The Lancet Infectious Diseases – Sept 2015

The Lancet Infectious Diseases
Sep 2015 Volume 15 Number 9 p987-1114
http://www.thelancet.com/journals/laninf/issue/current

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Articles
Effect of the Ebola-virus-disease epidemic on malaria case management in Guinea, 2014: a cross-sectional survey of health facilities
Published Online: 23 June 2015
DOI: http://dx.doi.org/10.1016/S1473-3099(15)00061-4
Dr Mateusz M Plucinski, PhD, Timothée Guilavogui, MD, Sidibe Sidikiba, MD, Nouman Diakité, MD, Souleymane Diakité, MD, Mohamed Dioubaté, MS, Ibrahima Bah, MS, Ian Hennessee, MPH, Jessica K Butts, MPH, Eric S Halsey, MD, Peter D McElroy, PhD, S Patrick Kachur, MD, Jamila Aboulhab, MD, Richard James, MD, Moussa Keita, MD
Summary
Background
The ongoing west Africa Ebola-virus-disease epidemic has disrupted the entire health-care system in affected countries. Because of the overlap of symptoms of Ebola virus disease and malaria, the care delivery of malaria is particularly sensitive to the indirect effects of the current Ebola-virus-disease epidemic. We therefore characterise malaria case management in the context of the Ebola-virus-disease epidemic and document the effect of the Ebola-virus-disease epidemic on malaria case management.
Methods
We did a cross-sectional survey of public health facilities in Guinea in December, 2014. We selected the four prefectures most affected by Ebola virus disease and selected four randomly from prefectures without any reported cases of the disease. 60 health facilities were sampled in Ebola-affected and 60 in Ebola-unaffected prefectures. Study teams abstracted malaria case management indicators from registers for January to November for 2013 and 2014 and interviewed health-care workers. Nationwide weekly surveillance data for suspect malaria cases reported between 2011 and 2014 were analysed independently. Data for malaria indicators in 2014 were compared with previous years.
Findings
We noted substantial reductions in all-cause outpatient visits (by 23 103 [11%] of 214 899), cases of fever (by 20249 [15%] of 131 330), and patients treated with oral (by 22 655 [24%] of 94 785) and injectable (by 5219 [30%] of 17 684) antimalarial drugs in surveyed health facilities. In Ebola-affected prefectures, 73 of 98 interviewed community health workers were operational (74%, 95% CI 65–83) and 35 of 73 were actively treating malaria cases (48%, 36–60) compared with 106 of 112 (95%, 89–98) and 102 of 106 (96%, 91–99), respectively, in Ebola-unaffected prefectures. Nationwide, the Ebola-virus-disease epidemic was estimated to have resulted in 74 000 (71 000–77 000) fewer malaria cases seen at health facilities in 2014.
Interpretation
The reduction in the delivery of malaria care because of the Ebola-virus-disease epidemic threatens malaria control in Guinea. Untreated and inappropriately treated malaria cases lead to excess malaria mortality and more fever cases in the community, impeding the Ebola-virus-disease response.
Funding
Global Fund to Fight AIDS, Tuberculosis and Malaria, and President’s Malaria Initiative.

Clinical features of patients isolated for suspected Ebola virus disease at Connaught Hospital, Freetown, Sierra Leone: a retrospective cohort study
Marta Lado, Naomi F Walker, Peter Baker, Shamil Haroon, Colin S Brown, Daniel Youkee, Neil Studd, Quaanan Kessete, Rishma Maini, Tom Boyles, Eva Hanciles, Alie Wurie, Thaim B Kamara, Oliver Johnson, Andrew J M Leather

Clinical features and viral kinetics in a rapidly cured patient with Ebola virus disease: a case report
Manuel Schibler, Pauline Vetter, Pascal Cherpillod, Tom J Petty, Samuel Cordey, Gaël Vieille, Sabine Yerly, Claire-Anne Siegrist, Kaveh Samii, Julie-Anne Dayer, Mylène Docquier, Evgeny M Zdobnov, Andrew J H Simpson, Paul S C Rees, Felix Baez Sarria, Yvan Gasche, François Chappuis, Anne Iten, Didier Pittet, Jérôme Pugin, Laurent Kaiser
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Articles
High titre neutralising antibodies to influenza after oral tablet immunisation: a phase 1, randomised, placebo-controlled trial
David Liebowitz, MD, Jonathan D Lindbloom, BA, Jennifer R Brandl, BS, Shaily J Garg, BS, Dr Sean N Tucker, PhD
DOI: http://dx.doi.org/10.1016/S1473-3099(15)00266-2
Summary
Background
Most influenza vaccines are manufactured in eggs, and the inactivated virus is purified for injection. For a seasonal influenza product, manufacturing, distribution, and perhaps even vaccine coverage, would be greatly improved with an oral tablet alternative made in cell culture. We aimed to assess the safety and immunogenicity of an oral tablet vaccine against influenza A H1N1 in healthy adults.
Methods
At a single site, we did a randomised, double-blind, placebo-controlled trial of a monovalent influenza A H1N1 vaccine to establish the safety and immunogenicity of a recombinant, non-replicating, adenovirus vector expressing haemagglutinin and double-stranded RNA adjuvant delivered orally by tablets. Participants had to have an initial haemagglutination inhibition titre of at most 1/20, be aged between 18 and 49 years, and be in good health. We randomly assigned (1:1) participants to receive either a single oral dose of vaccine or placebo. Randomisation was done by computer-generated assignment, and study drug was distributed with concealed identity to the masked staff by an unmasked pharmacist. Investigative site staff, people directly involved with immunological assays or the assessment of clinical safety, and participants were masked to treatment assignments. Solicited symptoms of reactogenicity were assessed, and all safety assessments were reported through the active phase of the study (day 28). Immunogenicity was assessed by haemagglutination inhibition titres, the percentage of participants that seroconverted, microneutralisation titres, and the number of antibody secreting cells. Descriptive statistics were used for continuous variables and t-tests or Fisher’s exact tests were used to compare treatment groups. The study is registered at ClinicalTrials.gov, number NCT01688297.
Findings
24 participants were enrolled in the study at WCCT Global between Dec 2, 2013, and April 15, 2014. Adverse events were mild in nature, and occurred with similar frequency in vaccine (four events) and placebo recipients (four events). After immunisation, 11 (92%) of 12 vaccine-treated participants had a four-fold increase in haemagglutination inhibition titres (group geometric mean fold rise of 7·7) and microneutralisation titres (group geometric mean fold rise of 29). No participants in the placebo group had a four-fold increase in haemagglutination inhibition titres (group geometric mean fold rise of 1·1) or microneutralisation titres (group geometric mean fold rise of 1·0). Neutralising antibody responses to influenza were not hindered by pre-existing immunity to the vector.
Interpretation
An oral recombinant adenovirus vaccine to influenza was well tolerated and can elicit neutralising antibody responses to influenza virus in human beings. These data are a step forward in making oral influenza vaccination possible.
Funding
Vaxart Inc.