novel treatments for Ebola, we have mixed news. As a backgrounder, I really liked this clear outline of the various Ebola lifecycle entry points for treatment, and available drugs, in an article by Dr Lai Kang-Yiu published late in November (Lai paper). I’m not a huge fan of the colour scheme, but this figure from the paper lays it all out for the more visual learners amongst us:

The idea of providing infected individuals with serum – roughly, the non-water part of blood – from recovered Ebola patients has been around for months, and in use in high-income settings.  A recent overview from Thomas Kriel highlighted the importance of virus-inactivating any blood collected (primarily for non-Ebola infections), as well as methods to negate the need for blood-matching.  In mid-December the first trial of convalescent serum in West Africa began in Liberia.

The not-so-good side of novel treatments is this story from a treatment centre in Freetown, where the antiarrhythmic amiodarone was being used without any formal testing process.  The (NHS) clinical team threatened to walk out of the Emergency-run facility , before agreement was reached to stop amiodarone’s use. I imagine that this is only one of many difficult processes that will arise in the roll-out of novel therapies.

I’ll also note this recent call for RCTs of proposed therapies in the NEJM.  Given the current fluctuations in mortality rates within and between hospitals, the case for randomized trials of some description may hold more water than it did when outcomes were pretty consistent. Especially in cases where effectiveness is not clear.

B3. Vaccines

No progress on in-country trials in West Africa, that I’ve heard of.  But there were a couple of vaccine stories in December.  First, the second Ebola vaccine in the pipeline (VSV-EBOV; originally Canadian, now NewLink/Merck) faced some hiccups during phase 1 (safety) trials, when some participants complained of joint pain and the trial was stopped early.  While some commentators saw this as a Very Bad Thing, the WHO claimed that such joint pain was not atypical for vaccines. I also noted with interest the final comment by Thomas Geisbert, who was involved in developing the VSV vaccine

[VSV-EBOV] is the best vaccine virus I’ve ever seen for the kind of viruses we work with. I don’t know why it’s so good…I’d never take [the GSK vaccine]. Not with the VSV. I’d take my chances with some joint pain.

Second, a phase 1b safety trial of a more general filovirus vaccine that has been running all year in Uganda was published showing effectiveness (in generating an immune response) and safety (Kibuuka paper). These findings have already been built into the related, but more advanced, Chimpanzee adenovirus ChAd3 that passed phase 1 testing in the US last month.  But researchers were happy to see that this family of vaccines had effect in African populations.  I’ll chalk this up as supporting evidence.

B4. Social factors/impact

There was some recent brouhaha over Alex Kentikelenis and several other Cambridge sociologists/epidemiologists’ letter to Lancet suggesting that the IMF’s policies in recent years had led to an underfunded healthcare system, and thus increased the impact of the current Ebola outbreak. (Kentikelenis letter).  The IMF responded to the say they didn’t see it that way, and had been proactive in providing funding once Ebola had emerged.  Chris Blattman, a Political Science professor at Columbia suggested the original authors misunderstood the IMF’s level of influence over health policy in the affected region. Of course, the impact of macroeconomic policy is very hard to evaluate – finding a realistic counterfactual for any action is close of impossible; so it all comes back down to how you read the tealeaves.  Or at least that’s how I see it…

The flip side of financial problems as a cause of the epidemic is financial problems as the fall-out.  In addition the massive macroeconomic impact of the epidemic, there are lower-level effects worth noting. Within the healthcare systems, clearly everything except Ebola treatment has been greatly scaled-back during the epidemic. This was highlighted in a recent paper by Håkon Bolkan and colleagues surveying changes in inpatient admissions and surgeries at 40 facilities across Sierra Leone in September and October  (Bolkan paper).  Not surprisingly, as Ebola rose, everything else fell precipitously:

On a side note, I really appreciated this paper as a nice, clean study that makes a simple point well.

The impact of Ebola on the healthcare system will have knock-on effects in years to come, especially for infectious diseases. (Although in some cases the effects are being felt already – see this recent report on the side-effects and complications being caused by antimalarials provided nationwide in Sierra Leone last month.) Effects on women are likely to be particularly severe, since they are both the most likely to be healthcare providers and consumers. Outside the healthcare sector, education has been put on hold for six months generally, agriculture and trading activity has been greatly affected, while NGO work in other sectors has also come to a halt. Food insecurity is not yet widespread, but may be considerable in rural subsistence settings.

C. Journalism

There are also a growing number of first-person narratives from foreign responders, worth reading to see what it is like working in ETCs or in other capacities on the front line.  I present these in no particular order (see also previous posts):

  • Paul Pronyk, infectious disease and public health physician working in Freetown.
  • John Wright, a British physician, was in Sierra Leone last month.
  • African platypus, an anonymous US nurse practitioner, was in Liberia in November/December.
  • Pieter Baker, a US epidemiologist working on surveillance in Sierra Leone.
  • Gillian McKay, a Canadian nurse and ETC PPE trainer in Sierra Leone.

I am only too aware that all of these are out-of-region persons who have arrived for this epidemic.  I would love to include more viewpoints from locals, but am not connected to them at present. I do see some one-off posts via American/European news sources, for example this report of a day in the life of a contact tracer in Monrovia. But more pointers very welcome.

The local person I read the most is Umaru Fofana, who writes for the BBC, Politico Sierra Leone and himself on Facebook.  But he is a journalist, rather than a practitioner. On that front, I’d also point you towards the range of other local journalism recently highlighted by Crawford Kilian.

D. Getting involved

  • For those of you with French language skills, there’s an Ebola MOOC from Unige (l’Université de Genève) and UNF3S (l’université numérique francophone des sciences du sport et de la santé), starting on January 12th.
  • If you are a modeller, you may be interested in the upcoming workshop on “Modeling the Spread and Control of Ebola in West Africa“, January 22-23 in Atlanta. They’re accepting posters too, but the deadline for that is January 8th.

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 intellectual shoulders I am standing.

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

1 This is mostly for my reference, but there was a paper published this month highlighting that phylodynamic methods can estimate key epidemiological parameters using only the 74 initial outbreak cases, as opposed to the larger number needed for count-based analysis (Samuel Alizon et al, Virulence 2014).