International Journal of Epidemiology
Volume 42 Issue 1 February 2013
http://ije.oxfordjournals.org/content/current

Global Health
Convergence of non-communicable and infectious diseases in low- and middle-income countries
Justin V Remais, Guang Zeng, Guangwei Li, Lulu Tian, and Michael M Engelgau
Int. J. Epidemiol. (2013) 42(1): 221-227 doi:10.1093/ije/dys135
http://ije.oxfordjournals.org/content/42/1/221.abstract

Abstract
The convergence of non-communicable disease (NCD) and infectious disease (ID) in low- and middle-income countries (LMICs) presents new challenges and new opportunities to enact responsive changes in policy and research. Most LMICs have significant dual disease burdens of NCDs such as cardiovascular disease, diabetes and cancer, and IDs including tuberculosis, HIV/AIDS and parasitic diseases. A combined strategy is needed in surveillance and disease control; yet, experts, institutions and policies that support prevention and control of these two overarching disease categories have limited interaction and alignment. NCDs and IDs share common features, such as long-term care needs and overlapping high-risk populations, and there are also notable direct interactions, such as the association between certain IDs and cancers, as well as evidence of increased susceptibility to IDs in individuals with NCDs. Enhanced simultaneous surveillance of NCD and ID comorbidity in LMIC populations would generate the empirical data needed to better understand the dual burden, and to target coordinated care. Where IDs and NCDs are endemic, focusing on vulnerable populations by strengthening social protections and improving access to health services is crucial, as is the re-alignment of efforts to combine NCD and ID screening, treatment programmes, and the assessment of their impact. Integrating public health activities for ID and NCD should extend beyond health care services to prevention, which is widely seen as crucial to successful NCD and ID control campaigns alike. The convergence of NCD and ID in LMICs has the potential to overstretch already strained health systems. With some LMICs now focused on major health system reforms, a unique opportunity is available to address NCD and ID challenges with newfound urgency and novel approaches.

Commentary: The global health multiplier: targeting common social causes of infectious and non-communicable diseases
David Stuckler1,2,*, Martin McKee1 and Sanjay Basu3
http://ije.oxfordjournals.org/content/42/1/232.extract

JAMA Pediatrics
March 2013, Vol 167, No. 3
http://archpedi.jamanetwork.com/issue.aspx

A Population-Based Cohort Study of Undervaccination in 8 Managed Care Organizations Across the United States
Jason M. Glanz, PhD; Sophia R. Newcomer, MPH; Komal J. Narwaney, MD, PhD; Simon J. Hambidge, MD, PhD; Matthew F. Daley, MD; Nicole M. Wagner, MPH; David L. McClure, PhD; Stan Xu, PhD; Ali Rowhani-Rahbar, MD, PhD; Grace M. Lee, MD, MPH; Jennifer C. Nelson, PhD; James G. Donahue, DVM, PhD; Allison L. Naleway, PhD; James D. Nordin, MD, MPH; Marlene M. Lugg, DrPH; Eric S. Weintraub, MPH
http://archpedi.jamanetwork.com/article.aspx?articleid=1558057

Abstract
Objectives  To examine patterns and trends of undervaccination in children aged 2 to 24 months and to compare health care utilization rates between undervaccinated and age-appropriately vaccinated children.

Design  Retrospective matched cohort study.

Setting  Eight managed care organizations of the Vaccine Safety Datalink.

Participants  Children born between 2004 and 2008.

Main Exposure  Immunization records were used to calculate the average number of days undervaccinated. Two matched cohorts were created: 1 with children who were undervaccinated for any reason and 1 with children who were undervaccinated because of parental choice. For both cohorts, undervaccinated children were matched to age-appropriately vaccinated children by birth date, managed care organization, and sex.

Main Outcome Measures  Rates of undervaccination, specific patterns of undervaccination, and health care utilization rates.

Results  Of 323 247 children born between 2004 and 2008, 48.7% were undervaccinated for at least 1 day before age 24 months. The prevalence of undervaccination and specific patterns of undervaccination increased over time (P < .001). In a matched cohort analysis, undervaccinated children had lower outpatient visit rates compared with children who were age-appropriately vaccinated (incidence rate ratio [IRR], 0.89; 95% CI, 0.89- 0.90). In contrast, undervaccinated children had increased inpatient admission rates compared with age-appropriately vaccinated children (IRR, 1.21; 95% CI, 1.18-1.23). In a second matched cohort analysis, children who were undervaccinated because of parental choice had lower rates of outpatient visits (IRR, 0.94; 95% CI, 0.93-0.95) and emergency department encounters (IRR, 0.91; 95% CI, 0.88-0.94) than age-appropriately vaccinated children.

Conclusions  Undervaccination appears to be an increasing trend. Undervaccinated children appear to have different health care utilization patterns compared with age-appropriately vaccinated children.

JAMA Pediatrics
March 2013, Vol 167, No. 3
http://archpedi.jamanetwork.com/issue.aspx

Editorial
The Enigma of Alternative Childhood Immunization Schedules – What Are the Questions?
Douglas J. Opel, MD, MPH; Edgar K. Marcuse, MD, MPH
http://archpedi.jamanetwork.com/article.aspx?articleid=1558058

Alternative childhood immunization schedules have emerged as a distinct phenomenon in response to parental concerns about the safety of the US immunization schedule and its component vaccines. Some alternative schedules have been put in writing,1 many more are ad hoc, and all endorse a spacing out, a delaying, or a forgoing of at least some vaccines (which is contrary to what is jointly recommended by the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices, the American Academy of Pediatrics, and the American Academy of Family Physicians). None of these alternative schedules have been tested for their safety and efficacy.

Journal of Infectious Diseases
Volume 207 Issue 8 April 15, 2013
http://www.journals.uchicago.edu/toc/jid/current

EDITORIAL COMMENTARIES
Therapeutic Vaccination: Hope for Untreatable Tuberculosis?
David N. McMurray
J Infect Dis. (2013) 207(8): 1193-1194 doi:10.1093/infdis/jis429
http://jid.oxfordjournals.org/content/207/8/1193.extract

Extract
Although tuberculosis remains a major public health threat globally [1], promising advances have been made in the past several years in the development of new tools to control the pandemic. These include rapid diagnostic tests [2], new drug regimens that may shorten the total treatment time and improve compliance [3], and novel drug delivery systems that may allow sustained therapeutic levels with lower drug doses [4]. There are currently more than a dozen tuberculosis vaccines in human trials that are based upon a variety of platforms, including viral-vectored, recombinant bacille Calmette-Guérin, and protein/peptide vaccines [5].

Thus, the progress made in recent years in the battle against this ancient scourge is remarkable.

Unfortunately, control of tuberculosis is complicated by a number of factors, not the least of which are the interactions with human immunodeficiency infection and the development of multidrug-resistant and extensively drug-resistant strains [6]. In parts of the world where these resistant strains are common, treatment of patients with tuberculosis is difficult, if not impossible, because of the paucity of effective drugs. For such patients, an immune-stimulatory therapy that effectively engages patients’ own immune systems to assist the drugs in controlling the infection would be a major asset in the clinic setting. The therapeutic vaccine described by Coler et al [7] in this issue of the Journal of Infectious …

Journal of Infectious Diseases
Volume 207 Issue 8 April 15, 2013
http://www.journals.uchicago.edu/toc/jid/current

HIV/AIDS
Extended Evaluation of the Virologic, Immunologic, and Clinical Course of Volunteers Who Acquired HIV-1 Infection in a Phase III Vaccine Trial of ALVAC-HIV and AIDSVAX B/E
Supachai Rerks-Ngarm, Robert M. Paris, Supamit Chunsutthiwat, Nakorn Premsri, Chawetsan amwat, Chureeratana Bowonwatanuwong, Shuying S. Li, Jaranit Kaewkungkal, Rapee Trichavaroj, Nampueng Churikanont, Mark S. de Souza, Charla Andrews, Donald Francis, Elizabeth Adams, Jorge Flores, Sanjay Gurunathan, Jim Tartaglia, Robert J. O’Connell, Chirapa Eamsila, Sorachai Nitayaphan, Viseth Ngauy, Prasert Thongcharoen, Prayura Kunasol, Nelson L. Michael, Merlin L. Robb, Peter B. Gilbert, and Jerome H. Kim
J Infect Dis. (2013) 207(8): 1195-1205 doi:10.1093/infdis/jis478
http://jid.oxfordjournals.org/content/207/8/1195.abstract

Abstract
Background. The Thai Phase III Trial of ALVAC-HIV and AIDSVAX B/E showed an estimated vaccine efficacy (VE) of 31% to prevent acquisition of human immunodeficiency virus (HIV). Here we evaluated the effect of vaccination on disease progression after infection.

Methods.CD4 + T-cell counts and HIV viral load (VL) were measured serially. The primary analysis evaluated vaccine efficacy (VEP) as the percent reduction (vaccine vs placebo) in cumulative probability of a primary composite endpoint of clinical and CD4+ count components at prespecified time points after infection. Secondary analyses of biomarker-based endpoints were assessed using marginal mean and linear mixed models.

Results. There were 61 endpoints in the modified intent-to-treat cohort (mITT; n=114). There was no evidence for efficacy at 30, 42, 54, and 60 months in the mITT and per protocol (n = 90) cohorts. Estimated VEP (mITT) was15.8% (−21.9, 41.8) at 60 months postinfection. There was weak evidence of lower VL and higher CD4+ count at 60 and 66 months in the vaccine group. Lower mucosal VL was observed among vaccine recipients, primarily in semen (P = .04).

Conclusions. Vaccination did not affect the clinical course of HIV disease after infection. A potential vaccine effect on the genital  mucosa warrants further study.

Trial registration.Clinicaltrials.gov identifier:  NCT00337181.

Journal of Infectious Diseases
Volume 207 Issue 8 April 15, 2013
http://www.journals.uchicago.edu/toc/jid/current

Therapeutic Immunization against Mycobacterium tuberculosis Is an Effective Adjunct to Antibiotic Treatment
Rhea N. Coler, Sylvie Berthelot, Samuel O. Pine, Mark T. Orr, Valerie Reese,
Hillarie Plessner Windish, Charles Davis, Maria Kahn, Susan L. Baldwin, and Steven G. Reed
J Infect Dis. (2013) 207(8): 1242-1252 doi:10.1093/infdis/jis425
http://jid.oxfordjournals.org/content/207/8/1242.abstract

Abstract
Background.  Recent advances in rational adjuvant design and antigen selection have enabled a new generation of vaccines with potential to treat and prevent infectious disease. The aim of this study was to assess whether therapeutic immunization could impact the course of Mycobacterium tuberculosis infection with use of a candidate tuberculosis vaccine antigen, ID93, formulated in a synthetic nanoemulsion adjuvant, GLA-SE, administered in combination with existing first-line chemotherapeutics rifampicin and isoniazid.

Methods. We used a mouse model of fatal tuberculosis and the established cynomolgus monkey model to design an immuno-chemotherapeutic strategy to increase long-term survival and reduce bacterial burden, compared with standard antibiotic chemotherapy alone.

Results. This combined approach induced robust and durable pluripotent antigen-specific T helper–1-type immune responses, decreased  bacterial burden, reduced the duration of conventional chemotherapy required for survival, and decreased M. tuberculosis–induced lung pathology, compared with chemotherapy alone.

Conclusions.  These results demonstrate the ability of therapeutic immunization to significantly enhance the efficacy of chemotherapy against tuberculosis and other infectious diseases, with implications for treatment duration, patient compliance, and more optimal resource allocation.

Journal of Medical Ethics
April 2013, Volume 39, Issue 4
http://jme.bmj.com/content/current

The concise argument
Biosecurity and the division of cognitive labour
Thomas Douglas, Associate Editor
http://jme.bmj.com/content/39/4/193.extract

The last 12 years have seen historically high levels of interest in biosecurity among life scientists, science policymakers, and academic experts on science and security policy. This interest was triggered by the 9/11 terrorist attacks, the ‘anthrax letters’ attack of the same year, and two virology papers, published early last decade, that were thought to raise serious biosecurity concerns.1 Ethicists have come relatively late to the game, but, in recent years, a lively debate has developed on ethical issues raised by biosecurity policy, and, more generally, on the ethics of producing and disseminating ‘dangerous’ biomedical knowledge. Unsurprisingly, this debate has taken on increased sense of urgency over the last 18 months as the journals Science and Nature, the United States National Science Advisory Board for Biosecurity, and the World Health Organization, among others, have been considering whether and how to publish two academic papers reporting means of enhancing the transmissibility of H5N1 influenza, or ‘bird flu’ (see, for discussion, Evans’ paper in this issue).

We hope that this issue of the Journal of Medical Ethics will substantially advance the emerging ethical debate in this area. The issue features five articles on the ethics of biosecurity: a feature article, by Allen Buchanan and Maureen Kelley (see page 195, Editor’s choice); three brief replies to this article, by Michael Selgelid (see page 205), Thomas May (see page 206), and Nicholas King (see page 207); and a stand-alone paper by Nicholas Evans (see page 209), which discusses the recent H5N1 controversy and analyses the appeals to scientific freedom that have been made by some of its protagonists…

The Lancet  
Mar 23, 2013  Volume 381  Number 9871  p963 – 1070
http://www.thelancet.com/journals/lancet/issue/current

Comment
A major event for new tuberculosis vaccines
Christopher Dye, Paul EM Fine
Preview |
One of the great quests of contemporary medical research is the search for an improved tuberculosis vaccine—one that provides greater and more consistent protection against tuberculosis than the BCG vaccine can achieve. The stakes are high. The venture is costly and risky, but has a huge potential payoff. A high-efficacy vaccine could revolutionise control of tuberculosis, shifting the emphasis from treatment to prevention. As the case numbers slowly fall in high-burden countries, and as new strains of drug-resistant tuberculosis emerge, a novel and transformational technology for tuberculosis control would be cause for great celebration.

Research Focus
Profile: SATVI—a leading light in tuberculosis vaccine research
Adele Baleta

Safety and efficacy of MVA85A, a new tuberculosis vaccine, in infants previously vaccinated with BCG: a randomised, placebo-controlled phase 2b trial
Michele D Tameris, Mark Hatherill, Bernard S Landry, Thomas J Scriba, Margaret Ann Snowden, Stephen Lockhart, Jacqueline E Shea, J Bruce McClain, Gregory D Hussey, Willem A Hanekom, Hassan Mahomed, Helen McShane, the MVA85A 020 Trial Study Team
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2813%2960177-4/abstract

Summary
Background
BCG vaccination provides incomplete protection against tuberculosis in infants. A new vaccine, modified Vaccinia Ankara virus expressing antigen 85A (MVA85A), was designed to enhance the protective efficacy of BCG. We aimed to assess safety, immunogenicity, and efficacy of MVA85A against tuberculosis and Mycobacterium tuberculosis infection in infants.

Methods
In our double-blind, randomised, placebo-controlled phase 2b trial, we enrolled healthy infants (aged 4—6 months) without HIV infection who had previously received BCG vaccination. We randomly allocated infants (1:1), according to an independently generated sequence with block sizes of four, to receive one intradermal dose of MVA85A or an equal volume of Candida skin test antigen as placebo at a clinical facility in a rural region near Cape Town, South Africa. We actively followed up infants every 3 months for up to 37 months. The primary study outcome was safety (incidence of adverse and serious adverse events) in all vaccinated participants, but we also assessed efficacy in a protocol-defined group of participants who received at least one dose of allocated vaccine. The primary efficacy endpoint was incident tuberculosis incorporating microbiological, radiological, and clinical criteria, and the secondary efficacy endpoint was M tuberculosis infection according to QuantiFERON TB Gold In-tube conversion (Cellestis, Australia). This trial was registered with the South African National Clinical Trials Register (DOH-27-0109-2654) and with ClinicalTrials.gov on July 31, 2009, number NCT00953927

Findings
Between July 15, 2009, and May 4, 2011, we enrolled 2797 infants (1399 allocated MVA85A and 1398 allocated placebo). Median follow-up in the per-protocol population was 24·6 months (IQR 19·2—28·1), and did not differ between groups. More infants who received MVA85A than controls had at least one local adverse event (1251 [89%] of 1399 MVA85A recipients and 628 [45%] of 1396 controls who received the allocated intervention) but the numbers of infants with systemic adverse events (1120 [80%] and 1059 [76%]) or serious adverse events (257 [18%] and 258 (18%) did not differ between groups. None of the 648 serious adverse events in these 515 infants was related to MVA85A. 32 (2%) of 1399 MVA85A recipients met the primary efficacy endpoint (tuberculosis incidence of 1·15 per 100 person-years [95% CI 0·79 to 1·62]; with conversion in 178 [13%] of 1398 infants [95% CI 11·0 to 14·6]) as did 39 (3%) of 1395 controls (1·39 per 100 person-years [1·00 to 1·91]; with conversion in 171 [12%] of 1394 infants [10·6 to 14·1]). Efficacy against tuberculosis was 17·3% (95% CI −31·9 to 48·2) and against M tuberculosis infection was −3·8% (—28·1 to 15·9).

Interpretation
MVA85A was well tolerated and induced modest cell-mediated immune responses. Reasons for the absence of MVA85A efficacy against tuberculosis or M tuberculosis infection in infants need exploration.

Funding
Aeras, Wellcome Trust, and Oxford-Emergent Tuberculosis Consortium (OETC).

The Lancet  
Mar 23, 2013  Volume 381  Number 9871  p963 – 1070
http://www.thelancet.com/journals/lancet/issue/current

Immunogenicity and safety of an enterovirus 71 vaccine in healthy Chinese children and infants: a randomised, double-blind, placebo-controlled phase 2 clinical trial
Feng-Cai Zhu, Zheng-Lun Liang, Xiu-Ling Li, Heng-Ming Ge, Fan-Yue Meng, Qun-Ying Mao, Yun-Tao Zhang, Yue-Mei Hu, Zhen-Yu Zhang, Jing-Xin Li, Fan Gao, Qing-Hua Chen, Qi-Yan Zhu, Kai Chu, Xing Wu, Xin Yao, Hui-Jie Guo, Xiao-Qin Chen, Pei Liu, Yu-Ying Dong, Feng-Xiang Li, Xin-Liang Shen, Jun-Zhi Wang
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2812%2961764-4/abstract

Summary
Background
Enterovirus 71 (EV71) outbreaks are a socioeconomic burden, especially in the western Pacific region. Results of phase 1 clinical trials suggest an EV71 vaccine has a clinically acceptable safety profile and immunogenicity. We aimed to assess the best possible dose and formulation, immunogenicity, and safety profile of this EV71 vaccine in healthy Chinese children.

Methods
This randomised, double-blind, placebo-controlled, phase 2 trial was undertaken at one site in Donghai County, Jiangsu Province, China. Eligible participants were healthy boys or girls aged 6—36 months. Participants were randomly assigned (1:1:1:1:1) to receive either 160 U, 320 U, or 640 U alum-adjuvant EV71 vaccine, 640 U adjuvant-free EV71 vaccine, or a placebo (containing alum adjuvant only), according to a blocked randomisation list generated by SAS 9.1. Participants and investigators were masked to the assignment. The primary endpoint was anti-EV71 neutralising antibody geometric mean titres (GMTs) at day 56, analysed according to protocol. The study is registered with ClinicalTrials.gov, number NCT01399853.

Findings
We randomly assigned 1200 participants, 240 (120 aged 6—11 months [infants] and 120 aged 12—36 months [children]) of whom were assigned to each dose. 1106 participants completed the study and were included in the according-to-protocol analysis. The main reasons for dropout were withdrawal of consent and refusal to donate a blood sample. Infants who received the 640 U adjuvant vaccine had the highest GMTs on day 56 (742·2 [95% CI 577·3—954·3]), followed by those who received the 320 U formulation (497·9 [383·1—647·0]). For children, those who received the 320 U formulation had the highest GMTs on day 56 (1383·2 [1037·3—1844·5]). Participants who received the vaccine had significantly higher GMTs than did who received placebo (p<0·0001). For the subgroup of participants who were seronegative at baseline, both infants and children who received the 640 U adjuvant vaccine had the highest GMTs on day 56 (522·8 [403·9—676·6] in infants and 708·4 [524·1—957·6] in children), followed by those who received the 320 U adjuvant vaccine (358·2 [280·5—457·5] in infants and 498·0 [383·4—646·9] in children). 549 (45·8%) of 1200 participants (95 CI 42·9—48·6%) reported at least one injection-site or systemic adverse reaction, but the incidence of adverse reactions did not differ significantly between groups (p=0·36). The 640 U alum-adjuvant vaccine group had a significantly higher incidence of induration than did the 640 U adjuvant-free group (p=0·001).

Interpretation
Taking immunogenicity, safety, and production capacity into account, the 320 U alum-adjuvant formulation of the EV71 vaccine is probably the best possible formulation for phase 3 trials.

Funding
The National Science and Technology Major Project (2011ZX10004-902) of the Chinese Ministry of Science and Technology, China’s 12—5 National Major Infectious Disease Program (2012ZX10002-001), and Beijing Vigoo Biological.

New England Journal of Medicine
March 21, 2013  Vol. 368 No. 12
http://www.nejm.org/toc/nejm/medical-journal

Perspective
Security of Health Care and Global Health
Robin Coupland, F.R.C.S.
N Engl J Med 2013; 368:1075-1076March 21, 2013DOI: 10.1056/NEJMp1214182
http://www.nejm.org/doi/full/10.1056/NEJMp1214182

My introduction to “global health” was rude. In the late 1980s and early 1990s, I worked as a surgeon in field hospitals of the International Committee of the Red Cross (ICRC). I treated hundreds of wounded people in eight different countries in Africa and Asia, where I visited many local health care facilities, the majority of which were hopelessly understaffed or undersupplied because of armed conflicts. Our surgical actions were just one part of a wide array of health care activities, and the ICRC is only one of many organizations attempting to support or deliver health care in contexts of violence. The security of facilities, patients, and staff was an everyday working consideration, and the problems we faced were common to all health care providers. Certain roads could not be traveled, ambulances were attacked, supplies were looted, staff and patients were subject to a variety of threats, and worst of all, patients and my colleagues were sometimes targeted directly and kidnapped or killed. Often such violence or widespread insecurity resulted in the termination of health care programs, which left entire already-vulnerable populations without health care.

Among all the constraints facing health care delivery in such settings, the most difficult one to address is a lack of security.1 One of our head nurses put it quite simply: “We can’t do anything without security.” In the bigger picture, the success or failure of our efforts to provide health care rested less on impeccable program planning and execution than in the hands of the people who were responsible for our security (or lack thereof), and it became clear to me that the relationships among security, insecurity, health, and health care are extremely complex.      Moreover, armed conflict generates immediate and additional health care requirements for wounded and sick people that exceed peacetime needs. Hospitals may fill rapidly with wounded people, both military and civilian, and the additional health care requirements arise at precisely the time when the accompanying insecurity makes it most difficult to address them. Even providing prehospital care for the wounded, including first aid and transport by ambulance, becomes dangerous, since health care personnel, ambulances, and health care facilities may be open to attack.

The uprisings in North Africa and the Middle East in the past 2 years have taken place largely in urban environments, where the preexisting facilities on which wounded people — whether civilian, police, or military — would normally depend for health care suffer a range of security problems, in part because these facilities and the people who staff them become integrated into the events. Ambulances may be attacked, and their staff harassed, because of the patients they are carrying. Health care providers may be prevented from treating members of one side of the dispute or the other. Hospitals may be seen as a place where enemies or “terrorists” can be arrested, interrogated, or even killed. Again, insecurity may be the factor determining whether people reach or benefit from health care. The problem is exacerbated by the fact that journalists, who are seeking to influence world opinion, know that telling images and testimonies may be found in overwhelmed, makeshift, or disrupted health care facilities; revealing the location and identity of wounded fighters can put these injured patients and those caring for them at considerable risk.

The lack of global attention to attacks on health care facilities and personnel was first appropriately highlighted in 2010.2 In 2011, the ICRC published a study analyzing various forms of violence and insecurity affecting health care in 16 countries in the midst of conflict. The study also drew attention to the massive domino effects on the health of entire communities that were being denied health care because of such violence and insecurity.3 It concluded that in terms of the numbers of people affected, violence, both real and threatened, against health care workers, facilities, and beneficiaries is one of the biggest, most complex, and yet most underrecognized humanitarian issues today. The study also raised the question of whether insecurity might be the primary reason why so many health care workers from developing countries seek work elsewhere. At the same time that it undertook the study, the ICRC launched the Health Care in Danger project, which aims to address a wide variety of issues related to delivering health care in insecure environments; the project includes engagement in a broader dialogue with those who are in a position to improve this security. It has drawn support from numerous health care institutions. In 2012, the World Health Assembly also formally recognized the need to address the insecurity of health care.4,5

So what can be done to address this insecurity? First, the health care community, broadly defined, must recognize this issue and be able to communicate about it: if we don’t express our concern, it’s unlikely that concern will be generated in other quarters. Health care workers who are likely to be working in areas of conflict need better preparation and training to deal with the many practical and ethical issues they will predictably face. For example, they should learn how to determine appropriate standards of care in such situations and how best to avoid discrimination in providing access to timely treatment.

But recommendations for the health care community don’t directly address the security issues. There must also be recognition and upholding of the rules of international humanitarian law and human rights law that require all authorities to respect and protect the wounded, the sick, health care personnel, and health care facilities. Armed forces and police forces need more and better training with respect to these laws, as well as training in such activities as running checkpoints in a way that avoids delaying the passage of ambulances and conducting search operations near or even in health care facilities without disrupting the provision of health care. Governments need to develop national laws to better protect health care personnel and facilities. These and other measures are currently being actively pursued by the ICRC’s Health Care in Danger project in partnership with national Red Cross or Red Crescent Societies.

Threats to health care during conflicts are not just an issue for humanitarian aid agencies. The global health community has taken a long time to recognize that conflict, violence, and insecurity are more than constraints on the delivery of health care in many parts of the world: they are showstoppers. The responsibility for addressing this massive global health issue does not ultimately lie with the global health community, but rather with the national and international organizations responsible for ensuring people’s security.1 The responsibilities of the health care community, however, must include fierce advocacy for the maintenance of this security.

New England Journal of Medicine
March 21, 2013  Vol. 368 No. 12
http://www.nejm.org/toc/nejm/medical-journal

Original Article
Four-Year Efficacy of RTS,S/AS01E and Its Interaction with Malaria Exposure
Ally Olotu, M.B., Ch.B., Gregory Fegan, Ph.D., Juliana Wambua, B.Sc., George Nyangweso, B.Sc., Ken O. Awuondo, H.N.D., Amanda Leach, M.R.C.P.C.H., Marc Lievens, M.Sc., Didier Leboulleux, M.D., Patricia Njuguna, M.B., Ch.B., Norbert Peshu, M.B., Ch.B., Kevin Marsh, F.R.C.P., and Philip Bejon, Ph.D.
N Engl J Med 2013; 368:1111-1120March 21, 2013DOI: 10.1056/NEJMoa1207564
http://www.nejm.org/doi/full/10.1056/NEJMoa1207564

Background
The candidate malaria vaccine RTS,S/AS01E has entered phase 3 trials, but data on long-term outcomes are limited.
Full Text of Background…

Methods
For 4 years, we followed children who had been randomly assigned, at 5 to 17 months of age, to receive three doses of RTS,S/AS01E vaccine (223 children) or rabies vaccine (224 controls). The end point was clinical malaria (temperature of ≥37.5°C and Plasmodium falciparum parasitemia density of >2500 parasites per cubic millimeter). Each child’s exposure to malaria was estimated with the use of the distance-weighted local prevalence of malaria.
Full Text of Methods…

Results
Over a period of 4 years, 118 of 223 children who received the RTS,S/AS01E vaccine and 138 of 224 of the controls had at least 1 episode of clinical malaria. Vaccine efficacies in the intention-to-treat and per-protocol analyses were 29.9% (95% confidence interval [CI], 10.3 to 45.3; P=0.005) and 32.1% (95% CI, 11.6 to 47.8; P=0.004), respectively, calculated by Cox regression. Multiple episodes were common, with 551 and 618 malarial episodes in the RTS,S/AS01E and control groups, respectively; vaccine efficacies in the intention-to-treat and per-protocol analyses were 16.8% (95% CI, −8.6 to 36.3; P=0.18) and 24.3% (95% CI, 1.9 to 41.6; P=0.04), respectively, calculated by the Andersen–Gill extension of the Cox model. For every 100 vaccinated children, 65 cases of clinical malaria were averted. Vaccine efficacy declined over time (P=0.004) and with increasing exposure to malaria (P=0.001) in the per-protocol analysis. Vaccine efficacy was 43.6% (95% CI, 15.5 to 62.3) in the first year but was −0.4% (95% CI, −32.1 to 45.3) in the fourth year. Among children with a malaria-exposure index that was average or lower than average, the vaccine efficacy was 45.1% (95% CI, 11.3 to 66.0), but among children with a malaria-exposure index that was higher than average it was 15.9% (95% CI, −11.0 to 36.4).
Full Text of Results…

Conclusions
The efficacy of RTS,S/AS01E vaccine over the 4-year period was 16.8%. Efficacy declined over time and with increasing malaria exposure.

(Funded by the PATH Malaria Vaccine Initiative and Wellcome Trust; ClinicalTrials.gov number, NCT00872963.)

Pediatrics
http://pediatrics.aappublications.org/current.shtml

Published online March 18, 2013
Reasons for Not Vaccinating Adolescents: National Immunization Survey of Teens, 2008–2010
Paul M. Darden, MDa,c, David M. Thompson, PhDb, James R. Roberts, MD, MPHc, Jessica J. Hale, MSa, Charlene Pope, PhD, MPH, RNd,e, Monique Naifeh, MD, MPHa, and Robert M. Jacobson, MDf
(doi: 10.1542/peds.2012-2384)
http://pediatrics.aappublications.org/content/early/2013/03/12/peds.2012-2384.abstract

Abstract
OBJECTIVE: To determine the reasons adolescents are not vaccinated for specific vaccines and how these reasons have changed over time.

METHODS: We analyzed the 2008–2010 National Immunization Survey of Teens examining reasons parents do not have their teens immunized. Parents whose teens were not up to date (Not-UTD) for Tdap/Td and MCV4 were asked the main reason they were not vaccinated. Parents of female teens Not-UTD for human papillomavirus vaccine (HPV) were asked their intent to give HPV, and those unlikely to get HPV were asked the main reason why not.

RESULTS: The most frequent reasons for not vaccinating were the same for Tdap/Td and MCV4, including “Not recommended” and “Not needed or not necessary.” For HPV, the most frequent reasons included those for the other vaccines as well as 4 others, including “Not sexually active” and “Safety concerns/Side effects.” “Safety concerns/Side effects” increased from 4.5% in 2008 to 7.7% in 2009 to 16.4% in 2010 and, in 2010, approaching the most common reason “Not Needed or Not Necessary” at 17.4% (95% CI: 15.7–19.1). Although parents report that health care professionals increasingly recommend all vaccines, including HPV, the intent to not vaccinate for HPV increased from 39.8% in 2008 to 43.9% in 2010 (OR for trend 1.08, 95% CI: 1.04–1.13).

CONCLUSIONS: Despite doctors increasingly recommending adolescent vaccines, parents increasingly intend not to vaccinate female teens with HPV. The concern about safety of HPV grew with each year. Addressing specific and growing parental concerns about HPV will require different considerations than those for the other vaccines.

Pharmaceutics
Volume 5, Issue 1 (March 2013)
http://www.mdpi.com/1999-4923/5/1

Article
Safety Monitoring in Clinical Trials
Bin Yao, Li Zhu, Qi Jiang and H. Amy Xia
Pharmaceutics 2013, 5(1), 94-106; doi:10.3390/pharmaceutics5010094

Abstract:
Monitoring patient safety during clinical trials is a critical component throughout the drug development life-cycle. Pharmaceutical sponsors must work proactively and collaboratively with all stakeholders to ensure a systematic approach to safety monitoring. The regulatory landscape has evolved with increased requirements for risk management plans, risk evaluation and minimization strategies. As the industry transitions from passive to active safety surveillance activities, there will be greater demand for more comprehensive and innovative approaches that apply quantitative methods to accumulating data from all sources, ranging from the discovery and preclinical through clinical and post-approval stages. Statistical methods, especially those based on the Bayesian framework, are important tools to help provide objectivity and rigor to the safety monitoring process.

PLoS One
[Accessed 23 March 2013]
http://www.plosone.org/

Risk in Vaccine Research and Development Quantified
Esther S. Pronker, Tamar C. Weenen, Harry Commandeur, Eric H. J. H. M. Claassen, Albertus D. M. E. Osterhaus
Research Article | published 20 Mar 2013 | PLOS ONE 10.1371/journal.pone.0057755

Abstract
To date, vaccination is the most cost-effective strategy to combat infectious diseases. Recently, a productivity gap affects the pharmaceutical industry. The productivity gap describes the situation whereby the invested resources within an industry do not match the expected product turn-over. While risk profiles (combining research and development timelines and transition rates) have been published for new chemical entities (NCE), little is documented on vaccine development. The objective is to calculate risk profiles for vaccines targeting human infectious diseases. A database was actively compiled to include all vaccine projects in development from 1998 to 2009 in the pre-clinical development phase, clinical trials phase I, II and III up to Market Registration. The average vaccine, taken from the preclinical phase, requires a development timeline of 10.71 years and has a market entry probability of 6%. Stratification by disease area reveals pandemic influenza vaccine targets as lucrative. Furthermore, vaccines targeting acute infectious diseases and prophylactic vaccines have shown to have a lower risk profile when compared to vaccines targeting chronic infections and therapeutic applications. In conclusion; these statistics apply to vaccines targeting human infectious diseases. Vaccines targeting cancer, allergy and autoimmune diseases require further analysis. Additionally, this paper does not address orphan vaccines targeting unmet medical needs, whether projects are in-licensed or self-originated and firm size and experience. Therefore, it remains to be investigated how these – and other – variables influence the vaccine risk profile. Although we find huge differences between the risk profiles for vaccine and NCE; vaccines outperform NCE when it comes to development timelines.

PLoS Medicine
(Accessed 23 March 2013)
http://www.plosmedicine.org/

Policy Forum
Strengthening the Expanded Programme on Immunization in Africa: Looking beyond 2015
Shingai Machingaidze, Charles S. Wiysonge, Gregory D. Hussey

Summary Points
– There have been significant improvements in the performance of the Expanded Programme on Immunization (EPI) in Africa since its inception in 1974. However, there exist wide inter- and intra-country differences.

– Successes such as the introduction of hepatitis B (HepB), Haemophilus influenzae type B (Hib), and meningococcal group A vaccines across the continent are milestones indicating growth and development in the right direction. Conversely polio and measles outbreaks, as well as high vaccine drop-out rates across the continent, indicate failures within the EPI system that require evidence-informed corrective interventions.

– With the 2015 deadline for the Millennium Development Goals (MDGs) approaching, it is necessary for Africa to take stock, critically assess its position, take ownership of the regional and country-specific problems, and develop precise strategies to overcome the challenges identified.

– There is need for increased immunisation systems strengthening, as many are plagued by weak infrastructure and shortage of skilled human resources. More affordable and adapted vaccines need to be made available.

– Increased political and financial commitments from African governments are key factors for both maintaining current achievements and making additional progress for EPI in Africa.

PLoS Neglected Tropical Diseases
February 2013
http://www.plosntds.org/article/browseIssue.action

Research Article
Will Dengue Vaccines Be Used in the Public Sector and if so, How? Findings from an 8-country Survey of Policymakers and Opinion Leaders
Don L. Douglas, Denise A. DeRoeck, Richard T. Mahoney, Ole Wichmann
http://www.plosntds.org/article/info%3Adoi%2F10.1371%2Fjournal.pntd.0002127

Abstract
Background
A face-to-face survey of 158 policymakers and other influential professionals was conducted in eight dengue-endemic countries in Asia (India, Sri Lanka, Thailand, Vietnam) and Latin America (Brazil, Colombia, Mexico, Nicaragua) to provide an indication of the potential demand for dengue vaccination in endemic countries, and to anticipate their research and other requirements in order to make decisions about the introduction of dengue vaccines. The study took place in anticipation of the licensure of the first dengue vaccine in the next several years.

Methods/Principal Findings
Semi-structured interviews were conducted on an individual or small group basis with government health officials, research scientists, medical association officers, vaccine producers, local-level health authorities, and others considered to have a role in influencing decisions about dengue control and vaccines. Most informants across countries considered dengue a priority disease and expressed interest in the public sector use of dengue vaccines, with a major driver being the political pressure from the public and the medical community to control the disease. There was interest in a vaccine that protects children as young as possible and that can fit into existing childhood immunization schedules. Dengue vaccination in most countries surveyed will likely be targeted to high-risk areas and begin with routine immunization of infants and young children, followed by catch-up campaigns for older age groups, as funding permits. Key data requirements for decision-making were additional local dengue surveillance data, vaccine cost-effectiveness estimates, post-marketing safety surveillance data and, in some countries vaccine safety and immunogenicity data in the local population.

Conclusions/Significance
The lookout for the public sector use of dengue vaccines in the eight countries appears quite favorable. Major determinants of whether and when countries will introduce dengue vaccines include whether WHO recommends the vaccines, their price, the availability of external financing for lower income countries, and whether they can be incorporated into countries’ routine immunization schedules.

Author Summary
Information gleaned from surveys of country-level policymakers and other opinion leaders can assist in planning the development, production and introduction of new or upcoming vaccines into public sector immunization programs. In the case of dengue vaccines, prevailing views among these leaders about the importance of the disease, their expressed level of interest in the government’s use of the vaccine, and preferred strategies for vaccine introduction (e.g., geographically-targeted vs. nation-wide vaccination, specific age groups to target) can help to identify “early adopter” countries and indicate the level of demand for the vaccine. This information can be critical to current producers of the vaccine in planning their production capacity and to potential future producers in deciding whether to pursue development of the vaccine. This information also helps donors and international technical agencies, such as WHO and UNICEF, in setting their priorities and determining their level of technical and financial support to countries for the introduction of dengue vaccines. In addition, these surveys can provide crucial information to national governments and the above stakeholders about potential barriers to introducing dengue vaccines into national immunization programs, and what additional studies and data countries will require in order to make decisions about use of the vaccines in the public sector.

Public Health Ethics
Volume 6 Issue 1 April 2013
http://phe.oxfordjournals.org/content/current

Human Papilloma Virus, Vaccination and Social Justice: An Analysis of a Canadian School-Based Vaccine Program
Alison Thompson
Public Health Ethics (2013) 6(1): 11-20 doi:10.1093/phe/pht010
http://phe.oxfordjournals.org/content/6/1/11.abstract

Abstract
Social justice has strong historical roots in public health. This does not mean that we always understand what it entails when conducting an ethical analysis of a particular public health program. This article shows that Powers and Faden’s theory of social justice can provide important insights and nuance to such an analysis. The Ontario human papilloma virus vaccination program that is underway in Canada provides an important and timely case where we can surface ethical issues pertaining to social justice that may otherwise remain unarticulated in the context of this program. This analysis focuses on the normative issues raised by the prioritization of a school-based program for girls only. It also examines the relevant domains of well-being identified in Powers and Faden’s theory to see whether the program is likely to enhance the well-being of those for whom it is most important. Finally, the role of vaccines in general in promoting well-being is discussed.

Public Health Ethics
Volume 6 Issue 1 April 2013
http://phe.oxfordjournals.org/content/current

Male Infant Circumcision as a ‘HIV Vaccine’
Barry Lyons
Public Health Ethics (2013) 6(1): 90-103 doi:10.1093/phe/phs039
http://phe.oxfordjournals.org/content/6/1/90.abstract

Abstract
This article deals with the specific claim that prophylactic male infant circumcision should be employed to prevent HIV transmission in countries in which the prevalence of HIV is relatively low. In a recent editorial, Australian researchers sought to promote the procedure as a ‘surgical vaccine’ against HIV in their country. This raises the question whether it would be reasonable for the UK to adopt a policy of mass infant male circumcision in order to protect individuals from heterosexually acquired infection with HIV. A review of the relevant data and associated commentary indicates that the actual benefits of real-world circumcision policies to prevent HIV transmission are disputed and that circumcision, at best, provides partial protection. In addition, it is uncertain whether infant circumcision confers the same benefits that the adult procedure is proposed to provide. Reasons for performing circumcisions on infants include that the procedure is easier, less complicated and cheaper. However, it is not risk free. Despite arguments to the contrary, this article contends that it is morally problematic to operate on thousands of male infants each year for little benefit to children qua children. It is also argued that the use of the term ‘surgical vaccine’ to describe the procedure is both inaccurate and misleading.

Science        
22 March 2013 vol 339, issue 6126, pages 1349-1476
http://www.sciencemag.org/current.dtl

Perspective – Medicine
Spatial Turn in Health Research
Douglas B. Richardson1, Nora D. Volkow2, Mei-Po Kwan3, Robert M. Kaplan4, Michael F. Goodchild5, Robert T. Croyle6
http://www.sciencemag.org/content/339/6126/1390.summary

Summary
Spatial analysis using maps to associate geographic information with disease can be traced as far back as the 17th century. Today, recent developments and the widespread diffusion of geospatial data acquisition technologies are enabling creation of highly accurate spatial (and temporal) data relevant to health research. This has the potential to increase our understanding of the prevalence, etiology, transmission, and treatment of many diseases.

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 31, Issue 16, Pages 2009-2108 (12 April 2013)

Editorial
Steps for clinicians and public health officials to take to reach persons of faith, for the sake of protecting all against vaccine-preventable diseases
Pages 2009-2010
Richard K. Zimmerman, Jonathan Raviotta
[No abstract]

What the World’s religions teach, applied to vaccines and immune globulins
Review Article
Pages 2011-2023
John D. Grabenstein

Abstract
For millennia, humans have sought and found purpose, solace, values, understanding, and fellowship in religious practices. Buddhist nuns performed variolation against smallpox over 1000 years ago. Since Jenner developed vaccination against smallpox in 1796, some people have objected to and declined vaccination, citing various religious reasons. This paper reviews the scriptural, canonical basis for such interpretations, as well as passages that support immunization. Populous faith traditions are considered, including Hinduism, Buddhism, Jainism, Judaism, Christianity, and Islam. Subjects of concern such as blood components, pharmaceutical excipients of porcine or bovine origin, rubella strain RA 27/3, and cell-culture media with remote fetal origins are evaluated against the religious concerns identified.

The review identified more than 60 reports or evaluations of vaccine-preventable infectious-disease outbreaks that occurred within religious communities or that spread from them to broader communities. In multiple cases, ostensibly religious reasons to decline immunization actually reflected concerns about vaccine safety or personal beliefs among a social network of people organized around a faith community, rather than theologically based objections per se. Themes favoring vaccine acceptance included transformation of vaccine excipients from their starting material, extensive dilution of components of concern, the medicinal purpose of immunization (in contrast to diet), and lack of alternatives. Other important features included imperatives to preserve health and duty to community (e.g., parent to child, among neighbors). Concern that ‘the body is a temple not to be defiled’ is contrasted with other teaching and quality-control requirements in manufacturing vaccines and immune globulins.

Health professionals who counsel hesitant patients or parents can ask about the basis for concern and how the individual applies religious understanding to decision-making about medical products, explain facts about content and processes, and suggest further dialog with informed religious leaders. Key considerations for observant believers for each populous religion are described.

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 31, Issue 16, Pages 2009-2108 (12 April 2013)

Proximity to safety-net clinics and HPV vaccine uptake among low-income, ethnic minority girls
Original Research Article
Pages 2028-2034
Jennifer Tsui, Rita Singhal, Hector P. Rodriguez, Gilbert C. Gee, Beth A. Glenn, Roshan Bastani

Abstract
Purpose
Human Papillomavirus (HPV) vaccine uptake remains low. Although publicly funded programs provide free or low cost vaccines to low-income children, barriers aside from cost may prevent disadvantaged girls from getting vaccinated. Prior studies have shown distance to health care as a potential barrier to utilizing pediatric preventive services. This study examines whether HPV vaccines are geographically accessible for low-income girls in Los Angeles County and whether proximity to safety-net clinics is associated with vaccine initiation.

Methods
Interviews were conducted in multiple languages with largely immigrant, low-income mothers of girls ages 9 to 18 via a county health hotline to assess uptake and correlates of uptake. Addresses of respondents and safety-net clinics that provide the HPV vaccine for free or low cost were geo-coded and linked to create measures of geographic proximity. Logistic regression models were estimated for each proximity measure on HPV vaccine initiation while controlling for other factors.

Results
On average, 83% of the 468 girls had at least one clinic within 3-miles of their residence. The average travel time on public transportation to the nearest clinic among all girls was 21 min. Average proximity to clinics differed significantly by race/ethnicity. Latinas had both the shortest travel distances (2.2 miles) and public transportation times (16 min) compared to other racial/ethnic groups. The overall HPV vaccine initiation rate was 25%. Increased proximity to the nearest clinic was not significantly associated with initiation. By contrast, daughter’s age and insurance status were significantly associated with increased uptake.

Conclusions
This study is among the first to examine geographic access to HPV vaccines for underserved girls. Although the majority of girls live in close proximity to safety-net vaccination services, rates of initiation were low. Expanding clinic outreach in this urban area is likely more important than increasing geographic access to the vaccine for this population.

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 31, Issue 16, Pages 2009-2108 (12 April 2013)

Parental perspectives of vaccine safety and experience of adverse events following immunisation
Original Research Article
Pages 2067-2074
Adriana Parrella, Michael Gold, Helen Marshall, Annette Braunack-Mayer, Peter Baghurst

Abstract
Introduction
We aimed to determine demographic predictors of parental vaccine safety and risk perceptions, and assess the relationship between the occurrence of children’s perceived adverse events following immunisation (AEFI) on parents’ opinions.

Methods
Computer-assisted telephone interviews (CATI) were conducted in 2011 with a cross-sectional, random general population sample of rural and metropolitan residents in South Australia. Multivariate ordinal logistic regression analyses examined associations between parental vaccine safety attitudes and socio-demographic factors, adjusting for whether children had ever experienced a previous suspected AEFI.

Results
Of 469 parents interviewed, 95% were confident in vaccine safety in general, but almost half expressed concern for pre-licensure testing of vaccines. Of all parents, 41% responded that at least one of their children had experienced an AEFI. Almost one third of the AEFI parent group indicated they reported their children’s symptoms to either a healthcare professional or the Department of Health. Parental acceptability of the risks of febrile convulsion and anaphylaxis were 73% and 76% respectively. Ordinal logistic regression analyses showed parents of children who had experienced a suspected AEFI were associated with greater concern for vaccine safety (OR:0.53, p ≤ 0.01) and more were likely to expect either a mild or a serious AEFI. After adjusting for demographics, parental confidence in vaccine safety was significantly associated with higher levels of education (OR:2.58, p = 0.01) and being born in Australia OR:2.30, p = 0.004. Mothers, when compared with fathers, were less accepting of the two vaccine risks presented: febrile convulsion (OR:0.57, p = 0.04) and anaphylaxis, (OR:0.55, p = 0.04).

Conclusions
Parents commonly perceive and report that their child has experienced an AEFI. In this group of parents the subsequent expectation of an AEFI and vaccine safety concerns may be heightened. Further research should investigate parental understandings of differentiating an expected event from an adverse event as this could inform immunization risk communication and consumer AEFI reporting strategies.

Vaccine
Volume 31, Issue 15, Pages 1879-2008 (8 April 2013)

Sustainability of National Immunization Programme (NIP) performance and financing following Global Alliance for Vaccines and Immunization (GAVI) support to the Democratic Republic of the Congo (DRC)
Review Article
Pages 1886-1891
Jean-Bernard Le Gargasson, J. Gabrielle Breugelmans, Benoît Mibulumukini, Alfred Da Silva, Anaïs Colombi

Abstract
Background
The Global Alliance for Vaccines and Immunization (GAVI) is a public–private global health partnership aiming to increase access to immunisation in poor countries. The Democratic Republic of the Congo (DRC) is the third largest recipient of GAVI funds in terms of cumulative disbursed support. We provided a comprehensive assessment of GAVI support and analysed trends in immunisation performance and financing in the DRC from 2002 to 2010.

Methods
The scope of the analysis includes GAVI’s total financial support and the value of vaccines and syringes purchased by GAVI for the DRC from 2002 to 2010. Data were collected through a review of published and grey literature and interviews with key stakeholders in the DRC. We assessed the allocation and use of GAVI funds for each of GAVI’s support areas, as well as trends in immunisation performance and financing.

Findings
DTP3 coverage increased from 2002 (38%) to 2007 (72%) but had decreased to a level below 70% in 2008 (68%) and 2010 (63%). The overall funding for vaccines increased from US$5.4 million in 2006 to US$30.5 million in 2010 (mostly from GAVI support for new vaccines). However, during the same period, the funding from national (government) and international (GAVI and other donors) sources for routine immunisation services (except vaccines) decreased from US$36.4 million to US$24.4 million. This drop in overall funding (33%) primarily affected surveillance, transport, and cold chain equipment.

Interpretation
GAVI support to DRC has enhanced significant progress in routine immunisation performance and financing during 2002–2010. Although progress has been partly sustained, the initial observed increase in DTP3 coverage and available funding for routine immunisation halted towards the end of the analysis period, coinciding with tetravalent and pentavalent vaccine introduction. These findings highlight the need for additional efforts to ensure the sustainability of routine immunization program performance and financing.

Vaccine
Volume 31, Issue 15, Pages 1879-2008 (8 April 2013)

Chlamydia trachomatis control requires a vaccine
Review Article
Pages 1892-1897
Robert C. Brunham, Rino Rappuoli

Abstract
As the most common reported communicable disease in North America and Europe, Chlamydia trachomatis is the focus of concerted public health control efforts based on screening and treatment. Unexpectedly control efforts are accompanied by rising reinfection rates attributed in part to arresting the development of herd immunity. Shortening the duration of infection through the testing and treatment program is the root cause behind the arrested immunity hypothesis and because of this a vaccine will be essential to control efforts. Advances in Chlamydia vaccinomics have revealed the C. trachomatis antigens that can be used to constitute a subunit vaccine and a vaccine solution appears to be scientifically achievable. We propose that an accelerated C. trachomatis vaccine effort requires coordinated partnership among academic, public health and private sector players together with a commitment to C. trachomatis vaccine control as a global public health priority.

Vaccine
Volume 31, Issue 15, Pages 1879-2008 (8 April 2013)

Impact of the introduction of rotavirus vaccine on the timeliness of other scheduled vaccines: The Australian experience
Original Research Article
Pages 1964-1969
Brynley P. Hull, Robert Menzies, Kristine Macartney, Peter B. McIntyre

Abstract
Strict age limits for receipt of rotavirus vaccines and simultaneous use of vaccines requiring two (Rotarix®) and three (RotaTeq®) doses in Australia may impact on coverage and timeliness of other vaccines in the infant schedule. Using data from the Australian Childhood Immunisation Register (ACIR), coverage and timeliness of rotavirus vaccines and changes in timeliness of other infant vaccines following rotavirus vaccine introduction was examined, with particular emphasis on Indigenous infants in whom coverage is less optimal. Final dose rotavirus coverage reached 83% within 21 months of program commencement but remained 7% lower than other vaccines due in infancy. Coverage was 11–17% lower in Indigenous infants. Adherence to the first dose upper age limits for rotavirus vaccine was high with >97% of children vaccinated by the recommended age, but for subsequent rotavirus doses, receipt beyond the upper age limits was more common, especially in Indigenous children. Following rotavirus vaccine introduction, there were improvements in timeliness of receipt of all doses of DTPa-containing and 7-valent pneumococcal conjugate vaccines. High population coverage can be attained with rotavirus vaccines, even with adherence to strict upper age restrictions for vaccine dose administration. Rotavirus vaccine introduction appears to have impacted upon the timeliness of other concomitantly scheduled vaccines. These factors should be considered when rotavirus programs are introduced.

Vaccine: Development and Therapy
(Accessed 23 March 2013)
http://www.dovepress.com/vaccine-development-and-therapy-journal

Key feasibility considerations when conducting vaccine clinical trials in Asia–Pacific countries
Lansang EZ, Tan K, Nayak S, Lee KJ, Wai K
Published Date March 2013 Volume 2013:3 Pages 1 – 9
DOI: http://dx.doi.org/10.2147/VDT.S41903
http://www.dovepress.com/key-feasibility-considerations-when-conducting-vaccine-clinical-trials-peer-reviewed-article-VDT

Introduction: Conducting clinical trial feasibility is an important first step in initiating a clinical trial. A robust feasibility process ensures that a realistic capability assessment is made before conducting a trial. A retrospective analysis of vaccine clinical trials was performed to understand changes which could affect feasibility recommendations.
Methods: Feasibilities conducted by Quintiles between January 2011 and August 2012 were reviewed. Vaccine studies only involving Asia–Pacific countries were selected, and common study parameters were identified. Information from Quintiles’ database was retrieved to examine changes in parameters over time.
Results: A total of six vaccine studies were identified within the 1.7-year period. Two studies were excluded because they did not contain feasibility information or had involved sites that were sponsor selected. Four studies were analyzed. Three cases required healthy volunteers, while one case involved a specific patient population. Age requirement and seasonality of disease mainly influenced recommendations for Study 1. Sponsor’s marketing strategy influenced the recommendations for Study 2. Study 3 showed the effect of a country’s immunization program and reimbursement of vaccines on a study’s success. In contrast to the other studies, Study 4 demonstrated the impact of eligibility criteria in recruitment recommendations for a vaccine trial requiring specific patient pools.
Conclusion: Feasibility recommendations for vaccine trials are largely based on (1) eligibility criteria; (2) cultural beliefs; (3) country’s past recruitment performance; (4) use of advertising; (5) site’s access to subject populations; (6) cooperation with local health professionals and government; (7) sponsor’s marketing strategies; (8) study design concordance with national immunization programs; (9) reimbursement of vaccines; (10) overall benefit of the vaccine to the population; and where applicable, (11) seasonality of the disease under study.

Financial Times
http://www.ft.com
Accessed 23 March 2013
March 21, 2013 8:35 pm

Vaccines: Trial setback fails to damp enthusiasm
By Clive Cookson, Science Editor
http://www.ft.com/cms/s/0/9522528c-870d-11e2-9dd7-00144feabdc0.html#axzz2OQIGNQy2

The Third Global Forum on TB Vaccines will open in Cape Town next week with several hundred researchers and clinicians determined to remain upbeat, despite the setback their field received last month.

The first large clinical trial for 90 years of a new vaccine against tuberculosis, MVA85A, failed to show efficacy when the Lancet published results.

The trial was intended to show MVA85A, developed at Oxford university in a £30m programme over 10 years, would boost the immune response of 2,800 South African babies inoculated with BCG. The Bacille Calmette – Guérin vaccine, introduced in 1921 and based on the bacterium that causes bovine tuberculosis, does not produce a good enough response to stop the TB pandemic.

But Professor McShane insists there is still mileage in MVA85A and says a dozen other vaccine candidates working by different mechanisms are in clinical development globally. “We need new drugs too, but the only way we’re going to tackle this epidemic in the long term is through an effective vaccine,” she says.

The team is not giving up on MVA85A. Samples from the infants in the trial will be analysed for clues about how the immune system reacts to vaccination and infection with the Mycobacterium tuberculosis, the TB germ. Researchers will look to improve the immune response with higher or multiple doses, combining MVA85A with other vaccine, or delivering it into the lungs.

Meanwhile a trial of MVA85A in 1,400 HIV-positive adults, at particular risk of developing TB, is going ahead in South Africa and Senegal with results due in 2015, says Prof McShane. The dozen vaccine candidates at earlier stages of clinical development, and a couple of dozen more in pre-clinical research, span a range of approaches. As with MVA85A, some are based on viruses genetically modified to stimulate the immune system against TB. Some, including BCG, are based on mycobacteria such as the one that causes TB. Some are proteins. For example   GlaxoSmithKline, the UK-based pharmaceutical group, has developed a vaccine, M72/AS01E, based on a combination of proteins and adjuvant (a booster chemical). Crucell of the Netherlands uses Ad35, a harmless adenovirus with antigens from Mycobacterium tuberculosis, to stimulate production of protective antibodies.

Two non-profit international bodies organise funding and logistical support for TB vaccine development: the Tuberculosis Vaccine Initiative in Europe and Aeras, based in the US. According to Ann Ginsberg, head of science at Aeras, it is too early to talk about which approach is likely to be most promising.

Dr Ginsberg is confident the MVA85A setback will not undermine funding for vaccine research, which will need hundreds of millions of dollars over the next few years: “Our funders, organisations like the Gates Foundation, [US] National Institutes of Health and the [UK] Department for International Development, are realistic about what it takes to develop a TB vaccine.”

But other TB experts say the challenge of developing an effective vaccine is so great that available money should be focused more on diagnostics and drug development. They express their reservations in an article due to appear in a forthcoming issue of The Lancet Infectious Diseases.

“Without a clear scientific basis for protective immunity against the disease and a biological marker for this, which we don’t have, it is difficult to know how to make an effective vaccine,” says one of the group, Richard Anthony of the Royal Tropical Institute, Amsterdam. One fundamental problem, he says, is past tuberculosis infection does not offer protection and patients recently treated for TB can become reinfected.

At next week’s Cape Town congress, however, most delegates will see the scientific challenge as a reason for making more rather than less effort. “I see the meeting as a rallying of the troops,” says Dr Ginsberg. “Now is the time to push forward, not pull back.”

Copyright The Financial Times Limited 2013.

Le Monde
http://www.lemonde.fr/
Accessed 23 March 2013
Revers pour un vaccin contre le paludisme
LE MONDE | 23 mars 2013 | 308 mots

Le vaccin antipaludique RTS, S/AS01E, actuellement le plus avancé de ceux en développement, perd de son efficacité au cours du temps et n’a plus guère d’effet protecteur chez les jeunes enfants au bout de quatre ans, selon les résultats d’un essai.

Editor’s Notes:

– Email Summary: Vaccines: The Week in Review is available as a weekly email summary: please send your request to david.r.curry@centerforvaccineethicsandpolicy.org.

– pdf version: A pdf of the current issues is available here: Vaccines_The Week in Review_16 March 2013_PDF

– Twitter: Readers can also follow developments on twitter: @vaxethicspolicy.

– Support: If you would like to join the growing list of individuals who support this service and its contribution to their roles in public health, clinical practice, government, IGOs/NGOs, research, industry and academia, please visit this page at The Wistar Institute, our co-founder and fiduciary. Thank you…

WHO IVB: Over 700 million children in 49 countries to be protected against measles and rubella.
Rwanda first sub-Saharan African country to introduce measles-rubella vaccine nationwide with GAVI support

Extract
“Kigali, Geneva, New York, Washington: 12 March 2013 – Rwanda’s measles-rubella vaccination campaign, which is being launched today, is the beginning of an effort to vaccinate more than 700 million children under 15 years of age against two disabling and deadly diseases. The combined measles-rubella vaccine will be introduced in 49 countries by 2020 thanks to financial support from the GAVI Alliance. The support builds on the efforts of the Measles & Rubella Initiative (M&RI) that have helped countries to protect 1.1 billion children against measles since 2001. Rwanda, which is already effectively controlling measles, becomes the first sub-Saharan African country to provide measles-rubella vaccine nationwide with GAVI support”…

“…Rwanda has made great strides over the past four years in child survival by introducing vaccines against leading child killers, including pneumonia and diarrhoea,” said Dr Agnes Binagwaho, Rwanda’s Minister of Health. “The introduction of the combined measles-rubella vaccine is one more important step to ensuring that all children in Rwanda receive the full immunization package. In our efforts to eliminate measles, we have raised measles coverage through campaigns and routine immunisation to higher than 95%.” …

http://www.who.int/immunization/newsroom/press/700_million_children_49_countries_protected_measles_rubella/en/index.html

GAVI and the Islamic Development Bank (IDB) signed a Memorandum of Understanding “to help save children’s lives by accelerating the introduction of life-saving vaccines in IDB member countries.” According to the MoU signed between Dr Ahmad Mohamed Ali, Chairman, IDB Group, and Dr Seth Berkley, CEO, GAVI, the IDB “will work closely with GAVI to help secure sufficient funds for immunisation. By 2020, GAVI plans to vaccinate more than 400 million children in at least 29 member countries with the objective of preventing 3.2 million deaths. An estimated US$ 7 billion will be required to reach this target. GAVI CEO Dr Seth Berkley said, “We are joining hands with the IDB to accelerate the introduction of life-saving vaccines in IDB member countries and ensure that children have a healthy start in life. We also aim to increase the uptake of new and underused vaccines in these countries and hopefully generate new sources of funding.”

Dr Ahmad Mohamed Ali stated that “promoting health is among the major strategic thrusts of the Vision 1440H (2020) of the IDB Group and that it was happy to enter into a cooperation agreement with GAVI to save the lives of millions of children in member countries, thereby playing a major role against child mortality. He mentioned that in the initial stage, IDB will try to support the governments of selected member countries to implement the vaccination programme through its “triple win financing model” in which it will seek collaboration with other partners while also providing the recipient countries the opportunity to contribute a portion of the cost along with IDB.”

11 March 2013 – http://www.gavialliance.org/library/news/press-releases/2013/islamic-development-bank-partners-with-gavi-to-save-children-s-lives-with-vaccines/

UNICEF announced that Japan will donate US$189.5 million from its supplementary budget for a wide range of programmes in 35 developing countries and territories. Over 80 per cent of the support will go toward 29 African countries; the remainder is earmarked for Afghanistan and five nations and territories in the Middle East, including Iraq, Jordan and Lebanon affected by the Syrian conflict. UNICEF Executive Director Anthony Lake said, “This extraordinary donation from the Japanese government and the people of Japan is a measure of their deep humanity. Their contribution will help transform the lives of millions of children enduring conflict and hardship. Even when times are tough at home, the generosity of the Japanese is not diminished. US$189.5 million is not only a very large number. It is polio vaccines, seats in classrooms, anti-retroviral drugs, clean water and so much more. The Japanese people should be very proud of making such a difference.”

http://www.unicef.org/media/media_68197.html

Update: Polio this week – As of 12 March 2013
Global Polio Eradication Initiative
http://www.polioeradication.org/Dataandmonitoring/Poliothisweek.aspx

[Editor’s Extract and bolded text]
– Efforts are continuing in DR Congo to further boost immunity levels and fill residual subnational surveillance gaps. Although the country has not reported a WPV case since December 2011, DR Congo was affected by a circulating vaccine-derived poliovirus type 2 (cVDPV2) outbreak, with 17 cases (the most recent had onset of paralysis on 4 April 2012).
– With Angola successfully coming off the re-established transmission list in July 2012, South Sudan in 2010 and now DR Congo, Chad remains the only country with re-established WPV transmission. Here too, however, strong progress continues to be achieved, and the country is on track to becoming again polio-free in June 2013 (most recent WPV case: 14 June 2012; however, Chad remains affected by a cVDPV2 outbreak, with 12 cases reported in the second half of 2012.

Nigeria
– One new WPV case was reported in the past week (WPV1 from Borno), bringing the total number of WPV cases for 2013 to 4. The total number of WPV cases for 2012 remains 122. The most recent WPV case had onset of paralysis on 31 January 2013 (from Yobe).
– Nationwide Immunization Plus Days (IPDs) were conducted using trivalent OPV on 2-5 March in 30 states, coordinated with activities in neighbouring Republic of Niger. IPDs have been postponed by one week in four southern states and the Federal Capital Territory because of the need for more time to adequately prepare for the round of immunization. IPDs have been postponed in Kano and Borno states due to security concerns. The security situation in the north remains fluid.

Pakistan
– The security situation continues to be monitored closely, in consultation with law enforcement agencies.
– Sub-national Immunization Days were conducted in 34 out of 51 planned districts/towns from 4-6 March. Activities have been delayed in other districts, but campaigns are underway in certain areas as possible.

The Weekly Epidemiological Record (WER) for 15 March 2013, vol. 88, 11 (pp. 117–128) includes:

– Antigenic and genetic characteristics of zoonotic influenza viruses and development of candidate vaccine viruses for pandemic preparedness
– Fact sheet on pneumonia
– Monthly report on dracunculiasis cases, January 2013 – FIRST MONTH WITH ZERO CASE

http://www.who.int/entity/wer/2013/wer8811.pdf

WHO – Global Alert and Response (GAR)
Disease Outbreak News –
http://www.who.int/csr/don/2013_03_12/en/index.html

12 March 2013  Novel coronavirus infection – update
The Ministry of Health in Saudi Arabia has informed WHO of a new confirmed case of infection with the novel coronavirus (nCoV).

The patient, a 39-year-old male, developed symptoms on 24 February 2013. He was hospitalized on 28 February 2013 and died on 2 March 2013. Preliminary investigation indicated that the patient had no contact with previously reported cases of nCoV infection. Other potential exposures are under investigation.

To date, WHO has been informed of a global total of 15 confirmed cases of human infection with nCoV, including nine deaths.

Based on the current situation and available information, WHO encourages all Member States (MS) to continue their surveillance for severe acute respiratory infections (SARI) and to carefully review any unusual patterns. WHO is currently working with international experts and countries where cases have been reported to assess the situation and review recommendations for surveillance and monitoring.

All MS are reminded to promptly assess and notify WHO of any new case of infection with nCoV, along with information about potential exposures that may have resulted in infection and a description of the clinical course.

WHO does not advise special screening at points of entry with regard to this event nor does it recommend that any travel or trade restrictions be applied.

WHO continues to closely monitor the situation.

Report: IVI Country Investment Case Study on Cholera Vaccination
International Vaccine Institute and funding partners
March 2013; 134 pages

http://www.ivi.int/web/www/04_03?p_p_id=EXT_BBS&p_p_lifecycle=1&p_p_state=exclusive&p_p_mode=view&p_p_col_id=column-1&p_p_col_pos=1&p_p_col_count=2&_EXT_BBS_struts_action=%2Fext%2Fbbs%2Fget_file&_EXT_BBS_bbsMessageId=503&_EXT_BBS_extFileId=1295

“As part of its global investment case for oral cholera vaccines, IVI developed a Bangladesh case study providing a local perspective. The report provides an estimate of the disease and economic burden, as well as financing needs, likely challenges, and cost, impact and cost-effectiveness estimates for several cholera vaccination strategies.”

Report: The European health report 2012 – charting the way to well-being
WHO Europe
March 2013
http://www.euro.who.int/en/what-we-do/data-and-evidence/european-health-report-2012

“Like its predecessors, the 2012 European health report describes both the overall improvements in health in the WHO European Region and their uneven distribution within and between countries. It breaks new ground, however, by helping both to define well-being, a goal of Europe’s new health policy, Health 2020, and to map the way towards achieving it.

“By describing health in Europe, this report provides policy-makers and public health professionals with the epidemiological evidence base that underpins Health 2020 and its six overarching targets. In addition, it sets out the agreed approach to monitoring progress towards Health 2020, outlines the collaborative agenda to address the challenges ahead and makes the case for measuring well-being as a marker of progress in health.”

Full report: The European health report 2012: charting the way to well-being

Report: The 2013 Human Development Report – The Rise of the South: Human Progress in a Diverse World
United Nations Development Programme (UNDP)
14 March 2013; 216 pages
http://hdr.undp.org/en/media/HDR_2013_EN_complete.pdf

Excerpt
“The 2013 Human Development Report examines the profound shift in global dynamics driven by the fast-rising new powers of the developing world and its long-term implications for human development.

“China has already overtaken Japan as the world’s second biggest economy while lifting hundreds of millions of its people out of poverty. India is reshaping its future with new entrepreneurial creativity and social policy innovation. Brazil is lifting its living standards through expanding international relationships and antipoverty programs that are emulated worldwide.

“But the “Rise of the South” analyzed in the Report is a much larger phenomenon: Turkey, Mexico, Thailand, South Africa, Indonesia and many other developing nations are also becoming leading actors on the world stage.

“The 2013 Human Development Report identifies more than 40 countries in the developing world that have done better than had been expected in human development terms in recent decades, with their progress accelerating markedly over the past ten years. The Report analyzes the causes and consequences of these countries achievements and the challenges that they face today and in the coming decades.

“Each of these countries has its own unique history and has chosen its own distinct development pathway. Yet they share important characteristics and face many of the same challenges. They are also increasingly interconnected and interdependent. And people throughout the developing world are increasingly demanding to be heard, as they share ideas through new communications channels and seek greater accountability from governments and international institutions.

“The 2013 Human Development Report identifies policies rooted in this new global reality that could promote greater progress throughout the world for decades to come. The Report calls for far better representation of the South in global governance systems and points to potential new sources of financing within the South for essential public goods. With fresh analytical insights and clear proposals for policy reforms, the Report helps chart a course for people in all regions to face shared human development challenges together, fairly and effectively…”

http://hdr.undp.org/en/mediacentre/humandevelopmentreportpresskits/2013report/

Report: Public-Private Partnerships for Global Health: How PATH Advances Technologies Through Cross-Sector Collaboration
PATH
March 2013; 8 pages
This policy report highlights the essential role that public-private partnerships play in driving global health product development and offers insights into the key components of successful multi-sector partnerships led by PATH.
http://www.path.org/publications/files/ER_app_ppp_policy_rpt.pdf

Excerpt
RECOMMENDATIONS
Adequately fund public-private partnerships to maximize global health impact
Public-private partnerships are an efficient and sustainable model for conducting global health research and development throughout the product lifecycle. They leverage the resources and expertise of different stakeholders to accelerate the development and delivery of high-impact, cost-effective products to improve public health. As the lead funder of global health research and development, the public sector should ensure that its investments support the critical work of public-private partnerships in accelerating the availability, accessibility, and affordability of global health technologies.

Provide support throughout the product lifecycle to accelerate innovation, introduction, and integration of global health technologies
To maximize impact, the public and private sectors and NGOs must begin with the end in mind. Support by the public sector for technology development alone does not guarantee that a product will reach those most in need. To ensure that innovative ideas become products that efficiently advance from development through wide-scale adoption for sustained public health impact, the public sector must support the products throughout their lifecycle. Thus, investment in market development from the very beginning is essential to build the foundation for supply, create demand, and provide an incentive for private-sector partners to sustain their investments.

Create incentives for private-sector engagement to advance health products for low-resource settings
Public-sector investment—through funding, capacity strengthening, or providing incentives—helps to create an enabling environment that encourages commercialinvestment in global health. Incentives such as accelerated regulatory reviews and pooled funding mechanisms enable commercial partners to meet the needs of the public and the private sectors. Such incentives need to be offered in combination with other innovative mechanisms—such as milestone prizes that provide rewards for incremental achievements along the product lifecycle—to ensure mutual benefits for the public and private sectors, as well as for the global health missions of NGOs like PATH.

Video Report: Now is the time
http://www.path.org/news/an130313-video-optimize.php

New video highlights importance of strengthening vaccine supply and logistics systems
“Recent advances in vaccine science have enabled more countries to provide newer, lifesaving vaccines to more people. However, the impact of these vaccines is often constrained by delays and vaccine waste due to stressed and aging vaccine supply and logistics systems. To harness the power of new vaccines, a new video from Optimize argues, it is critical to upgrade and strengthen vaccine supply and logistics systems throughout the world.

“Optimize, a collaboration between PATH and the World Health Organization with support from many other partners, has begun to demonstrate and document the impact of new technologies, systems, and approaches on supply system efficiency. These partners have agreed on a global vision to improve vaccine supply and logistics by 2020.

“Titled Now Is the Time, the video illustrates the immediate need for all immunization partners to support countries as they embark on meaningful changes in their vaccine supply systems and prepare for the introduction of new and lifesaving vaccines.”

WHO IVB: Request For Proposals – Systematic review of missed opportunities for vaccination
Application deadline: 15 April 2013
– Introduction and Background

Excerpt
Introduction
This request for proposals (RFP) is made by the WHO Department of Immunization Vaccines and Biologicals (IVB). IVB seeks proposals for the rigorous systematic review and meta-analysis of all available data from published and unpublished studies relevant to missed opportunities for vaccination. IVB encourages proposals that include collaboration between institutions/groups in industrialized countries and institutions/groups in low and middle income countries.

Background
As early as 1983, the Expanded Programme on Immunization (EPI) has recommended using every opportunity to immunize all eligible people as a direct strategy to increase vaccination coverage. Protocols for the assessment of “missed opportunities” (defined as any contact with a health service that did not result in an eligible child or woman receiving the needed vaccines) were developed in 1984 and 1988 and widely distributed.

Missed opportunities for vaccination occur in two major settings:
– during visits for immunization and other preventive services (e.g. growth monitoring, nutrition assessments and oral rehydration training sessions, etc.).
– during visits for curative services.

In both settings, eliminating missed opportunities has the potential to raise immunization coverage in a population, particularly when the availability and use of health services is high. When the availability and use of health services is low, immunizing at health care contact is extremely important because the risk for vaccine-preventable diseases is likely to be high in these areas…
– Research objectives
– Proposal Submission/Research Plan
– Deliverables
– Eligibility and How to Apply

More at: http://www.who.int/immunization/rfp_review_missed_opportunities_vaccination/en/index.html

British Medical Journal
16 March 2013 (Vol 346, Issue 7899)
http://www.bmj.com/content/346/7899

Research
Comparative effect sizes in randomised trials from less developed and more developed countries: meta-epidemiological assessment
Orestis A Panagiotou, research associate1, Despina G Contopoulos-Ioannidis, clinical associate professor23, John P A Ioannidis, director4, C F Rehnborg professor in disease prevention, professor of medicine, and professor of health research and policy5
BMJ 2013; 346 doi: http://dx.doi.org/10.1136/bmj.f707 (Published 12 February 2013)
Cite this as: BMJ 2013;346:f707

Abstract
Objective  To compare treatment effects from randomised trials conducted in more developed versus less developed countries.

Design  Meta-epidemiological study.

Data sources C Cochrane Database of Systematic Reviews (August 2012).

Data extraction  Meta-analyses with mortality outcomes including data from at least one randomised trial conducted in a less developed country and one in a more developed country. Relative risk estimates of more versus less developed countries were compared by calculating the relative relative risks for each topic and the summary relative risks across all topics. Similar analyses were performed for the primary binary outcome of each topic.

Results  139 meta-analyses with mortality outcomes were eligible. No nominally significant differences between more developed and less developed countries were found for 128 (92%) meta-analyses. However, differences were beyond chance in 11 (8%) cases, always showing more favourable treatment effects in trials from less developed countries. The summary relative risk was 1.12 (95% confidence interval 1.06 to 1.18; P<0.001; I2=0%), suggesting significantly more favourable mortality effects in trials from less developed countries. Results were similar for meta-analyses with nominally significant treatment effects for mortality (1.15), meta-analyses with recent trials (1.14), and when excluding trials from less developed countries that subsequently became more developed (1.12). For the primary binary outcomes (127 meta-analyses), 20 topics had differences in treatment effects beyond chance (more favourable in less developed countries in 15/20 cases).

Conclusions  Trials from less developed countries in a few cases show significantly more favourable treatment effects than trials in more developed countries and, on average, treatment effects are more favourable in less developed countries. These discrepancies may reflect biases in reporting or study design as well as genuine differences in baseline risk or treatment implementation and should be considers when generalising evidence across different settings.

Eurosurveillance
Volume 18, Issue 11, 14 March 2013
http://www.eurosurveillance.org/Public/Articles/Archives.aspx?PublicationId=11678

Review articles
Outbreaks associated to large open air festivals, including music festivals, 1980 to 2012
by E Botelho-Nevers, P Gautret

Abstract
In the minds of many, large scale open air festivals have become associated with spring and summer, attracting many people, and in the case of music festivals, thousands of music fans. These festivals share the usual health risks associated with large mass gatherings, including transmission of communicable diseases and risk of outbreaks. Large scale open air festivals have however specific characteristics, including outdoor settings, on-site housing and food supply and the generally young age of the participants. Outbreaks at large scale open air festivals have been caused by Cryptosporium parvum, Campylobacter spp., Escherichia coli, Salmonella enterica, Shigella sonnei, Staphylococcus aureus, hepatitis A virus, influenza virus, measles virus, mumps virus and norovirus. Faecal-oral and respiratory transmissions of pathogens result from non-compliance with hygiene rules, inadequate sanitation and insufficient vaccination coverage. Sexual transmission of infectious diseases may also occur and is likely to be underestimated and underreported. Enhanced surveillance during and after festivals is essential. Preventive measures such as immunisations of participants and advice on-site and via social networks should be considered to reduce outbreaks at these large scale open air festivals.

Journal of Medical Microbiology
April 2013; 62 (Pt 4)
http://jmm.sgmjournals.org/content/current

Review
Global spread of antibiotic resistance: the example of New Delhi metallo-β-lactamase (NDM)-mediated carbapenem resistance
Alan P. Johnson and Neil Woodford
J Med Microbiol April 2013 62:499-513; published ahead of print January 17, 2013, doi:10.1099/jmm.0.052555-0
[Open Access] http://jmm.sgmjournals.org/content/62/Pt_4/499.abstract

Abstract 
The rapidity with which new types of antibiotic resistance can disseminate globally following their initial emergence or recognition is exemplified by the novel carbapenemase New Delhi metallo-β-lactamase (NDM). The first documented case of infection caused by bacteria producing NDM occurred in 2008, although retrospective analyses of stored cultures have identified the gene encoding this enzyme (blaNDM) in Enterobacteriaceae isolated in 2006. Since its first description, NDM carbapenemase has been reported from 40 countries worldwide, encompassing all continents except South America and Antarctica. The spread of NDM has a complex epidemiology involving the spread of a variety of species of NDM-positive bacteria and the inter-strain, inter-species and inter-genus transmission of diverse plasmids containing blaNDM, with the latter mechanism having played a more prominent role to date. The spread of NDM illustrates that antibiotic resistance is a public health problem that transcends national borders and will require international cooperation between health authorities if it is to be controlled.

Journal of Medical Microbiology
April 2013; 62 (Pt 4)
http://jmm.sgmjournals.org/content/current

Clinical microbiology and virology
Hand contamination during routine care in medical wards: the role of hand hygiene compliance
J Med Microbiol April 2013 62:623-629; published ahead of print January 17, 2013, doi:10.1099/jmm.0.050328-0
Olga Monistrol, M. Liboria López, Montserrat Riera, Roser Font, Carme Nicolás, Miguel Angel Escobar, Núria Freixas, Javier Garau, and Esther Calbo
http://jmm.sgmjournals.org/content/62/Pt_4/623.abstract

Abstract
The hands of healthcare workers (HCWs) are the most common vehicle for the transmission of micro-organisms from patient to patient and within the healthcare environment. The aim of this study was to evaluate the impact of a multimodal campaign on the type and amount of resident and transient flora and the presence of potential risk factors for hand contamination during routine care. A before–after (PRE and POST periods) interventional study was carried out in medical wards of a tertiary care hospital. Eighty-nine samples were analysed. Samples were cultured immediately before patient contact using a glove-juice method. Data collected included socio-demographic and risk factors for hand contamination. Flora was measured as log10 c.f.u. ml−1 and evaluated by comparing median values in the PRE and POST periods. Transient flora was isolated from the hands of 67.4 and 46.1 % of HCWs in the PRE and POST periods, respectively (P<0.001). Enterobacteriaceae, Pseudomonas spp. and meticillin-sensitive Staphylococcus aureus were the predominant contaminants. Resident flora was isolated from 92.1 % of HCWs in the PRE period and from 70.8 % in the POST period (P<0.001). The meticillin-resistant coagulase-negative staphylococci log10 c.f.u. count ml−1 decreased from 1.96±1.2 to 0.89±1.2 (mean±sd; P<0.001), and the global flora count decreased from 2.77±1.1 to 1.56±1.4 (P<0.001). In the POST period, the wearing of fewer rings (P<0.001), shorter fingernail length (P = 0.008), a shorter time since recent hand hygiene (HH) (P = 0.007) and an increased use of alcohol-based hand rub instead of soap (P<0.001) were documented.   The HH multimodal strategy reduced the number of risk factors and the level of HCW hand contamination.

The Lancet  
Mar 16, 2013  Volume 381  Number 9870  p875 – 962
http://www.thelancet.com/journals/lancet/issue/current
[No relevant content]

Early Online Publication, 13 March 2013
Association between Guillain-Barré syndrome and influenza A (H1N1) 2009 monovalent inactivated vaccines in the USA: a meta-analysis
Dr Daniel A Salmon PhD Michael Proschan PhD d, Richard Forshee PhD e, Paul Gargiullo PhD f, William Bleser MSPH a, Dale R Burwen MD e, Francesca Cunningham PharmD g, Patrick Garman PhD h, Sharon K Greene PhD i, Grace M Lee MD i, Claudia Vellozzi MD f, W Katherine Yih PhD i, Bruce Gellin MD a, Nicole Lurie MD b, the H1N1 GBS Meta-Analysis Working Group†
doi:10.1016/S0140-6736(12)62189-8

Summary
Background
The influenza A (H1N1) 2009 monovalent vaccination programme was the largest mass vaccination initiative in recent US history. Commensurate with the size and scope of the vaccination programme, a project to monitor vaccine adverse events was undertaken, the most comprehensive safety surveillance agenda in the USA to date. The adverse event monitoring project identified an increased risk of Guillain-Barré syndrome after vaccination; however, some individual variability in results was noted. Guillain-Barré syndrome is a rare but serious health disorder in which a person’s own immune system damages their nerve cells, causing muscle weakness, sometimes paralysis, and infrequently death. We did a meta-analysis of data from the adverse event monitoring project to ascertain whether influenza A (H1N1) 2009 monovalent inactivated vaccines used in the USA increased the risk of Guillain-Barré syndrome.

Methods
Data were obtained from six adverse event monitoring systems. About 23 million vaccinated people were included in the analysis. The primary analysis entailed calculation of incidence rate ratios and attributable risks of excess cases of Guillain-Barré syndrome per million vaccinations. We used a self-controlled risk-interval design.

Findings
Influenza A (H1N1) 2009 monovalent inactivated vaccines were associated with a small increased risk of Guillain-Barré syndrome (incidence rate ratio 2·35, 95% CI 1·42—4·01, p=0·0003). This finding translated to about 1·6 excess cases of Guillain-Barré syndrome per million people vaccinated.

Interpretation
The modest risk of Guillain-Barré syndrome attributed to vaccination is consistent with previous estimates of the disorder after seasonal influenza vaccination. A risk of this small magnitude would be difficult to capture during routine seasonal influenza vaccine programmes, which have extensive, but comparatively less, safety monitoring. In view of the morbidity and mortality caused by 2009 H1N1 influenza and the effectiveness of the vaccine, clinicians, policy makers, and those eligible for vaccination should be assured that the benefits of inactivated pandemic vaccines greatly outweigh the risks.

Funding
US Federal Government.

The Milbank Quarterly
A Multidisciplinary Journal of Population Health and Health Policy
March 2013  Volume 91, Issue 1  Pages 1–218
http://onlinelibrary.wiley.com/doi/10.1111/milq.2013.91.issue-1/issuetoc

Summarizing Social Disparities in Health (pages 5–36)
YUKIKO ASADA, YOKO YOSHIDA and ALYCE M. WHIPP
Article first published online: 14 MAR 2013 | DOI: 10.1111/milq.12001
[Open Access: http://onlinelibrary.wiley.com/doi/10.1111/milq.12001/full ]

Abstract
Context
Reporting on health disparities is fundamental for meeting the goal of reducing health disparities. One often overlooked challenge is determining the best way to report those disparities associated with multiple attributes such as income, education, sex, and race/ethnicity. This article proposes an analytical approach to summarizing social disparities in health, and we demonstrate its empirical application by comparing the degrees and patterns of health disparities in all fifty states and the District of Columbia (DC).

Methods
We used the 2009 American Community Survey, and our measure of health was functional limitation. For each state and DC, we calculated the overall disparity and attribute-specific disparities for income, education, sex, and race/ethnicity in functional limitation. Along with the state rankings of these health disparities, we developed health disparity profiles according to the attribute making the largest contribution to overall disparity in each state.

Findings
Our results show a general lack of consistency in the rankings of overall and attribute-specific disparities in functional limitation across the states. Wyoming has the smallest overall disparity and West Virginia the largest. In each of the four attribute-specific health disparity rankings, however, most of the best- and worst-performing states in regard to overall health disparity are not consistently good or bad. Our analysis suggests the following three disparity profiles across states: (1) the largest contribution from race/ethnicity (thirty-four states), (2) roughly equal contributions of race/ethnicity and socioeconomic factor(s) (ten states), and (3) the largest contribution from socioeconomic factor(s) (seven states).

Conclusions
Our proposed approach offers policy-relevant health disparity information in a comparable and interpretable manner, and currently publicly available data support its application. We hope this approach will spark discussion regarding how best to systematically track health disparities across communities or within a community over time in relation to the health disparity goal of Healthy People 2020.

PLoS Medicine
(Accessed 16 March 2013)
http://www.plosmedicine.org/

Policy Forum
Adapting Standards: Ethical Oversight of Participant-Led Health Research
Effy Vayenal, John Tasioulas

Summary Points
– Online social media and digital technologies have facilitated formation of communities of individuals engaged in establishing and conducting health research projects. The results of such participant-led research (PLR) have already appeared in leading biomedical journals.

– These projects involve research with human participants. Hence, what are the requirements for ethical oversight? To what extent is standard ethics review also suitable for PLR?

– A comparison of PLR with standard research reveals six areas that are of potential relevance to ethical oversight: institutionalization, state recognition and support, incentive structures, openness, bottom-up approach, and self-experimentation.

– The distinctive nature of PLR requires adaptation of ethical oversight standards to the character of such research. These should strike a balance between protecting interests of research participants and achieving promised benefits of PLR.

– The appropriate form of ethical oversight for PLR projects depends on which of three categories they fall into. If they meet the “institution-plus” criterion, standard ethics review applies. If not, then the appropriate form of oversight depends on the application of a minimal risk criterion.

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 31, Issue 14, Pages 1765-1878 (3 April 2013)

Legal considerations surrounding mandatory influenza vaccination for healthcare workers in the United States
Review Article
Pages 1771-1776
Lisa H. Randall, Eileen A. Curran, Saad B. Omer

Abstract
Recent years have brought increased focus on the desirability of vaccinating more healthcare workers against influenza. The concern that novel 2009 H1N1 influenza A would spark a particularly severe influenza season in 2009–2010 spurred several institutions and one state to institute mandatory vaccination policies for healthcare workers, and several new mandates have been introduced since then. Some healthcare workers, however, have voiced objections in the media and in legal proceedings. This paper reviews the characteristics of influenza and how it is transmitted in the healthcare setting; surveys possible constitutional, administrative, and common law arguments against mandates; assesses the viability of those arguments; and identifies potential new legal strategies to support influenza vaccine mandates. It is intended to assist those involved in the regulation and administration of public and private healthcare institutions who may be considering approaches to mandates but have concerns about legal challenges.

Vaccine
http://www.sciencedirect.com/science/journal/0264410X

Active immunotherapy for chronic diseases
Review Article
Pages 1777-1784
Martin F. Bachmann, Piers Whitehead

Abstract
With the effective control of infectious diseases in many parts of the world, chronic, non-communicable diseases have become the major cause of death and disability. Monoclonal antibodies (mAbs) have become an important class of drugs for the treatment of such diseases. Nevertheless, mAbs suffer from major shortcomings in a chronic setting: most notably, generation of anti-antibodies and high cost of goods. Here, we discuss a novel approach to treat chronic diseases based on active rather than passive immunization and contrast the 2 treatment modalities to highlight their respective advantages and disadvantages.