Vaccines and Global Health: The Week in Review 28 February 2015

Vaccines and Global Health: The Week in Review is a weekly digest  summarizing news, events, announcements, peer-reviewed articles and research in the global vaccine ethics and policy space. Content is aggregated from key governmental, NGO, international organization and industry sources, key peer-reviewed journals, and other media channels. This summary proceeds from the broad base of themes and issues monitored by the Center for Vaccine Ethics & Policy in its work: it is not intended to be exhaustive in its coverage. You are viewing the blog version of our weekly digest, typically comprised of between 30 and 40 posts below all dated with the current issue date

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- pdf version A pdf of the current issue is available here: Vaccines and Global Health_The Week in Review_28 February 2015

- blog edition: comprised of the approx. 35+ entries posted below on this date.

- Twitter:  Readers can also follow developments on twitter: @vaxethicspolicy.
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Links:  We endeavor to test each link as we incorporate it into any post, but recognize that some links may become “stale” as publications and websites reorganize content over time. We apologize in advance for any links that may not be operative. We believe the contextual information in a given post should allow retrieval, but please contact us as above for assistance if necessary.
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David R. Curry, MS
Executive Director
Center for Vaccine Ethics and Policy
a program of the
– Division of Medical Ethics, NYU Medical School
– The Wistar Institute Vaccine Center
– Children’s Hospital of Philadelphia Vaccine Education Center
Associate Faculty, Division of Medical Ethics, NYU Medical School

EBOLA/EVD [to 28 February 2015]

EBOLA/EVD [to 28 February 2015]
Public Health Emergency of International Concern (PHEIC); “Threat to international peace and security” (UN Security Council)

WHO: Ebola Situation Report – 25 February 2015
[Excerpt; Editor’s text bolding]
SUMMARY
:: A total of 99 new confirmed cases of Ebola virus disease (EVD) were reported in the week to 22 February. Guinea reported 35 new confirmed cases. Cases continue to arise from unknown chains of transmission. Transmission remains widespread in Sierra Leone, with 63 new confirmed cases. A spike of 20 new confirmed cases in Bombali is linked to the previously reported cluster of cases in the Aberdeen fishing community of the capital, Freetown. There were 14 new confirmed cases in Freetown over the same period, with cases still arising from unknown chains of transmission in Freetown and elsewhere. Transmission continues at very low levels in Liberia, with 1 new confirmed case reported in the 7 days to 22 February: a registered contact associated with a known chain of transmission in the capital, Monrovia.

:: Engaging effectively with communities remains a challenge in several geographical areas. Nearly one-third of prefectures in Guinea reported at least one security incident in the week to 22 February, often as a result of rumours and misinformation linking response efforts with the spread of EVD. A total of 16 new confirmed cases were identified in Guinea and Sierra Leone after post-mortem testing of individuals who died in the community, indicating that a significant number of individuals are still either unable or reluctant to seek treatment. Ideally these individuals would have been identified as contacts associated with known chains of transmission, and have been rapidly diagnosed, isolated, and treated after the initial onset of symptoms. In Guinea and Sierra Leone, 19 and 15 unsafe burials were reported, respectively.

:: Most new cases in Guinea were reported from 3 neighbouring western prefectures: Conakry (6 new confirmed cases), Coyah (8 new confirmed cases), and Forecariah (16 confirmed cases). However, the eastern prefecture of Lola, on the border with Côte d’Ivoire, reported 1 new confirmed case. Case incidence has fluctuated in this prefecture. The northern prefecture of Mali, which borders Senegal, also reported 1 new confirmed case.

:: The steep decline in case incidence nationally in Sierra Leone from December until the end of January has halted. Transmission remains widespread, with 8 districts reporting new confirmed cases. A significant proportion of cases are still arising from unknown chains of transmission.

:: Of laboratories that report results to the relevant ministry of health, between 84% and 98% of laboratory samples were tested within 1 day of collection in the 22 days to 22 February. At present there are no data on how rapidly results are communicated to patients.

:: In the week to 22 February, 3 new health worker infections were reported (2 from Guinea, 1 from Sierra Leone), bringing the total of health worker infections reported since the start of the outbreak to 837, with 490 deaths.

COUNTRIES WITH WIDESPREAD AND INTENSE TRANSMISSION
:: There have been over 23,500 reported confirmed, probable, and suspected cases cases of EVD in Guinea, Liberia and Sierra Leone (table 1), with over 9,500 reported deaths (outcomes for many cases are unknown). A total of 35 new confirmed cases were reported in Guinea, 1 in Liberia, and 63 in Sierra Leone in the 7 days to 22 February….

Liberia-U.S. clinical research partnership opens trial to test Ebola treatments

NIH Watch [to 28 February 2015]
http://www.nih.gov/news/index.html

:: Liberia-U.S. clinical research partnership opens trial to test Ebola treatments
Initial study will evaluate experimental drug cocktail ZMapp
February 27, 2015
In partnership with the Liberian government, the National Institute of Allergy and Infectious Diseases (NIAID) today launched a clinical trial to obtain safety and efficacy data on the investigational drug ZMapp as a treatment for Ebola virus disease. The study, which will be conducted in Liberia and the United States, is a randomized controlled trial enrolling adults and children with known Ebola virus infection.

“Although ZMapp has been used to treat several Ebola-infected patients in recent months, we cannot determine if the drug actually benefitted those patients because it was not administered within the context of a clinical trial,” said Anthony S. Fauci, M.D., director of the NIAID, at the National Institutes of Health (NIH). “This clinical trial will help us determine if ZMapp and other treatments are safe and effective for use in the current devastating outbreak in West Africa as well as in future outbreaks.”…

…All participants will receive the optimized standard of care for treating Ebola infection, which includes providing intravenous fluids, balancing electrolytes, maintaining oxygen status and blood pressure and treating other infections if they occur. Participants will then be assigned randomly to one of two groups: the first group, which will act as the control, will continue to receive the current optimized standard of care. The second group will receive the optimized standard of care plus three separate intravenous infusions of ZMapp administered three days apart. The total dose of ZMapp at each infusion will depend on the weight of the participant. Study participants will be monitored up to 30 days following discharge from the hospital and may return for outpatient visits for additional follow up.

Researchers designed the study protocol to include a series of two-arm comparisons (the first being ZMapp compared to the current standard of care) to establish a framework to evaluate multiple potential Ebola treatments in the future. If one investigational treatment proves to be statistically more effective, it will then become the basis of the new standard of care against which additional investigational Ebola interventions could be tested and compared. Each experimental therapy will be examined in up to 100 participants per arm. If scientists are unable to establish a significant difference after enrolling 100 participants per arm, then that particular treatment will be declared ineffective and scientists will begin testing the next therapy.

These additional treatments may also include the following:
– Tekmira siRNA from Tekmira Pharmaceuticals Corp., based in Burnaby, British Columbia
– Favipiravir from Toyama Chemical Co. LTD, based in Tokyo
– Convalescent or post-immunization plasma collected from recent Ebola infection survivors. It is possible that this category could potentially be expanded to include plasma donors who have participated in Phase 1 Ebola vaccine clinical trials and whose plasma shows high neutralizing activity against the virus.
– BCX4430 from BioCryst, based in Durham, North Carolina
– AVI-7537 from Sarepta, based in Cambridge, Massachusetts…

MSF: Preliminary Results of the JIKI Clinical Trial to test the Efficacy of Favipiravir in Reducing Mortality in Individuals Infected by Ebola Virus in Guinea

MSF: Preliminary Results of the JIKI Clinical Trial to test the Efficacy of Favipiravir in Reducing Mortality in Individuals Infected by Ebola Virus in Guinea
February 24, 2015
NEW YORK—Preliminary data from the JIKI clinical trial, which is testing the efficacy of favipiravir in reducing mortality associated with Ebola, provide two important pieces of information:
– absence of efficacy in individuals who arrive at treatment centers with a very high level of viral replication and who already have serious visceral involvement, and
– encouraging signs of efficacy in individuals arriving at treatment centers with a high or moderate level of viral replication, who have not yet developed overly severe visceral lesions.

With this classification into two groups, we have a much better understanding of Ebola virus disease, and can redefine the role of antiviral monotherapies in the therapeutic arsenal used against the disease.

The trial, sponsored by INSERM and funded by the European Commission from the Horizon 2020 Initiative under the project title REACTION, is supported by two NGOs, Doctors Without Borders/Médecins Sans Frontières (MSF) and Alliance for International Medical Action (ALIMA); two laboratory networks, Belgian First Aid and Support Team (B-FAST) and European Mobile Laboratory (EMLab); the French Red Cross, and the French Military Health Service.

These preliminary data are being presented on Wednesday, February 25, as a late-breaking abstract at the CROI international conference (Conference on Retroviruses and Opportunistic Infections) in Seattle.

Given the high mortality associated with Ebola virus despite high-quality symptomatic treatment, study of specific innovative therapeutic agents is essential. Potentially useful drugs against the virus include favipiravir (T-705), an antiviral drug already tested against influenza virus in adult humans (and well tolerated). The latter (no more than other potential treatments) has never been tested in humans for treating Ebola, but its efficacy has been demonstrated in vitro and in mice.

As part of the mission given to Aviesan to organize the research as a matter of urgency, the JIKI clinical trial, a phase II multicentre non-comparative trial, began in Guinea on December 17, 2014, to test the ability of favipiravir to reduce mortality in individuals infected by Ebola virus.

Sponsored by INSERM, and jointly funded by the European Commission, the JIKI trial is being conducted in partnership with MSF, ALIMA, the French Red Cross, EMLab, B-Fast and the French Military Health Service, and is taking place in four Ebola treatment centers in Guékédou (MSF), Nzérékoré (ALIMA), Macenta (French Red Cross) and Conakry (carers’ treatment centre).

In these centers, adults and children over one year of age with a positive Ebola PCR test who agree to take part (parental consent in the case of minors) receive treatment with favipiravir for 10 days along with basic care. Favipiravir comes in the form of 20 mg tablets (the tablets can be dissolved in a drink) and is administered according to the following dose regimen[1]:
– Adults: Day 0: 2,400 mg at H0, 2,400 mg at H8 and 1,200 mg at H16, then 1,200 mg twice a day for nine days;
– Children: doses adjusted to body weight.

The JIKI trial is being followed by an independent monitoring committee, which met on December 11, 2014, and on January 5, January 14, and January 26, 2015. At this last meeting, the committee authorized the investigators to publish the interim data, which they judged to contain messages that should be quickly shared with the international community. These messages, obtained from the first 80 participants (69 adolescents or adults, and 11 children) are as follows:
– 42 percent of participants arrived at the treatment centers with a strongly positive PCR test (cycle threshold value, CT, < 20), reflecting a very high viral load[2]. Of these patients, 81 percent had refractory renal failure and 93 percent died. In the three months preceding the trial, mortality among individuals presenting with the same features was 85 percent. Comparison of the trial and pretrial data shows that it is highly unlikely that favipiravir monotherapy will ultimately be proven to reduce mortality in this population with advanced disease.
– 58 percent of participants arrived in the treatment centers with a cycle threshold (CT) ≥ 20, reflecting a high or moderate viral load. Of these patients, 42 percent had renal failure, but only 15 percent died. In the three months preceding the trial, mortality among individuals presenting with a CT ≥ 20 was 30 percent. Comparison of the trial and pretrial data therefore leads us to hope that favipiravir monotherapy may reduce mortality in this population with less advanced disease.

For the researchers, these preliminary data encourage us:
– to continue the trial while trying to provide favipiravir treatment as soon as possible after the symptoms appear, so as to treat patients in whom viral multiplication can be controlled, and who have not yet developed visceral lesions (especially renal lesions);
– to explore other therapeutic options for patients who come to the treatment centers when their disease is too far advanced.

Yves Levy, the chairman and CEO of INSERM said: “The results of this non-comparative trial have to be confirmed using a larger number of patients. However, they open up other therapeutic opportunities in drug combinations, in particular for the treatment of patients suffering from more advanced stages of this disease. They also clearly show that research plays an essential role in tackling such epidemics. I would also like to stress that without the excellent Guinean-French cooperation, the pioneering role of MSF in this research, the fruitful partnerships with all NGOs involved, and the European Commission’s responsiveness, this progress could not have been accomplished.”

Commissioner Moedas said: “I am excited about the encouraging results of one of our EU-funded projects to tackle Ebola. We have preliminary evidence that the antiviral drug favipiravir may be effective against early Ebola disease. If these results are confirmed by the ongoing clinical trial, it will be the first-ever treatment to be deployed against this deadly disease during the current outbreak. These results show the success of the European Commission’s quick reaction to the Ebola outbreak to support urgent research on several potential treatments and vaccines against Ebola with funding from our Horizon 2020 research program. This is an astounding example of what the best brains can achieve with EU support when there is so much at stake. It shows how EU funding can lead to discoveries that save people’s lives and which are the result of rapid EU, international, and industry cooperation.”

According to Agustin Augier, Secretary-General of Alima, “Those positive results will reinforce the confidence between affected populations and the treatment center. This therapeutic solution, even if partial, will significatively attract ebola patients to the treatment center. It is a significant step towards tackling the outbreak in the villages where it still goes on.”

“MSF is pleased to see that favipiravir seems to have a positive effect for certain patients suffering from Ebola Viral Disease (EVD). But it also seems that the most vulnerable patients, the people that are most likely to die from the disease, don’t benefit at all from favipiravir. That fact, and the fact that these are only preliminary results, show that it is really too soon to start using favipiravir outside a trial environment. Research into favipiravir, and into other potential treatments for EVD, must be continued, and MSF is willing to play a role in these clinical trials,” says Dr. Bertrand Draguez, medical director of MSF.

[1] Details of this dose regimen are the subject of a publication in the journal The Lancet Infectious Diseases.
[2] In the laboratories taking part in the trial, a CT < 20 is equivalent to a viral load of over 108 copies of the virus per ml of blood.

CDC/MMWR Watch [to 28 February 2015]

CDC/MMWR Watch [to 28 February 2015]
http://www.cdc.gov/media/index.html

:: MMWR Weekly, February 27, 2015 / Vol. 64 / No. 7
– Rapid Intervention to Reduce Ebola Transmission in a Remote Village — Gbarpolu County, Liberia, 2014
– Community Quarantine to Interrupt Ebola Virus Transmission — Mawah Village, Bong County, Liberia, August–October, 2014
– Implementation of Ebola Case–Finding Using a Village Chieftaincy Taskforce in a Remote Outbreak — Liberia, 2014
– Update: Ebola Virus Disease Epidemic — West Africa, February 2015
– Rapid Response to Ebola Outbreaks in Remote Areas — Liberia, July–November 2014

EVD – African Union; World Bank; USAID [to 28 February 2015]

African Union [to 28 February 2015]
http://www.au.int/en/
Feb.24.2015
:: African Unions Welcomes Back the First Group of its Heroines and Heroes in the Fight Against Ebola
Addis Ababa, 24 February 2014- 17 ASEOWA (African Union Support to the Ebola Outbreak in West Africa) health workers, who were the first to be deployed to fight Ebola, returned from Liberia on 22nd February, upon completion of their tour of duty and were welcomed back by the Chairperson of the African Union Commission Dr Nkosazana Dlamini Zuma.
Attending the meeting were the AUC Commissioner for Social Affairs Dr Mustapha Sidiki Kaloko, the Director of Social Affairs Dr Olawale Maiyegun, ambassadors from the health workers’ member states and a representative from Liberia. It was a unique event- the first time ever that the AU had welcomed back heroines and heroes in the fight against Ebola, and, without any infections among the health workers.
Dr Dlamini Zuma thanked the health workers for their pioneering role and assured them that the AU’s is determined to defeat Ebola: “You personified Pan Africanism and solidarity. The African Union will stay the course until the affected countries are declared Ebola free. We are very happy that you undertook this mission”, she told them.
All returnees were awarded certificates of service in recognition of their contribution to the fight against Ebola and their selfless dedication. The returnees were from Nigeria, Rwanda, Ethiopia, Uganda and the Democratic Republic of Congo. Among them were doctors, hygienists and communications experts. One of them was a trainer of other medical personnel in the treatment of Ebola patients….

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World Bank [to 28 February 2015]
http://www.worldbank.org/en/news/all
:: Ebola: World Bank and Liberia to Work with Japan to Launch a Psychological Support Project
Some 18,000 Beneficiaries to Receive Mental Health and Psychosocial Support to Alleviate Consequences of Epidemic
MONROVIA, February 25, 2015 – The Liberian Government and the World Bank Group in partnership with the Government of Japan, today launched a new $3 million project to address the psychological effects of Liberia’s Ebola crisis and to promote psychosocial health in the country. The ceremony was held at the World Bank Liberia Office.The project, Supporting Psychosocial Health and Resilience in Liberia, is funded by Japan through the Japanese Social Development Fund (JSDF), a trust fund administered by the World Bank. The Carter Center will implement this three-year project, which is expected to reach approximately 18,000 beneficiaries in Montserrado (hosting Monrovia) and Margibi counties.
Date: February 25, 2015

:: Households Begin Returning To Work in Liberia as Ebola Crisis Wanes
Long-term welfare remains a concern as country moves toward economic recovery
WASHINGTON, February 24, 2015— Nearly 20 percent of the Liberians who had stopped working since the Ebola crisis have returned to work in the last month, according to the World Bank Group’s most recent round of cell-phone surveys, signaling both important progress and the magnitude of the challenge ahead. This improvement, an encouraging sign of a shift toward economic normalization, was mainly driven by a large increase in wage work in urban areas. A substantial percentage of those working pre-crisis remain out of work, however; those in self-employment continue to be the hardest hit by the Ebola crisis, pointing to a lack of working capital and a lack of customers as the main barriers to their operation. As the pressing health crisis in Liberia slows, it will be important to identify and support those who are most vulnerable to a sluggish economy…
Date: February 24, 2015

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USAID [to 28 February 2015]
http://www.usaid.gov/news-information/press-releases
:: USAID Announces Education Crisis Response Program in Liberia
February 25, 2015
The U.S. Agency for International Development (USAID) announced the $18.7 million Education Crisis Response program today to assist the Government of Liberia in restoring basic education in the Ebola-affected country and help return children to school safely. The program was announced today while Liberian President Ellen Johnson Sirleaf visited with staff from USAID.

:: U.S. Government Launches President’s Malaria Initiative Next Six-Year Strategy for 2015-2020
February 25, 2015
The U.S. President’s Malaria Initiative, led by the U.S. Agency for International Development and implemented together with the Centers for Disease Control and Prevention (CDC), launched its next six-year strategy to further reduce malaria deaths and substantially decrease malaria illness, toward the long-term goal of elimination at the White House today.

POLIO [to 28 February 2015]

POLIO [to 28 February 2015]
Public Health Emergency of International Concern (PHEIC)

GPEI Update: Polio this week – As of 25 February 2014
Global Polio Eradication Initiative
[Editor’s Excerpt and text bolding]
Full report: http://www.polioeradication.org/Dataandmonitoring/Poliothisweek.aspx
:: The fourth meeting of the International Health Regulations Emergency Committee concerning the international spread of wild poliovirus was convened last week. Outcomes and the Committee’s final report will be made available on www.polioeradication.org

Selected country report content:
Afghanistan
:: One new case of wild poliovirus type 1 (WPV1) has been reported in the past week in Reg district, Hilmand province. This was the first case reported in 2015, with onset of paralysis on 21 January. The total number of WPV1 cases for 2014 remains 28. Most of the cases from 2014 were linked to cross-border transmission with neighbouring Pakistan.
Pakistan
:: Two new wild poliovirus type 1 (WPV1) cases were reported in the past week. One case was reported in Khyber district in the Federally Administered Tribal Areas, and the other in Peshawar, in Khyber Pakhtunkhwa. The total number of WPV1 cases in 2014 remains 306, and 9 for 2015. The most recent onset of paralysis was on 31 January in Peshawar.
:: A panel of experts was convened on 14 – 15 February for a consultation to review the current epidemiological situation and the status of implementation of the existing ‘low transmission season’ polio eradication plan. With 8 weeks remaining until the end of the low season, the panel urged that Emergency Operations Centres continue strengthening the roll-out of the plan and that, at the provincial level, teams more completely and accurately track its’ implementation.
West Africa
:: Even as polio programme staff across West Africa help to control the Ebola outbreak affecting the region, efforts are being made in those countries not affected by Ebola to vaccinate children against polio to create a buffer zone surrounding the affected countries. The Ebola crisis in western Africa continues to have an impact on the implementation of polio eradication activities in Liberia, Guinea and Sierra Leone. Twenty two experts from the National Polio Surveillance Programme (NPSP) in India have been deployed for 3 months to strengthen surveillance systems and data collection for the Ebola response, demonstrating the polio legacy in action.