EBOLA Watch [to 4 October 2014]

UNMEER (UN Mission for Ebola Emergency Response)
:: UN Ebola Crisis Centre: External Situation Report – 3 October 2014
– SRSG Banbury continues his visit in Liberia, including to a treatment facility in Lofa County
– Appointment of Victor Kisob to lead the Ebola Response Liaison office at UN Headquarters in New York
– Numerous new pledges made during the “Defeating Ebola in Sierra Leone” conference held in London yesterday attended by Special Envoy Nabarro; U.K. announces pilot scheme for community healthcare centres in Sierra Leone
– WFP and UNDP raise concerns about the impact of Ebola on West African economies, trade activities and food security

WHO Ebola virus disease – web site
:: Situation report update – 3 October 2014 pdf, 1.78 Mb

:: Liberia: Ebola treatment centre sets a new pace 2 October 2014
:: Liberia: Ebola clinic fills up within hours of opening 29 September 2014

:: International meetings attended by individuals from Ebola virus disease-affected countries
WHO Interim guidance
3 October 2014 :: 12 pages
WHO reference number: WHO/EVD/GUIDANCE/MG/14.1
Download the full version in English
The transmission of Ebola virus disease across country borders remains a risk, and should be taken into account when planning international meetings and large mass gatherings.
This interim guidance is aimed at assisting organizers of international meetings attended by individuals from EVD-affected countries and individuals with a travel history to EVD-affected countries within the previous 3 weeks.
The first part is intended for organizers of international meetings, to safely plan and conduct these events. The second part is addressed to public health authorities directly involved in supporting such international meetings.

:: Map: West Africa: Ebola Virus Disease (EVD) Outbreak (as of 30 Sep 2014)

:: Democratic Republic of the Congo: D.R. Congo: Humanitarian Fund releases USD 2.5 million to join the Government’s efforts to fight Ebola in Equateur Province 04 Oct 2014
Source: UN Office for the Coordination of Humanitarian Affairs Country: Democratic Republic of the Congo (Kinshasa, 3 October 2014): The Humanitarian Coordinator in the Democratic Republic of Congo (DRC), Moustapha Soumaré, has allocated USD 2.56 million from the Common Humanitarian Fund (CHF) to fight the country’s latest outbreak of Ebola in Equateur Province. As of 2 October, the highly contagious viral disease has killed 43 people out of 70 cases in the Boende district, over 1,000 km…

:: Liberia: CERF response to Ebola outbreak, as of 3 October 2014 03 Oct 2014
Source: UN Office for the Coordination of Humanitarian Affairs Country: Guinea, Liberia, Nigeria, Sierra Leone CERF regional response overview (in US$ million) CERF RESPONSE TIMELINE 15.2 US$ million Allocations April–July • At the onset of the emergency, CERF provided three rapid response allocations, totaling $2.3 million, for Guinea, Sierra Leone and Liberia. The majority of funds supported emergency health activities, including training of medical personnel, disease detection and…

:: Democratic Republic of the Congo: Update on the ebola virus disease in DRC, No.13, 29 September 2014–7pm [EN/FR] 30 Sep 2014
Source: UN Office for the Coordination of Humanitarian Affairs Country: Democratic Republic of the Congo Coordination/ Keys developments
8 health personnel have died of Ebola Virus Disease (EVD) since the outbreak of the epidemic. On 28 September, the total number of cases (see table above for details) [had] … an overall lethality rate of around 60%. The latest confirmed case was on 24 September…

UNICEF Watch [to 4 October 2014]
:: Thousands of children orphaned by Ebola: UNICEF
DAKAR/GENEVA/NEW YORK, 30 September 2014 – At least 3,700 children in Guinea, Liberia and Sierra Leone have lost one or both parents to Ebola since the start of the outbreak in West Africa, according to preliminary UNICEF estimates, and many are being rejected by their surviving relatives for fear of infection.


03 Oct 2014
Top United Nations Development officials to visit Ebola-affected countries
UNDP is carrying out a high-level mission to Guinea, Sierra Leone, Liberia and Senegal, aiming to boost efforts to contain Ebola outbreak while helping to preserve essential services and livelihoods.

03 October 2014 – Dispatch
Fear of health workers fuels Ebola crisis in Guinea
CONAKRY/NEW YORK – Panic over the Ebola outbreak in Guinea has inflamed distrust of health officials, impeding access to critical health services. UNFPA is reaching out to journalists and community leaders to dispel rumours about the disease and to encourage people to seek proper care – not only for suspected Ebola infections but also for other essential health needs.
UN Ebola Response MPTF [Multi-Partner Trust Fund]
:: Terms of Reference
:: Ebola MPTF Fact-Sheet
:: Frequently Asked Questions

CDC/MMWR Watch [to 4 October 2014]
:: CDC Update on First Ebola Case Diagnosed in the United States, 10-03-2014 – Transcript
Friday, October 3, 2014
CDC hosted a telebriefing to update the investigation of the first Ebola case diagnosed in the United States.
MMWR, October 3, 2014 / Vol. 63 / No. 39
:: Typhoid Fever Surveillance and Vaccine Use — South-East Asia and Western Pacific Regions, 2009–2013
:: Update: Influenza Activity — United States and Worldwide, May 18–September 20, 2014
:: Ebola Virus Disease Outbreak — West Africa, September 2014
:: Ebola Virus Disease Outbreak — Nigeria, July–September 2014
:: Importation and Containment of Ebola Virus Disease — Senegal, August–September 2014

GPEI Update: Polio this week – As of 24 September 2014

POLIO [to 4 October 2014]
GPEI Update: Polio this week – As of 24 September 2014
Global Polio Eradication Initiative
Editor’s Excerpt and text bolding
Full report: http://www.polioeradication.org/Dataandmonitoring/Poliothisweek.aspx
:: All cases of wild poliovirus type 1 reported this week were from Pakistan. In 2014, Pakistan has accounted for 83% of cases reported globally. Khyber Pakhtunkhwa province and the Federally Administered Tribal Areas (FATA) constitute the most heavily infected area of the world, with 73% of cases worldwide occurring within these provinces.
:: The risk of international spread of polio from Pakistan remains high. The bulk of cases in neighbouring Afghanistan are linked to cross-border transmission with Pakistan, and the outbreak affecting the Middle East originated in Pakistan.
:: The Global Polio Eradication Initiative’s Independent Monitoring Board (IMB) is meeting this week in London to review the progress of the past months. The IMB report will be published in 3 weeks.
:: Eight new wild poliovirus type 1 (WPV1) cases were reported in the past week. Of these, 3 are from the Federally Administered Tribal Areas (FATA) (1 from North Waziristan Agency and 2 from Khyber Agency); 2 are from Khyber Pakhtunkhwa province (1 from Tank and 1 from Torghar district, which had been uninfected so far in 2014); 2 from Balochistan province (1 in Killa Abdulah and 1 in Quetta district); and 1 case in Sindh province in the previously uninfected Liaqat town of Karachi city. This brings the total number of WPV1 cases in 2014 to 174 compared to 36 in 2013 by this date. The most recent case had onset of paralysis on 14 September in Khyber Agency.
:: Immunization activities are continuing with particular focus on known high-risk areas, in particular the newly opened areas of Khyber Pakhtunkhwa province. At exit and entry points, 182 permanent vaccination points are being used to reach internally displaced families as they leave their homes.
West Africa
:: Even as polio programme staff across West Africa support efforts to control the Ebola outbreak affecting the region, efforts are being made in those countries not affected by Ebola to vaccinate children against polio. National Immunization Days (NIDs) are planned in Burkina Faso, Cape Verde, Côte d’Ivoire, Gambia, Ghana, Guinea Bissau, Mali, Mauritania, Niger, Senegal and Togo on 31 October to 2 November.

WHO & Regionals [to 4 October 2014]

WHO & Regionals [to 4 October 2014]
:: MERS-CoV – WHO statement on the Seventh Meeting of the IHR Emergency Committee
1 October 2014
[Full text]
The seventh meeting of the Emergency Committee (EC) convened by the Director-General under the International Health Regulations (IHR 2005) regarding the Middle East respiratory syndrome coronavirus (MERS-CoV) was conducted with members and advisors of the Emergency Committee through electronic correspondence from 26 September 2014 through 30 September 2014.1
The WHO Secretariat provided an update on and assessment of epidemiological and scientific developments, including a description of recently reported cases and transmission patterns. Islamic Republic of Iran and Saudi Arabia provided an update on and assessment of MERS-CoV, including progress towards implementation of the Emergency Committee’s temporary recommendations. 2
The Committee noted that: (i) there have been significant efforts made to strengthen infection prevention and control measures, with an epidemiological situation that has not changed since the 6th meeting of the IHR EC; (ii) the number of cases has fallen since the April upswing, and cases continues to appear sporadically with no evidence of sustained human-to-human transmission in communities; (iii) although transmission in health care settings is still occurring in small clusters, transmission seems generally contained; (iv) activities conducted to reduce the international spread of MERS-CoV seem to be effective; and (v) the current data suggest that MERS-CoV transmission could be seasonal, with an upsurge expected next spring.
The Committee reiterated that its previous advice remains relevant and that significant efforts should be made to:
:: continue to strengthen infection prevention control (IPC) practices, build capacity of heath-care workers and provide protective equipment in vulnerable countries, especially African countries;
:: improve awareness about MERS-CoV among pilgrims going for Hajj, and conduct surveillance for MERS-CoV among pilgrims during and after Hajj;
:: harmonise laboratory testing algorithms;
:: reinforce epidemiological surveillance in camels in the Middle East and in Africa, as well as surveillance in humans and address critical gaps in knowledge of human and animal transmission.
The Committee unanimously concluded that the conditions for a Public Health Emergency of International Concern (PHEIC) have not yet been met.
Based on the Committee’s advice, and information currently available, the Director-General accepted the Committee’s assessment. She thanked the Committee for its work.
The WHO Secretariat will continue to provide regular updates to the Committee Members and Advisors. The Emergency Committee will be reconvened in three months, or earlier if circumstances require.

:: WHO SAGE Meeting: Geneva, 21-23 October 2014 – Draft agenda (as of 29 September 2014)

:: WHO Global Alert and Response (GAR) :: Disease Outbreak News (DONs)
– Middle East respiratory syndrome coronavirus (MERS-CoV) – Austria 2 October 2014
– Middle East respiratory syndrome coronavirus (MERS-CoV) – Saudi Arabia 2 October 2014
– Ebola virus disease – United States of America 1 October 2014

:: The Weekly Epidemiological Record (WER) 3 October 2014, vol. 89, 40 (pp. 429–440) includes:
– Typhoid fever surveillance and vaccine use, South-East Asia and Western Pacific Regions, 2009–2013

:: GIN September 2014 pdf, 1.64Mb

:: WHO Europe
– WHO delivers tetanus toxoid vaccine to Ukraine 03-10-2014
On 26 September 2014, WHO delivered a second tranche of medicine to Kyiv. The shipment included 300 000 doses of tetanus toxoid (TT) vaccine, which will cover Ukraine’s needs until the end of 2015.
– Statement regarding interim findings of WHO assessment of deaths of children in Idleb governorate, Syrian Arab Republic 29-09-2014
A WHO assessment of the cause of the death of 15 children in rural Idleb, northern Syrian Arab Republic, has concluded that the most likely cause of the event was the incorrect use of a drug called Atracurium as a diluent for measles/rubella vaccine. There is no evidence that the measles/rubella vaccine itself or its correct diluent were the cause of this tragic event.

– Health officials from the Americas chart a path toward universal health coverage (10/02/2014)
– Ministries of health of the Americas seek to strengthen coordination of humanitarian assistance in emergencies and disasters (10/02/2014)
– Health officials seek to reduce blindness and visual impairment in the Americas (10/02/2014)
– Ministers of health of the Americas pledge action to improve mental health care (10/02/2014)
– Countries of the Americas seek to ensure safe and ample blood supplies through 100% voluntary donation (10/01/2014)
– Countries of the Americas agree to promote health in all public policies that have potential health impact (09/30/2014)

: NIH awards seven new vaccine adjuvant discovery contracts

NIH Watch [to 4 October 2014]
:: NIH awards seven new vaccine adjuvant discovery contracts
The National Institute of Allergy and Infectious Diseases (NIAID awarded seven research contracts to discover and characterize new adjuvants, or substances formulated as part of vaccines to enhance their protective ability.
“The goal of this research is to identify novel adjuvant candidates that safely and selectively boost vaccine-induced immune responses,” said NIAID Director Anthony S. Fauci, M.D. “Such adjuvants could be used to improve current vaccines, extend the vaccine supply or enhance vaccine efficacy in people with immature or weakened immune systems, such as infants and the elderly.”
Total funding for these contracts, which are accelerating progress toward the goals described in NIAID’s Strategic Plan for Research on Vaccine Adjuvants, could reach approximately $70 million over five years.
The following institutions received the new contracts
:: University of California, San Diego, La Jolla. Dennis Carson, M.D., principal investigator
:: Boston Children’s Hospital. Ofer Levy, M.D., Ph.D., principal investigator
:: Vaxine PTY LTD, South Australia, Australia. Nikolai Petrovsky, Ph.D., principal investigator
Corixa Corporation (now part of GlaxoSmithKline), Hamilton, Montana. Jay Evans, Ph.D., principal investigator
:: Duke University, Durham, North Carolina. Herman Staats, Ph.D., principal investigator
:: Oregon Health & Science University, Portland. Jay Nelson, Ph.D., principal investigator
:: University of Kansas, Lawrence. Sunil David, M.D., Ph.D., principal investigator

IVI appoints Jerome H. Kim as Director General

:: IVI appoints Jerome H. Kim as Director General
Media Release
SEOUL, Republic Of Korea, Sept. 29, 2014 /PRNewswire/
The International Vaccine Institute (IVI)…announced the appointment of Jerome H. Kim, M.D., as the organization’s Director General, effective early 2015.
“Jerome’s scientific knowledge, technical expertise, and organizational and leadership skills make him an ideal fit for the position,” said Prof. Adel A. Mahmoud, Chair of IVI’s Board of Trustees. “With his distinguished track record in vaccine research & development and passionate commitment to vaccines, he will bring strong scientific leadership and management of a dynamic international organization.”
“I am honored by the opportunity to join IVI, and I look forward to working with the IVI team, partners, and donors,” said Dr. Kim, “IVI is a very unique organization. Its breadth in vaccinology spans research & development, epidemiology, technology transfer, policy and access. Together, we will improve the health and wellbeing of the world’s poorest populations through fulfilling IVI’s mission – to discover, develop, and deliver safe, effective and affordable vaccines for developing nations.”…
Dr. Kim is a Professor of Medicine at the Uniformed Services University of the Health Sciences and is a Fellow of the American College of Physicians and the Infectious Diseases Society of America. He received his M.D. from the Yale University School of Medicine, and completed his training in Internal Medicine and fellowship in Infectious Diseases at Duke University Medical Center…

:: In Memoriam: Prof. Ragnar Norrby (1943 – 2014)
IVI is greatly saddened by the recent passing of Prof. Ragnar Norrby. Prof. Norrby was a member of the IVI Board of Trustees (BOT), first as a representative of Sweden from 2005 to 2007, then as Board Chair and member-at –large from 2007 to 2012. Prof. Norrby was the Director General of the Swedish Institute for Infectious Disease Control in Stockholm, Sweden. His extensive expertise and experience in public health allowed him to make many contributions to IVI and its Board over the years. His presence will be missed.

Round-up: IAVI; GAVI, Global Fund

:: IAVI Welcomes Korean Women against AIDS to India
October 2, 2014
Group’s Grant to IAVI Will Support AIDS Vaccine Research in Asia and Globally
The International AIDS Vaccine Initiative (IAVI) announced a $50,000 grant from Korean Women against AIDS (KOWA), a newly formed advocacy organization comprised of leading members of the business and legislative communities of the Republic of Korea. KOWA awarded the grant shortly before embarking on a five-day visit in September, organized by IAVI and UNAIDS, to learn more about HIV/AIDS in India. “We are grateful for this commitment from such an illustrious group of leaders and innovators to help advance IAVI’s mission to ensure development of an effective and accessible AIDS vaccine,” said IAVI President & CEO Margie McGlynn…
GAVI Watch [to 4 October 2014]
:: Norway to commit at least US$ 215 million a year to Gavi between 2016 and 2020
Commitment will support immunisation programmes in developing countries to save lives and protect children’s health.
Global Fund Watch [to 4 October 2014]
:: Luxembourg Raises Contribution to the Global Fund
29 September 2014
NEW YORK – Luxembourg is increasing its financial commitment to the Global Fund for 2014, thereby unlocking additional contributions from the United States and the United Kingdom.
Prime Minister Xavier Bettel announced at the 2014 Global Citizen Festival in New York on Saturday that Luxembourg is making an additional pledge of €500,000 for 2014, in addition to its earlier pledge of €2.5 million. Both the United States and the United Kingdom have geared their own contributions to the Global Fund in a way that maximizes donations by other countries.

Use of Japanese Encephalitis Vaccine in US Travel Medicine Practices in Global TravEpiNet

American Journal of Tropical Medicine and Hygiene
October 2014; 91 (4)

Use of Japanese Encephalitis Vaccine in US Travel Medicine Practices in Global TravEpiNet
Bhushan R. Deshpande, Sowmya R. Rao, Emily S. Jentes, Susan L. Hills, Marc Fischer, Mark D. Gershman, Gary W. Brunette, Edward T. Ryan, Regina C. LaRocque, and the Global TravEpiNet Consortium
Am J Trop Med Hyg 2014 91:694-698; Published online July 28, 2014, doi:10.4269/ajtmh.14-0062
Few data regarding the use of Japanese encephalitis (JE) vaccine in clinical practice are available. We identified 711 travelers at higher risk and 7,578 travelers at lower risk for JE who were seen at US Global TravEpiNet sites from September of 2009 to August of 2012. Higher-risk travelers were younger than lower-risk travelers (median age = 29 years versus 40 years, P < 0.001). Over 70% of higher-risk travelers neither received JE vaccine during the clinic visit nor had been previously vaccinated. In the majority of these instances, clinicians determined that the JE vaccine was not indicated for the higher-risk traveler, which contradicts current recommendations of the Advisory Committee on Immunization Practices. Better understanding is needed of the clinical decision-making regarding JE vaccine in US travel medicine practices.

Formative Investigation of Acceptability of Typhoid Vaccine During a Typhoid Fever Outbreak in Neno District, Malawi

American Journal of Tropical Medicine and Hygiene
October 2014; 91 (4)

Formative Investigation of Acceptability of Typhoid Vaccine During a Typhoid Fever Outbreak in Neno District, Malawi
Lauren S. Blum*, Holly Dentz, Felix Chingoli, Benson Chilima, Thomas Warne, Carla Lee, Terri Hyde, Jacqueline Gindler, James Sejvar and Eric D. Mintz
Author Affiliations
Waterborne Disease Prevention Branch, Division of Foodborne, Waterborne, and Environmental Diseases, National Center for Emerging and Zoonotic Infectious Diseases, (NCEZID), CDC, Atlanta, Georgia; Strengthening Immunization Systems Branch, Global Immunization Division, Center for Global Health (CGH), CDC, Atlanta, Georgia; Neno District Health Office, Neno, Malawi; Community Health Services Unit, MOH, Lilongwe, Malawi; Global AIDS Program Malawi, Division of Global HIV AIDS, CGH, CDC, Lilongwe, Malawi; Office of the Director, Division of High Consequence Pathogens and Pathology, NCEZID, CDC, Atlanta, Georgia
Typhoid fever affects an estimated 22 million people annually and causes 216,000 deaths worldwide. We conducted an investigation in August and September 2010 to examine the acceptability of typhoid vaccine in Neno District, Malawi where a typhoid outbreak was ongoing. We used qualitative methods, including freelisting exercises, key informant and in-depth interviews, and group discussions. Respondents associated illness with exposure to “bad wind,” and transmission was believed to be airborne. Typhoid was considered extremely dangerous because of its rapid spread, the debilitating conditions it produced, the number of related fatalities, and the perception that it was highly contagious. Respondents were skeptical about the effectiveness of water, sanitation, and hygiene (WaSH) interventions. The perceived severity of typhoid and fear of exposure, uncertainty about the effectiveness of WaSH measures, and widespread belief in the efficacy of vaccines in preventing disease resulted in an overwhelming interest in receiving typhoid vaccine during an outbreak.

BMC Public Health (Accessed 4 October 2014)

BMC Public Health
(Accessed 4 October 2014)

Research article
BCG coverage and barriers to BCG vaccination in Guinea-Bissau: an observational study
Sanne Marie Thysen, Stine Byberg, Marie Pedersen, Amabelia Rodrigues, Henrik Ravn, Cesario Martins, Christine Stabell Benn, Peter Aaby and Ane Bærent Fisker
Author Affiliations
BMC Public Health 2014, 14:1037 doi:10.1186/1471-2458-14-1037
Published: 4 October 2014
Abstract (provisional)
BCG vaccination is recommended at birth in low-income countries, but vaccination is often delayed. Often 20-dose vials of BCG are not opened unless at least ten children are present for vaccination (“restricted vial-opening policy”). BCG coverage is usually reported as 12-month coverage, not disclosing the delay in vaccination. Several studies show that BCG at birth lowers neonatal mortality. We assessed BCG coverage at different ages and explored reasons for delay in BCG vaccination in rural Guinea-Bissau.
Bandim Health Project (BHP) runs a health and demographic surveillance system covering women and their children in 182 randomly selected village clusters in rural Guinea-Bissau. BCG coverage was assessed for children born in 2010, when the restricted vial-opening policy was universally implemented, and in 2012-2013, where BHP provided BCG to all children at monthly visits in selected intervention regions. Factors associated with delayed BCG vaccination were evaluated using logistic regression models. Coverage between intervention and control regions were evaluated in log-binomial regression models providing prevalence ratios.
Among 3951 children born in 2010, vaccination status was assessed for 84%. BCG coverage by 1 week of age was 11%, 38% by 1 month, and 92% by 12 months. If BCG had been given at first contact with the health system, 1-week coverage would have been 35% and 1-month coverage 54%. When monthly visits were introduced in intervention regions, 1-month coverage was higher in intervention regions (88%) than in control regions (51%), the prevalence ratio being 1.74 (1.53-2.00). Several factors, including socioeconomic factors, were associated with delayed BCG vaccination in the 2010-birth cohort. When BCG was available at monthly visits these factors were no longer associated with delayed BCG vaccination, only region of residence was associated with delayed BCG vaccination.
BCG coverage during the first months of life is low in Guinea-Bissau. Providing BCG at monthly vaccination visits removes the risk factors associated with delayed BCG vaccination.

Research article
Evidence of effective delivery of the human papillomavirus (HPV) vaccine through a publicly funded, school-based program: the Ontario Grade 8 HPV Vaccine Cohort Study
W Ting Lim, Kim Sears, Leah M Smith, Guoyuan Liu, Linda E Lévesque BMC Public Health 2014, 14:1029 (3 October 2014)
Abstract | Provisional PDF

Research article
Perceptions of consent, permission structures and approaches to the community: a rapid ethical assessment performed in North West Cameroon
Jonas A Kengne-Ouafo, Theobald M Nji, William F Tantoh, Doris N Nyoh, Nicholas Tendongfor, Peter A Enyong, Melanie J Newport, Gail Davey and Samuel Wanji
Author Affiliations
BMC Public Health 2014, 14:1026 doi:10.1186/1471-2458-14-1026
Published: 2 October 2014
Abstract (provisional)
Understanding local contextual factors is important when conducting international collaborative studies in low-income country settings. Rapid ethical assessment (a brief qualitative intervention designed to map the ethical terrain of a research setting prior to recruitment of participants), has been used in a range of research-naive settings. We used rapid ethical assessment to explore ethical issues and challenges associated with approaching communities and gaining informed consent in North West Cameroon.
This qualitative study was carried out in two health districts in the North West Region of Cameroon between February and April 2012. Eleven focus group discussions (with a total of 107 participants) were carried out among adult community members, while 72 in-depth interviews included health workers, non-government organisation staff and local community leaders. Data were collected in English and pidgin, translated where necessary into English, transcribed and coded following themes.
Many community members had some understanding of informed consent, probably through exposure to agricultural research in the past. Participants described a centralised permission-giving structure in their communities, though there was evidence of some subversion of these structures by the educated young and by women. Several acceptable routes for approaching the communities were outlined, all including the health centre and the Fon (traditional leader). The importance of time spent in sensitizing the community and explaining information was stressed.
Respondents held relatively sophisticated understanding of consent and were able to outline the structures of permission-giving in the community. Although the structures are unique to these communities, the role of certain trusted groups is common to several other communities in Kenya and Ethiopia explored using similar techniques. The information gained through Rapid Ethical Assessment will form an important guide for future studies in North West Cameroon.

Clinical Infectious Diseases (CID) – 8 October 15, 2014

Clinical Infectious Diseases (CID)
Volume 59 Issue 8 October 15, 2014

Editorial Commentary: Treatment for Multidrug-Resistant Tuberculosis: It’s Worse Than We Thought!
Charles L. Daley and C. Robert Horsburgh, Jr
Clin Infect Dis. (2014) 59 (8): 1064-1065 doi:10.1093/cid/ciu578

Impact of 13-Valent Pneumococcal Conjugate Vaccination in Invasive Pneumococcal Disease Incidence and Mortality
Zitta Barrella Harboe, Tine Dalby, Daniel M. Weinberger, Thomas Benfield, Kåre Mølbak, Hans Christian Slotved, Camilla H. Suppli, Helle Bossen Konradsen, and Palle Valentiner-Branth
Clin Infect Dis. (2014) 59 (8): 1066-1073 doi:10.1093/cid/ciu524
Introduction of PCV13-valent pneumococcal conjugate vaccine in the Danish childhood immunization program has led to further reduction in the incidence of invasive pneumococcal disease shortly after the vaccine’s introduction. A substantial population-level decline in pneumococcal-related mortality of nearly 30% among nonvaccinated persons was also observed.

Transforming the Fight Against Tuberculosis: Targeting Catalysts of Transmission
David W. Dowdy, Andrew S. Azman, Emily A. Kendall, and Barun Mathema
Clin Infect Dis. (2014) 59 (8): 1123-1129 doi:10.1093/cid/ciu506
Transmission of tuberculosis in communities is driven by heterogeneities in human behavior, mycobacterial activity, and host susceptibility. The only realistic way to achieve ambitious targets for tuberculosis elimination is to tailor local interventions to these catalysts of tuberculosis transmission.

Globalization and Health [Accessed 4 October 2014]

Globalization and Health
[Accessed 4 October 2014]

The limits of global health diplomacy: Taiwan’s observer status at the world health assembly
Herington J and Lee K Globalization and Health 2014, 10:71 (1 October 2014)

Country progress towards the millennium development goals: adjusting for socioeconomic factors reveals greater progress and new challenges
Cohen RL, Alfonso YN, Adam T, Kuruvilla S, Schweitzer J and Bishai D Globalization and Health 2014, 10:67 (1 October 2014)

Interaction between climatic, environmental, and demographic factors on cholera outbreaks in Kenya

Infectious Diseases of Poverty
[Accessed 4 October 2014]

Research Article
Interaction between climatic, environmental, and demographic factors on cholera outbreaks in Kenya
James D Stoltzfus, Jane Y Carter, Muge Akpinar-Elci, Martin Matu, Victoria Kimotho, Mark J Giganti, Daniel Langat and Omur Cinar Elci
Author Affiliations
Infectious Diseases of Poverty 2014, 3:37 doi:10.1186/2049-9957-3-37
Published: 1 October 2014
Abstract (provisional)
Cholera remains an important public health concern in developing countries including Kenya where 11,769 cases and 274 deaths were reported in 2009 according to the World Health Organization (WHO). This ecological study investigates the impact of various climatic, environmental, and demographic variables on the spatial distribution of cholera cases in Kenya.
District-level data was gathered from Kenya’s Division of Disease Surveillance and Response, the Meteorological Department, and the National Bureau of Statistics. The data included the entire population of Kenya from 1999 to 2009.
Multivariate analyses showed that districts had an increased risk of cholera outbreaks when a greater proportion of the population lived more than five kilometers from a health facility (RR: 1.025 per 1% increase; 95% CI: 1.010, 1.039), bordered a body of water (RR: 5.5; 95% CI: 2.472, 12.404), experienced increased rainfall from October to December (RR: 1.003 per 1 mm increase; 95% CI: 1.001, 1.005), and experienced decreased rainfall from April to June (RR: 0.996 per 1 mm increase; 95% CI: 0.992, 0.999). There was no detectable association between cholera and population density, poverty, availability of piped water, waste disposal methods, rainfall from January to March, or rainfall from July to September.
Bordering a large body of water, lack of health facilities nearby, and changes in rainfall were significantly associated with an increased risk of cholera in Kenya.

Evaluating Novel Therapies During the Ebola Epidemic

October 1, 2014, Vol 312, No. 13

Viewpoint | October 1, 2014
Evaluating Novel Therapies During the Ebola Epidemic
Steven Joffe, MD, MPH1
Author Affiliations
JAMA. 2014;312(13):1299-1300. doi:10.1001/jama.2014.12867.

The Ebola hemorrhagic fever outbreak in West Africa poses acute and novel challenges for health policy and research ethics. Faced with an exceptionally virulent infectious agent, limited resources, and danger to health workers, local and international authorities struggle to deploy proven public health techniques that can limit the spread of the disease.1 In the midst of the crisis, experimental interventions that have never been evaluated in human trials have captured professional and public attention. The prospect of first-in-human use of these interventions during an uncontrolled epidemic raises at least 4 pressing ethical questions. First, is there a role for “compassionate use” of agents in the absence of human safety, efficacy, or dosing data? Second, given the critical scarcity of these agents, which patients should receive priority access? Third, what trial designs should be used to study these agents? Fourth, how should efforts to evaluate experimental agents coexist with established clinical and public health interventions to treat patients and to minimize spread?

Two fundamental principles should guide responses to these questions. Decisions must aim to prevent the maximum number of deaths during the current outbreak. Equally important, policy makers must seek to optimize knowledge gained for use in confronting future Ebola epidemics.

A small biotechnology company, Mapp Biopharmaceutical, has conducted preclinical testing of ZMapp, a passive immunotherapy that combines 3 humanized monoclonal antibodies produced in Nicotinia plants. A recent trial of this product, administered up to 5 days after experimental inoculation of macaque monkeys with a virulent Ebola strain, suggests impressive efficacy at preventing lethal disease.2 Based on these data, 6 health workers and a priest have received doses of ZMapp, and media reports suggest that at least some of these patients benefited from the product. However, the absolute scarcity of the product—the available supply is depleted, and scaling production will take months—limits broader access. Other novel agents under development may also have a role and may be more amenable to rapid scale-up of production.3

Prompted by the controversy surrounding this immunotherapy product and other novel agents, the World Health Organization (WHO) convened an expert panel on August 11, 2014, to advise on its role. The panel “concluded unanimously that it would be acceptable on both ethical and evidential grounds to use as potential treatments or for prevention unregistered interventions that have shown promising results in the laboratory and in animal models but have not yet been evaluated for safety and efficacy in humans, provided that certain conditions are met.”4

The vernacular term “compassionate use” refers to the use of an unapproved agent, outside the context of a scientific protocol, with the goal of benefiting an individual patient with a serious, usually life-threatening condition. In the face of a disease such as Ebola, with a case-fatality rate greater than 50%, the inclination to administer promising but unproven new agents in a compassionate-use manner is understandable. Compassionate use is theoretically compatible with learning; as the WHO advisory panel noted, “physicians overseeing [the administration of unproven new agents] have a moral obligation to collect and share all scientifically relevant data generated…in order to establish the safety and efficacy of the interventions.”4

Allowing considerations of rescue rather than scientific hypotheses to drive use of novel agents, however, risks compromising the acquisition of knowledge needed to clarify their role in the next epidemic and ultimately to maximize benefits for patients. In addition, particularly in the first-in-human setting, a compassionate use approach will not necessarily prevent more deaths than would administration of the drug in a well-designed clinical trial. Moreover, when the novel agent is scarce, clinicians and health system authorities will need to confront the difficult question of who among the many deserving patients should receive access regardless of whether a compassionate use or clinical trial framework is adopted. For these reasons, policy makers should advocate for clinical trials organized around appropriate scientific questions, rather than endorsing compassionate use.

In the short term, production of ZMapp and other novel agents will be insufficient to provide these therapies to all patients who might benefit. As a result, clinicians and health authorities will inevitably need to ration the available supplies. In the context of clinical trials, decisions about eligibility criteria should incorporate judgments about 2 factors: which patient groups are most likely to benefit from receiving the agent and which are most likely to generate scientific insights that will inform its evidence-based use in the next epidemic. The inclination to conduct initial trials among critically ill Ebola patients, rather than among patients with less advanced disease, will be strong. However, in the macaque trials that ought to inform design of the first-in-human studies, ZMapp was effective when administered within 5 days after experimental inoculation. Extrapolating from this preclinical experience—and acknowledging that evidence about the efficacy of this form of immunotherapy when administered late in the course of infection is lacking—both patient-benefit and scientific rationales suggest limiting eligibility in the initial trials to patients with early rather than advanced disease. Furthermore, in situations of extreme scarcity of therapy, considerations of consent, reciprocity, and logistics might justify prioritizing health care workers and others on the front lines of the Ebola epidemic for access to trials.

Given the urgent circumstances, individuals and organizations involved in planning clinical trials may consider administering the experimental agent to a consecutive series of patients and then attempt to evaluate its safety and efficacy in light of what is known about the natural history of the disease. This would be a mistake. Investigators should instead move directly to randomized trials that compare best supportive care plus an experimental agent with best supportive care alone. Without a concurrent randomized control group, individuals who receive the drug will differ systematically from the untreated individuals with whom they are compared. Study participants may be sicker or less ill, younger or older, or identified at an earlier or later stage of disease than those in historical—or even contemporary—comparison groups. These differences will confound efforts to reach valid inferences about the safety and efficacy of the drug.

Objections to the use of randomization in the midst of a devastating epidemic will center on ethical and scientific concerns. Scientific questions will focus on whether dose-finding and feasibility considerations require a pilot single-treatment group, uncontrolled trial. Yet even these preliminary questions are best answered in the context of a randomized control group. Furthermore, it is possible that early hints of either efficacy or serious toxicity in an uncontrolled trial, even if difficult to interpret given inevitable selection biases, will derail the possibility of conducting a subsequent randomized trial.

Some will argue that it is unethical to randomize patients with a disease that has a 55% to 60% short-term case fatality rate to a control group when an intervention that holds any promise for reducing their likelihood of death is available. This objection does not consider that, given the scarcity of the drug, a finite number of patients will receive access regardless of what study design is used. It also fails to acknowledge that alternative means for prioritizing access, such as first-come first-served and sickest first, are themselves ethically unsatisfactory.5 Especially in the setting of absolute scarcity of the novel agent, where nothing ethically is lost by allocating access through a lottery,6 randomization should begin with the very first trials.7

Perhaps most important in confronting the present epidemic, efforts to evaluate novel agents risk diverting attention and human and material assets from proven therapeutic and public health measures.4 Well-motivated initiatives directed at promising new therapies must not jeopardize existing health infrastructures. Rather, local and international health authorities must ensure that the resources needed to conduct clinical trials represent dedicated additional capacity. Without attention to this issue, efforts to study novel agents may ironically increase, not reduce, the death toll from this epidemic.
Scientifically and ethically justified use of scarce new agents in the midst of the Ebola epidemic, or any other epidemic for which novel agents hold promise, requires reflection on the understandable desire to rescue imminently dying patients. Clinicians, investigators, and policy makers must deploy novel agents in ways that address pressing scientific questions, prioritize research in populations that will be most scientifically informative as well as most likely to benefit, ensure valid answers through the use of supportive care controls, and protect critical clinical and public health resources from diversion to longer-term aims. By doing so, they can maximize lives saved in the present epidemic and ensure knowledge gains for the next.
Published Online: September 11, 2014. doi:10.1001/jama.2014.12867.
Conflict of Interest Disclosures: The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Joffe reports being a paid member of a data monitoring committee for Genzyme/Sanofi until November 2012.

1 Gostin LO, Lucey D, Phelan A. The Ebola epidemic: a global health emergency. JAMA. 2014;312(11):1095-1096.
PubMed | Link to Article
2 Qiu X, Wong G, Audet J, et al. Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp [published online August 29, 2014]. Nature. doi:10.1038/nature13777.
3 Hampton T. Largest-ever outbreak of Ebola virus disease thrusts experimental therapies, vaccines into spotlight [published online August 27, 2014]. JAMA. doi:10.1001/jama.2014.11170.
4 Advisory Panel to the World Health Organization. Ethical considerations for use of unregistered interventions for Ebola viral disease. http://apps.who.int/iris/bitstream/10665/130997/1/WHO_HIS_KER_GHE_14.1_eng.pdf?ua=1&ua=1. August 11, 2014. Accessed September 1, 2014.
5 Persad G, Wertheimer A, Emanuel EJ. Principles for allocation of scarce medical interventions. Lancet. 2009;373(9661):423-431.
PubMed | Link to Article
6 STREPTOMYCIN treatment of pulmonary tuberculosis. Br Med J. 1948;2(4582):769-782.
PubMed | Link to Article
7 Chalmers TC. Randomization of the first patient. Med Clin North Am. 1975;59(4):1035-1038.

Why Should High-Income Countries Help Combat Ebola?

October 1, 2014, Vol 312, No. 13

Viewpoint | October 1, 2014
Why Should High-Income Countries Help Combat Ebola?
Annette Rid, MD1; Ezekiel J. Emanuel, MD, PhD2
Author Affiliations
JAMA. 2014;312(13):1297-1298. doi:10.1001/jama.2014.12869.

The outbreak of Ebola in West Africa is devastating to the affected countries. With no specific treatments or preventive measures available, Ebola has, to date, caused almost 2300 deaths,1 overwhelmed fragile health care systems and thereby led to inadequate care for other serious diseases, and slowed economic activity.
Yet Ebola most likely will not become a global health threat.2 Ebola only spreads through direct contact with infected bodily fluids, and containment is readily achievable in high-income countries. This undermines the standard rationale for these countries to address infectious disease outbreaks in other regions—namely, to protect their own populations. For example, fear of global spread has been a key motivation for addressing influenza outbreaks in southeast Asia.

Why, then, should high-income countries help the affected countries combat Ebola and strengthen their health systems and infrastructure in the longer term? Three independent reasons justify action.

First, everyone has obligations of humanitarian assistance to help others in dire need if the cost or imposition is minimal.3 This idea underlies the notion of a “Good Samaritan.” Most people recognize that, if a person is walking past a shallow pond and sees a child drowning in it, that person should wade in and pull the child out—even if that means risking minor injury or being delayed. Severe moral opprobrium and social stigmatization—if not legal penalties—are appropriate if you do not rescue the child. By analogy, societies have an obligation to help people affected by Ebola when the cost or imposition of doing so is minimal. Severe morbidity and mortality from Ebola are tragic occurrences, independent of where people live and whether societies or other countries have special relationships with those affected.

Effective help for Ebola is available at relatively minimal cost for high-income countries. Supportive treatment and containment measures—implementing isolation of suspected cases, infection control and universal precautions, contact tracing and monitoring, surveillance, and raising awareness in local communities and internationally—have a proven track record of controlling Ebola outbreaks.

Moreover, the resources necessary for these measures are small, even trivial. So far, the World Health Organization (WHO) has pledged $100 million, the World Bank $200 million, the European Commission $181 million, and the United States $75 million to combat this outbreak.4 Even if ultimately $1.5 billion is needed, this represents less than 1 penny for every $100 of the US $16 trillion gross domestic product in 2012, and just 1 penny for every $390 of the gross domestic product of the world’s 20 largest economies. By any measure, this constitutes an insignificant imposition on citizens of high-income countries. Virtually all high-income countries are thus in a position to effectively help curb the Ebola epidemic, without sacrificing much of importance. The moral obligation of humanitarian assistance requires doing so.

Second, there are obligations of global justice to combat Ebola and strengthen health systems and infrastructure in affected countries in the longer term. Advocates of so-called cosmopolitanism—a key position in the philosophical debate about global justice—argue that national borders have no moral significance and that all people, regardless of where they live, are entitled to the same education, health care services, and other social resources.5

Cosmopolitanism implies substantial support and resource transfers from high- to low-income countries. For example, it underlies the WHO’s position that people in all countries are entitled to first-line antiretroviral treatment for HIV/AIDS, although using earlier and less expensive—yet more toxic—antiretrovirals would allow treating more patients in resource-poor settings.6 Thus, cosmopolitanism requires high-income countries to assist with containing Ebola as well as strengthening health systems and infrastructure in the longer term. After all, the Ebola outbreak is an urgent manifestation of fragile health systems. For example, Sierra Leone has 2 physicians per 100 000 people and spends $96 per person a year on health, compared with 245 physicians per 100 000 people and $8895 in annual health expenditures in the United States.7
Conversely, another important position in the philosophical debate about global justice—so-called statism—maintains that obligations of justice are primarily focused on fellow citizens.8 But even statists endorse minimal obligations of global justice. While rejecting demands to equalize living standards, statists recognize that high-income countries have obligations to meet the basic needs of people living in extreme poverty on $1.25 a day or less. Moreover, the world is now interconnected through communications, collaboration, trade, finance, and pollution.

This interconnection implies that everyone’s life prospects are influenced by global events. For example, the devastating civil wars in Sierra Leone in the 1990s were fueled by the illicit international diamond trade. Governmental corruption—often facilitated by corporate contracts for mineral or other resources—keeps many countries, including in sub-Saharan Africa, in poverty and lacking basic infrastructure. Even statists acknowledge that high-income countries have obligations to compensate for such injustices. Statist advocates thus endorse obligations to ensure that people everywhere can lead a minimally decent life. This would include obligations of high-income countries to help contain Ebola and—given that the affected countries are some of the least developed worldwide—to offer limited assistance with strengthening health systems and infrastructure in the longer term.

Importantly, even those scholars and policy makers who typically reject foreign aid as counterproductive support international health programs.9 Health aid is different, in their view, because the great benefits of saving and improving lives outweigh the costs of undermining local governance and democracy. Therefore, even in the most restrictive and skeptical views, obligations of global justice support containing Ebola and continuing limited assistance to strengthen health systems after the epidemic subsides.

Ethical requirements for research demand that sponsors provide fair benefits to communities who are engaged in any research in this, or future, outbreaks.10 While there are many benefits that sponsors and communities could consider—such as making any proven interventions available to the population (“reasonable availability”) or building schools—the most pressing benefit likely is contributing to containment and strengthening local health systems and infrastructure.
High-income countries are sponsoring research evaluating specific Ebola treatments and vaccines largely because Ebola is perceived as a potential national security threat. For example, the US government has already spent millions of dollars on Ebola research, partly because it regards the disease as a threat to US soldiers and aid workers, and partly because it fears development of Ebola as a bioterrorist weapon.

Yet clinical testing of investigational Ebola interventions can only be conducted in affected African regions, not in high-income countries. Such externally sponsored research in developing countries raises concerns about exploitation of individuals and local communities, and these concerns are heightened during an epidemic. It is therefore essential that research sponsors from high-income countries contribute to containment and strengthening of health systems or provide other fair benefits from the research to the involved communities.10

The Ebola epidemic in West Africa is harrowing, but it is unlikely to become a global health threat. High-income countries nevertheless have 3 compelling reasons to help combat Ebola and strengthen health systems and infrastructure in affected countries in the longer term: the duty to provide humanitarian assistance; obligations of global justice to ensure, at least, that people everywhere can lead a minimally decent life; and the ethical requirement to provide fair benefits from any research conducted during the epidemic.

Corresponding Author: Annette Rid, MD, Department of Social Science, Health & Medicine, King’s College London, Strand, London WC2R 2LS, United Kingdom (annette.rid@kcl.ac.uk).
Published Online: September 11, 2014. doi:10.1001/jama.2014.12869.
Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Rid reported receiving funding from the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant agreement 301816. Dr Emanuel reported receiving payment for speaking engagements unrelated to this work.
1 World Health Organization. Ebola Response Roadmap Update, 8 September 2014. http://apps.who.int/iris/bitstream/10665/132834/1/roadmapupdate8sept14_eng.pdf?ua=1&ua=1. Accessed September 9, 2014.
2 Gostin LO, Lucey D, Phelan A. The Ebola epidemic: a global health emergency. JAMA. 2014;312(11):1095-1096.
PubMed | Link to Article
3 Singer P. Famine, affluence and morality. Philos Public Aff. 1972;1(3):229-243.
4 Bennett S. Ebola fight gets $250 million U.S., Europe funding boost. http://www.bloomberg.com/news/2014-09-04/obama-help-sought-on-ebola-as-who-cites-budget-cut-limits.html. September 5, 2014. Accessed September 9, 2014.
5 Caney S. Justice Beyond Borders: A Global Political Theory. New York, NY: Oxford University Press; 2005.
6 World Health Organization. Rapid advice: antiretroviral therapy for HIV infection in adults and adolescents. http://www.who.int/hiv/pub/arv/rapid_advice_art.pdf. November 2009. Accessed September 9, 2014.
7 World Health Organization. Global Health Observatory: density of physicians and per capita total expenditures on health at average exchange rate. http://www.who.int/gho/health_systems/en/. Accessed September 9, 2014.
8 Rawls J. The Law of Peoples. Boston, MA: Harvard University Press; 1999.
9 Deaton A. The Great Escape: Health, Wealth and the Origins of Inequality. Princeton, NJ: Princeton University Press; 2013.
10 Emanuel EJ, Wendler D, Killen J, Grady C. What makes clinical research in developing countries ethical? the benchmarks of ethical research. J Infect Dis. 2004;189(5):930-937.

Estimation of Geographic Variation in Human Papillomavirus Vaccine Uptake in Men and Women: An Online Survey Using Facebook Recruitment

Journal of Medical Internet Research
Vol 16, No 9 (2014): September

Estimation of Geographic Variation in Human Papillomavirus Vaccine Uptake in Men and Women: An Online Survey Using Facebook Recruitment
Erik J Nelson, John Hughes, J Michael Oakes, James S Pankow, Shalini L Kulasingam
J Med Internet Res 2014 (Sep 01); 16(9):e198
Background: Federally funded surveys of human papillomavirus (HPV) vaccine uptake are important for pinpointing geographically based health disparities. Although national and state level data are available, local (ie, county and postal code level) data are not due to small sample sizes, confidentiality concerns, and cost. Local level HPV vaccine uptake data may be feasible to obtain by targeting specific geographic areas through social media advertising and recruitment strategies, in combination with online surveys.
Objective: Our goal was to use Facebook-based recruitment and online surveys to estimate local variation in HPV vaccine uptake among young men and women in Minnesota.
Methods: From November 2012 to January 2013, men and women were recruited via a targeted Facebook advertisement campaign to complete an online survey about HPV vaccination practices. The Facebook advertisements were targeted to recruit men and women by location (25 mile radius of Minneapolis, Minnesota, United States), age (18-30 years), and language (English).
Results: Of the 2079 men and women who responded to the Facebook advertisements and visited the study website, 1003 (48.2%) enrolled in the study and completed the survey. The average advertising cost per completed survey was US $1.36. Among those who reported their postal code, 90.6% (881/972) of the participants lived within the previously defined geographic study area. Receipt of 1 dose or more of HPV vaccine was reported by 65.6% women (351/535), and 13.0% (45/347) of men. These results differ from previously reported Minnesota state level estimates (53.8% for young women and 20.8% for young men) and from national estimates (34.5% for women and 2.3% for men).
Conclusions: This study shows that recruiting a representative sample of young men and women based on county and postal code location to complete a survey on HPV vaccination uptake via the Internet is a cost-effective and feasible strategy. This study also highlights the need for local estimates to assess the variation in HPV vaccine uptake, as these estimates differ considerably from those obtained using survey data that are aggregated to the state or federal level.

Power and Persuasion in the Vaccine Debates: An Analysis of Political Efforts and Outcomes in the United States, 1998-2012

The Milbank Quarterly
A Multidisciplinary Journal of Population Health and Health Policy
September 2014 Volume 92, Issue 3 Pages 407–631

Global Polio Eradication: Espionage, Disinformation, and the Politics of Vaccination
First published: 9 September 2014
DOI: 10.1111/1468-0009.12065
[No abstract]

Original Investigation
Power and Persuasion in the Vaccine Debates: An Analysis of Political Efforts and Outcomes in the United States, 1998-2012
Article first published online: 9 SEP 2014
DOI: 10.1111/1468-0009.12075
This article examines trends in state-level childhood vaccine policies in the United States from 1998 to 2012 and explains the trajectories for both vaccine-critical and proimmunization legislative efforts. Successful mobilization by vaccine critics during the height of the autism and thimerosal scares (roughly 1998 to 2003) yielded a few state-level expansions for the most permissive type of exemption from vaccine mandates for public school attendance, those based on personal beliefs. Vaccine-critical positions, however, have largely become discredited. How has vaccine critics’ ability to advance preferred policies and prevent the passage of unfavorable legislation changed over time?
We created a unique data set of childhood vaccine bills (n = 636), introduced from 1998 to 2012 across the 50 state legislatures, and coded them by type of effort (exemption, mandate, mercury ban, and information policies) and outcome. We then mapped out the trends in vaccine policies over time. In order to contextualize the trends we identified, we also reviewed numerous primary sources and conducted interviews with stakeholders.
In general, we found that vaccine critics’ legislative success has begun to wane. In only 20 bills in our data set were vaccine critics able to change policy in their preferred direction via the legislative process. Only 5 of those wins were significant (such as obtaining a new philosophical exemption to vaccine mandates), and the last of these was in 2007. Critics were more successful at preventing passage of proimmunization legislation, such as mandates for the human papillomavirus (HPV) vaccine.
Recent legislation in California, Oregon, and Washington that tightened philosophical exemptions by means of informational requirements suggests that vaccine politics may be entering another phase, one in which immunization supporters may be able to counter increasing opt-out rates, particularly in states with recent outbreaks and politicians favoring science-based policies.

Ebola outbreak shuts down malaria-control efforts; Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp

Volume 514 Number 7520 pp5-134 2 October 2014

Ebola outbreak shuts down malaria-control efforts
Public-health experts fear that one epidemic may fuel another in West Africa.
Erika Check Hayden
As the Ebola death toll spirals into the thousands in West Africa, the outbreak could have a spillover effect on the region’s deadliest disease. The outbreak has virtually shut down malaria control efforts in Liberia, Guinea and Sierra Leone, raising fears that cases of the mosquito-borne illness may start rising — if they haven’t already.
So far, at least 3,000 people are estimated to have died of Ebola in Guinea, Sierra Leone and Liberia in the current outbreak, although World Health Organization (WHO) staff acknowledge that official figures vastly underestimate the total. By contrast, malaria killed more than 6,300 people in those countries in 2012, most of them young children. Overall, malaria deaths have fallen by about 30% in Africa since 2000 thanks to national programmes supported by international funding agencies such as the Global Fund to Fight AIDS, Tuberculosis and Malaria, the US Agency for International Development and the WHO’s Roll Back Malaria initiative. The schemes distribute free bed nets to protect sleeping children from mosquitoes, train health workers to find malaria cases and offer tests and treatment at no charge to patients.
But the Ebola outbreak has brought those efforts to a standstill in the three affected countries. “Nobody is doing a thing,” says Thomas Teuscher, acting executive director of the Roll Back Malaria Partnership, based in Geneva, Switzerland…

Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp
Xiangguo Qiu, Gary Wong, Jonathan Audet, Alexander Bello, Lisa Fernando, Judie B. Alimonti, Hugues Fausther-Bovendo, Haiyan Wei, Jenna Aviles, Ernie Hiatt, Ashley Johnson, Josh Morton,
Kelsi Swope, Ognian Bohorov, Natasha Bohorova, Charles Goodman, Do Kim, Michael H. Pauly,
Jesus Velasco, James Pettitt, Gene G. Olinger, Kevin Whaley, Bianli Xu, James E. Strong, Larry Zeitlin et al.
Nature 514, 47–53 (02 October 2014) doi:10.1038/nature13777
Without an approved vaccine or treatments, Ebola outbreak management has been limited to palliative care and barrier methods to prevent transmission. These approaches, however, have yet to end the 2014 outbreak of Ebola after its prolonged presence in West Africa. Here we show that a combination of monoclonal antibodies (ZMapp), optimized from two previous antibody cocktails, is able to rescue 100% of rhesus macaques when treatment is initiated up to 5 days post-challenge. High fever, viraemia and abnormalities in blood count and blood chemistry were evident in many animals before ZMapp intervention. Advanced disease, as indicated by elevated liver enzymes, mucosal haemorrhages and generalized petechia could be reversed, leading to full recovery. ELISA and neutralizing antibody assays indicate that ZMapp is cross-reactive with the Guinean variant of Ebola. ZMapp exceeds the efficacy of any other therapeutics described so far, and results warrant further development of this cocktail for clinical use.

Etiologies for Seizures Around the Time of Vaccination

October 2014, VOLUME 134 / ISSUE 4

Etiologies for Seizures Around the Time of Vaccination
Nienke E. Verbeek, MD, MSca, Floor E. Jansen, MD, PhDb, Patricia E. Vermeer-de Bondt, MDc, Carolien G. de Kovel, PhDa, Marjan J.A. van Kempen, PhDa, Dick Lindhout, MD, PhDa, Nine V.A.M. Knoers, MD, PhDa, Nicoline A.T. van der Maas, MDc, and Eva H. Brilstra, MD, PhDa
Author Affiliations
aDepartment of Medical Genetics, and
bRudolph Magnus Institute of Neurosciences, Department of Child Neurology, University Medical Centre Utrecht, Utrecht, Netherlands; and
cNational Institute for Public Health and Environment (RIVM), Bilthoven, Netherlands
OBJECTIVES: This study was an assessment of the incidence, course, and etiology of epilepsy with vaccination-related seizure onset in a population-based cohort of children.
METHODS: The medical data of 990 children with seizures after vaccination in the first 2 years of life, reported to the National Institute for Public Health and Environment in the Netherlands in 1997 through 2006, were reviewed. Follow-up data were obtained of children who were subsequently diagnosed with epilepsy and had had seizure onset within 24 hours after administration of an inactivated vaccine or 5 to 12 days after a live attenuated vaccine.
RESULTS: Follow-up was available for 23 of 26 children (median age: 10.6 years) with epilepsy onset after vaccination. Twelve children developed epileptic encephalopathy, 8 had benign epilepsy, and 3 had encephalopathy before seizure onset. Underlying causes were identified in 15 children (65%) and included SCN1A–related Dravet syndrome (formerly severe myoclonic epilepsy of infancy) or genetic epilepsy with febrile seizures plus syndrome (n = 8 and n = 1, respectively), a protocadherin 19 mutation, a 1qter microdeletion, neuronal migration disorders (n = 2), and other monogenic familial epilepsy (n = 2).
CONCLUSIONS: Our results suggest that in most cases, genetic or structural defects are the underlying cause of epilepsy with onset after vaccination, including both cases with preexistent encephalopathy or benign epilepsy with good outcome. These results have significant added value in counseling of parents of children with vaccination-related first seizures, and they might help to support public faith in vaccination programs.

Parental Tdap Boosters and Infant Pertussis: A Case-Control Study

October 2014, VOLUME 134 / ISSUE 4

Parental Tdap Boosters and Infant Pertussis: A Case-Control Study
Helen E. Quinn, PhD, MAEa,b, Thomas L. Snelling, BMBS, PhDc,d, Andrew Habig, MBBS, MPHa, Clayton Chiu, MBBS, MPH, TMa,b, Paula J. Spokes, RN, MIPHe, and Peter B. McIntyre, MBBS, PhDa,b
Author Affiliations
aNational Centre for Immunisation Research and Surveillance of Vaccine Preventable Diseases, and
bDiscipline of Paediatrics and Child Health, University of Sydney, Children’s Hospital at Westmead, Westmead, Australia;
cTelethon Institute for Child Health Research, University of Western Australia, Subiaco, Australia;
dMenzies School of Health Research, Charles Darwin University, Casuarina, Australia; and
eNew South Wales Ministry of Health, North Sydney, Australia
BACKGROUND: Although recommended for almost a decade, evidence for field effectiveness of vaccinating close adult contacts of newborn infants against pertussis (“cocooning”) is lacking. We evaluated the impact of a government-funded cocoon program during a pertussis epidemic in New South Wales, Australia.
METHODS: We matched all New South Wales laboratory-confirmed pertussis cases aged <4 months with onset between April 1, 2009, to March 30, 2011 to controls from the state birth register by date of birth and area of residence. Parental vaccine receipt was by self-report, with a subset verified. Parents were considered “immunized” if vaccinated ≥4 weeks before case symptom onset. The effectiveness of parental immunization (versus neither vaccinated) was quantified as (1 – odds ratio) × 100%.
RESULTS: Case households had fewer immunized mothers (22% vs 32%) or fathers (20% vs 31%) but were more likely to include additional and older children. After adjustment, when both parents met our definition of immunized, risk of pertussis at<4 months of age was reduced by 51% (95% confidence interval 10% to 73%). Maternal vaccination prepregnancy and an immunized father reduced the risk by 51% (95% confidence interval 0% to 76%).
CONCLUSIONS: Timely parental pertussis boosters provided significant protection. Evidence of protection from maternal vaccination prepregnancy is biologically plausible, and more precise data on the magnitude and duration of this is important for future policy recommendations.

Parental Financial Incentives for Increasing Preschool Vaccination Uptake: Systematic Review

October 2014, VOLUME 134 / ISSUE 4

Review Article
Parental Financial Incentives for Increasing Preschool Vaccination Uptake: Systematic Review
Sarah Wigham, PhD, Laura Ternent, PhD, Andrew Bryant, MSc, Shannon Robalino, MSc,
Falko F. Sniehotta, PhD, and Jean Adams, PhD
Author Affiliations
Institute of Health and Society, Newcastle University, Newcastle upon Tyne, United Kingdom
BACKGROUND AND OBJECTIVE: Financial incentives have been used to promote vaccination uptake but are not always viewed as acceptable. Quasimandatory policies, such as requiring vaccinations for school enrollment, are widely implemented in some countries. A systematic review was conducted to determine the effectiveness, acceptability, and economic costs and consequences of parental financial incentives and quasimandatory schemes for increasing the uptake of preschool vaccinations in high-income countries.
METHODS: Electronic databases and gray literature were searched for randomized controlled trials, controlled before-and-after studies, and time series analyses examining the effectiveness of parental financial incentives and quasimandatory schemes, as well as any empirical studies exploring acceptability. All included studies were screened for information on economic costs and consequences. Two reviewers independently assessed studies for inclusion, extracted data, and assessed the quality of selected articles by using established instruments. Studies were synthesized in narrative reviews.
RESULTS: Four studies on the effectiveness and 6 on the acceptability of parental financial incentives and quasimandatory interventions met the inclusion criteria. Only 1 study reported on costs and consequences. Studies of effectiveness had low risk of bias but displayed substantial heterogeneity in terms of interventions and methods.
CONCLUSIONS: There was insufficient evidence to conclude whether these interventions were effective. Studies of acceptability suggested a preference, in settings where this already occurs, for incentives linking vaccinations to access to education. There was insufficient evidence to draw conclusions on economic costs and consequences.

Challenges to School-Located Vaccination: Lessons Learned

October 2014, VOLUME 134 / ISSUE 4

Special Article
Challenges to School-Located Vaccination: Lessons Learned
Heather M. Limper, MPHa,b, Jennifer L. Burns, APNa, LaKesha M. Lloyd, ASa, Jennifer Atilano, BSa, Kenneth A. Alexander, MD, PhDa, and Rachel N. Caskey, MD, MPPb
Author Affiliations
aDepartment of Pediatrics, University of Chicago Medicine, Chicago, Illinois; and
bDepartment of Pediatrics, University of Illinois at Chicago Medical Center, Chicago, Illinois
School-located vaccination (SLV) has a long history in the United States and has successfully contributed to lower morbidity and mortality due to vaccine-preventable diseases.1 Historically, SLV efforts, which tended to be single-vaccine programs intended to provide catch-up immunization to a defined school-age cohort or were implemented in response to an outbreak, were unfunded, funded by local health department, or were funded by industry or federal grants. The growing palette of vaccines recommended for routine use in adolescents along with limited success of office-based adolescent immunization create a compelling argument for the creation of financially sustainable SLV programs. An arguably significant barrier to both office-based and school-located adolescent immunization is the modest reimbursement rates afforded to immunizers. Because the immunization promotion and consent process is expensive, these costs must be reduced to a minimum to reach financial viability. Although there are challenges to creating a financially sustainable SLV program coordinated by an academic medical center, (AMC), the ability of AMCs to bill private and public insurers, the nonprofit status of medical centers, the allowances for faculty for academic pursuit, and the substantial infrastructure already present make AMCs a potentially practical site for the administration of SLV programs. Alternatively, as health departments throughout the nation continue to explore methods for billing private insurance, we may find health departments to be uniquely suited for coordinating the administration and billing of these services.

Cognitive Deficit and Poverty in the First 5 Years of Childhood in Bangladesh

October 2014, VOLUME 134 / ISSUE 4

Cognitive Deficit and Poverty in the First 5 Years of Childhood in Bangladesh
Jena D. Hamadani, MBBS, DCH, PhDa, Fahmida Tofail, MBBS, PhDa, Syed N. Huda, MBBS, PhDb, Dewan S. Alam, MBBS, PhDa, Deborah A. Ridout, PhDc, Orazio Attanasio, PhDd, and
Sally M. Grantham-McGregor, MBBS, MD, FRCPe
Author Affiliations
aInternational Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh;
bInstitute of Nutrition and Food Science, Dhaka University, Dhaka, Bangladesh; and
cCentre for Paediatric Epidemiology and Biostatistics,
eCentre for International Health and Development, Institute of Child Health, and
dDepartment of Economics, University College London, London, United Kingdom
OBJECTIVE: We aimed to determine the timing and size of the cognitive deficit associated with poverty in the first 5 years of life and to examine the role of parental characteristics, pre- and postnatal growth, and stimulation in the home in Bangladeshi children. We hypothesized that the effect of poverty on cognition begins in infancy and is mainly mediated by these factors.
METHODS: We enrolled 2853 singletons, a subsample from a pregnancy supplementation trial in a poor rural area. We assessed mental development at 7, 18, and 64 months; anthropometry at birth, 12, 24, and 64 months; home stimulation at 18 and 64 months; and family’s socioeconomic background. In multiple regression analyses, we examined the effect of poverty at birth on IQ at 64 months and the extent that other factors mediated the effect.
RESULTS: A mean cognitive deficit of 0.2 (95% confidence interval –0.4 to –0.02) z scores between the first and fifth wealth quintiles was apparent at 7 months and increased to 1.2 (95% confidence interval –1.3 to –1.0) z scores of IQ by 64 months. Parental education, pre- and postnatal growth in length, and home stimulation mediated 86% of the effects of poverty on IQ and had independent effects. Growth in the first 2 years had larger effects than later growth. Home stimulation had effects throughout the period.
CONCLUSIONS: Effects of poverty on children’s cognition are mostly mediated through parental education, birth size, growth in the first 24 months, and home stimulation in the first 5 years.

The early spread and epidemic ignition of HIV-1 in human populations

3 October 2014 vol 346, issue 6205, pages 1-136

The early spread and epidemic ignition of HIV-1 in human populations
Nuno R. Faria, Andrew Rambaut, Marc A. Suchard, Guy Baele, Trevor Bedford, Melissa J. Ward,
Andrew J. Tatem, João D. Sousa, Nimalan Arinaminpathy, Jacques Pépin, David Posada, Martine Peeters, Oliver G. Pybus, and Philippe Lemey
Science 3 October 2014: 56-61.
The early history of HIV centered on Kinshasa before accelerating in 1960 as a result of seismic social change after independence.
Thirty years after the discovery of HIV-1, the early transmission, dissemination, and establishment of the virus in human populations remain unclear. Using statistical approaches applied to HIV-1 sequence data from central Africa, we show that from the 1920s Kinshasa (in what is now the Democratic Republic of Congo) was the focus of early transmission and the source of pre-1960 pandemic viruses elsewhere. Location and dating estimates were validated using the earliest HIV-1 archival sample, also from Kinshasa. The epidemic histories of HIV-1 group M and nonpandemic group O were similar until ~1960, after which group M underwent an epidemiological transition and outpaced regional population growth. Our results reconstruct the early dynamics of HIV-1 and emphasize the role of social changes and transport networks in the establishment of this virus in human populations.

When Ebola protection fails (HCWs)

3 October 2014 vol 346, issue 6205, pages 1-136

Infectious Diseases
When Ebola protection fails
Jon Cohen
More than 300 health care workers have contracted Ebola in the current epidemic and half have died. Three survivors explain that they only have hunches about how they became infected, and they discuss the role of transmission in places outside of Ebola treatment units, including emergency rooms and even between the crew decontaminating people taking off their personal protective equipment. Scant data exist about the infectiousness of different bodily fluids and environmental factors like countertops, but the one study that has looked at this question had surprising results. Training is ramping up of health care workers about to travel to affected countries to help, and this should address one of the key factors that clearly increase the risk of transmission: a shortage of trained people to do the difficult job of caring for the infected.

CFR – Ebola and Cultures of Engagement: Chinese Versus Western Health Diplomacy

Council on Foreign Relations
Accessed 4 October 2014

Council of Councils Global Memos
Ebola and Cultures of Engagement: Chinese Versus Western Health Diplomacy
October 3, 2014
The Ebola outbreak in West Africa has killed more than 3,000 people, highlighting the ineffectiveness of existing health institutions in Africa. This brief considers Western and Chinese approaches to the Ebola outbreak as well as their long-term health diplomacy strategies, while considering how these contrasts reflect the differences in Western and Chinese diplomatic engagement on the continent more generally. Considering the merits and gaps of both horizontal and vertical healthcare approaches, Erica Penfold and Pieter Fourie argue that international health diplomacy should place greater emphasis on building horizontal, integrated healthcare systems to avoid similar pandemics.

Media Conference Call: Laurie Garrett on Ebola
with Laurie Garrett, Thomas E. Novotny October 1, 2014
Laurie Garrett, CFR’s senior fellow for global health, discusses the recent arrival of a traveler infected with Ebola in the United States, as well as the virus’ rapid spread throughout West Africa.

Five Ethical Points Now That Ebola Has Entered The USA

Accessed 4 October 2014

Five Ethical Points Now That Ebola Has Entered The USA
Arthur Caplan, Contributor Sep 30, 2014
The first case of Ebola to occur on American soil has now occurred. The CDC announced a hospital in Dallas, Texas, has hospitalized a man who came there to visit his family. Sadly, this news is going to create a lot of panic. For example, the Internet will likely soon be […]

Guardian: The Observer view on the Ebola outbreak

The Guardian
Accessed 4 October 2014

The Observer view on the Ebola outbreak
Observer editorial
Saturday 4 October 2014 19.03 EDT
The world needs to face up to this global crisis
The world’s most deadly Ebola outbreak, which has killed more than 3,000 people in west Africa and set belated alarm bells ringing throughout the international community, has its probable origin in a remote village in Guinea, close to the border with Liberia and Sierra Leone. On 26 December 2013, a two-year-old boy fell sick with a mysterious illness whose symptoms local people and medical workers had never seen before. Within two days, the boy was dead. As more people in the area succumbed and others began to flee, perplexed staff from the French-founded medical aid charity, Médecins Sans Frontières (MSF), developed a nightmarish suspicion.

“Samples [were sent] to the Institut Pasteur in Paris,” a World Health Organisation (WHO) investigation reported. “The first news was shocking: the causative agent was indeed the Ebola virus.” Who could ever have guessed that such a notorious disease, previously confined to Central Africa and Gabon, would crop up in another distant part of the continent? The news from subsequent virological analyses was even worse: this was Ebola Zaire, the most lethal in the family of five distinct Ebola species.

The finding was recorded on the WHO’s website on 23 March. Since then, for a variety of causes, some wholly preventable, some less so, the often imagined but never seriously confronted prospect of a lethal, global pandemic with no readily available cure, spiralling out of control, has drawn ever closer. “Six months into the worst Ebola epidemic in history, the world is losing the battle to contain it,” MSF’s president, Joanne Liu, told the UN last month. “The WHO announcement on 8 August that the epidemic constituted a ‘public health emergency of international concern’ has not led to decisive action. States have essentially joined a global coalition of inaction,” she said.

The reasons why this most devastating strain of Ebola suddenly sprang up in west Africa remain uncertain, but the under-resourced, often panicky and chronically unco-ordinated reaction to its arrival there has been only too painfully obvious. Last week’s report that the Aids pandemic originated in Kinshasa, capital of the Democratic Republic of Congo, in the 1920s is instructive. In that case, researchers say, increased urban population density, disrupted societal norms leading to sexual promiscuity, and railway travel – the by-products of Belgian colonialism – encouraged the spread of HIV.

Similarly, in Guinea, Sierra Leone and Liberia, recent, prolonged periods of armed conflict and population upheavals, coupled with the unchecked exploitation of natural resources by international timber and mining companies, have altered regional ecology, rendering it more vulnerable physically as well as politically. Due to loss of habitat, fruit bats, widely believed to be the natural reservoir of the virus, moved closer to human settlements. People hunted and ate infected forest animals such as monkeys, squirrel and antelopes, the WHO report found. “Though no one knew it at the time, the Ebola virus had found a new home in a highly vulnerable population.”

Whatever its causes, it is evident now that the rapid and accelerating spread of Ebola – the virus is infecting five additional people every hour in Sierra Leone and a similar number in Liberia – is the avoidable result of a lack of hospital beds, isolation wards and basic facilities. It is the result, also, of too few doctors and nurses, of underprotected health workers who are themselves falling ill in large numbers, of traditional healing and burial practices, of generally underfunded healthcare systems, of corrupt misappropriation of foreign aid earmarked for healthcare and, crucially, of the lack of a vaccine in the face of a mutating virus. Of the 20,000 new cases predicted by the end of November, 70% on current trends will result in death. By the end of January, the Centres for Disease Control in Atlanta warns, there could be 1.4m new cases.
West Africa’s particular circumstances apart, the Ebola outbreak has now become a matter of truly international concern, not least because, as last week’s unseemly panic in Texas has shown, the epidemic potentially threatens us all. After a slow start, the Obama administration showed a lead in sending 3,000 troops to Liberia to boost its health defences. But its efforts are proceeding at a snail’s pace, reflecting a too familiar lack of preparedness.

The UK, despite parliamentary criticism last week, has been at the forefront of international efforts, concentrating £125m in assistance on Sierra Leone, building a new treatment centre outside Freetown and mobilising 400 NHS volunteers. David Cameron’s commitment to maintaining Britain’s overseas aid and development budget has never looked more sensible. France has been supplying direct assistance to Guinea. But in the face of a potential world-wide crisis, where is the rest of the world?

The European Commission makes all the right noises, but its financial contribution has been paltry. One of its main concerns appears to be how to airlift EU nationals in the affected countries. Germany, Europe’s supposed powerhouse, has only belatedly joined the fight. Meanwhile, other big international players are conspicuous by their absence. What of China, with its extensive commercial interests in west Africa? What of Russia, with its noisome pretensions to great power status? What of the other Brics countries, whose aspirations to a global role are so often heard? It is long past time they stepped up to mark and did their bit.

The scary truth of the Ebola pandemic is that, starting with the WHO last March, the world’s leading governments and institutions were, for the most part, caught napping. They thought (as did much of the western media) that this outbreak was another grisly but isolated act in Africa’s ongoing human tragedy. They thought it would not affect us. Now it is plain that it will, they badly need to get organised. They must act together, and quickly, not just to beat Ebola now, but in order to better deal with future pandemics when they come, as they surely will.

Peter Piot, the German scientist who discovered Ebola and a veteran of many battles against killer viruses, describes in an interview that we publish today how a “perfect storm” of mischance, miscalculation and mutation makes this epidemic unlike any that has gone before. We should all heed his words: “This isn’t just an epidemic anymore. This is a humanitarian catastrophe. We don’t just need care personnel, but also logistics experts, trucks, jeeps and foodstuffs. Such an epidemic can destabilise entire regions. I can only hope that we will be able to get it under control. I really never thought it could get this bad.”