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.
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.