Mandatory HPV Vaccination

January 18, 2012, Vol 307, No. 3, pp 223-320

Mandatory HPV Vaccination
Melissa B. Gilkey, Noel T. Brewer
JAMA. 2012;307(3):252-253.doi:10.1001/jama.2011.2018

To the Editor: Mr Gostin’s Commentary questioned whether mandates for human papillomavirus (HPV) vaccination are effective enough to risk alienating the public.1 Data in studies he cites address this matter. In the 2 places that have adopted mandates, Virginia and the District of Columbia, coverage remains modest. Compared with 49% of female adolescents nationwide, just 54% of those in Virginia and 58% of those in the District of Columbia had received 1 or more doses of HPV vaccine by 2010 according to medical records.2 Existing mandates include generous opt-out provisions that, in the case of the District of Columbia, more than 40% of parents used to circumvent the policy.

Gostin suggested widespread educational campaigns and mandates without generous opt-outs as a last resort, but we think this focus on the public is likely misguided. Numerous surveys indicate that many people already agree with HPV vaccination mandates. Most recently, …

Mandatory HPV Vaccination
Lynn C. Berger, Debra Blog, Guthrie S. Birkhead
JAMA. 2012;307(3):253-254.doi:10.1001/jama.2011.2019

To the Editor: Mr Gostin,1 in his Commentary, highlighted the unique issues and controversies surrounding the institution of a state vaccination law, or mandate, with regard to the HPV vaccine. The Commentary provided a much-needed focus on the undisputed safety and efficacy of the HPV vaccine in light of recent negative public attention.

We think, however, that it is important to clarify the author’s statement that “research on the effectiveness of mandates is unavailable.”1 While specific evidence does not yet exist regarding the effectiveness of school mandates on HPV vaccination rates, it is clear that school mandates have uniformly increased state vaccination rates for other vaccines. In 1999, the Task Force on Community Preventive Services concluded, after a review of all available studies on the effectiveness of school-entry vaccination laws, that these laws are both effective at reducing disease rates and outbreaks as well as increasing overall vaccination …

Mandatory HPV Vaccination
Lucija Tomljenovic, Christopher A. Shaw
JAMA. 2012;307(3):254.doi:10.1001/jama.2011.2020

To the Editor: Mr Gostin made an important point in his Commentary on mandatory HPV vaccination: “Above all, health policy must be driven by science.”1 However, the author’s recommendation that “if voluntary vaccination proves unsuccessful, states should seriously consider compulsory vaccination laws without generous exemptions” appears premature. As Gostin noted, clinical trial evidence has not demonstrated that  HPV vaccines can actually prevent invasive cervical cancer, let alone cervical cancer deaths.2,3 Because HPV vaccines were specifically developed to protect against cervical cancer, we conclude that in the absence of long-term data, their true benefits remain speculative. The Food and Drug Administration acknowledges that “It is believed that prevention of cervical precancerous lesions is highly likely to result in the prevention of those cancers.”4

Clinical trials show that HPV vaccine efficacy against persistent HPV infection and precancerous lesions only lasts for 8.4 and 5 years for Cervarix …

Mandatory HPV Vaccination—Reply
Lawrence O. Gostin
JAMA. 2012;307(3):254-255.doi:10.1001/jama.2011.2021

In Reply: This collection of 3 letters in response to my Commentary vividly demonstrates the political and social divisiveness of HPV vaccination, which sets it apart from most childhood immunizations. Each letter is thoughtful, and yet all 3 letters come to distinctly different policy conclusions. Drs Gilkey and Brewer find that health system factors such as cost and enhanced access are more effective than mandates; Dr Berger and colleagues urge immediate state adoption of HPV mandates with limited opt-outs; and Drs Tomljenovic and Shaw reject HPV mandates as a flawed policy. Each letter expresses strong agreement with my view, “Above all, health policy must be driven by science,” and yet each draws different conclusions based on the available scientific evidence. How is this possible?

Gilkey and Brewer cite studies showing strong parental support for mandates—either with generous opt-outs (84%-92%) or without (47%-59%). But these polls have underlying flaws. First, the …

Lancet Editorial: Global health in 2012 – development to sustainability

The Lancet  
Jan 21, 2012  Volume 379  Number 9812  p193 – 286  e – 19

Global health in 2012: development to sustainability
The Lancet

In 2012 there will be a major strategic shift in global health, away from development and towards sustainability. Since 2000, the Millennium Development Goals (MDGs), driven by a macroeconomic diagnosis of global poverty, have focused on investment in a small number of diseases as the most effective approach to decrease poverty.   Institutions such as the Global Fund to Fight AIDS, Tuberculosis and Malaria, Roll Back Malaria, and GAVI have been created to respond to that diagnosis.

But this approach is now delivering diminishing returns. The AIDS epidemic has peaked, both in terms of deaths and new infections, non-communicable diseases (NCDs) are increasing, and the climate change crisis is an ever present threat. India is a good example of a country facing these new challenges. It has an NCD epidemic and yet still endures the highest number of maternal and child deaths in the world. The old macroeconomic approach to solving poverty-related disease is simply insufficient to meet the demand of countries. At the same time, institutional tensions are growing—the Global Fund is in difficulty and WHO is facing a financial emergency. And there are new concepts forcing their way into global health agendas—such as integration and accountability. There is a view among some development experts that health has had its decade. It is time now for other sectors to take centre stage, such as agriculture or energy.

All these issues will come into sharp focus later this year at Rio+20, the UN Conference on Sustainable Development in Rio de Janeiro, Brazil (June 20—22). The summit marks the 20th anniversary of the 1992 UN Conference on Environment and Development and the tenth anniversary of the 2002 World Summit on Sustainable Development. World leaders, stakeholders from the public and private sectors, as well as representatives from environment and development communities will convene to define a new roadmap towards economic growth, social equity, and environmental protection. The objectives of Rio+20 will be to review progress on sustainable development from previous summits, identify gaps in implementation, renew political commitment on past action plans, and find ways to safeguard the planet from future destruction from emerging threats. The two core themes will be a move towards a green economy (in the context of sustainable development and poverty eradication) and strengthening the institutional framework for sustainable development, which to date has not fulfilled its potential because of a lack of coordination and coherence. The zero draft outcome document published last week lists seven priority areas for Rio+20. They are: job creation, food security, water, energy, sustainable cities, oceans, and disasters. There will be ten new sustainable development goals to be decided by governments just before the meeting—and introduced in 2015 as part of the post-2015 UN development agenda. There will be no legally binding agreements and countries will set their own targets, working voluntarily towards them. Disappointingly, health is hardly mentioned in this draft.

It is vital that this major shift from development to sustainability is governed by a clear set of principles and values. One report to draw from is The Lancet’s 2010 Commission titled: The Millennium Development Goals: a cross-sectoral analysis and principles for goal setting after 2015. The authors of this multidisciplinary analysis represent many different sectors, and explain that much more could have been achieved if the MDGs were better integrated. They conclude that future goals should be built on a shared vision of development across the lifecourse, and suggest five principles: holism, equity, sustainability, ownership, and global obligation. Their report exemplifies the positive contribution the health community can make to sustainability after 2015.

The health sector has a vital part to play during the next 12 months. We need to make a strong case for health as part of sustainable development and future sustainable development goals—to protect the gains of the past decade and ensure that the unfinished agenda of the past decade is continued. However, we also need to embrace a new and emerging health agenda—one that includes NCDs and climate change. And we must sharpen our advocacy for health as we rightly integrate other sectors into this broader vision. We have an extraordinary opportunity to re-vivify global health. But we are unprepared to do so. We must identify the lessons learned from the MDGs, as well as bringing to the fore evidence for new threats and emerging challenges. The Lancet plans to be a strong partner in shaping this future health and sustainability agenda—towards finding equitable solutions to improve the health and lives of people worldwide.

Preventing pandemics: The fight over flu (H5N1 research)

Volume 481 Number 7381 pp237-404  19 January 2012

Preventing pandemics: The fight over flu
Nature 481, 257–259 (19 January 2012)
Published online 15 January 2012

A proposal to restrict the planned publication of research on a potentially deadly avian influenza virus is causing a furor. Ten experts suggest ways to proceed.

Ron Fouchier & AB Osterhaus: Globalize the discussion

John Steinbruner: A system for redacted papers

Kwok-Yung Yuen: The Hong Kong perspective

D. A. Henderson: The ultimate biological threat

Lynn Klotz & Ed Sylvester: Worry about lab infections

Jeffery K. Taubenberger: Study how viruses swap hosts

Richard H. Ebright: Mitigate the risks of release

David L. Heymann: We will always need vaccines

Invasive Pneumococcal Disease in Spain in the Heptavalent Conjugate Vaccine Era

The Pediatric Infectious Disease Journal
February 2012 – Volume 31 – Issue 2  pp: A11-A12,109-214,e37-e51

Clinical Presentation of Invasive Pneumococcal Disease in Spain in the Era of Heptavalent Conjugate Vaccine
de Sevilla, Maria F.; García-García, Juan-José; Esteva, Cristina; Moraga, Fernando; Hernández, Sergi; Selva, Laura; Coll, Francisco; Ciruela, Pilar; Planes, Ana Maria; Codina, Gemma; Salleras, Luis; Jordan, Iolanda; Domínguez, Angela; Muñoz-Almagro, Carmen
Pediatric Infectious Disease Journal. 31(2):124-128, February 2012.
doi: 10.1097/INF.0b013e318241d09e

Background: The aim of this study was to analyze the rate of incidence, clinical presentation, serotype, and clonal distribution of invasive pneumococcal disease (IPD) in the era of heptavalent pneumococcal conjugate vaccine (PCV7) in Barcelona, Spain.

Methods: This was a prospective study comprising all children <5 years with IPD who were managed in 2 tertiary-care, pediatric hospitals between January 2007 and December 2009. IPD was defined as the presence of clinical findings of infection together with isolation or detection of DNA of Streptococcus pneumoniae in a sterile fluid sample.

Results: In this study, 319 patients (53.3% male), mean age 29.6 months, were included. Comparing rates in 2007 and 2009 (76.2 and 109.9 episodes/100,000 population, respectively), an increase of 44% (95% confidence interval, 10%–89%) was observed. The main clinical presentation was pneumonia (254 episodes, 79.6%), followed by meningitis (29, 9.1%), and bacteremia (25, 7.8%).The diagnosis was made by positive culture in 123 (38.6%) patients and in 196 (61.4%) by real-time polymerase chain reaction. Serotype study was performed in 300 episodes, and 273 (91%) were non-PCV7 serotypes. The most frequent serotypes were 1 (20.7%), 19A (15.7%), and 3 (12.3%). A minimal inhibitory concentration ≥0.12 μg/mL to penicillin was detected in 34.4% of isolates. Sequence type 306 expressing serotype 1 was the most frequent clonal type detected (20.3% of studied strains).

Conclusions: IPD continues to increase in Barcelona, and the rate is higher than previously reported as a result of low sensitivity of bacterial culture. Non-PCV7 serotypes were responsible for 91% of episodes and pneumonia was the main clinical presentation.

Vaccination Attitudes of Pediatricians and Primary Health Center Physicians in India

The Pediatric Infectious Disease Journal
February 2012 – Volume 31 – Issue 2  pp: A11-A12,109-214,e37-e51

Attitudes of Pediatricians and Primary Health Center Physicians in India Concerning Routine Immunization, Barriers to Vaccination, and Missed Opportunities to Vaccinate
Gargano, Lisa M.; Thacker, Naveen; Choudhury, Panna; Weiss, Paul S.; Pazol, Karen; Bahl, Sunil; Jafari, Hamid S.; Arora, Manisha; Orenstein, Walter A.; Hughes, James M.; Omer, Saad B.
Pediatric Infectious Disease Journal. 31(2):e37-e42, February 2012.
doi: 10.1097/INF.0b013e3182433bb3

Background: India has some of the lowest immunization rates in the world. The objective of this study was to determine the attitudes and practices of pediatricians and physicians working in primary health centers (PHCs) regarding routine immunization and identify correlates of missed opportunities to vaccinate children. We focused on Uttar Pradesh and Bihar, which has faced some of the greatest challenges to achieving high routine immunization coverage.

Methods: A sample of pediatricians from Uttar Pradesh and Bihar was selected from the national membership of the Indian Academy of Pediatrics to participate in either a phone or mail survey. For the sampling frame, the PHCs within selected blocks were enumerated to provide a list from which individuals could be randomly sampled. In all, 614 PHCs in Uttar Pradesh and 159 PHCs were selected for in-person surveys.

Results: The response rate for pediatricians was 47% (238/505) and 93% for PHC physicians (719/773). The greatest barrier to vaccinating children with routine immunizations, reported by both pediatricians (95.7%) and PHC physicians (95.1%), was parents’ lack of awareness of their importance. Correlates of missing an opportunity to vaccinate for PHC physicians included holding other health care workers responsible for vaccination. PHC physicians were 50% to 70% less likely to vaccinate a child themselves if they thought another type of health care worker was responsible.

Conclusions: Future interventions to increase vaccination coverage should address parental knowledge about the importance of vaccines. Understanding and addressing factors associated with missed opportunities to vaccinate may help improve vaccine coverage in Uttar Pradesh and Bihar.

MenAfriVac: Whom and Where Are We Not Vaccinating?

PLoS One
[Accessed 22 January 2012];jsessionid=577FD8B9E1F322DAA533C413369CD6F3.ambra01?field=date

Whom and Where Are We Not Vaccinating? Coverage after the Introduction of a New Conjugate Vaccine against Group A Meningococcus in Niger in 2010
Sung Hye Kim, Lorenzo Pezzoli, Harouna Yacouba, Tiekoura Coulibaly, Mamoudou H. Djingarey, William A. Perea, Thomas F. Wierzba
Research Article, published 20 Jan 2012 10.1371/journal.pone.0029116

MenAfriVac is a new conjugate vaccine against Neisseria meningitidis serogroup A developed for the African “meningitis belt”. In Niger, the first two phases of the MenAfriVac introduction campaign were conducted targeting 3,135,942 individuals aged 1 to 29 years in the regions of Tillabéri, Niamey, and Dosso, in September and December 2010. We evaluated the campaign and determined which sub-populations or areas had low levels of vaccination coverage in the regions of Tillabéri and Niamey. After Phase I, conducted in the Filingué district, we estimated coverage using a 30×15 cluster-sampling survey and nested lot quality assurance (LQA) analysis in the clustered samples to identify which subpopulations (defined by age 1–14/15–29 and sex) had unacceptable vaccination coverage (<70%). After Phase II, we used Clustered Lot Quality Assurance Sampling (CLQAS) to assess if any of eight districts in Niamey and Tillabéri had unacceptable vaccination coverage (<75%) and estimated overall coverage. Estimated vaccination coverage was 77.4% (95%CI: 84.6–70.2) as documented by vaccination cards and 85.5% (95% CI: 79.7–91.2) considering verbal history of vaccination for Phase I; 81.5% (95%CI: 86.1–77.0) by card and 93.4% (95% CI: 91.0–95.9) by verbal history for Phase II. Based on vaccination cards, in Filingué, we identified both the male and female adult (age 15–29) subpopulations as not reaching 70% coverage; and we identified three (one in Tillabéri and two in Niamey) out of eight districts as not reaching 75% coverage confirmed by card. Combined use of LQA and cluster sampling was useful to estimate vaccination coverage and to identify pockets with unacceptable levels of coverage (adult population and three districts). Although overall vaccination coverage was satisfactory, we recommend continuing vaccination in the areas or sub-populations with low coverage and reinforcing the social mobilization of the adult population.

Typhoid Vaccine Use in Africa

PLoS One
[Accessed 22 January 2012];jsessionid=577FD8B9E1F322DAA533C413369CD6F3.ambra01?field=date

Population-Based Incidence of Typhoid Fever in an Urban Informal Settlement and a Rural Area in Kenya: Implications for Typhoid Vaccine Use in Africa
Robert F. Breiman, Leonard Cosmas, Henry Njuguna, Allan Audi, Beatrice Olack, John B. Ochieng, Newton Wamola, Godfrey M. Bigogo, George Awiti, Collins W. Tabu, Heather Burke, John Williamson, Joseph O. Oundo, Eric D. Mintz, Daniel R. Feikin and a Rural Area in Kenya: Implications for Typhoid Vaccine … Population-Based Incidence of Typhoid Fever in an Urban Informal Settlement and a Rural Area in Kenya: Implications for Typhoid Vaccine Use in Africa … of typhoid vaccines in increasingly urban Africa PLoS ONE: Research Article, published 19 Jan 2012 10.1371/journal.pone.0029119


High rates of typhoid fever in children in urban settings in Asia have led to focus on childhood immunization in Asian cities, but not in Africa, where data, mostly from rural areas, have shown low disease incidence. We set out to compare incidence of typhoid fever in a densely populated urban slum and a rural community in Kenya, hypothesizing higher rates in the urban area, given crowding and suboptimal access to safe water, sanitation and hygiene.

During 2007-9, we conducted population-based surveillance in Kibera, an urban informal settlement in Nairobi, and in Lwak, a rural area in western Kenya. Participants had free access to study clinics; field workers visited their homes biweekly to collect information about acute illnesses. In clinic, blood cultures were processed from patients with fever or pneumonia. Crude and adjusted incidence rates were calculated.

In the urban site, the overall crude incidence of Salmonella enterica serovar Typhi (S. Typhi) bacteremia was 247 cases per 100,000 person-years of observation (pyo) with highest rates in children 5–9 years old (596 per 100,000 pyo) and 2–4 years old (521 per 100,000 pyo). Crude overall incidence in Lwak was 29 cases per 100,000 pyo with low rates in children 2–4 and 5–9 years old (28 and 18 cases per 100,000 pyo, respectively). Adjusted incidence rates were highest in 2–4 year old urban children (2,243 per 100,000 pyo) which were >15-fold higher than rates in the rural site for the same age group. Nearly 75% of S. Typhi isolates were multi-drug resistant.

This systematic urban slum and rural comparison showed dramatically higher typhoid incidence among urban children <10 years old with rates similar to those from Asian urban slums. The findings have potential policy implications for use of typhoid vaccines in increasingly urban Africa.

Ensemble Modeling of Likely Public Health Impact: Pre-Erythrocytic Malaria Vaccine

PLoS Medicine
(Accessed 22 January 2012)

Ensemble Modeling of the Likely Public Health Impact of a Pre-Erythrocytic Malaria Vaccine
Thomas Smith, Amanda Ross, Nicolas Maire, Nakul Chitnis, Alain Studer, Diggory Hardy, Alan Brooks, Melissa Penny, Marcel Tanner Research Article, published 17 Jan 2012

The RTS,S malaria vaccine may soon be licensed. Models of impact of such vaccines have mainly considered deployment via the World Health Organization’s Expanded Programme on Immunization (EPI) in areas of stable endemic transmission of Plasmodium falciparum, and have been calibrated for such settings. Their applicability to low transmission settings is unclear. Evaluations of the efficiency of different deployment strategies in diverse settings should consider uncertainties in model structure.

Methods and Findings
An ensemble of 14 individual-based stochastic simulation models of P. falciparum dynamics, with differing assumptions about immune decay, transmission heterogeneity, and treatment access, was constructed. After fitting to an extensive library of field data, each model was used to predict the likely health benefits of RTS,S deployment, via EPI (with or without catch-up vaccinations), supplementary vaccination of school-age children, or mass vaccination every 5 y. Settings with seasonally varying transmission, with overall pre-intervention entomological inoculation rates (EIRs) of two, 11, and 20 infectious bites per person per annum, were considered. Predicted benefits of EPI vaccination programs over the simulated 14-y time horizon were dependent on duration of protection. Nevertheless, EPI strategies (with an initial catch-up phase) averted the most deaths per dose at the higher EIRs, although model uncertainty increased with EIR. At two infectious bites per person per annum, mass vaccination strategies substantially reduced transmission, leading to much greater health effects per dose, even at modest coverage.

In higher transmission settings, EPI strategies will be most efficient, but vaccination additional to the EPI in targeted low transmission settings, even at modest coverage, might be more efficient than national-level vaccination of infants. The feasibility and economics of mass vaccination, and the circumstances under which vaccination will avert epidemics, remain unclear. The approach of using an ensemble of models provides more secure conclusions than a single-model approach, and suggests greater confidence in predictions of health effects for lower transmission settings than for higher ones.

Editors’ Summary 
The World Health Organization estimates that there are over 200 million cases of malaria each year, and that more than three-quarters of a million people (mostly children living in sub-Saharan Africa) die as a result. Several Plasmodium parasites cause malaria, the most deadly being Plasmodium falciparum. Plasmodium parasites, which are transmitted to people through the bites of infected night-flying mosquitoes, cause recurring fever and can cause life-threatening organ damage. Malaria transmission can be prevented by using insecticides to control the mosquitoes that spread the parasite and by sleeping under insecticide-treated bed nets to avoid mosquito bites. Treatment with antimalarial drugs also reduces transmission. Together, these preventative measures have greatly reduced the global burden of malaria over recent years, but a malaria vaccine could be a valuable additional tool against the disease. At present there is no licensed malaria vaccine, but one promising vaccine—RTS,S—is currently undergoing phase III clinical trials (the last stage of testing before licensing) in infants and children in seven African countries.

Why Was This Study Done?
If the RTS,S vaccine fulfills its promise and is licensed, how should it be used to maximize its effect on the global malaria burden? Should it be given through the World Health Organization’s Expanded Programme on Immunization (EPI), which aims to provide universal access to immunization against several infectious diseases during the first three months of life, for example, or through mass vaccination campaigns? Individual mathematical models have been used to investigate this type of question, but the predictions made by these models may be inaccurate because malaria immunity is poorly understood, because little is known about the levels of variability (heterogeneity) in host responses to malaria infection and in malaria transmission, and because it is unclear what the structure of models used to predict vaccine efficacy should be. In this study, the researchers use an “ensemble” approach to model the likely public health impact of the RTS,S malaria vaccine. That is, they simultaneously consider the effect of the vaccine in multiple models of P. falciparum dynamics. Ensemble modeling is widely used in weather forecasting and has been used to investigate several other infectious diseases.

What Did the Researchers Do and Find?
The researchers constructed an ensemble of 14 individual-based stochastic simulation models of P. falciparum dynamics that included different assumptions about immune decay, transmission heterogeneity, and access to treatment. Such models simulate the passage of thousands of hypothetical individuals through different stages of malaria infection; movement between stages occurs stochastically (by chance) at a probability based on field data. Each model was used to predict the health benefits over 14 years of RTS,S deployment through EPI (with and without catch-up vaccination for infants who were not immunized during their first three months of life), through EPI and supplementary vaccination of school children, and through mass vaccination campaigns every five years at malaria transmission levels of 2, 11, and 20 infectious bites per person per annum (low, medium, and high entomological inoculation rates [EIRs], respectively). The predicted benefits of EPI vaccination programs over the 14-year period were modest and similar over a wide range of settings. However, EPI with an initial catch-up phase averted the most deaths per vaccine dose at higher EIRs. At the lowest EIR, mass vaccination strategies substantially reduced transmission, leading to much greater health effects per dose than other strategies, even at modest coverage.

What Do These Findings Mean?
The ensemble approach taken here suggests that targeted mass vaccination with RTS,S in low transmission settings may have greater health benefits than vaccination through national EPI programs. Importantly, this computer-intensive approach, which used computers made available over the internet by volunteers, provides more secure predictions than can be obtained using single models. In addition, it suggests that predictions made about the health effects of RTS,S vaccination for low transmission settings are more likely to be accurate than those made for higher transmission settings. However, this study only reports the first stages of using ensemble modeling to predict the health effects of RTS,S vaccination. Future studies will need to combine the outputs of multiple models with economic analyses to provide a rational basis for the design of vaccine-containing malaria control and elimination programs.

Pneumococcal Conjugate Vaccines in West Africa: Population-Based Surveillance System

PLoS Medicine
(Accessed 22 January 2012)

Monitoring the Introduction of Pneumococcal Conjugate Vaccines into West Africa: Design and Implementation of a Population-Based Surveillance System
Grant A. Mackenzie, Ian D. Plumb, Sana Sambou, Debasish Saha, Uchendu Uchendu, Bolanle Akinsola, Usman N. Ikumapayi, Ignatius Baldeh, Effua Usuf, Kebba Touray, Momodou Jasseh, Stephen R. C. Howie, Andre Wattiaux, Ellen Lee, Maria Deloria Knoll, Orin S. Levine, Brian M. Greenwood, Richard A. Adegbola, Philip C. Hill Health in Action, published 17 Jan 2012

Summary Points
– Routine use of pneumococcal conjugate vaccines (PCVs) in developing countries is expected to lead to a significant reduction in childhood deaths. However, PCVs have been associated with replacement disease with non-vaccine serotypes.

- We established a population-based surveillance system to document the direct and indirect impact of PCVs on the incidence of invasive pneumococcal disease (IPD) and radiological pneumonia in those aged 2 months and older in The Gambia, and to monitor changes in serotype-specific IPD.

- Here we describe how this surveillance system was set up and is being operated as a partnership between the Medical Research Council Unit and the Gambian Government.

This surveillance system is expected to provide crucial information for immunisation policy and serves as a potential model for those introducing routine PCV vaccination in diverse settings.

Knowledge Systems for Sustainable Development

PNAS – Proceedings of the National Academy of Sciences of the United States
of America

(Accessed 22 January 2012)

Knowledge Systems for Sustainable Development Special Feature Sackler Colloquium – Social Sciences – Sustainability Science
Lorrae van Kerkhoff and Nicole A. Szlezák

It is becoming increasingly recognized that our collective ability to tackle complex problems will require the development of new, adaptive, and innovative institutional arrangements that can deal with rapidly changing knowledge and have effective learning capabilities. In this paper, we applied a knowledge-systems perspective to examine how institutional innovations can affect the generation, sharing, and application of scientific and technical knowledge. We report on a case study that examined the effects that one large innovative organization, The Global Fund to Fight AIDS, Tuberculosis, and Malaria, is having on the knowledge dimensions of decision-making in global health. The case study shows that the organization created demand for new knowledge from a range of actors, but it did not incorporate strategies for meeting this demand into their own rules, incentives, or procedures. This made it difficult for some applicants to meet the organization’s dual aims of scientific soundness and national ownership of projects. It also highlighted that scientific knowledge needed to be integrated with managerial and situational knowledge for success. More generally, the study illustrates that institutional change targeting implementation can also significantly affect the dynamics of knowledge creation (learning), access, distribution, and use. Recognizing how action-oriented institutions can affect these dynamics across their knowledge system can help institutional designers build more efficient and effective institutions for sustainable development.

Particle-based adjuvants for subunit vaccines

Proceedings of the National Academy of Sciences of the United States
of America

(Accessed 22 January 2012)

Commentary: Reorienting our view of particle-based adjuvants for subunit vaccines
Steven R. Little
PNAS 2012 ; published ahead of print January 17, 2012, doi:10.1073/pnas.1120993109

[No abstract]

Evidence-based medical guidelines: LMIC countries

Tropical Medicine & International Health
February 2012  Volume 17, Issue 2  Pages 143–261

Medical Guidelines
Transfer of evidence-based medical guidelines to low- and middle-income countries (pages 144–146)
Stephan Ehrhardt and Christian G. Meyer
Article first published online: 21 OCT 2011 | DOI: 10.1111/j.1365-3156.2011.02910.x

[No abstract; Free full text]

Infectious diseases among refugees and immigrants compared to native Danes

Tropical Medicine & International Health
February 2012  Volume 17, Issue 2  Pages 143–261

Migrant Health
Mortality from infectious diseases among refugees and immigrants compared to native Danes: a historical prospective cohort study (pages 223–230)
M. Norredam, M. Olsbjerg, J. H. Petersen, I. Bygbjerg and A. Krasnik
Article first published online: 27 OCT 2011 | DOI: 10.1111/j.1365-3156.2011.02901.x

Objectives Refugees and immigrants are likely to be vulnerable to mortality from infectious diseases as a result of high prevalences in their countries of origin and barriers in access to healthcare in the recipient countries. Consequently, we aimed to compare and investigate differences in mortality from infectious diseases among refugees and immigrants and native Danes.

Methods A register-based, historical prospective cohort design. All refugees (n = 29 139) and family-reunited immigrants (n = 27 134) who, between 1 January1993 and 31 December1999, were granted the right to reside in Denmark were included and matched 1:4 on age and sex with native Danes. Civil registration numbers were cross-linked to the Register of Causes of Death, and fatalities owing to infectious diseases (based on ICD-10 diagnosis) were identified. Mortality ratios were estimated separately for men and women by migrant status and region of birth; adjusting for age and income; using a Cox regression model, after a mean follow-up of 10–12 years after arrival.

Results Female [hazard ratio (HR) = 4.15; 95% CI: 2.38, 7.25] and male (HR = 2.05; 95% CI: 1.27, 3.33) refugees experienced significantly higher mortality risks from infectious diseases than did native Danes, as was the case for male immigrants (HR = 2.39; 95% CI: 1.20, 4.76) but less so for female immigrants (HR = 1.23; 95% CI: 0. 50-3.01). Mortality by region of origin was notably higher for individuals from North Africa and sub-Saharan Africa.

Conclusions Higher mortality among refugees and immigrants than among the native population should lead to reflections on medical reception systems in recipient countries and subsequent possibilities of access to specialised diagnostic and curative healthcare.

Modeling Effects of H1N1 Vaccine Distribution in the U.S.

Value in Health
January 2012, Vol. 15, No. 1

Modeling the Effects of H1N1 Influenza Vaccine Distribution in the U.S.

Richard C. Larson, Anna Teytelman

We analyzed the effects of the timing of vaccine distribution in 11 US states during the 2009 H1N1 influenza pandemic.

By using reported data on the fraction of patients presenting with flu-related symptoms, we developed a transformation that allowed estimation of the state-specific temporal flu wave curve, representing the number of new infections during each week. We also utilized data describing the weekly numbers of vaccine doses delivered and administered. By using a simple difference equations model of flu progression, we developed two influenza wave curves: first, an “observable” curve that included the beneficial effects of vaccinations, and second, an unobservable curve that depicted how the flu would have progressed with no vaccine administered. We fit the observable curve to match the estimated epidemic curve and early exponential growth associated with R0, the reproductive number. By comparing the number of infections in each scenario, we estimated the infections averted by the administration of vaccine.

Southern states experienced peak infection several weeks before northern states, and most of the vaccine was delivered well after the peak of the southern flu wave. Our models suggest that the vaccine had minimal ameliorative impact in the southern states and measurable positive impact in the northern states. Vaccine delivery after peak also results in a smaller fraction of the population’s seeking the vaccine.

Our analysis suggests that current Centers for Disease Control and Prevention policy of allocating flu vaccine over time in direct proportion to states’ populations may not be best in terms of averting nationally the maximum possible number of infections.

India records full year without new polio cases

   India recorded a full year without new polio cases. A WHO report noted that India “appears to have interrupted wild poliovirus transmission, completing one year without polio since its last case, in a 2-year-old girl in the state of West Bengal, on 13 January 2011.” WHO noted that India was once recognized as the world’s epicentre of polio. If all pending laboratory investigations return negative, in the coming weeks India will officially be deemed to have stopped indigenous transmission of wild poliovirus. The number of polio-endemic countries, those which have never stopped indigenous wild poliovirus transmission, will then be reduced to a historical low of three: Afghanistan, Nigeria and Pakistan.

The WHO announcement noted that “global health leaders paid tribute to the Government of India for its leadership and financial commitment to the polio eradication effort, and to the millions of vaccinators, community mobilizers, Rotarians, parents and caregivers who have supported polio eradication for more than a decade. The scale of the eradication effort in India is mind-boggling: each year, more than 170 million children under the age of 5 are vaccinated in two national immunization campaigns, with up to 70 million children in the highest-risk areas vaccinated multiple times in additional special campaigns; the whole effort requires nearly a billion doses of oral polio vaccine annually.”

WHO Director-General Margaret Chan said, “India’s success is arguably its greatest public health achievement and has provided a global opportunity to push for the end of polio. The Global Polio Eradication Initiative is in full emergency mode and focused on using this momentum to close this crippling disease down. Stopping polio in India required creativity, perseverance and professionalism – many of the innovations in polio eradication were sparked by the challenges in India. The lessons from India must now be adapted and implemented through emergency actions to finish polio everywhere.”

India is described as one of the largest donors to polio eradication, largely self-financing its immunization efforts. By 2013, India will have contributed US$2 billion for its polio campaigns.

Global Network for Neglected Tropical Diseases launches END7 Campaign

    The Global Network for Neglected Tropical Diseases, an initiative of the Sabin Vaccine Institute, launched the END7 Campaign, “dedicated to eliminating seven major neglected tropical diseases (NTDs) as a public health threat to poor communities by the end of 2020.” The campaign noted that NTDs infect one in six people worldwide, including 500 million children, carry a higher health burden than malaria and tuberculosis, and that treatment for NTDs is one of the most cost-effective health programs available today. Pills to treat the seven leading NTDs are donated by pharmaceutical companies and many programs use existing infrastructure, such as schools and community centers, to administer the treatments. The END7 campaign “raises the public awareness and funding required to cover the costs of distributing medicine and setting up treatment programs in impoverished communities.” The annual cost works out to approximately 50 cents to treat and protect one person for a whole year against all seven diseases. The announcement said that the UK and U.S. governments, as well as major pharmaceutical companies, have already made significant contributions. END7 works with global partners such as the World Health Organization and the Bill & Melinda Gates Foundation. The campaign will be managed through a Facebook hub “to promote campaign videos, photographs, success stories and other content —including a real-time donation ticker.”

SAGE publishes November 2011 meeting report

WHO’s Strategic Advisory Group of Experts (SAGE) on immunization published the report of its November 2011 meeting. The announcement noted that SAGE “recommended…that to eradicate polio there must be accountability and consequences at all levels for individuals, institutions and governments who fail to deliver on their mandates. SAGE stated unequivocally that the risk of failure to finish global polio eradication constitutes a programmatic emergency of global proportions for public health and is not acceptable under any circumstances. Moreover, the country reports produced by the Global Polio Eradication Initiative Independent Monitoring Board must identify the root causes why some infected countries are failing to interrupt transmission and hold appropriate individuals, agencies and authorities responsible. Failure, SAGE warned, would lead to a resurgence of the disease and would be seen as the most expensive public health failure in history.

“SAGE welcomed the Decade of Vaccines collaboration as a new initiative to create a global coalition to fully realize the potential of immunization in saving lives. SAGE reviewed the draft Decade of Vaccines global action plan and although the expert group supported the overall direction, it was agreed that the plan needed to be more exciting and innovative, extending the benefits of immunization beyond childhood. SAGE requested the planning teams to identify a few major “game-changers” which if implemented would have a significant impact.

“Other topics were also discussed during the meeting such as: the negotiations around the legally binding instrument on mercury and thiomersal containing vaccines; monitoring national immunization coverage and reinforcing surveillance; optimizing immunization schedules for conjugate pneumococcal vaccines; use of hepatitis A vaccines; and progress of tuberculosis vaccine candidate trials.”

Full report of the SAGE November 2011 meetingpdf, 869kb

Background documents and presentations

Agenda, list of participants and declarations of interests

DoVC opens online consultation on draft Global Vaccine Action Plan (GVAP)

 The Decade of Vaccines Collaboration (DoVC) initiated an online consultation capability seeking feedback on the draft Global Vaccine Action Plan (GVAP) via its website. The consultation, which complements ongoing meetings with a range of civil society organizations, governments and other stakeholders, runs 16 January – 1 February 2012. Participants are invited to register for the consultation at which leads to a password-protected area of the website where the GVAP draft is made available and an online survey is provided. The survey is focused to four questions about the GVAP draft:

- Do you feel the Global Vaccine Action Plan accurately reflects what is needed over the next decade? If not, can you provide suggestions to improve the document?

- What are the top five most transformational changes you could see in the next 10 years that would truly be “game changing?” Are they captured in the document?

- Do you feel that your stakeholder group is sufficiently and appropriately represented in the document? If not, can you provide suggestions to improve the document?

- Do you have any other comments or suggestions?

The GVAP draft will continue to evolve and will be submitted in March 2012 for World Health Assembly action when WHA meets in May, 2012.

PhRMA Report: 282 medicines in development for children and adolescents

The Pharmaceutical Research and Manufacturers of America (PhRMA), in a new report, said that America’s biopharmaceutical companies are researching 282 medicines currently in clinical trials or under review by the FDA “to help meet the unique health care needs of children and adolescents.” The reviews these medicines noting:

- 54 for cancer which, despite significant progress, is still the leading cause of death by disease among American children,

- 49 for infectious diseases, resulting in more than 164 million missed school days annually in American public schools due to the spread of infectious diseases,

- 48 for genetic disorders, including medicines for cystic fibrosis, which affects 30,000 American children and adults,

- 25 for neurologic disorders, including medicines for epilepsy, which affects more than 300,000 school children under age 14 in the United States.

The report is available here:

Twitter Watch to 15 January 2012

Twitter Watch 
Items of interest from a variety of twitter feeds associated with immunization, vaccines and global public health. This capture is highly selective and is by no means intended to be exhaustive.

GAVIAlliance GAVI Alliance
Learn more about #GAVI ‘s pneumococcal AMC! Step by step guide to the method behind the AMC mechanism- #globalhealth
2 hours ago

UNDP UN Development
Be involved: @WorldBank asks for input on Global Partnership For Enhanced Social Accountability
3 hours ago

MSF_USA Doctors w/o Borders
Two years after the EQ, the health care system in Port-au-Prince and surrounding areas is still in disarray. #Haiti
5 hours ago

GAVIAlliance GAVI Alliance
Rigorous monitoring and the bivalent oral #polio vaccine are main factors in India’s 1 year Polio-free success - @Rotary
14 Jan

historyvaccines History of Vaccines
Dr. Hotez gives Hilleman Lecture at CHOP: Innovations in neglected tropical diseases #vaccine #NTD
12 Jan

globalfundnews The Global Fund
We’re reading: ‘French Government Defends Global AIDS Fund’
13 Jan

Congratulations to #India for 12 months without #polio – a remarkable milestone
12 Jan

GAVIAlliance GAVI Alliance
Good news in the fight against measles! China’s #measles incidence hits record low in 2011- #globalhealth
11 Jan

Healthy volunteers needed for NIAID #clinicaltrials testing #vaccines to prevent #malaria, #HIV and more
11 Jan

sabinvaccine Sabin Vaccine Inst.
Water and sanitation is a human right- Dr Roses @pahowho #StopCholera
11 Jan

Evaluation: Functioning of the International Health Regulations (IHR)

Globalization and Health
[Accessed 15 January 2012]

Descriptive Review and Evaluation of the Functioning of the International Health Regulations (IHR) Annex 2
Anema A, Druyts E, Hollmeyer HG, Hardiman MC and Wilson K Globalization and Health 2012, 8:1 (10 January 2012)
Open Access

Abstract (provisional)
The International Health Regulations (IHRs) (2005) was developed with the aim of governing international responses to public health risks and emergencies. The document requires all 194 World Health Organization (WHO) Member States to detect, assess, notify and report any potential public health emergency of international concern (PHEIC) under specific timelines. Annex 2 of the IHR outlines decision-making criteria for State-appointed National Focal Points (NFP) to report potential PHEICs to the WHO, and is a critical component to the effective functioning of the IHRs.

The aim of the study was to review and evaluate the functioning of Annex 2 across WHO-reporting States Parties. Specific objectives were to ascertain NFP awareness and knowledge of Annex 2, practical use of the tool, activities taken to implement it, its perceived usefulness and user-friendliness. Qualitative telephone interviews, followed by a quantitative online survey, were administered to NFPs between October, 2009 and February, 2010.

A total of 29 and 133 NFPs participated in the qualitative and quantitative studies, respectively. Qualitative interviews found most NFPs had a strong working knowledge of Annex 2; perceived the tool to be relevant and useful for guiding decisions; and had institutionalized management, legislation and communication systems to support it. NFPs also perceived Annex 2 as human and disease-centric, and emphasized its reduced applicability to potential PHEICs involving bioterrorist attacks, infectious diseases among animals, radio-nuclear and chemical spills, and water- or food-borne contamination. Among quantitative survey respondents, 88% reported having excellent/good knowledge of Annex 2; 77% reported always/usually using Annex 2 for assessing potential PHEICs; 76% indicated their country had some legal, regulatory or administrative provisions for using Annex 2; 95% indicated Annex 2 was always/usually useful for facilitating decisions regarding notifiability of potential PHEICs.

This evaluation, including a large sample of WHO-reporting States Parties, found that the IHR’s Annex 2 is perceived as useful for guiding decisions about notifiability of potential PHEICs. There is scope for the WHO to expand training and guidance on application of the IHR’s Annex 2 to specific contexts. Continued monitoring and evaluation of the functioning of the IHR is imperative to promoting global health security.

Confronting The Urgent Challenge Of Diabetes

Health Affairs
January 2012; Volume 31, Issue 1

Issue Theme: Confronting The Growing Diabetes Crisis [23 articles covering a range of issue relevant to this theme]
Overview Of The Crisis
Confronting The Urgent Challenge Of Diabetes: An Overview
Judith E. Fradkin
Health Aff January 2012 31:12-19; doi:10.1377/hlthaff.2011.1150

The rising tide of diabetes has an unacceptable human and societal toll. Rates of all major forms of diabetes are increasing at enormous individual and societal cost: 8.3 percent of the US population is afflicted today, and financial costs reached $174 billion for 2007. A major cause of blindness, renal failure, amputation, and cardiovascular disease, diabetes also increases the risk of cancer and dementia and more than doubles individual health care costs. Control of glucose, blood pressure, and lipids improves outcomes. Yet diabetes management is nonetheless suboptimal, particularly in disproportionately affected poor and minority populations. Safer, less burdensome, and more personalized approaches to therapy are needed. People at high risk for type 2 diabetes must be identified if society is to realize the benefits of therapies proven to delay or prevent the disease. We have many of the tools we need to address this challenge, and we must apply them now.

Use Of 13 Disease Registries In 5 Countries and Health Care Value

Health Affairs
January 2012; Volume 31, Issue 1

Web first
Use Of 13 Disease Registries In 5 Countries Demonstrates The Potential To Use Outcome Data To Improve Health Care’s Value
Stefan Larsson, Peter Lawyer, Göran Garellick, Bertil Lindahl, and Mats Lundström
Health Aff January 2012 31:220-227; published ahead of print December 7, 2011, doi:10.1377/hlthaff.2011.0762

As health care systems worldwide struggle with rising costs, a consensus is emerging to refocus reform efforts on value, as determined by the evaluation of patient outcomes relative to costs. One method of using outcome data to improve health care value is the disease registry. An international study of thirteen registries in five countries (Australia, Denmark, Sweden, the United Kingdom, and the United States) suggests that by making outcome data transparent to both practitioners and the public, well-managed registries enable medical professionals to engage in continuous learning and to identify and share best clinical practices. The apparent result: improved health outcomes, often at lower cost. For example, we calculate that if the United States had a registry for hip replacement surgery comparable to one in Sweden that enabled reductions in the rates at which these surgeries are performed a second time to replace or repair hip prostheses, the United States would avoid $2 billion of an expected $24 billion in total costs for these surgeries in 2015.

Global Financial Crisis and Health Funding In Developing Countries

Health Affairs
January 2012; Volume 31, Issue 1

Web first
The Global Financial Crisis Has Led To A Slowdown In Growth Of Funding To Improve Health In Many Developing Countries
Katherine Leach-Kemon, David P. Chou, Matthew T. Schneider, Annette Tardif, Joseph L. Dieleman, Benjamin P.C. Brooks, Michael Hanlon, and Christopher J.L. Murray
Health Aff January 2012 31:228-235; published ahead of print December 14, 2011, doi:10.1377/hlthaff.2011.1154

How has funding to developing countries for health improvement changed in the wake of the global financial crisis? The question is vital for policy making, planning, and advocacy purposes in donor and recipient countries alike. We measured the total amount of financial and in-kind assistance that flowed from both public and private channels to improve health in developing countries during the period 1990–2011. The data for the years 1990–2009 reflect disbursements, while the numbers for 2010 and 2011 are preliminary estimates. Development assistance for health continued to grow in 2011, but the rate of growth was low. We estimate that assistance for health grew by 4 percent each year from 2009 to 2011, reaching a total of $27.73 billion. This growth was largely driven by the World Bank’s International Bank for Reconstruction and Development and appeared to be a deliberate strategy in response to the global economic crisis. Assistance for health from bilateral agencies grew by only 4 percent, or $444.08 million, largely because the United States slowed its development assistance for health. Health funding through UN agencies stagnated, and the Global Fund to Fight AIDS, Tuberculosis, and Malaria announced that it would make no new grants for the next two years because of declines in funding. Given the international community’s focus on meeting the Millennium Development Goals by 2015 and persistent economic hardship in donor countries, continued measurement of development assistance for health is essential for policy making.

Influenza-Associated Pneumococcal Pneumonia (H1N1)

Journal of Infectious Diseases
Volume 205 Issue 3 February 1, 2012

Editorial Commentaries
Carlos G. Grijalva and Marie R. Griffin
Unveiling the Burden of Influenza-Associated Pneumococcal Pneumonia
J Infect Dis. (2012) 205(3): 355-357 doi:10.1093/infdis/jir753

In the United States alone, seasonal (interpandemic) influenza is responsible for an average of 226 000 hospitalizations and >23 000 deaths per year [1, 2]. Although all age groups are susceptible to influenza virus infections, children experience the highest disease incidence, whereas older adults suffer the most serious disease-related complications and mortality. Many of these events are secondary bacterial pneumonias, most of which are thought to be caused by Streptococcus pneumoniae (the pneumococcus). Although several observations have suggested that influenza plays an important role in the pneumococcal pneumonia incidence, its contribution has been difficult to appreciate. In this issue of the Journal, Weinberger and colleagues present an elegant assessment that helps to clarify the contribution of influenza virus infections to pneumococcal pneumonia hospitalizations during the 2009 influenza pandemic [3].

Several lines of evidence indirectly support an interaction between influenza virus and the pneumococcus: First, pneumococcal nasopharyngeal acquisition patterns mirror the seasonal patterns of influenza outbreaks [4]. Second, increases in pneumococcal pneumonias during previous influenza pandemics have been documented [5, 6]. Third, concurrent influenza infections and pneumococcal pneumonias have been described [7, 8], and prevention of these pneumonias has been demonstrated in an efficacy trial of a 9-valent pneumococcal conjugate vaccine in South African children. In that randomized study, vaccination with pneumococcal conjugate vaccine reduced the incidence of influenza-associated pneumonia (ie, pneumococcal pneumonia with concurrent influenza infection) by 45% compared with controls [9]. This decline, however, was seen only in human immunodeficiency virus–infected children, and significant reductions were also observed for concurrent infections with parainfluenza viruses and human metapneumovirus [9 …

Daniel M. Weinberger, Lone Simonsen, Richard Jordan, Claudia Steiner, Mark Miller, and Cécile Viboud
Impact of the 2009 Influenza Pandemic on Pneumococcal Pneumonia Hospitalizations in the United States
J Infect Dis. (2012) 205(3): 458-465 doi:10.1093/infdis/jir749

Background. Infection with influenza virus increases the risk for developing pneumococcal disease. The A/H1N1 influenza pandemic in autumn 2009 provided a unique opportunity to evaluate this relationship.

Methods. Using weekly age-, state-, and cause-specific hospitalizations from the US State Inpatient Databases of the Healthcare Cost and Utilization Project 2003–2009, we quantified the increase in pneumococcal pneumonia hospitalization rates above a seasonal baseline during the pandemic period.

Results. We found a significant increase in pneumococcal hospitalizations from late August to mid-December 2009, which corresponded to the timing of highest pandemic influenza activity. Individuals aged 5–19 years, who have a low baseline level of pneumococcal disease, experienced the largest relative increase in pneumococcal hospitalizations (ratio, 1.6 [95% confidence interval {CI}, 1.4–1.7]), whereas the largest absolute increase was observed among individuals aged 40–64 years. In contrast, there was no excess disease in the elderly. Geographical variation in the timing of excess pneumococcal hospitalizations matched geographical patterns for the fall pandemic influenza wave.

Conclusions. The 2009 influenza pandemic had a significant impact on the rate of pneumococcal pneumonia hospitalizations, with the magnitude  of this effect varying between age groups and states, mirroring observed variations in influenza activity.

Editorial: WHO and Margaret Chan – the next 5 years

The Lancet  
Jan 14, 2012  Volume 379  Number 9811 p93 – 192  e5 – 11

WHO and Margaret Chan: the next 5 years
The Lancet

WHO is in the process of appointing a Director-General whose tenure will run from June, 2012, to June, 2017. Margaret Chan, the current incumbent, is the only candidate standing. WHO’s Executive Board will consider her appointment when they meet later this month, and the World Health Assembly will ratify the Board’s decision in May. It is certain that Dr Chan will win a second term.

Her renewed appointment comes at a perilous moment for WHO. As a letter we publish online this week from Oxfam reveals, WHO is in crisis. Rescue is needed. But is this predicament a fair reflection of the Director-General’s performance? No, it is not.  When Dr Chan was elected she made a promise—namely, that she wanted her term to be judged by progress on health for Africa and for women. WHO’s leadership of Every Woman, Every Child, the UN Secretary-General’s Global Strategy on Women’s and Children’s Health, has been her great success these past 5 years. Add to that the remarkable achievement in September, 2011, of a political declaration on non-communicable diseases, together with her refashioning of a failing health systems agenda around universal coverage, and you have a record that is a surprising success for an agency in the vortex of a financial emergency.

One cannot judge Dr Chan’s legacy without recalling that her first priority 5 years ago was to deliver the initiatives begun by her predecessor, Dr Lee Jong-wook, who tragically died during his first term as Director-General. The most important project left unfinished was the Commission on Social Determinants of Health. Initially sceptical, Dr Chan not only saw this important report through to completion, but also became a significant champion of the social determinants agenda. Also recall that Dr Chan deftly led communications with the media and public during the 2009 influenza A H1N1 pandemic.

None of this is to say that there have not been disappointments. Her leadership team has not been a success. Only recently have the right people been selected for crucial portfolios. Several regional offices of WHO remain lacklustre backwaters. And sometimes one wishes for a sharper message, a stronger articulation of what WHO is for in the 21st century. These matters can be addressed during a second term. But that term will depend on proper financing of WHO by its donors. And here Dr Chan faces her greatest test of all.

Online First
Jan 13, 2012
Action to preserve WHO’s core functions cannot wait for organisational reform
Mohga M Kamal-Yanni

While WHO undergoes a wide-ranging reform sparked by a US$300 million budget shortfall, the agency is facing an exodus of qualified staff that is affecting its ability to work.1 The Executive Board is due to meet on Jan 16 to agree long-term principles and priorities for the organisation; it must ensure, in particular, that core functions are accorded the priority they merit. Oxfam is especially concerned that inadequate funding will severely diminish the WHO Essential Medicines Department, which for more than three decades has had an indispensable role in enabling developing countries to access affordable medicines.

Global movement for health equity: from Santiago to Rio and beyond

The Lancet  
Jan 14, 2012  Volume 379  Number 9811 p93 – 192  e5 – 11

Health Policy
Building of the global movement for health equity: from Santiago to Rio and beyond
Michael Marmot, Jessica Allen, Ruth Bell, Peter Goldblatt

Health inequalities are present throughout the world, both within and between countries. The Commission on Social Determinants of Health drew attention to dramatic social gradients in health within most countries and made proposals for action. These inequalities are not inevitable. The purpose of this article is to report on activity that has taken place worldwide after the report by the Commission on Social Determinants of Health. First, we summarise the global situation. Second, we summarise an interim report of the emerging findings from an independent review of social determinants and the health divide, which was commissioned by the WHO European region. The world conference on social determinants of health will be held in Rio de Janeiro, Brazil, in October, 2011. This summit provides an opportunity to galvanise support, prioritise action, and respond to the call by the Commission on Social Determinants of Health for social justice as a route to a fair distribution of health.

Opinion: Controlling H5N1 mutation data

Volume 481 Number 7380 pp113-230  12 January 2012

World View
Don’t censor life-saving science
Controlling who is allowed access to information about mutations in the H5N1 bird flu virus is unacceptable, says Peter Palese.
11 January 2012

The recent arguments over the creation of a transmissible form of the bird flu virus (H5N1) feel very familiar. My colleagues and I were at the centre of a similar controversy in 2005, when we reconstructed the 1918 flu virus, which had killed up to 50 million people worldwide. News stories around the globe debated the merits of our research and television pundits argued opposing viewpoints. Naturally, the US government was concerned — as it is now. Yet our research was published in full. So why are similar concerns being used now to demand unacceptable censorship of the H5N1 scientific papers?

I have spent my career studying potentially dangerous pathogens — 20 years ago, my lab developed the technique that has enabled the H5N1 researchers to insert the mutations that render the virus more easily transmissible. In the 1990s, researchers discovered degraded samples of the 1918 virus in lung tissue from US soldiers who had died from the ‘Spanish flu’. Using polymerase chain reaction technology, they amplified and sequenced the virus’s RNA. We then took an existing influenza virus and, one by one, swapped its genes with those from the 1918 virus, eventually recreating a live version.

As we prepared our results for publication, the US government convened the National Science Advisory Board for Biosecurity (NSABB), which advises the community about research using agents that pose threats to national security or public health. Our experiments had made some people nervous.

During our discussions with members of the NSABB, we explained the importance of bringing such a deadly pathogen back to life. Although these experiments may seem dangerously foolhardy, they are actually the exact opposite. They gave us the opportunity to make the world safer, allowing us to learn what makes the virus dangerous and how it can be disabled. Thankfully, the discussions were largely constructive — within a week, the NSABB recommended that we continue to study the virus under biocontainment conditions, and publish the results so that other scientists could participate in the research. After we published our full paper in 2005 (T. M. Tumpey et al. Science 310, 77–80; 2005), researchers poured into the field who probably would not otherwise have done, leading to hundreds of papers about the 1918 virus. As a result, we now know that the virus is sensitive to the seasonal flu vaccine, as well as to the common flu drugs amantadine (Symmetrel) and oseltamivir (Tamiflu). Had we not reconstructed the virus and shared our results with the community, we would still be in fear that a nefarious scientist would recreate the Spanish flu and release it on an unprotected world. We now know such a worst-case scenario is no longer possible.

This experience has made the NSABB’s latest recommendation — that the H5N1 researchers not reveal the mutations behind the virus’s transmissibility — all the more frustrating. I make the same argument today that we made in 2005 — publishing those experiments without the details is akin to censorship, and counter to science, progress and public health. Why did the (different) members of the committee come to a different conclusion in this case? I can only hope that they take a more sensible stance and change their minds, or that the scientific community at large convinces them to do so. Certainly, the authors of the papers, as well as the journals considering them for publication (including this one), should resist the committee’s unworkable compromise that the full information should be released only to approved experts, and insist on full disclosure.

Giving the full details to vetted scientists is neither practical nor sufficient. Once 20–30 laboratories with postdoctoral fellows and students have such information available, it will be impossible to keep the details secret. Even more troublesome, however, is the question of who should decide which scientists are allowed to have the information. We need more people to study this potentially dangerous pathogen, but who will want to enter a field in which you can’t publish your most scientifically interesting results?

“Who will want to enter a field in which you can’t publish your most scientifically interesting results?”

Knowing which mutations render the virus more dangerous could help on a public-health level — if an outbreak of bird flu occurs in Taiwan, for instance, and researchers sequence the virus and see those mutations, we would know to ramp up the production of appropriate vaccines and antiviral drugs.

Incidentally, I believe that the risk of future outbreaks in humans is low: H5N1 has had the opportunity to cause widespread pandemics for many, many decades, yet it has not done so. Although we know the virus is transmissible between ferrets, little is known about how it will behave in other animals, including humans.

The more danger a pathogen poses, the more important it is to study it (under appropriate containment conditions), and to share the results with the scientific community. Slowing down the scientific enterprise will not ‘protect’ the public — it only makes us more vulnerable.

Vaccination Timing and the A(H1N1) Pandemic in Norway

PLoS One
[Accessed 15 January 2012];jsessionid=577FD8B9E1F322DAA533C413369CD6F3.ambra01?field=date

Effect of Vaccines and Antivirals during the Major 2009 A(H1N1) Pandemic Wave in Norway – And the Influence of Vaccination Timing
Birgitte Freiesleben de Blasio, Bjørn G. Iversen, Gianpaolo Scalia Tomba
PLoS ONE: Research Article, published 10 Jan 2012 10.1371/journal.pone.0030018

To evaluate the impact of mass vaccination with adjuvanted vaccines (eventually 40% population coverage) and antivirals during the 2009 influenza pandemic in Norway, we fitted an age-structured SEIR model using data on vaccinations and sales of antivirals in 2009/10 in Norway to Norwegian ILI surveillance data from 5 October 2009 to 4 January 2010. We estimate a clinical attack rate of approximately 30% (28.7–29.8%), with highest disease rates among children 0–14 years (43–44%). Vaccination started in week 43 and came too late to have a strong influence on the pandemic in Norway. Our results indicate that the countermeasures prevented approximately 11–12% of potential cases relative to an unmitigated pandemic. Vaccination was found responsible for roughly 3 in 4 of the avoided infections. An estimated 50% reduction in the clinical attack rate would have resulted from vaccination alone, had the campaign started 6 weeks earlier. Had vaccination been prioritized for children first, the intervention should have commenced approximately 5 weeks earlier in order to achieve the same 50% reduction. In comparison, we estimate that a non-adjuvanted vaccination program should have started 8 weeks earlier to lower the clinical attack rate by 50%.

In conclusion, vaccination timing was a critical factor in relation to the spread of the 2009 A(H1N1) influenza. Our results also corroborate the central role of children for the transmission of A(H1N1) pandemic influenza.

Compulsory Licensing of Pharmaceuticals Since the Doha Declaration

PLoS Medicine
(Accessed 15 January 2012)

Trends in Compulsory Licensing of Pharmaceuticals Since the Doha Declaration: A Database Analysis
Reed Beall, Randall Kuhn
Research Article, published 10 Jan 2012

It is now a decade since the World Trade Organization (WTO) adopted the “Declaration on the TRIPS Agreement and Public Health” at its 4th Ministerial Conference in Doha. Many anticipated that these actions would lead nations to claim compulsory licenses (CLs) for pharmaceutical products with greater regularity. A CL is the use of a patented innovation that has been licensed by a state without the permission of the patent title holder. Skeptics doubted that many CLs would occur, given political pressure against CL activity and continued health system weakness in poor countries. The subsequent decade has seen little systematic assessment of the Doha Declaration’s impact.

Methods and Findings
We assembled a database of all episodes in which a CL was publically entertained or announced by a WTO member state since 1995. Broad searches of CL activity were conducted using media, academic, and legal databases, yielding 34 potential CL episodes in 26 countries. Country- and product-specific searches were used to verify government participation, resulting in a final database of 24 verified CLs in 17 nations. We coded CL episodes in terms of outcome, national income, and disease group over three distinct periods of CL activity. Most CL episodes occurred between 2003 and 2005, involved drugs for HIV/AIDS, and occurred in upper-middle-income countries (UMICs). Aside from HIV/AIDS, few CL episodes involved communicable disease, and none occurred in least-developed or low-income countries.

Given skepticism about the Doha Declaration’s likely impact, we note the relatively high occurrence of CLs, yet CL activity has diminished markedly since 2006. While UMICs have high CL activity and strong incentives to use CLs compared to other countries, we note considerable countervailing pressures against CL use even in UMICs. We conclude that there is a low probability of continued CL activity. We highlight the need for further systematic evaluation of global health governance actions.

Editors’ Summary 
The development of a new drug is a time-consuming and expensive process. To stimulate investment in drug development, the creators of new drugs (including the pharmaceutical companies that undertake the development and testing that is needed before any drug can be used in patients) can apply for “intellectual property rights” (a patent). Intellectual property rights protect the investments made by companies during drug development by preventing other companies from making the new drug for a fixed period of time and by providing a means by which creators of new drugs can negotiate payment from other companies for the use of their creation. Until recently, the extent and enforcement of intellectual property rights varied widely around the world. Then, in 1995, the World Trade Organization (WTO) was established. By providing a set of ground rules for trade among nations, the WTO aims to ensure that trade flows as smoothly, predictably, and freely as possible around the world. One of the founding documents of the WTO is the Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS Agreement), which attempts to bring the protection of intellectual property rights (including patents) under common international rules.

Why Was This Study Done?
Unfortunately, patent protection for drugs (pharmaceuticals) means that many medicines are too expensive for use in developing countries. While maintaining incentives for drug development, the TRIPS Agreement allows governments to license the use of patented inventions to someone else without the consent of the patent owner. Such “compulsory licensing” normally occurs only after negotiations for a voluntary license have failed, and the patent owner still receives an appropriate payment. It soon became clear that some governments were unsure of their right to use compulsory licensing and other flexibilities in the TRIPS Agreement, a situation likely to affect public health in poor countries by hindering universal access to medicines. Consequently, the WTO issued the “Declaration on the TRIPS Agreement and Public Health” at its 4th Ministerial Conference in Doha in November 2001. Reaction to the Doha Declaration, which reaffirms that the “TRIPS Agreement does not and should not prevent members from taking measures to protect public health,” has been mixed. Some experts predicted that it would increase compulsory licensing of pharmaceuticals, but others suggested that political pressure against compulsory licensing and health system weaknesses in poor countries would limit claims for compulsory licenses. In this database analysis, the researchers systematically assess the impact of the Doha Declaration on the compulsory licensing of pharmaceuticals.

What Did the Researchers Do and Find?
By systematically searching media archives for reports of WTO member states considering or announcing compulsory licensing of pharmaceuticals, the researchers identified 24 verified compulsory licensing episodes in 17 nations that occurred between January 1995 and June 2011. Half of these episodes ended with an announcement of a compulsory license, and the majority ended in a price reduction for a specific pharmaceutical product for the potential issuing nation through a compulsory license, a voluntary license, or a negotiated discount. Sixteen of the compulsory licensing episodes involved drugs for HIV/AIDS, four involved drugs for other communicable diseases, and four involved drugs for non-communicable diseases such as cancer. More than half the compulsory licensing episodes occurred in upper-middle-income countries (including Brazil and Thailand). Finally, most compulsory licensing episodes occurred between 2003 and 2005. There was a smaller peak of activity in the months leading up to the Doha conference, but after 2006 activity declined substantially.

What Do These Findings Mean?
Given these findings, the researchers suggest that the Doha Declaration is unlikely to have an important long-term impact on the use of compulsory licensing or on access to pharmaceuticals for communicable diseases other than HIV/AIDS in developing and low-income countries. Most notably, the researchers found no evidence of a spike in compulsory licensing episodes immediately after the Doha Declaration, and they note that the lagged spike that occurred between 2003 and 2005 could have resulted in large part from the global antiretroviral advocacy campaign. Moreover, compulsory licensing activity has diminished greatly since 2006. Thus, the researchers conclude, health advocates who pushed for the Doha Declaration reforms have had little success in engaging trade as a positive, proactive force for addressing health gaps.

Dr. Christian Loucq inaugurated Director General at International Vaccine Institute (IVI)

    Dr. Christian Loucq was inaugurated as the new head of the International Vaccine Institute (IVI) based in Seoul, South Korea. Dr. Loucq will serve an initial four-year term to build upon the Institute’s successes achieved under the leadership of his predecessor Dr. John Clemens, IVI said.  Dr. Loucq commented, “I am humbled, honored, and very enthusiastic to be joining the IVI team as Director-General. Since its establishment in 1997, IVI has been a pioneering organization in many aspects of vaccinology – from R&D to epidemiology and from local manufacturing to access – aimed at preventing infectious diseases among the world’s poorest children. As the new Director-General, I will strive to increase IVI’s impact in the fight against infectious diseases in developing countries, based on its scientific contributions to the research, development and optimal use of new and improved vaccines.”

Nigeria Immunization Challenge update

The Gates Foundation said that Nigeria’s 36 Executive Governors and the Federal Capital Territory have signed up to the Nigeria Immunization Challenge launched by the foundation last year. Gates Foundation CEO Jeff Raikes said, “Renewed political resolve and accountability are critical to stopping polio in Nigeria and we find it encouraging to witness both through the support expressed by every Executive Governor across the country for this initiative. By collectively signing up to this challenge, they are sending a very clear message about their commitment to lead the fight to eliminate polio in Nigeria.” The Nigeria Immunization Challenge “sets specific objectives that need to be met during each quarter of 2012. If met, Nigeria will significantly improve its chances of stopping polio and protecting more children against vaccine-preventable diseases such as measles and whooping cough…The Nigerian states that meet all the necessary threshold criteria by the end of 2012 will be awarded a $500,000 grant from the Bill & Melinda Gates Foundation to support their top health priorities.” The foundation announcement noted that as of December 30, 2011, 51 cases of wild poliovirus had been reported in eight Nigerian states, compared with 21 cases in 2010.

CHOP launches new HPV-related website

   The Children’s Hospital of Philadelphia Vaccine Education Center launched a new HPV-related The site “features a video by Dr. Paul Offit as well videos of families discussing their decision to get the HPV vaccine. There are also links to additional information, questions and answers, and opportunities to share via social media.”

AMA Virtual Mentor (January, 2012): Vaccines and Ethics

   The AMA said it published a new issue of Virtual Mentor (January, 2012) focused on Vaccines and Ethics at ( which includes:

- A clinical case concerning HPV vaccine

- A consideration of how American society has handled its vaccine controversies, co-authored by Art Caplan

- Ethical implications of current research into a possible stress vaccine

- A contribution from researchers at the Jenner Institute, Oxford, about vaccine research ethics

- A look at residents’ role in adult immunizations on the “front lines” by Jay Jacobson, MD

MMWR Weekly for January 6, 2012

The MMWR Weekly for January 6, 2012 / Vol. 60 / Nos. 51 & 52 includes:
Severe Influenza Among Children and Young Adults with Neurologic and Neurodevelopmental Conditions — Ohio, 2011

- Imported Human Rabies — New Jersey, 2011

- Receipt of A(H1N1)pdm09 Vaccine by Prisons and Jails — United States, 2009–10 Influenza Season

- Update: Influenza A (H3N2)v Transmission and Guidelines — Five States, 2011

Twitter Watch to 8 January 2012

Twitter Watch 
Items of interest from a variety of twitter feeds associated with immunization, vaccines and global public health. This capture is highly selective and is by no means intended to be exhaustive.

GAVIAlliance GAVI Alliance
MenAfriVac #vaccine could prevent 150,000 deaths by 2015 in Africa’s “meningitis belt”-
11 hours ago

gatesfoundation Gates Foundation
Op-Ed: It’s part of our social responsibility to get our children vaccinated: #vaccines
6 Jan

bmj_latest BMJ
BBC News – Hepatitis C vaccine: Oxford researchers’ trial ‘promising’
5 Jan

#HHS releases 1st Global Health Strategy. Sec Sebelius talks about building a healthier, safer planet:
6 Jan

CDCgov CDCgov
Read about Dr. Claire Huang & her team at #CDC247, who have developed a dengue vaccine candidate, now in human trials.
6 Jan

ArthurCaplan Arthur Caplan
outcome of bachmann hpv challenge gifts put to good use
4 Jan

DofVC DoV Collaboration
Keen to know the status of the Global #Vaccine Action Plan? Check out our new post on GVAP progress:
3 Jan

The Anthrax Attacks 10 Years Later

Annals of Internal Medicine
January 3, 2012; 156 (1 Part 1)

Ideas and Opinions
The Anthrax Attacks 10 Years Later
Larry M. Bush and Maria T. Perez
Ann Intern Med January 3, 2012 156:41-44; published ahead of print October 3, 2011,

Ten years ago, just weeks after the September 11 attacks, the United States experienced a deliberate act of bioterrorism. Through use of the postal service, anthrax spores were widely disseminated, including to homes, the Senate, and major newsrooms, resulting in morbidity and mortality and effectively disrupting our way of life and revealing our vulnerability. Even though such attacks had been the subject of much writing and had been planned for, detection of and the appropriate response to an attack with an agent from the so-called “Category ‘A’ List” had only been considered in theoretical terms. What transpired during the following difficult weeks, including how public health and federal government agencies performed, has been both praised and criticized. An intertwined epidemiologic and criminal investigation of such magnitude was unprecedented in U.S. history. To address the question of whether we as a nation are now better prepared for future threats involving biologic agents, it is important to learn from the lessons of the 2001 anthrax attacks, including the critical role of clinicians in surveillance. As physicians involved in diagnosing anthrax in the index case and alerting authorities, we offer our perspective on these events a decade after their occurrence

Managing scarce health resources in developing countries

British Medical Journal
07 January 2012 (Vol 344, Issue 7838)

Twenty criteria to make the best of scarce health resources in developing countries
BMJ 2011; 343 doi: 10.1136/bmj.d7023 (Published 25 November 2011)
James D Shelton, science adviser

The needs of developing countries are so great and potential interventions so numerous that priorities are essential. James D Shelton suggests a simple checklist for deciding on priorities and improving implementation

It is difficult to exaggerate the health needs of developing countries. Consider the formidable core list of priorities in President Obama’s Global Health Initiative: maternal health, diarrhoea, pneumonia, routine immunisable diseases, family planning, nutrition, sanitation, malaria, HIV, tuberculosis, and priority neglected tropical diseases—and each has multiple interventions. Yet, numerous other worthy health conditions clamour for attention. These include infectious diseases such as influenza, meningitis, cholera, and emerging zoonoses but also injuries, mental illness, surgery, palliative care, and chronic diseases. The immense needs dwarf the available resources and fragile overloaded systems. Even basic infrastructure is often lacking—for example, national service provision assessments from Uganda and Tanzania indicate that only 24% and 35%, respectively, of health facilities have regular electricity and only 31% and 34%, respectively, have regular water supply.1 2 Health worker shortages and related system dysfunctions have been described as a “slow-burning crisis.”3 Health workers can perform only a limited number of tasks, and organisational system structures are fragile as well. Accordingly, many effective public health approaches such as water and sanitation, food fortification, or alcohol taxation bypass clinical services entirely.

So what is the best use of resources? Much of the advocacy for health interventions stresses the importance of a particular health problem and the clinical efficacy of proposed interventions. However, true success on a large scale in resource constrained environments requires much more. To help a more systematic approach, I suggest some key criteria that should help both to inform priorities and to improve interventions

European Health Systems: Comparative Research

Health Economics, Policy and Law 
Volume 7 – Special Issue 01 – January 2012

Special Focus Issue
Back to the future: 10 years of European health reforms
Anna Dixon and Emmi Poteliakhoff
Health Economics, Policy and Law / Volume 7 / Special Issue 01, pp 1 – 10
Copyright © Cambridge University Press 2012
Published online: 05 January 2012

The challenges facing European health systems have changed little over 30 years but the responses to them have. Policy ideas that emerged in some countries spread to others; however, the way policies were implemented and the impact they have had has been shaped by specific national contexts. Comparative policy analysis has evolved in response to this, moving away from simple classifications of health systems and crude rankings to studies that try and understand more deeply what works, where and why. For policymakers interested in how other countries have dealt with common challenges, it is important that they avoid the naïve transplantation of policy solutions but understand the need to translate policies to fit the institutional context of a particular country. Policies that cross borders will necessarily be shaped by the social and political institutions of a country. These dimensions should not be ignored in comparative research. The next decade will require health systems to deliver improved care for people with complex needs while at the same time delivering greater value. Policymakers will benefit from looking backwards as well as to their neighbours in order to develop appropriate policy solutions.

The role of comparative health studies for policy learning
Richard B. Saltman

The folly of cross-country ranking exercises
Adam Oliver

The unwritten rules of cross-national policy analysis
Theodore Marmor

Shall we dance? The intricate project of comparison in the study of health policy
Carolyn H. Tuohy

Reflections on the evolution of health technology assessment in Europe
Corinna Sorenson and Kalipso Chalkidou

Choice policies in Northern European health systems
Karsten Vrangbaek, Ruth Robertson, Ulrika Winblad, Hester Van de Bovenkamp and Anna Dixon

Paying for hospital care: the experience with implementing activity-based funding in five European countries
Jacqueline O’Reilly, Reinhard Busse, Unto Häkkinen, Zeynep Or, Andrew Street and Miriam Wiley

The rise of the regulatory state in health care: a comparative analysis of the Netherlands, England and Italy
Jan-Kees Helderman, Gwyn Bevan and George France

Overcoming fragmentation in health care: chronic care in Austria, Germany and the Netherlands
Ellen Nolte, Cécile Knai, Maria Hofmarcher, Annalijn Conklin, Antje Erler, Arianne Elissen, Maria Flamm, Brigit Fullerton, Andreas Sönnichsen and Hubertus J. M. Vrijhoef

Human Vaccines Special Issue: Influenza Vaccines

Human Vaccines & Immunotherapeutics (formerly Human Vaccines)
Volume 8, Issue 1  January 2012

Editor’s Corner
Special Focus: Influenza Vaccines
Susanna Esposito

We have been living with influenza for many years, and have become so used to it becoming a part of our lives to which we usually do not pay much attention. After the excitement of the initial discovery of influenza viruses in 1933 and the development of the first vaccines in the 1940s, relatively little happened in the field during the rest of the 20th century except for the development of the first serological assays, the definition of some correlates of protection, and the expansion of worldwide production capacity.

However, the coming of the 21st century brought new epidemiological data and technological innovations in the production of vaccines. The epidemiological studies showed that influenza viruses are underestimated global killers; they cause annual epidemics and occasional pandemics that have claimed the lives of millions, and the emergence of new strains continues to challenge public health authorities and scientific communities. The real-time monitoring of the evolution of influenza viruses has improved our understanding of the factors leading to viral pathogenicity and/or transmissibility, and the development of new vaccines will be critical for controlling future outbreaks of the disease. The correlates of protection continue to rely on serum antibodies, but live attenuated vaccines also employ another mechanism of protection, and the use of adjuvants and intradermal vaccination has improved the effectiveness of inactivated vaccines. Furthermore, alternatives to eggs have become available, and reverse genetics has allowed us to navigate new horizons. All of these findings have had a significant impact on public health policies and the recommendations for influenza vaccination in different age groups.

The aim of this special issue is to provide a comprehensive update of the state-of-the-art concerning influenza and its prevention. It begins with an overview of influenza viruses that also covers influenza in birds and animals, moves on to deal with the epidemiological, clinical and diagnostic aspects of the disease in different age groups, and finally discusses the various issues associated with its prevention. There are chapters on newly available influenza vaccines, the new technologies used to prepare them, and why there is a need for a quadrivalent vaccine. The recommendations concerning vaccination in children, adults and the elderly are described in detail, and the differences between countries are explained and discussed. The reasons for the low vaccination coverage rate even in high-risk categories are critically reviewed, and there is a discussion of the economic value of vaccination and its impact on public health. Finally, consideration is given to the use of influenza vaccination in special situations such as pregnancy, and there is a summary of the lessons learned from the last pandemic.

I hope that these articles by representative highly experienced authors will make this issue useful to experts in pediatrics, infectious diseases, public health and internal medicine, and believe they can make a significant contribution to our fight against influenza.

Special Focus Review
Economic value of influenza vaccination
Volume 8, Issue 1   January 2012
Chiara de Waure, Maria Assunta Veneziano, Chiara Cadeddu, Silvio Capizzi, Maria Lucia Specchia, Stefano Capri and Walter Ricciardi

Influenza epidemics are responsible for high mortality and morbidity rates in particular among elderly and high risk groups. This review is aimed at assessing the economic value of vaccination in these groups. A search of full economic evaluations of influenza vaccination in comparison with no interventions was performed on PubMed from January 1990 to May 2011. Only economic evaluations dealing with elderly and high risk groups were considered. The quality of selected articles was assessed through Drummond’s checklist. Sixteen cost-effectiveness analyses and four cost-benefit analyses were included: overall, the quality of studies was fairly good. The vaccination was demonstrated to be cost-effective or cost-saving in almost all studies, independently by the perspective and the type of analysis. Influenza vaccination is a worthwhile intervention from the pharmacoeconomic view-point, anyway a standardization of methods should be desirable in order to guarantee the comparability and transferability of results.

Herpes Simplex Vaccine: Trial Efficacy Results

New England Journal of Medicine
January 5, 2012  Vol. 366 No. 1

Original Articles
Efficacy Results of a Trial of a Herpes Simplex Vaccine
R.B. Belshe and Others

Two previous studies of a herpes simplex virus type 2 (HSV-2) subunit vaccine containing glycoprotein D in HSV-discordant couples revealed 73% and 74% efficacy against genital disease in women who were negative for both HSV type 1 (HSV-1) and HSV-2 antibodies. Efficacy was not observed in men or HSV-1 seropositive women.

We conducted a randomized, double-blind efficacy field trial involving 8323 women 18 to 30 years of age who were negative for antibodies to HSV-1 and HSV-2. At months 0, 1, and 6, some subjects received the investigational vaccine, consisting of 20 μg of glycoprotein D from HSV-2 with alum and 3-O-deacylated monophosphoryl lipid A as an adjuvant; control subjects received the hepatitis A vaccine, at a dose of 720 enzyme-linked immunosorbent assay (ELISA) units. The primary end point was occurrence of genital herpes disease due to either HSV-1 or HSV-2 from month 2 (1 month after dose 2) through month 20.

The HSV vaccine was associated with an increased risk of local reactions as compared with the control vaccine, and it elicited ELISA and neutralizing antibodies to HSV-2. Overall, the vaccine was not efficacious; vaccine efficacy was 20% (95% confidence interval [CI], −29 to 50) against genital herpes disease. However, efficacy against HSV-1 genital disease was 58% (95% CI, 12 to 80). Vaccine efficacy against HSV-1 infection (with or without disease) was 35% (95% CI, 13 to 52), but efficacy against HSV-2 infection was not observed (−8%; 95% CI, −59 to 26).

In a study population that was representative of the general population of HSV-1– and HSV-2–seronegative women, the investigational vaccine was effective in preventing HSV-1 genital disease and infection but not in preventing HSV-2 disease or infection. (Funded by the National Institute of Allergy and Infectious Diseases and GlaxoSmithKline; number, NCT00057330.)

Risk Factors for Nonreceipt of Hepatitis B Vaccine in the Newborn Nursery

The Pediatric Infectious Disease Journal
January 2012 – Volume 31 – Issue 1  pp: A11-A12,1-9,e1-e36

Original Studies
Maternal Characteristics and Hospital Policies as Risk Factors for Nonreceipt of Hepatitis B Vaccine in the Newborn Nursery
O’Leary, Sean T.; Nelson, Christina; Duran, Julie
Pediatric Infectious Disease Journal. 31(1):1-4, January 2012.
doi: 10.1097/INF.0b013e3182345995

Background: A birth dose of hepatitis B vaccine (HBV) is a primary focus of the Advisory Committee on Immunization Practices’ strategy to eliminate transmission of hepatitis B virus in the United States. We sought to assess the impact of maternal characteristics and hospital policy on the receipt of a birth dose of HBV.

Methods: A retrospective cohort study was performed using data from the 2008 Colorado birth registry. Hospital policy was assessed by state health department personnel. Univariate and multivariate logistic regression analyses were used to examine the association of maternal characteristics and hospital policy with nonreceipt of HBV.

Results: A total of 64,425 infants were identified in the birth cohort, of whom 61.6% received a birth dose of HBV. Higher maternal education and income were associated with nonreceipt of HBV (master’s degree vs. eighth grade or less: adjusted odds ratio [OR] = 1.66, 95% confidence interval [CI] = 1.49–1.85; >$75,000 vs. <$15,000: adjusted OR = 1.21, 95% CI = 1.13–1.30). Lack of a hospital policy stipulating a universal birth dose strongly predicted nonreceipt of a birth dose of HBV (policy with no birth dose vs. policy with a birth dose: adjusted OR = 2.21, 95% CI = 2.13–2.30).

Conclusions: Maternal characteristics such as higher education and income are associated with nonreceipt of the HBV during the perinatal period. To effectively reduce risk of perinatal hepatitis B transmission, hospitals should stipulate that all infants are offered HBV and ensure that these policies are implemented and followed.

Prioritization of Zoonoses in Canada: A Stakeholder-Informed Approach

PLoS One
[Accessed 8 January 2012];jsessionid=577FD8B9E1F322DAA533C413369CD6F3.ambra01?field=date

A Stakeholder-Informed Approach to the Identification of Criteria for the Prioritization of Zoonoses in Canada
Victoria Ng, Jan M. Sargeant
PLoS ONE: Research Article, published 06 Jan 2012 10.1371/journal.pone.0029752

Zoonotic diseases account for over 60% of all communicable diseases causing illness in humans and 75% of recently emerging infectious diseases. As limited resources are available for the control and prevention of zoonotic diseases, it is necessary to prioritize diseases in order to direct resources into those with the greatest needs. The selection of criteria for prioritization has traditionally been on the basis of expert opinion; however, details of the methods used to identify criteria from expert opinion often are not published and a full range of criteria may not be captured by expert opinion.

Methodology/Principal Findings
This study used six focus groups to identify criteria for the prioritization of zoonotic diseases in Canada. Focus groups included people from the public, animal health professionals and human health professionals. A total of 59 criteria were identified for prioritizing zoonotic diseases. Human-related criteria accounted for the highest proportion of criteria identified (55%), followed by animal-related criteria (26%) then pathogen/disease-related criteria (19%).

Similarities and differences were observed in the identification and scoring of criteria for disease prioritization between groups; the public groups were strongly influenced by the individual-level of disease burden, the responsibility of the scientific community in disease prioritization and the experiences of recent events while the professional groups were influenced by the societal- and population-level of disease burden and political and public pressure.

This was the first study to describe a mixed semi-quantitative and qualitative approach to deriving criteria for disease prioritization. This was also the first study to involve the opinion of the general public regarding disease prioritization. The number of criteria identified highlights the difficulty in prioritizing zoonotic diseases. The method presented in this paper has formulated a comprehensive list of criteria that can be used to inform future disease prioritization studies.

Genetic Variation in Susceptibility to Infectious Diseases in Humans

PLoS One
[Accessed 8 January 2012];jsessionid=577FD8B9E1F322DAA533C413369CD6F3.ambra01?field=date

Evolutionary Determinants of Genetic Variation in Susceptibility to Infectious Diseases in Humans
Christi Baker, Janis
PLoS ONE: Research Article, published 05 Jan 2012 10.1371/journal.pone.0029089

Although genetic variation among humans in their susceptibility to infectious diseases has long been appreciated, little focus has been devoted to identifying patterns in levels of variation in susceptibility to different diseases. Levels of genetic variation in susceptibility associated with 40 human infectious diseases were assessed by a survey of studies on both pedigree-based quantitative variation, as well as studies on different classes of marker alleles. These estimates were correlated with pathogen traits, epidemiological characteristics, and effectiveness of the human immune response. The strongest predictors of levels of genetic variation in susceptibility were disease characteristics negatively associated with immune effectiveness. High levels of genetic variation were associated with diseases with long infectious periods and for which vaccine development attempts have been unsuccessful. These findings are consistent with predictions based on theoretical models incorporating fitness costs associated with the different types of resistance mechanisms. An appreciation of these observed patterns will be a valuable tool in directing future research given that genetic variation in disease susceptibility has large implications for vaccine development and epidemiology.