The Lancet Global Health
Volume 3, No. 3, e162–e168, March 2015
http://www.thelancet.com/journals/langlo/issue/current
Editorial
Ebola vaccines: an uncertain future?
Zoë Mullan
Published Online: 11 February 2015
Open Access
DOI: http://dx.doi.org/10.1016/S2214-109X(15)70083-5
On Jan 28, the preliminary phase 1 safety data for GlaxoSmithKline’s (GSK’s) candidate Ebola vaccine were published. The chimpanzee adenovirus vector (ChAd3) vaccine, which encodes a wild-type surface glycoprotein from Zaire Ebolavirus, raised no safety concerns in the 60 healthy volunteers from the UK tested and showed reasonable immunogenicity. Five days later, the first dose was given to a Liberian man as part of an expedited phase 3 trial in west Africa. Phase 1 trials of at least two other candidates are in progress: Merck’s Zaire-strain-encoding vesicular stomatitis virus (VSV) vector, and Johnson & Johnson’s heterologous prime-boost vaccine based on human Ad26 and modified vaccinia Ankara (MVA) vectors expressing Zaire strain glycoprotein.
The rapid roll-out of these trials has been tremendously impressive. Yet none of the vaccines were originally developed with African public health in mind: they were created out of fear that the virus could be used as a bioweapon. Concerns over limited market size and recipient governments’ ability to pay meant that the business case for a population-level Ebola vaccine was flimsy. Now, as the epidemic wanes and phase 3 trials and licensing become more complex, there is a risk that manufacturers will revert back to this previous state of thinking. Declining case numbers have already led drug manufacturer Chimerix to pull out of a trial of brincidofovir in Liberia. This is disheartening to say the least.
The reduction in incidence of Ebola virus disease has been brought about by means of a combination of scaled-up treatment capacity, safe burial practices, and rigorous case and contact finding. Vital communication and consultation work with communities has improved trust and understanding. But, as Brian McCloskey from the Office of the UN Special Envoy on Ebola was at pains to point out at a seminar in London last week, the outbreak cannot yet be considered under control. In fact a slight uptick in cases since the beginning of February illustrates his point. He further emphasised that the outlook is now not one of a single epidemic across three countries, but of perhaps 60 or more localised outbreaks with the very real potential to spread across borders into countries such as Mali and Côte d’Ivoire.
The UN’s response strategy is now moving away from a concentration on treating the vast volume of cases and towards elimination of transmission. Here vaccines play a vital role. It was ring vaccination—ie, the vaccination of a “ring” of individuals potentially exposed to a case—that saw the eradication of smallpox in 1980. Furthermore, as Peter Piot noted at the same seminar, Ebola’s ability to disrupt the whole health system by means of decimating the workforce is as potent a threat as its case–fatality rate. Vaccination of health workers could neutralise this threat. With the UN’s focus now on case and contact finding and with a still-uncertain epidemic trajectory, the drive to bring vaccines (and the more the better) to licensing and production should not falter.
So what of the realities of this for vaccine manufacturers? There is hope. First, a willingness to collaborate between governments, funding bodies, and companies has been key to the success of the vaccine trials so far. The phase 1 GSK vaccine trial in the UK, for example, was funded by the Wellcome Trust, the UK Department for International Development, the UK Medical Research Council, and the UK National Institute for Health Research. Financial support for its further development is being provided by the European Union, the Bill & Melinda Gates Foundation, and the Swiss Government. GSK has committed to scaling up vaccine production even as later-phase trials are ongoing. Second, governments are offering levers such as tax incentives and extended exclusivity rights to drive manufacturers on. And third, regulators are showing signs of flexibility in terms of accelerated licensure in the event that the waning epidemic delays the ability to demonstrate efficacy.
Vaccines are not a magic bullet. Nothing can replace the basic tenets of public health epidemiology and community mobilisation. But in the early days of a new outbreak in an unprepared population, as in all likelihood will happen again, vaccines can be a vital early weapon. Once we are reasonably assured of safety and efficacy, everything must be done to ensure that stockpiles are ready and the necessary clearances for their use are in place.
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Comment
Trafficking, migration, and health: complexities and future directions
Shira M Goldenberg
Open Access
DOI: http://dx.doi.org/10.1016/S2214-109X(15)70082-3
Summary
Documenting the health-related harms associated with human trafficking is crucial for the development of strategies to protect and promote the health of individuals who experience this serious human rights violation. In The Lancet Global Health, Ligia Kiss and colleagues1 report the results of a study of 1102 men, women, and children receiving post-trafficking services in Cambodia, Thailand, and Vietnam—the largest quantitative study of its kind. They document the health-related harms experienced by men, women, and children trafficked for sex work (32%), fishing (27%), and factory work (13%).
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Comment
Effectiveness of oral cholera vaccine in Haiti
Francisco J Luquero, David A Sack
DOI: http://dx.doi.org/10.1016/S2214-109X(15)70015-X
Summary
Although killed, whole-cell oral cholera vaccines (OCVs) have been known to be efficacious since 1986,1 and the bivalent whole-cell vaccine Shanchol has been licensed in India since 2009,2 OCV was not regarded as useful for controlling cholera outbreaks until recently.2 Many public health officials questioned the use of OCV,3 including concerns about its cost, the feasibility of undertaking large campaigns, the acceptability of OCV among vaccinated communities, and the possibility of diverting resources from other interventions.
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Articles
Dietary quality among men and women in 187 countries in 1990 and 2010: a systematic assessment
Fumiaki Imamura, Renata Micha, Shahab Khatibzadeh, Saman Fahimi, Peilin Shi, John Powles, Dariush Mozaffarian, on behalf of the Global Burden of Diseases Nutrition and Chronic Diseases Expert Group (NutriCoDE)
e132
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Cost-effectiveness of two versus three or more doses of intermittent preventive treatment for malaria during pregnancy in sub-Saharan Africa: a modelling study of meta-analysis and cost data
Silke Fernandes, Elisa Sicuri, Kassoum Kayentao, Anne Maria van Eijk, Jenny Hill, Jayne Webster, Vincent Were, James Akazili, Mwayi Madanitsa, Feiko O ter Kuile, Kara Hanson
e143
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Health of men, women, and children in post-trafficking services in Cambodia, Thailand, and Vietnam: an observational cross-sectional study
Ligia Kiss, Nicola S Pocock, Varaporn Naisanguansri, Soksreymom Suos, Brett Dickson, Doan Thuy, Jobst Koehler, Kittiphan Sirisup, Nisakorn Pongrungsee, Van Anh Nguyen, Rosilyne Borland, Poonam Dhavan, Cathy Zimmerman
e154
Summary
Background
Trafficking is a crime of global proportions involving extreme forms of exploitation and abuse. Yet little research has been done of the health risks and morbidity patterns for men, women, and children trafficked for various forms of forced labour.
Methods
We carried out face-to-face interviews with a consecutive sample of individuals entering 15 post-trafficking services in Cambodia, Thailand, and Vietnam. We asked participants about living and working conditions, experience of violence, and health outcomes. We measured symptoms of anxiety and depression with the Hopkins Symptoms Checklist and post-traumatic stress disorder with the Harvard Trauma Questionnaire, and used adjusted logistic regression models to estimate the effect of trafficking on these mental health outcomes, controlling for age, sector of exploitation, and time in trafficking.
Findings
We interviewed 1102 people, of whom 1015 reached work destinations. Participants worked in various sectors including sex work (329 [32%]), fishing (275 [27%]), and factories (136 [13%]). 481 (48%) of 1015 experienced physical violence, sexual violence, or both, with 198 (35%) of 566 women and girls reporting sexual violence. 478 (47%) of 1015 participants were threatened and 198 (20%) were locked in a room. 685 (70%) of 985 who had data available worked 7 days per week and 296 (30%) of 989 worked at least 11 hours per day. 222 (22%) of 983 had a serious injury at work. 61•2% (95% CI 58•2–64•2) of participants reported symptom of depression, 42•8% (39•8–45•9) reported symptoms of anxiety, and 38•9% (36•0–42•0) reported symptoms of post-traumatic stress disorder. 5•2% (4•0–6•8) had attempted suicide in the past month. Participants who experienced extremely excessive overtime at work, restricted freedom, bad living conditions, threats, or severe violence were more likely to report symptoms of depression, anxiety, and post-traumatic stress disorder.
Interpretation
This is the first health study of a large and diverse sample of men, women, and child survivors of trafficking for various forms of exploitation. Violence and unsafe working conditions were common and psychological morbidity was associated with severity of abuse. Survivors of trafficking need access to health care, especially mental health care.
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Articles
Effectiveness of reactive oral cholera vaccination in rural Haiti: a case-control study and bias-indicator analysis
Dr Louise C Ivers, MBBCh, Isabelle J Hilaire, MD, Jessica E Teng, MPH, Charles P Almazor, MD, J Gregory Jerome, MD, Ralph Ternier, MD, Jacques Boncy, MD, Josiane Buteau, MD, Prof Megan B Murray, MD, Jason B Harris, MD, Molly F Franke, ScD
DOI: http://dx.doi.org/10.1016/S2214-109X(14)70368-7
Open access funded by the Author(s)
Summary
Background
Between April and June, 2012, a reactive cholera vaccination campaign was done in Haiti with an oral inactivated bivalent whole-cell vaccine. We aimed to assess the effectiveness of the vaccine in a case-control study and to assess the likelihood of bias in that study in a bias-indicator study.
Methods
Residents of Bocozel or Grand Saline who were eligible for the vaccination campaign (ie, age ≥12 months, not pregnant, and living in the region at the time of the vaccine campaign) were included. In the primary case-control study, cases had acute watery diarrhoea, sought treatment at one of three participating cholera treatment units, and had a stool sample positive for cholera by culture. For each case, four control individuals who did not seek treatment for acute watery diarrhoea were matched by location of residence, enrolment time (within 2 weeks of the case), and age (1–4 years, 5–15 years, and >15 years). Cases in the bias-indicator study were individuals with acute watery diarrhoea with a negative stool sample for cholera. Controls were selected in the same manner as in the primary case-control study. Trained staff used standard laboratory procedures to do rapid tests and stool cultures from study cases. Participants were interviewed to collect data on sociodemographic characteristics, risk factors for cholera, and self-reported vaccination. Data were analysed by conditional logistic regression, adjusting for matching factors.
Findings
From Oct 24, 2012, to March 9, 2014, 114 eligible individuals presented with acute watery diarrhoea and were enrolled, 25 of whom were subsequently excluded. 47 participants were analysed as cases in the vaccine effectiveness case-control study and 42 as cases in the bias-indicator study. 33 (70%) of 47 cholera cases self-reported vaccination versus 167 (89%) of 188 controls (vaccine effectiveness 63%, 95% CI 8–85). 27 (57%) of 47 cases had certified vaccination versus 147 (78%) of 188 controls (vaccine effectiveness 58%, 13–80). Neither self-reported nor verified vaccination was significantly associated with non-cholera diarrhoea (vaccine effectiveness 18%, 95% CI −208 to 78 by self-report and −21%, −238 to 57 by verified vaccination).
Interpretation
Bivalent whole-cell oral cholera vaccine effectively protected against cholera in Haiti from 4 months to 24 months after vaccination. Vaccination is an important component of efforts to control cholera epidemics.
Funding
National Institutes of Health, Delivering Oral Vaccines Effectively project, and Department of Global Health and Social Medicine at Harvard Medical School.
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