The Lancet
Aug 29, 2015 Volume 386 Number 9996 p829-930
http://www.thelancet.com/journals/lancet/issue/current

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Editorial
An Ebola vaccine: first results and promising opportunities
The Lancet
Published Online: 03 August 2015
DOI: http://dx.doi.org/10.1016/S0140-6736(15)61177-1
Today, The Lancet publishes the first results from a phase 3 cluster randomised trial of a novel Ebola virus vaccine. The study, sponsored and led by WHO, is a remarkable scientific and logistical achievement. In the midst of an extreme public health emergency, researchers, health workers, and community facilitators in Guinea included 7651 people in a trial to test the efficacy of a recombinant, replication-competent vesicular stomatitis virus-based vaccine expressing a surface glycoprotein of Ebola (Zaire). The authors conclude that their interim analysis indicates the vaccine “might be highly efficacious and safe”.

The technique used in the trial was “ring vaccination”. This method involves identifying a newly diagnosed person with Ebola, and then tracking down their contacts and contacts of contacts. This procedure is not without its challenges (it was the same approach used to eradicate smallpox). To identify this often complex network of contacts required the help of family and friends in many small and dispersed communities across the most affected parts of the country. That such a trial was even possible is a testament not only to the skill of the research teams but also to the commitment of communities to defeating an epidemic that has devastated their nation. Over 90% of the study’s staff were from Guinea. Before this work, no clinical trial on this scale had ever been performed in the country.

This study will be the subject of intense scientific scrutiny and debate. But what do the results mean for those most at risk of Ebola virus infection in west Africa? The vaccine is not yet licensed. More data on efficacy are needed before it can be widely deployed. But if the evidence proves sufficient for licensing, a Global Ebola Vaccine Implementation Team, also under WHO’s leadership, has been preparing the ground for its introduction—creating guidelines for the vaccine’s use, strategies for community engagement, and mechanisms to expand country capacity for the vaccine’s distribution and delivery. In addition, the GAVI Alliance has approved substantial funding for the procurement and deployment of the vaccine.

One important message goes beyond even Ebola—the power of multilateralism and inclusive partnership to devise and execute critical clinical research. Ebola has been a catastrophe for west Africa. But out of this epidemic has come the opportunity to build unprecedented collaborations to generate evidence to advance health. There have been few better examples to prove the value and importance of WHO to strengthen global health security.

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Articles
Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein: interim results from the Guinea ring vaccination cluster-randomised trial
Ana Maria Henao-Restrepo, Ira M Longini, Matthias Egger, Natalie E Dean, W John Edmunds, Anton Camacho, Miles W Carroll, Moussa Doumbia, Bertrand Draguez, Sophie Duraffour, Godwin Enwere, Rebecca Grais, Stephan Gunther, Stefanie Hossmann, Mandy Kader Kondé, Souleymane Kone, Eeva Kuisma, Myron M Levine, Sema Mandal, Gunnstein Norheim, Ximena Riveros, Aboubacar Soumah, Sven Trelle, Andrea S Vicari, Conall H Watson, Sakoba Kéïta, Marie Paule Kieny, John-Arne Røttingen
Published Online: 03 August 2015
DOI: http://dx.doi.org/10.1016/S0140-6736(15)61117-5
Summary
Background
A recombinant, replication-competent vesicular stomatitis virus-based vaccine expressing a surface glycoprotein of Zaire Ebolavirus (rVSV-ZEBOV) is a promising Ebola vaccine candidate. We report the results of an interim analysis of a trial of rVSV-ZEBOV in Guinea, west Africa.
Methods
For this open-label, cluster-randomised ring vaccination trial, suspected cases of Ebola virus disease in Basse-Guinée (Guinea, west Africa) were independently ascertained by Ebola response teams as part of a national surveillance system. After laboratory confirmation of a new case, clusters of all contacts and contacts of contacts were defined and randomly allocated 1:1 to immediate vaccination or delayed (21 days later) vaccination with rVSV-ZEBOV (one dose of 2 × 107 plaque-forming units, administered intramuscularly in the deltoid muscle). Adults (age ≥18 years) who were not pregnant or breastfeeding were eligible for vaccination. Block randomisation was used, with randomly varying blocks, stratified by location (urban vs rural) and size of rings (≤20 vs >20 individuals). The study is open label and masking of participants and field teams to the time of vaccination is not possible, but Ebola response teams and laboratory workers were unaware of allocation to immediate or delayed vaccination. Taking into account the incubation period of the virus of about 10 days, the prespecified primary outcome was laboratory-confirmed Ebola virus disease with onset of symptoms at least 10 days after randomisation. The primary analysis was per protocol and compared the incidence of Ebola virus disease in eligible and vaccinated individuals in immediate vaccination clusters with the incidence in eligible individuals in delayed vaccination clusters. This trial is registered with the Pan African Clinical Trials Registry, number PACTR201503001057193.
Findings
Between April 1, 2015, and July 20, 2015, 90 clusters, with a total population of 7651 people were included in the planned interim analysis. 48 of these clusters (4123 people) were randomly assigned to immediate vaccination with rVSV-ZEBOV, and 42 clusters (3528 people) were randomly assigned to delayed vaccination with rVSV-ZEBOV. In the immediate vaccination group, there were no cases of Ebola virus disease with symptom onset at least 10 days after randomisation, whereas in the delayed vaccination group there were 16 cases of Ebola virus disease from seven clusters, showing a vaccine efficacy of 100% (95% CI 74·7–100·0; p=0·0036). No new cases of Ebola virus disease were diagnosed in vaccinees from the immediate or delayed groups from 6 days post-vaccination. At the cluster level, with the inclusion of all eligible adults, vaccine effectiveness was 75·1% (95% CI −7·1 to 94·2; p=0·1791), and 76·3% (95% CI −15·5 to 95·1; p=0·3351) with the inclusion of everyone (eligible or not eligible for vaccination). 43 serious adverse events were reported; one serious adverse event was judged to be causally related to vaccination (a febrile episode in a vaccinated participant, which resolved without sequelae). Assessment of serious adverse events is ongoing.
Interpretation
The results of this interim analysis indicate that rVSV-ZEBOV might be highly efficacious and safe in preventing Ebola virus disease, and is most likely effective at the population level when delivered during an Ebola virus disease outbreak via a ring vaccination strategy.
Funding
WHO, with support from the Wellcome Trust (UK); Médecins Sans Frontières; the Norwegian Ministry of Foreign Affairs through the Research Council of Norway; and the Canadian Government through the Public Health Agency of Canada, Canadian Institutes of Health Research, International Development Research Centre, and Department of Foreign Affairs, Trade and Development.

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Articles
ReEBOV Antigen Rapid Test kit for point-of-care and laboratory-based testing for Ebola virus disease: a field validation study
Mara Jana Broadhurst, John Daniel Kelly, Ann Miller, Amanda Semper, Daniel Bailey, Elisabetta Groppelli, Andrew Simpson, Tim Brooks, Susan Hula, Wilfred Nyoni, Alhaji B Sankoh, Santigi Kanu, Alhaji Jalloh, Quy Ton, Nicholas Sarchet, Peter George, Mark D Perkins, Betsy Wonderly, Megan Murray, Nira R Pollock
Summary
Background
At present, diagnosis of Ebola virus disease requires transport of venepuncture blood to field biocontainment laboratories for testing by real-time RT-PCR, resulting in delays that complicate patient care and infection control efforts. Therefore, an urgent need exists for a point-of-care rapid diagnostic test for this disease. In this Article, we report the results of a field validation of the Corgenix ReEBOV Antigen Rapid Test kit.
Methods
We performed the rapid diagnostic test on fingerstick blood samples from 106 individuals with suspected Ebola virus disease presenting at two clinical centres in Sierra Leone. Adults and children who were able to provide verbal consent or assent were included; we excluded patients with haemodynamic instability and those who were unable to cooperate with fingerstick or venous blood draw. Two independent readers scored each rapid diagnostic test, with any disagreements resolved by a third. We compared point-of-care rapid diagnostic test results with clinical real-time RT-PCR results (RealStar Filovirus Screen RT-PCR kit 1·0; altona Diagnostics GmbH, Hamburg, Germany) for venepuncture plasma samples tested in a Public Health England field reference laboratory (Port Loko, Sierra Leone). Separately, we performed the rapid diagnostic test (on whole blood) and real-time RT-PCR (on plasma) on 284 specimens in the reference laboratory, which were submitted to the laboratory for testing from many clinical sites in Sierra Leone, including our two clinical centres.
Findings
In point-of-care testing, all 28 patients who tested positive for Ebola virus disease by RT-PCR were also positive by fingerstick rapid diagnostic test (sensitivity 100% [95% CI 87·7–100]), and 71 of 77 patients who tested negative by RT-PCR were also negative by the rapid diagnostic test (specificity 92·2% [95% CI 83·8–97·1]). In laboratory testing, all 45 specimens that tested positive by RT-PCR were also positive by the rapid diagnostic test (sensitivity 100% [95% CI 92·1–100]), and 214 of 232 specimens that tested negative by RT-PCR were also negative by the rapid diagnostic test (specificity 92·2% [88·0–95·3]). The two independent readers agreed about 95·2% of point-of-care and 98·6% of reference laboratory rapid diagnostic test results. Cycle threshold values ranged from 15·9 to 26·3 (mean 22·6 [SD 2·6]) for the PCR-positive point-of-care cohort and from 17·5 to 26·3 (mean 21·5 [2·7]) for the reference laboratory cohort. Six of 16 banked plasma samples from rapid diagnostic test-positive and altona-negative patients were positive by an alternative real-time RT-PCR assay (the Trombley assay); three (17%) of 18 samples from individuals who were negative by both the rapid diagnostic test and altona test were also positive by Trombley.
Interpretation
The ReEBOV rapid diagnostic test had 100% sensitivity and 92% specificity in both point-of-care and reference laboratory testing in this population (maximum cycle threshold 26·3). With two independent readers, the test detected all patients who were positive for Ebola virus by altona real-time RT-PCR; however, this benchmark itself had imperfect sensitivity.
Funding
Abundance Foundation.

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Viewpoint
Public health, universal health coverage, and Sustainable Development Goals: can they coexist?
Harald Schmidt, Lawrence O Gostin, Ezekiel J Emanuel
Published Online: 29 June 2015
DOI: http://dx.doi.org/10.1016/S0140-6736(15)60244-6