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.

 

What’s new in Ebola research: October 2015

Another round-up of new publications on Ebola, primarily items first put out in public in the month of October 2015. This is largely a list, with a little light curation and commentary.  Comments, missed items and disagreements welcome.

A. Clinical epidemiology

Papers this month highlight how Ebola differentially affects healthcare workers, children, mothers and infants and survivors and their sexual partners.

Epidemiology of Ebola virus disease transmission among health care workers in Sierra Leone, May to December 2014: a retrospective descriptive studyOlushayo Olu and MoH/WHO colleagues interviewed 293 infected healthcare workers and found the main (presumed) locations of infection to be the workers’ homes and non-Ebola healthcare settings. Over one-third of infected HCWs reported not having been trained in infection prevention/control pre-infection.

Did Ebola relatively spare children? Stephane Helleringer and colleagues cast some doubt on previous estimates that children had lower Ebola incidence rates than children, noting age-specific differences in: (i) historic health-seeking behaviour; (ii) speed of disease progression; and (iii) identification as contacts of infected individuals, each of which may have led to selective underreporting.

Ebola viral disease and pregnancy. Benjamin Black and colleagues review the many complications of pregnancy and birth for women infected with Ebola, including the absence of any recorded neonatal survival, potential for transmission perinatally to healthcare workers and ongoing risk from breast milk which may be infected. The authors suggest a focus on maternal support, given the very low probability of child survival.

Ebola RNA Persistence in Semen of Ebola Virus Disease Survivors — Preliminary Report. Gibrilla Deen and colleagues analysed one-off semen from 93 Ebola survivors, finding RT-PCR positive results as late as 9 months post-infection: although there was a notable fall-off in detection probability after 5 months. Crucially, the authors note we do not know how RT-PCR positivity is associated with virus infectivity.

Molecular Evidence of Sexual Transmission of Ebola Virus. Suzanne Mate and colleagues present genomic evidence to support the claim that the last known Ebola infection in Liberia (in March 2015) was infected via sexual transmission from an Ebola survivor six months post-disease onset.

Not a published paper yet, but Miles Carroll and colleagues presented ongoing work that suggested a woman had acquired Ebola antibodies without apparently ever contracting the virus. This could be very important for understanding both individual immunity, and evidence that a minority of those living in West Africa had Ebola antibodies prior to 2014. This was part of a larger body of work studying Ebola infected survivors and close contacts of infected individuals.

B. Non-Ebola impact of the epidemic

Papers this month include the past and continuing impact of Ebola on those giving birth, TB, measles, the healthcare system as a whole and GDP.

A case series study on the effect of Ebola on facility-based deliveries in rural LiberiaJody Lori and colleagues show the rapid fall-off in use of maternal waiting homes as Ebola advanced in the middle of 2014 in Bong county. Impact on MCH.

Ebola, fragile health systems and tuberculosis care: a call for pre-emptive action and operational research. Rony Zachariah and colleagues highlight the potential spillover of the Ebola epidemic in affecting tuberculosis control efforts in affected countries, due to repurposing or mothballing of TB resources, fear of healthcare generally and loss of healthcare staff to Ebola. The authors highlight the lack of research into the impact of Ebola on TB to date.

Mitigating measles outbreaks in West Africa post-Ebola. Shaun Truelove and colleagues are not the first to point out the risk of re-emerging infectious diseases in the countries most affected by Ebola (see also, TB, malaria, maternal and infant health, nutrition, etc).  Their editorial, however, does point to the need to fill gaps left by the Ebola epidemic, and to leverage systems set up for Ebola to fight the potential wave of post-Ebola health issues.

Impact of the Ebola outbreak on health systems and population health in Sierra Leone. James Elston and colleagues highlight (using both quantitative and qualitative methods) the multiple ways in which the Ebola epidemic has led to a loss of trust in the healthcare system in Sierra Leone, even as the epidemic has waned, and the need for investment in rebuilding the system and engagement between community and healthcare providers.

Indirect costs associated with deaths from the Ebola virus disease in West Africa.  Joses Muthuri Kirigia (at WHO AFRO) and colleagues calculated the future loss of GDP due to productive years of life lost from Ebola morbidity and mortality. They estimate that the three most-affected nations will lose approximately I$ 150m from this epidemic due to non-health GDP losses.


 C. Operational research

A range of topics here: three evaluations of epidemic responses – contact tracing, healthcare workers as infection vectors, treatment beds as prevention – as well as estimates of epidemic underreporting and variation in numbers of secondary cases created by those infected.

Contact Tracing Activities during the Ebola Virus Disease Epidemic in Kindia and Faranah, Guinea, 2014Meredith Dixon and colleagues highlight the limited capacity of contact tracing to find cases before they became symptomatic in Guinea in late 2014.

Role of healthcare workers in early epidemic spread of Ebola: policy implications of prophylactic compared to reactive vaccination policy in outbreak prevention and controlCordelia Coltart and colleagues highlight the potential benefits of inoculating healthcare workers in at-risk settings with any Ebola vaccine that proved to provide long-lived immunity: not just in terms of maintaining a motivated and healthy workforce during any future outbreak, but also as a means of dramatically reducing take-off of infection chains – based on evidence from past outbreaks.

Measuring the impact of Ebola control measures in Sierra LeoneAdam Kucharski and colleagues highlight (via a mathematical model) that the exact timing of effective control measures (specifically the expansion of treatment beds) in late 2014 had a huge impact on the total number cases and deaths seen – since it altered the whole trajectory of the epidemic.

Use of Capture–Recapture to Estimate Underreporting of Ebola Virus Disease, Montserrado County, Liberia. Etienne Gignoux and colleagues at MSF triangulated data from Ministry of Health case investigation records and ETU records from June to August 2014, to estimate that three-quarters of all cases in this period were unreported.

MERS, SARS and Ebola: The role of super-spreaders in infectious disease. Gary Wong and colleagues highlight the importance of heterogeneity in numbers of cases caused by each infectious person in Ebola, as in key emerging respiratory infections over the past few years.

 

D. Miscellanea

Each of the issues raised below is important, I just could not easily find a theme under which to categorize them.

Effectively Communicating the Uncertainties Surrounding Ebola Virus Transmission. Andy Kilianski and Nicholas Evans draw on academic literature debating the possibility of airborne Ebola at the peak of the epidemic to highlight the importance of making claims with clear markers of uncertainty of evidence and relative likelihood of competing hypotheses, for the good of both the research community’s reputation and the public’s future health.

Beyond Ebola Ethics: Do Nurses have a Duty to Treat? Miriam Walter explores the duty of care that nurses and other healthcare workers may have to patients of highly virulent or infectious diseases, such as Ebola, and whether society has the legal or moral right to require such service. No easy answers, but a thought-provoking read.

The Ebola response in West Africa Exposing the politics and culture of international aid. Marc DuBois and colleageus at the ODI have compiled a report looking at the humanitarian aid system in light of the Ebola outbreak. The authors are damning, but not in a blanket manner, and highlight the importance of political rather than technical changes in achieving better results in the future.