The pdf version of Vaccines: The Week in Review  27 February 2012, comprising the posts for this date below, is available here: Vaccines_The Week in Review_27 February 2012

UNICEF reported that the Central African Republic (CAR) launched a national immunization campaign to eradicate polio “aimed at reaching all children in the country, including hard-to-reach populations living in conflict and post-conflict zones with limited access to health services…in urgent response to four imported cases of polio discovered in CAR in 2011, the first in two years.” Mary Louise Eagleton Meaney, Deputy Representative for UNICEF, CAR, said “Routine data shows that only 68 per cent of children in CAR under five years of age are completely vaccinated against polio, which means that 260,000 children under five are at risk of contracting the virus.” UNICEF noted that health workers “will be going door-to-door to deliver polio vaccines starting February 24th to 806,825 children between the ages of 0-59 months; to administer vitamin A supplements to 725,102 children between 6-59 months; and to provide deworming for 643,595 children between 12-59 months of age.” http://www.unicef.org/media/media_61805.html

Interview: Voice of America interviews Dagfinn Høybråten

GAVI Board Chair Dagfinn Høybråten talks to the official United States government broadcaster about the role of vaccines in achieving MDGs 4 and 5

Source: Health Alliance/2011

In an interview with Voice of America, GAVI Alliance Board Chairman Dagfinn Høybråten discusses a wide range of issues with VoA correspondent Linord Moudou. He traces GAVI’s history and explains that vaccines have created a moral imperative to act in order to save lives….Høybråten adds that without achieving high levels of vaccination, it will be impossible to reach Millennium Development Goals 4 and 5 to reduce child mortality and improve maternal health. By responding to country demand and prioritising uptake of new and underused vaccines, GAVI support has helped countries to avert more than five and a half million future deaths.

http://www.gavialliance.org/library/news/gavi-features/2012/hoybraten-voice-of-america/

The MMWR weekly for February 24, 2012 / Vol. 61 / No. 7 includes:
– Influenza Vaccination Coverage Among Pregnant Women — 29 States and New York City, 2009–10 Season

– Update: Influenza Activity — United States, October 2, 2011–February 11, 2012

– Announcement: Release of Online U.S. and State Trend Data for Health-Related Quality of Life

The Weekly Epidemiological Record (WER) for 24 February 2012, vol. 87, 7 (pp 65–72) includes WHO Quantitative Immunization and Vaccine-Related Research meeting, October 2011 – summary; Dengue and severe dengue factsheet (Revised in January 2012)

http://www.who.int/entity/wer/2012/wer8708.pdf

Twitter Watch  [accessed 26 February 17:35]
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.

GAVI Alliance ‏ @GAVIAlliance
Helen Evans – GAVI Deputy CEO – shares her insights into #GAVI‘s challenges and opportunities. ht.ly/9dSKY
7:01 AM – 25 Feb 12 via web · Details

EndPolioNow ‏ @EndPolioNow
At Polio Summit, India just announces that WHO has removed India from the polio endemic list #polio
1:15 AM – 25 Feb 12

IHME at UW ‏ @IHME_UW
Track #polio vaccination activities using Polio Campaign Monitoring Reports: bit.ly/w1iMey #GHDxData #globalhealth
1:05 PM – 24 Feb 12

WHO ‏ @WHO
If we eradicate polio, we’ll save US$40-50b in the next 20yrs. We can use these $ to fight other diseases bit.ly/ycRnFG #poliochat
12:08 PM – 24 Feb 12

HarvardPublicHealth ‏ @HarvardHSPH
Today in #publichealth history: Children receive the first polio vaccine in 1954 ht.ly/9fFuq #TodayinHistory

EndPolioNow ‏ @EndPolioNow
View a NEW infographic of the progress and current state of polio eradication. twitpic.com/8npwrg
1:46 PM – 23 Feb 12

Dagfinn Høybråten ‏ @Hoybraten
Great opportunity to speak about the power of #vaccines to save lives at Voice of America: ht.ly/9c3vl
Retweeted by GAVI Alliance
9:26 AM – 21 Feb 12

PAHO/WHO ‏ @pahowho
#PAHO Funds Training in Epidemiology for Health Officials in the Region – bit.ly/zzFPYE
7:55 PM – 22 Feb 12

Sabin Vaccine Inst. ‏ @sabinvaccine
Today on the blog: an update on sustainable immunization financing activities in Cambodia bit.ly/xQcWcO
3:42 PM – 22 Feb 12

GAVI Alliance ‏ @GAVIAlliance
 Nearly 70% of all vax consumed come from India; great potential 2 sustain growth momentum –RajeevDhere,SerumInstitute ht.ly/9bQqK
8:20 AM – 22 Feb 12

Measles Initiative ‏ @MeaslesInit
Why do measles outbreaks occur in middle- and higher-income communities? wp.me/p1UXPA-38
Retweeted by ECDC Eurovaccine
5:41 AM – 17 Feb 12

ECDC Eurovaccine ‏ @Eurovaccine
Latest ECDC #measles monitoring provides 2011 analyses of surveillance data; 2011 cases is 4-fold increase from 2009. bit.ly/xkePx5
10:47 AM – 21 Feb 12

GAVI Alliance ‏ @GAVIAlliance
GAVI Board Chair, @Hoybraten talks about the role of vaccines in achieving MDGs 4 and 5: ht.ly/9c3vl
8:28 AM – 21 Feb 12

Health Policy and Planning
Volume 27 Issue 1 January 2012
http://heapol.oxfordjournals.org/content/current
Advanced access  February 13, 2012

Original Paper:
Marko Vujicic, Stephanie E Weber, Irina A Nikolic, Rifat Atun, and Ranjana Kumar
An analysis of GAVI, the Global Fund and World Bank support for human resources for health in developing countries
Health Policy Plan. first published online February 13, 2012 doi:10.1093/heapol/czs012 (9 pages)

Abstract
Shortages, geographic imbalances and poor performance of health workers pose major challenges for improving health service delivery in developing countries. In response, multilateral agencies have increasingly recognized the need to invest in human resources for health (HRH) to assist countries in achieving their health system goals. In this paper we analyse the HRH-related activities of three agencies: the Global Alliance for Vaccines and Immunisation (GAVI); the Global Fund for Aids, Tuberculosis, and Malaria (the Global Fund); and the World Bank. First, we reviewed the type of HRH-related activities that are eligible for financing within each agency. Second, we reviewed the HRH-related activities that each agency is actually financing. Third, we reviewed the literature to understand the impact that GAVI, Global Fund and World Bank investments in HRH have had on the health workforce in developing countries. Our analysis found that by far the most common activity supported across all agencies is short-term, in-service training. There is relatively little investment in expanding pre-service training capacity, despite large health worker shortages in developing countries. We also found that the majority of GAVI and the Global Fund grants finance health worker remuneration, largely through supplemental allowances, with little information available on how payment rates are determined, how the potential negative consequences are mitigated, and how payments are to be sustained at the end of the grant period. Based on the analysis, we argue there is an opportunity for improved co-ordination between the three agencies at the country level in supporting HRH-related activities. Existing initiatives, such as the International Health Partnership and the Health Systems Funding Platform, could present viable and timely vehicles for the three agencies to implement this improved co-ordination.

JAMA   
February 22/29, 2012, Vol 307, No. 8, pp 749-874
http://jama.ama-assn.org/current.dtl

Original Contributions
Cost-effectiveness of Adult Vaccination Strategies Using Pneumococcal Conjugate Vaccine Compared With Pneumococcal Polysaccharide Vaccine
Kenneth J. Smith, Angela R. Wateska, Mary Patricia Nowalk, Mahlon Raymund, J. Pekka Nuorti, Richard K. Zimmerman
JAMA. 2012;307(8):804-812.doi:10.1001/jama.2012.169

Abstract
Context  The cost-effectiveness of 13-valent pneumococcal conjugate vaccine (PCV13) compared with 23-valent pneumococcal polysaccharide vaccine (PPSV23) among US adults is unclear.

Objective  To estimate the cost-effectiveness of PCV13 vaccination strategies in adults.

Design, Setting, and Participants A Markov state-transition model, lifetime time horizon, societal perspective. Simulations were performed in hypothetical cohorts of US 50-year-olds. Vaccination strategies and effectiveness estimates were developed by a Delphi expert panel; indirect (herd immunity) effects resulting from childhood PCV13 vaccination were extrapolated based on observed PCV7 effects. Data sources for model parameters included Centers for Disease Control and Prevention Active Bacterial Core surveillance, National Hospital Discharge Survey and Nationwide Inpatient Sample data, and the National Health Interview Survey.

Main Outcome  Measures Pneumococcal disease cases prevented and incremental costs per quality-adjusted life-year (QALY) gained.

Results In the base case scenario, administration of PCV13 as a substitute for PPSV23 in current recommendations (ie, vaccination at age 65 years and at younger ages if comorbidities are present) cost $28 900 per QALY gained compared with no vaccination and was more cost-effective than the currently recommended PPSV23 strategy. Routine PCV13 at ages 50 and 65 years cost $45 100 per QALY compared with PCV13 substituted in current recommendations. Adding PPSV23 at age 75 years to PCV13 at ages 50 and 65 years gained 0.00002 QALYs, costing $496 000 per QALY gained. Results were robust in sensitivity analyses and alternative scenarios, except when low PCV13 effectiveness against nonbacteremic pneumococcal pneumonia was assumed or when greater childhood vaccination indirect effects were modeled. In these cases, PPSV23 as currently recommended was favored.

Conclusion  Overall, PCV13 vaccination was favored compared with PPSV23, but the analysis was sensitive to assumptions about PCV13 effectiveness against nonbacteremic pneumococcal pneumonia and the magnitude of potential indirect effects from childhood PCV13 on pneumococcal serotype distribution.

JAMA   
February 22/29, 2012, Vol 307, No. 8, pp 749-874
http://jama.ama-assn.org/current.dtl

Original Contributions
Risk of Febrile Seizures and Epilepsy After Vaccination With Diphtheria, Tetanus, Acellular Pertussis, Inactivated Poliovirus, and Haemophilus Influenzae Type b
Yuelian Sun, Jakob Christensen, Anders Hviid, Jiong Li, Peter Vedsted, Jørn Olsen, Mogens Vestergaard
JAMA. 2012;307(8):823-831.doi:10.1001/jama.2012.165

Abstract
Context  Vaccination with whole-cell pertussis vaccine carries an increased risk of febrile seizures, but whether this risk applies to the acellular pertussis vaccine is not known. In Denmark, acellular pertussis vaccine has been included in the combined diphtheria-tetanus toxoids-acellular pertussis–inactivated poliovirus– Haemophilus influenzae type b (DTaP-IPV-Hib) vaccine since September 2002.

Objective To estimate the risk of febrile seizures and epilepsy after DTaP-IPV-Hib vaccination given at 3, 5, and 12 months.

Design, Setting, and Participants  A population-based cohort study of 378 834 children who were born in Denmark between January 1, 2003, and December 31, 2008, and followed up through December 31, 2009; and a self-controlled case series (SCCS) study based on children with febrile seizures during follow-up of the cohort.

Main Outcome  Measures Hazard ratio (HR) of febrile seizures within 0 to 7 days (0, 1-3, and 4-7 days) after each vaccination and HR of epilepsy after first vaccination in the cohort study. Relative incidence of febrile seizures within 0 to 7 days (0, 1-3, and 4-7 days) after each vaccination in the SCCS study.

Results  A total of 7811 children were diagnosed with febrile seizures before 18 months, of whom 17 were diagnosed within 0 to 7 days after the first (incidence rate, 0.8 per 100 000 person-days), 32 children after the second (1.3 per 100 000 person-days), and 201 children after the third (8.5 per 100 000 person-days) vaccinations. Overall, children did not have higher risks of febrile seizures during the 0 to 7 days after the 3 vaccinations vs a reference cohort of children who were not within 0 to 7 days of vaccination. However, a higher risk of febrile seizures was found on the day of the first (HR, 6.02; 95% CI, 2.86-12.65) and on the day of the second (HR, 3.94; 95% CI, 2.18-7.10), but not on the day of the third vaccination (HR, 1.07; 95% CI, 0.73-1.57) vs the reference cohort. On the day of vaccination, 9 children were diagnosed with febrile seizures after the first (5.5 per 100 000 person-days), 12 children after the second (5.7 per 100 000 person-days), and 27 children after the third (13.1 per 100 000 person-days) vaccinations. The relative incidences from the SCCS study design were similar to the cohort study design. Within 7 years of follow-up, 131 unvaccinated children and 2117 vaccinated children were diagnosed with epilepsy, 813 diagnosed between 3 and 15 months (2.4 per 1000 person-years) and 1304 diagnosed later in life (1.3 per 1000 person-years). After vaccination, children had a lower risk of epilepsy between 3 and 15 months (HR, 0.63; 95% CI, 0.50-0.79) and a similar risk for epilepsy later in life (HR, 1.01; 95% CI, 0.66-1.56) vs unvaccinated children.

Conclusions  DTaP-IPV-Hib vaccination was associated with an increased risk of febrile seizures on the day of the first 2 vaccinations given at 3 and 5 months, although the absolute risk was small. Vaccination with DTaP-IPV-Hib was not associated with an increased risk of epilepsy.

JAMA   
February 22/29, 2012, Vol 307, No. 8, pp 749-874
http://jama.ama-assn.org/current.dtl

Editorials
Prevention of Pneumococcal Infection With Vaccines: An Evolving Story
Eugene D. Shapiro
JAMA. 2012;307(8):847-849.doi:10.1001/jama.2012.194

Extract [first 150 words per JAMA convention]
The first vaccines to prevent pneumococcal infections, crude preparations of killed bacteria, were developed by Sir Almroth Wright in 1911 to try to alleviate the high mortality and morbidity among gold miners in South Africa.1 Discovery that antibodies against purified polysaccharides of the capsular surface of pneumococci were protective led to development of polysaccharide vaccines that were marketed in the 1940s. These vaccines were commercial failures because the advent of antimicrobials led to a perception that pneumococcal infections were no longer a major threat.2 Subsequent evidence of the persistence of significant morbidity from pneumococcal infections, as well as mortality rates of 25% to 30% in patients with invasive (including bacteremic) pneumococcal infections despite early treatment with antimicrobials, led to redevelopment of a polysaccharide vaccine, approved in the United States in 1977, that contained 14 of the more than 90 serotypes of pneumococci (responsible for about 80% of invasive …

The Lancet  
Feb 25, 2012  Volume 379  Number 9817  p685 – 776
http://www.thelancet.com/journals/lancet/issue/current

Comment
Community-based treatment of severe childhood pneumonia
Robert E Black, Shams El Arifeen

In 2010, an estimated 7·6 million children died before their fifth birthday, and more than a million of these deaths were due to pneumonia.1 Although progress is being made in expanding the use of vaccines to prevent pneumonia, many countries have yet to introduce these vaccines, especially the pneumococcal vaccine.2 Correct breastfeeding of children can also help prevent pneumonia deaths, but a high prevalence of suboptimum breastfeeding practices (eg, low rates of exclusive breastfeeding up to 6 months of age) is seen in all regions of the world.

The Lancet Infectious Disease
Mar 2012  Volume 12  Number 3  p167 – 254
http://www.thelancet.com/journals/laninf/issue/current

Editorial
Avian influenza and the dual-use research debate
The Lancet Infectious Diseases

Preview
Since the first human cases of infection with avian influenza H5N1 were reported 15 years ago, the disease has caused 344 deaths among 583 known cases—a case fatality of nearly 60%. Despite the highly lethal nature of this virus, it is very rarely transmitted from birds to people, and even less frequently, if ever, transmitted from person to person. Nonetheless, the possibility of the virus mutating or recombining with another to develop pandemic potential is a bleak prospect for public health. So it is not surprising that the news that two groups of researchers have purposefully generated H5N1 strains that are transmitted easily in aerosols among ferrets, a widely used model of human influenza transmission, has generated a fierce debate about the conduct and dissemination of dual-use research, as reported in this month’s Newsdesk.

The Lancet Infectious Disease
Mar 2012  Volume 12  Number 3  p167 – 254
http://www.thelancet.com/journals/laninf/issue/current

Series
Infectious disease surveillance and modelling across geographic frontiers and scientific specialties
Kamran Khan, Scott JN McNabb, Ziad A Memish, Rose Eckhardt, Wei Hu, David Kossowsky, Jennifer Sears, Julien Arino, Anders Johansson, Maurizio Barbeschi, Brian McCloskey, Bonnie Henry, Martin Cetron, John S Brownstein

Summary
Infectious disease surveillance for mass gatherings (MGs) can be directed locally and globally; however, epidemic intelligence from these two levels is not well integrated. Modelling activities related to MGs have historically focused on crowd behaviours around MG focal points and their relation to the safety of attendees. The integration of developments in internet-based global infectious disease surveillance, transportation modelling of populations travelling to and from MGs, mobile phone technology for surveillance during MGs, metapopulation epidemic modelling, and crowd behaviour modelling is important for progress in MG health. Integration of surveillance across geographic frontiers and modelling across scientific specialties could produce the first real-time risk monitoring and assessment platform that could strengthen awareness of global infectious disease threats before, during, and immediately after MGs. An integrated platform of this kind could help identify infectious disease threats of international concern at the earliest stages possible; provide insights into which diseases are most likely to spread into the MG; help with anticipatory surveillance at the MG; enable mathematical modelling to predict the spread of infectious diseases to and from MGs; simulate the effect of public health interventions aimed at different local and global levels; serve as a foundation for scientific research and innovation in MG health; and strengthen engagement between the scientific community and stakeholders at local, national, and global levels.

Research agenda for mass gatherings: a call to action
John S Tam, Maurizio Barbeschi, Natasha Shapovalova, Sylvie Briand, Ziad A Memish, Marie-Paule Kieny

Summary
Public health research is essential for the development of effective policies and planning to address health security and risks associated with mass gatherings (MGs). Crucial research topics related to MGs and their effects on global health security are discussed in this review. The research agenda for MGs consists of a framework of five major public health research directions that address issues related to reducing the risk of public health emergencies during MGs; restricting the occurrence of non-communicable and communicable diseases; minimisation of the effect of public health events associated with MGs; optimisation of the medical services and treatment of diseases during MGs; and development and application of modern public health measures. Implementation of the proposed research topics would be expected to provide benefits over the medium to long term in planning for MGs.

The Lancet Infectious Disease
Mar 2012  Volume 12  Number 3  p167 – 254
http://www.thelancet.com/journals/laninf/issue/current

Review
Antiviral resistance during the 2009 influenza A H1N1 pandemic: public health, laboratory, and clinical perspectives
Aeron C Hurt, Tawee Chotpitayasunondh, Nancy J Cox, Rod Daniels, Alicia M Fry, Larisa V Gubareva, Frederick G Hayden, David S Hui, Olav Hungnes, Angie Lackenby, Wilina Lim, Adam Meijer, Charles Penn, Masato Tashiro, Timothy M Uyeki, Maria Zambon, on behalf of the WHO Consultation on Pandemic Influenza A (H1N1) 2009 Virus Resistance to Antivirals

Summary
Influenza A H1N1 2009 virus caused the first pandemic in an era when neuraminidase inhibitor antiviral drugs were available in many countries. The experiences of detecting and responding to resistance during the pandemic provided important lessons for public health, laboratory testing, and clinical management. We propose recommendations for antiviral susceptibility testing, reporting results, and management of patients infected with 2009 pandemic influenza A H1N1. Sustained global monitoring for antiviral resistance among circulating influenza viruses is crucial to inform public health and clinical recommendations for antiviral use, especially since community spread of oseltamivir-resistant A H1N1 2009 virus remains a concern. Further studies are needed to better understand influenza management in specific patient groups, such as severely immunocompromised hosts, including optimisation of antiviral treatment, rapid sample testing, and timely reporting of susceptibility results.

Nature  
Volume 482 Number 7386 pp439-562  23 February 2012
http://www.nature.com/nature/current_issue.html

Editorial
Flu papers warrant full publication
Nature 482, 439 (23 February 2012)
doi:10.1038/482439a
Published online  22 February 2012

Although more debate is needed, the benefits of publishing sensitive data outweigh the risks that have so far been made public.

“No one should presume to know all the ways in which influenza virus could be misused, and the motivations for doing so, but the consequences could be catastrophic.  There are many scenarios to consider, ranging from mad lone scientists, desperate despots and members of millennial doomsday cults to nation states wanting mutually assured destruction options, bioterrorists or a single person’s random acts of craziness.   These are low-probability events, but they could introduce a new evolutionary H5N1 seed into the environment that seems not to exist in nature. This might not cause a pandemic instantly, but it could start the virus on a new path for pandemic evolution.”

That is the rationale provided by Paul Keim, acting chair of the US National Science Advisory Board for Biosecurity (NSABB), in response to questions posed by Nature (P. S. Keim Nature 482, 156–157; 2012) about the NSABB’s recommendation that recent work on the transmissibility in mammals of artificial strains of avian H5N1 influenza virus should not be published in full. The work was conducted in ferrets — generally considered the best animal models for human transmission — and shows that avian H5N1 viruses have a greater potential to evolve into transmissible forms in mammals, including humans, than had been thought. The work is reported in two papers accepted but not yet published in Nature and Science.

Last week, a group of flu and public-health experts gathered at the World Health Organization (WHO) headquarters in Geneva, Switzerland, to discuss the matter (see go.nature.com/uyr1uu). And it was clear at the meeting that the above opening quote expresses the only rationale that attendees had received.

To its credit and that of the US government, the NSABB is the only body in the world set up to review these issues in a systematic fashion. It includes ex-officio representatives of all relevant government departments (including intelligence and security agencies), as well as independent researchers. The NSABB’s guidance was an important first step in public consideration of the impacts and potential regulation of such research. The second step was last week’s meeting at the WHO — again, like the NSABB, a body empowered only to make recommendations.

Some context is important in considering the issues surrounding publication. In 2003, Nature and many other journals met to establish editorial procedures for considering papers that have public-health and scientific benefits but that might also have biosecurity risks (see Nature 421, 771; 2003). The statement that emerged from that meeting envisaged the possibility that a journal would reject a paper if it was clear that the risks of publication outweighed the benefits. Nature accordingly used independent advisers in considering the submission of the latest paper, and most of the advisers recommended publication in full. This is also the first paper submitted to any Nature journal for which recommendations have been made against publication on biosecurity grounds.

Rather than simply reject the papers, given also the NSABB’s opinion, both Nature and Science decided to investigate another option: to publish a redacted version omitting key methods and data. But a condition of such an approach was that a method should exist for distributing a full version to those in need of the results for public-health reasons and those capable of pursuing the science. Both journals accordingly prepared full and redacted versions.

“There is already a substantial immediate risk to humans.”

Those at the WHO meeting, under conditions of strict security, examined both versions of the two papers. It had already been said in blogs and news coverage that, because the methods used are not novel, and because one of the papers had been presented at an open meeting, redaction would be pointless. As one WHO participant said: “It was only when I’d seen both versions that I realized how ineffective redaction would be.” What was also concluded was that a system for distributing the full paper only to selected individuals would be impossible to set up on any relevant timescale.

But what also became clear, partly from unpublished data, was that not only does the mammalian transmissibility threat seem greater than previously thought, but also that current avian viruses have some of the mutations identified in the new work. In other words, there is already a substantial immediate risk to humans. The meeting also concluded that the new data are of value for surveillance, and that the results should be built on to explore the mechanisms underlying transmissibility and the high fatality rate observed in humans infected by H5N1.

Given the inadequacy of redaction, and the immediate risks to global public health, the biosecurity objections expressed above seem too general and hypothetical to justify obstructing publication and further research. Moreover, with regard to the NSABB’s recommendations and the recommendations of the WHO meeting (see go.nature.com/ky2skc), neither of the discussions that preceded them were sufficiently inclusive of the security, societal and research interests at stake.

Therefore, further discussion is essential. That must include a review of the safety regimes (lab equipment, buildings and practices) in which future work should be conducted. The two laboratories in which the latest research originated are categorized as ‘BSL-3 enhanced’ (see Nature 480, 421–422; 2011), a classification that, although rigorous in these cases, is not well defined in general. The Public Health Agency of Canada has deemed the highest level of BSL-4 to be required (see page 447). Safety-standards committees in the United States and Europe are currently assessing required safety levels, and may report within a few weeks.

As was agreed by the journals and the lead authors at the meeting, publication of the papers must wait at least for the outcome of those discussions. There may yet be regulatory or legal obstacles to publication, or biosecurity or biosafety risks sufficient to outweigh the health risks. Otherwise, it is Nature’s view that the papers should ultimately be published in full.

The Pediatric Infectious Disease Journal
March 2012 – Volume 31 – Issue 3  pp: 217-286,e52-e58,A11-A12
http://journals.lww.com/pidj/pages/currenttoc.aspx

Original Studies
Comparative Coverage of Supplementary and Universally Recommended Immunizations in Children at 24 Months of Age
Hug, Salome; Weibel, Daniel; Delaporte, Elisabeth; Gervaix, Alain; Heininger, Ulrich
Pediatric Infectious Disease Journal. 31(3):217-220, March 2012.
doi: 10.1097/INF.0b013e31823cbaa5

Abstract:
Background: The introduction of pneumococcal and meningococcal group C conjugate vaccinations as supplementary (a new category in Swiss immunization recommendations) to universally recommended vaccinations in 2006 prompted this study to investigate their acceptance.

Methods: The study was performed in 24-month-old healthy children born in the Geneva or Basel areas in Switzerland between January and April 2007. After informed consent had been obtained from caregivers (for this particular study in Basel and in general for providing immunization data in Geneva on an ongoing basis), all universally recommended and supplementary vaccinations administered by ≤24 months of age were analyzed for completeness and timeliness according to set definitions. Sample size calculations and standard statistical tests were applied for comparative data analyses.

Results: Of 592 children at the age of 12 months, 94% and 73% had received complete diphtheria-tetanus-pertussis component combination and pneumococcal conjugate vaccinations, respectively. At the age of 24 months, coverage rates for complete booster doses were 77% and 70%, respectively. Rates for MMR doses 1 and 2 at 24 months were 92% and 72%, respectively, and the rate for meningococcal conjugate vaccine (single dose) was 62%. On an average, coverage rates were similar in the 2 study regions except those for pneumococcal conjugate and second dose of MMR, which were approximately 10% higher in Geneva.

Conclusions: Compliance with supplementary vaccinations was lower than that with universally recommended vaccinations. This can be explained by the recent introduction of supplementary vaccinations or by the public perception that they are less important than universal vaccinations.

The Pediatric Infectious Disease Journal
March 2012 – Volume 31 – Issue 3  pp: 217-286,e52-e58,A11-A12
http://journals.lww.com/pidj/pages/currenttoc.aspx

Original Studies
The Changing Epidemiology of Invasive Pneumococcal Disease at a Tertiary Children’s Hospital Through the 7-valent Pneumococcal Conjugate Vaccine Era: A Case for Continuous Surveillance
Ampofo, Krow; Pavia, Andrew T.; Stockmann, Chris; Hersh, Adam L.; Bender, Jeffrey M.; Blaschke, Anne J.; Weng, Hsin Yi Cindy; Korgenski, Kent E.; Daly, Judy; Mason, Edward O.; Byington, Carrie L.
Pediatric Infectious Disease Journal. 31(3):228-234, March 2012.
doi: 10.1097/INF.0b013e31823dcc72

Abstract:
Background: In 2000, a 7-valent pneumococcal conjugate vaccine (PCV7) was licensed for use among US children. Many sites have since reported changes in invasive pneumococcal disease (IPD). We recognized an opportunity to describe the changes in epidemiology, clinical syndromes, and serotype distribution during a 14-year period including 4 years before vaccine introduction and spanning the entire PCV7 era.

Methods: Cases were defined as children <18 years of age who were cared for at Primary Children’s Medical Center for culture-confirmed IPD. We defined the prevaccine period as the time frame spanning from 1997 to 2000 and the postvaccine period from 2001 to 2010. Demographics, clinical data, and outcomes were collected through electronic query and chart review. Streptococcus pneumoniae serotyping was performed using the capsular swelling method.

Results: The median age of children with IPD increased from 19 months during the prevaccine period to 27 months during postvaccine period (P = 0.02), with a larger proportion of IPD among children older than 5 years. The proportion of IPD associated with pneumonia increased substantially from 29% to 50% (P < 0.001). This increase was primarily attributable to an increase in complicated pneumonia (17% to 33%, P < 0.001). Nonvaccine serotypes 7F, 19A, 22F, and 3 emerged as the dominant serotypes in the postvaccine period. In children with IPD who were younger than 5 years, for whom vaccine is recommended, 67% of the cases were caused by serotypes in 13-valent PCV during 2005 to 2010.

Conclusions: After PCV7 was introduced, significant changes in IPD were noted. One-third of IPD occurred in children older than 5 years, who were outside the age-group for which PCV is recommended. Continued surveillance is warranted to identify further evolution of the epidemiology, clinical syndromes, and serotype distribution of S. pneumoniae after 13-valent PCV licensure.

The Pediatric Infectious Disease Journal
March 2012 – Volume 31 – Issue 3  pp: 217-286,e52-e58,A11-A12
http://journals.lww.com/pidj/pages/currenttoc.aspx

Vaccine Reports
Incidence of Intussusception Among Infants in a Large Commercially Insured Population in the United States
Mona Eng, Patricia; Mast, T. Christopher; Loughlin, Jeanne; Clifford, C. Robin; Wong, Judy; Seeger, John D.
Pediatric Infectious Disease Journal. 31(3):287-291, March 2012.
doi: 10.1097/INF.0b013e31824213b1

Abstract:
Background: To estimate the incidence of intussusception among infants treated in inpatient and emergency department settings during the period preceding the US launch of second-generation rotavirus vaccines.

Methods: From a large US health insurance claims database, we sampled 100,000 infants aged 1 to 3 months at first diphtheria-tetanus-acellular pertussis vaccination between 2001 and 2005. Potential intussusception cases were identified on the basis of claims and were confirmed by medical record review. Incidence rates (IRs) and 95% confidence intervals (CIs) were estimated based on follow-up from first diphtheria-tetanus-acellular pertussis dose to up to 1 year of age, and within 21, 30, and 60 days after each dose.

Results: The IR of intussusception in the first year of life was 0.33/1000 person-years based on 22 confirmed cases (95% CI: 0.21–0.50/1000 person-years). The age-specific incidence peaked among infants aged 5 months (IR: 0.82/1000 person-years; 95% CI: 0.30–1.78/1000 person-years). During the 21, 30, and 60 days following any dose, the incidence per 1000 person-years was 0.27, 0.24, and 0.33, respectively.

Conclusion: The rates described in this study can serve as a benchmark for comparison with incidences observed after the introduction of the second-generation rotavirus vaccines.

Postmarketing Evaluation of the Short-term Safety of the Pentavalent Rotavirus Vaccine
Loughlin, Jeanne; Mast, T. Christopher; Doherty, Michael C.; Wang, Florence T.; Wong, Judy; Seeger, John D.
Pediatric Infectious Disease Journal. 31(3):292-296, March 2012.
doi: 10.1097/INF.0b013e3182421390

Abstract:
Background: A pentavalent rotavirus vaccine (RV5) demonstrated efficacy and safety in a large clinical trial before US licensure in 2006. The primary objective of this observational study was to assess the occurrence of intussusception (IS) among infants who received RV5 in routine use. Secondary objectives assessed the occurrence of Kawasaki disease (KD) and general safety.

Methods: We identified and followed infants with a health insurance claim for RV5 during the first 2 years of RV5 availability. Concurrent and historical cohorts receiving diphtheria-tetanus-acellular pertussis (DTaP) vaccine were used as comparators; the historical DTaP cohort informed sequential monitoring boundaries for IS and KD. Medical records from potential IS and KD cases were reviewed to confirm outcomes. General safety was evaluated across a wide range of outcomes using prespecified criteria. Incidence rates for outcomes along with relative risks and 95% confidence intervals (CIs) were estimated.

Results: The 85,397 RV5 and 62,820 DTaP recipients contributed 17,433 and 12,339 person-years, resulting in 6 and 5 confirmed cases of IS, respectively, within 30 days following any dose. The relative risk of IS was 0.8 (95% confidence interval: 0.22–3.52). The number of IS or KD cases did not cross the monitoring boundaries. The general safety evaluation did not identify any specific diagnoses or patterns of diagnoses that might suggest other safety concerns.

Conclusion: RV5 was not associated with an increased risk of IS, KD, or any other recognized health outcome.

PLoS Medicine
(Accessed 26 February 2012)
http://www.plosmedicine.org/article/browse.action?field=date

Mobile Phone Text Messaging: Tool for Malaria Control in Africa
Dejan Zurovac, Ambrose O. Talisuna, Robert W. Snow Essay, published 21 Feb 2012
doi:10.1371/journal.pmed.1001176

Summary Points
– Across many malaria-endemic areas in rural Africa, the communication gap between managers, health workers, and patients is a significant barrier to efficient malaria control.

– The rapid expansion of mobile network coverage and the widespread availability of basic handsets have the potential to substantively bridge the communication gap.

– Text messaging, as the least-expensive mobile phone function found on all handsets, could improve the delivery of health services and health outcomes.

– Six major areas of malaria control in which deficiencies are apparent and text messaging interventions could be beneficial are: (1) disease and treatment effectiveness surveillance, (2) monitoring of the availability of health commodities, (3) pharmacovigilance and post-marketing surveillance of the safety and quality of antimalarial drugs, (4) health worker adherence to guidelines, (5) patient adherence to medication regimens, and (6) post-treatment review.

– Text messages transmitting information from the periphery of the health systems to malaria control managers are in the first three malaria control areas: (1) disease and treatment effectiveness surveillance, (2) monitoring of the availability of health commodities, and (3) pharmacovigilance and post-marketing surveillance of the safety and quality of antimalarial medicines. Future projects in these three areas should demonstrate responses to data signals and comparative advantages with routine information systems.

– Text messages in the second three areas transmit information to health workers and patients to support the management of malaria patients by improving (4) health workers’ adherence to guidelines, (5) patient adherence to medicines, and (6) post-treatment review. Future priorities in these areas are cost-effectiveness evaluations, qualitative research, and studies measuring impact on the processes of care and health outcomes.

Tropical Medicine & International Health
March 2012  Volume 17, Issue 3  Pages 263–403
http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1365-3156/currentissue

Child Health
Expanding and improving urban outreach immunization in Patna, India
Narottam Pradhan, Tove K. Ryman, Sherin Varkey, Alok Ranjan, Satish K. Gupta, Gopal Krishna, R. P. Swetanki and Randall Young
Article first published online: 14 DEC 2011 | DOI: 10.1111/j.1365-3156.2011.02916.x

Abstract
Objectives  We conducted a case study of an urban immunization outreach strategy to determine the feasibility of the intervention and to measure administrative immunization coverage outcomes.

Methods  A multipronged strategy for improving immunization coverage in Urban Patna, India, was implemented for 1 year (2009/2010). The strategy was designed to increase immunization sites, shift human resources, plan logistics, improve community mobilization, provide supervision, strengthen data flow and implement special vaccination drives.

Results  Over 1 year, the coverage of all primary vaccines of the Universal Immunization Program improved by over 100%.

Conclusion  Coverage can be rapidly improved through outreach immunization in low socioeconomic areas if existing opportunities are carefully utilized.

Tropical Medicine & International Health
March 2012  Volume 17, Issue 3  Pages 263–403
http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1365-3156/currentissue

Malaria
Acceptability of coupling Intermittent Preventive Treatment in infants with the Expanded Programme on Immunization in three francophone countries in Africa
Alexandra de Sousa, Leon P. Rabarijaona, Jean L. Ndiaye, Doudou Sow, Mouhamed Ndyiae, Jacques Hassan, Nilda Lambo, Paul Adovohekpe, Flavia Guidetti, Judith Recht and Alphonse Affo
Article first published online: 29 NOV 2011 | DOI: 10.1111/j.1365-3156.2011.02915.x

Abstract
Objective  Intermittent preventive treatment in infants (IPTi) is a malaria control strategy currently recommended by WHO for implementation at scale in Africa, consisting of administration of sulphadoxine-pyrimethamine (SP) coupled with routine immunizations offered to children under 1 year. In this study, we analysed IPTi acceptability by communities and health staff.

Methods  Direct observation, in-depth interviews (IDIs) and focus group discussions (FGDs) were conducted in Benin, Madagascar and Senegal during IPTi pilot implementation. Villages were stratified by immunization coverage. Data were transcribed and analysed using NVivo7 software.

Results  Communities’ knowledge of malaria aetiology and diagnosis was good, although generally villagers did not seek treatment at health centres as their first choice. Perceptions and attitudes towards IPTi were very positive among communities and health workers. A misconception that SP was an antipyretic that prevents post-vaccinal fever contributed to IPTi’s acceptability. No refusals or negative rumours related to IPTi coupling with immunizations were identified, and IPTi did not negatively influence attitudes towards other malaria control strategies. Healthcare decisions about children, normatively made by the father, are starting to shift to educated and financially independent mothers.

Discussion  Intermittent preventive treatment in infants is well accepted by providers and communities, showing a synergic acceptability when coupled with routine immunizations. However, a misconception that SP alleviates fever should be addressed when scaling up implementation.

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 30, Issue 12 pp. 2037-2236 (9 March 2012)

Regular Papers
Knowledge, attitude and practice in primary and secondary cervical cancer prevention among young adult Italian women
Original Research Article
Pages 2075-2082
Serena Donati, Cristina Giambi, Silvia Declich, Stefania Salmaso, Antonietta Filia, Marta Luisa Ciofi degli Atti, Maria Pia Alibrandi, Silvia Brezzi, Francesca Carozzi, Natalina Collina, Daniela Franchi, Amedeo Lattanzi, Margherita Meda, Maria Carmela Minna, Roberto Nannini, Giuseppina Gallicchio, Antonino Bella, The PreGio Working group

Abstract
In Italy since 2007 vaccination against human papillomavirus (HPV) is offered to 11-year-old females, whereas vaccination for older age groups is still a matter of debate. To assess Italian young women’s knowledge, attitudes and practice regarding primary and secondary cervical cancer prevention a cross-sectional study among young women aged 18–26 years was conducted in 2008. The survey collected information on in-depth awareness and knowledge regarding Pap testing, HPV infection, HPV vaccine and cervical cancer. The response rate was 57.7% with a wide range of variability (34–84%) amongst local health units. Among 667 women who participated in the survey poor awareness and various misconceptions regarding HPV and cervical cancer prevention were detected. Overall women were found to be more knowledgeable about Pap smears and cervical cancer than about HPV infection and the HPV vaccine. Respondents pointed to their healthcare providers as their most trusted source for medical information. Understanding women’s knowledge on cervical cancer prevention, as well as related factors is important in helping to achieve and maintain adherence to cervical cancer preventive strategies. Moreover in order to minimize cervical cancer risk by improving women’s adherence to preventive strategies, appropriate and adequate information dissemination, and guidance from health professionals appear to be crucial elements.

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 30, Issue 12 pp. 2037-2236 (9 March 2012)

Regular Papers
Risk factors of underutilization of childhood immunizations in ultraorthodox Jewish communities in Israel despite high access to health care services
Original Research Article
Pages 2109-2115
Khitam Muhsen, Reem Abed El-Hai, Anat Amit-Aharon, Haim Nehama, Mervat Gondia, Nadav Davidovitch, Sophy Goren, Dani Cohen

Abstract
Background
The risk factors of underutilization of childhood vaccines in populations with high access to health services are not fully understood.

Objectives
To determine vaccination coverage and factors associated with underutilization of childhood vaccines in a population with sub-optimal vaccination compliance, despite a high health care access.

Methods
The study was conducted among 430 children from ultraorthodox Jewish communities in the Bnei Brak city and Jerusalem district. Data on immunization status, socio-demographic factors and on parents’ attitudes regarding vaccines were obtained from medical records and through parents’ interviews.

Results
The proportion of fully vaccinated children was 65% in 2- to 5-year-old ultraorthodox children from Jerusalem district, and 86% in 2.5-year-old children from Bnei Brak city. The factors that were significantly associated with vaccines underutilization in Bnei Brak were having >6 siblings, maternal academic education, parental religious beliefs against vaccination, perceived risk of vaccine preventable diseases as low, and mistrust in the Ministry of Health (MOH). Similarly, in Jerusalem, religious beliefs against vaccination, and the perceived low risk of vaccine preventable diseases significantly increased the likelihood of under-immunization, while having a complementary health insurance was inversely related with vaccines underutilization.

Conclusions
The risk factors of under-immunization are in part modifiable, by means of health education on the risks of vaccine preventable diseases and by improving the trust in the MOH. The leaders of the ultraorthodox communities could play an important role in such interventions.

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 30, Issue 12 pp. 2037-2236 (9 March 2012)

Regular Papers
Pneumococcal disease in South Australia: Vaccine success but no time for complacency
Original Research Article
Pages 2206-2211
David R. Johnson, Katina D’Onise, Ros A. Holland, Jane C.A. Raupach, Ann P. Koehler

Abstract
Background
Trends in age specific and serotype specific incidence rates for invasive pneumococcal disease (IPD) were examined in South Australia 4 years before and 5 years after the commencement of the Australian universal childhood 7 valent pneumococcal conjugate vaccine (7vPCV) program.

Methods
IPD cases were identified by routine enhanced surveillance. IPD serotypes were grouped according to those covered by the 7vPCV, the six serotypes specific to the 13 valent pneumococcal conjugate vaccine (13vPCV), the 11 serotypes specific to the 23 valent pneumococcal polysaccharide vaccine (23vPPV), as well as non-13vPCV and non-23vPPV groups. Poisson regression was used to calculate age-specific and serotype-specific incident rate ratios (IRRs) comparing pre (2002–2004) and post (2007–2009) universal childhood 7vPCV periods.

Results
Following the introduction of the 7vPCV program, the rate of IPD in children aged <2 years decreased by 81% for all serotypes (IRR 0.19, 95% CI, 0.13–0.28) and by 98% for 7vPCV serotypes (IRR 0.02, 95% CI, 0.007–0.07). At the same time, there was some evidence for an increase in IPD caused by 13vPCV specific serotypes (IRR 1.58, 95% CI, 0.78–3.21) and non-13vPCV serotypes (IRR 1.80, 95% CI, 0.45–7.21). Among adults aged ≥65 years, overall there was a 27% reduction in IPD caused by all serotypes following introduction of the 7vPCV program (IRR 0.73, 95% CI, 0.58–0.93). However, the rate of IPD increased in the last 2 years of the study period. The initial decrease was a result of a 74% reduction in the rate of IPD due to 7vPCV serotypes (IRR 0.26, 95% CI, 0.17–0.40). At the same time, the rate of IPD increased for 13vPCV specific serotypes (IRR 1.55, 95% CI, 0.94–2.54), 23vPPV specific serotypes (IRR 1.91, 95% CI, 0.99–3.71) and particularly non-23vPPV serotypes (IRR 5.3, 95% CI, 1.83–15.34).

Conclusion
There has been a large direct and sustained benefit from the universal 7vPCV program in children, particularly those aged <2 years, with some evidence for serotype replacement. There is also good evidence that the childhood program has provided indirect benefits to adults aged ≥65 years, although serotype replacement has reduced the initial benefits.

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 30, Issue 11 pp. 1911-2036 (2 March 2012)

Regular Papers
Cost-effectiveness of pneumococcal conjugate vaccines of 7, 10, and 13 valences in Colombian children
Original Research Article
Pages 1936-1943
Carlos Castañeda-Orjuela, Nelson Alvis-Guzmán, Martha Velandia-González, Fernando De la Hoz-Restrepo

Abstract
Background
Currently there are three pneumococcal conjugate vaccines with different coverage of serotypes for use in children under one year. We evaluate the cost-effectiveness of the introduction of pneumococcal conjugate vaccines of 7, 10, and 13 valences in the Colombian EPI.

Methods
A Markov model, which followed a cohort of children under one year to life expectancy, was developed. Parameters of occurrence and care costs were based on data from National Health System and literature review. PCV-7 is a dominated strategy. PCV-10 and PCV-13 were each compared to no vaccination or PCV-10 vaccination, respectively. A 2 + 1 schedule and a vaccination price of US$ 14.00, US$ 14.85 and US$ 16.34 per dose were assumed in the base case for PCV-7, -10, and PCV-13 vaccines.

Results
Introduction of PCV-13 rather than PCV-10 increases the number of life years gained (LYG). From the societal perspective, in the ‘competing choice’ framework cost per LYG was US$ 1837 with PCV-10 and US$ 9514 with PCV-13, while PCV-7 is a dominated strategy. The ICER of PCV-13 is above the per capita Gross Domestic Product. Incremental cost-effectiveness ratios (ICERs) were influenced mainly by effectiveness against radiologically-confirmed pneumonia and AOM, vaccine price, and discount rate.

Conclusion
Routine vaccination against Streptococcus pneumoniae in Colombia would be cost-effective with PCV-10, with ICER below the per-capita GDP, but its inclusion requires evaluating the budget impact. PCV-13 would prevent more disease and deaths with a higher LYG, but PCV-10 would save more cost to the healthcare system due its higher impact in the prevention of AOM. There is limitation in the clinical evidence of both strategies.

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 30, Issue 11 pp. 1911-2036 (2 March 2012)

Regular Papers
Toward rubella elimination in Europe: An epidemiological assessment
Original Research Article
Pages 1999-2007
Mark Muscat, Laura Zimmerman, Sabrina Bacci, Henrik Bang, Steffen Glismann, Kåre Mølbak, Susan Reef, the EUVAC.NET group

Abstract
Background
The elimination of rubella and prevention of congenital rubella syndrome (CRS) by 2015 are established goals for Europe. Our aim was to review the epidemiology of rubella in relation to this goal.

Material and methods
National surveillance institutions from 32 European countries provided information on rubella and CRS surveillance systems and data for 2000–08. We reported the number of notified rubella cases by year for countries with a national mandatory notification system for rubella covering total country population consistently throughout 2000–08 and analysed rubella surveillance data for 2008.

Results
Throughout 2000–08, 24 countries conducted passive routine surveillance based on mandatory reporting rubella covering total country population. Altogether these countries reported 526,751 rubella cases. The median incidence per million inhabitants declined from 7.2 in 2000 to 0.3 in 2008. By 2008, the number of countries with mandatory notification systems for rubella increased to 28. These countries reported 21,475 rubella cases of which 1.5% (n = 317) were laboratory-confirmed. Most cases (n = 21,075; 98%) were reported from Poland, Italy and Romania. Ten countries reported zero rubella cases and five others reported an incidence of <1 per million inhabitants. In 2008, 20 CRS cases were reported from five countries.

Conclusion
The overall decline in rubella incidence and increase in the number of countries conducting rubella surveillance through a mandatory notification system are notable achievements toward the goal of rubella elimination in Europe. However, in a few countries with high rubella incidence the risk for CRS still exists. Achievement and maintenance of the required high vaccination coverage and high-quality surveillance of rubella and CRS including laboratory testing of all suspected cases are fundamental to eliminate rubella and prevent CRS in Europe.

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 30, Issue 11 pp. 1911-2036 (2 March 2012)

VAERS Reports
Febrile seizures after 2010–2011 influenza vaccine in young children, United States: A vaccine safety signal from the vaccine adverse event reporting system
Pages 2020-2023
Z. Leroy, K. Broder, D. Menschik, T. Shimabukuro, D. Martin

Signal identification and evaluation for risk of febrile seizures in children following trivalent inactivated influenza vaccine in the Vaccine Safety Datalink Project, 2010–2011
Original Research Article
Pages 2024-2031
Alison Tse, Hung Fu Tseng, Sharon K. Greene, Claudia Vellozzi, Grace M. Lee, On behalf of the VSD Rapid Cycle Analysis Influenza Working Group

Bridging the gap between data and public health needs. In the heat of a signal: Responding to a vaccine safety signal for febrile seizures after 2010–11 influenza vaccine in young children, United States
Pages 2032-2034
Karen R. Broder, David B. Martin, Claudia Vellozzi

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 30, Issue 10 pp. 1753-1910 (27 February 2012)

Editorials
The nursing profession and patient safety and healthcare provider influenza immunization: The puzzling stance of the American Nursing Association
Pages 1753-1755
Gregory A. Poland, Sharon Tucker
[No abstract]

Nursing leadership to ensure patient and health worker protection from influenza
Pages 1756-1758
Jo Anne Bennett, Derryl Block
[No abstract]

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 30, Issue 10 pp. 1753-1910 (27 February 2012)

Regular Papers
Impact of vaccine protection against multiple HPV types on the cost-effectiveness of cervical screening
Original Research Article
Pages 1813-1822
Veerle M.H. Coupé, Johannes A. Bogaards, Chris J.L.M. Meijer, Johannes Berkhof

Abstract
Cross-protection against non-HPV16/18 types and the emergence of broad spectrum vaccines protecting against multiple HPV types will influence the cost-effectiveness of future screening.

To assess this influence we used an individual-based simulation model describing the relation between 14 HPV types and cervical disease, allowing the occurrence of multiple type infections. Screening scenarios for vaccinated women were evaluated, firstly for HPV16/18 vaccination with partial cross-protection against HPV 31, 33, 45 and 58 and secondly, for broad spectrum vaccination against 5–13 HPV types. The vaccine-induced incidence reduction of type-specific infection was varied from 0 to 95% in the cross-protection setting and set at 100% in the setting of broad spectrum vaccines. Scenarios of either cytology or HPV DNA screening were considered under varying lifetime number of screening rounds. At a cost-effectiveness threshold of €20,000/QALY, four times HPV DNA screening between 30 and 60 years was the selected scenario in addition to HPV16/18 vaccination, whether or not cross-protection was conferred (€6707 and €9994/QALY, respectively). In the absence of cross-protection, a fifth screening round might be considered (ICER €22,967/QALY). In addition to broad spectrum vaccination, one screen during lifetime was cost-effective up to an 11-valent vaccine. If the vaccine-induced type-specific incidence reduction was lowered to 99%, one screen during lifetime was cost-effective even in addition to 13-valent vaccination. In conclusion, in a cohort of HPV16/18 vaccinated women, four rounds of HPV DNA screening is cost-effective. One screen during lifetime remains cost-effective in addition to broad spectrum vaccination offering protection against many high-risk HPV types.

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 30, Issue 10 pp. 1753-1910 (27 February 2012)

Regular Papers
UK parents’ decision-making about measles–mumps–rubella (MMR) vaccine 10 years after the MMR-autism controversy: A qualitative analysis
Original Research Article
Pages 1855-1864
Katrina F. Brown, Susannah J. Long, Mary Ramsay, Michael J. Hudson, John Green, Charles A. Vincent, J. Simon Kroll, Graham Fraser, Nick Sevdalis

Abstract
Background and objectives
Public concern about an unsubstantiated link between MMR vaccine and autism stemmed from a 1998 paper by Dr Andrew Wakefield and colleagues, and the substantial media coverage which that work attracted. Though the Wakefield paper is now discredited and an MMR-autism link has never been demonstrated empirically, this concern has manifested in over a decade of suboptimal MMR uptake. Few qualitative studies have explored parents’ MMR decision-making since uptake began to improve in 2004. This study updates and adds methodological rigour to the evidence base.

Methods
24 mothers planning to accept, postpone or decline the first MMR dose (MMR1) for their 11–36 month-old children, described their decision-making in semi-structured interviews. Mothers were recruited via General Practice, parents’ groups/online forums, and chain referral. MMR1 status was obtained from General Practice records 6 months post-interview. Interview transcripts were coded and interpreted using a modified Grounded Theory approach.

Results
Five themes were identified: MMR vaccine and controversy; Social and personal consequences of MMR decision; Health professionals and policy; Severity and prevalence of measles, mumps and rubella infections; Information about MMR and alternatives. Results indicated that MMR1 acceptors were sympathetic toward Wakefield as a person, but universally rejected his study which sparked the controversy; parents opting for single vaccines expressed the sense that immune overload is not a consideration but that not all three components of MMR are warranted by disease severity; and MMR1 rejectors openly criticised other parents’ MMR decisions and decision-making.

Conclusions
This study corroborated some previous qualitative work but indicated that the shrinking group of parents now rejecting MMR comprises mainly those with more extreme and complex anti-immunisation views, whilst parents opting for single vaccines may use second-hand information about the controversy. In response, policymakers and practitioners should revise their expectations of today’s MMR decision-makers, and their methods for supporting them.

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 30, Issue 10 pp. 1753-1910 (27 February 2012)

Regular Papers
The population based socioeconomic burden of pediatric influenza-associated hospitalization in Hong Kong
Original Research Article
Pages 1895-1900
Susan S. Chiu, Kwok-Hung Chan, Lok Yee So, Robin Chen, Eunice L.Y. Chan, J.S.M. Peiris

Abstract
We described the monetary and non-monetary cost incurred by children hospitalized for virologically confirmed influenza virus infection in a population-based prospective 3-year study. The mean direct and indirect cost of each child hospitalized was $1217.82 (95% CI, 1111.54–1324.23) and $1328.33 (95% CI, $1136.79–1520.00) for influenza A and B, respectively. School age patients took a mean (SD) of 4.70 (3.05) days and 5.31 (3.62) days of sick leave for influenza A and B infection, respectively. Pediatric influenza A and B hospitalization was associated with 662–1046 days of school absenteeism and 214–336 days of parental work loss per 10,000 population <18 years of age per year. We showed that the cost incurred by hospitalization alone, was comparable to the cost of annual universal pediatric influenza vaccination especially in children 6 months to under 6 years of age and vaccination would result in much larger cost-savings when non-monetary costs are included.

The pdf version of Vaccines: The Week in Review  20 February 2012, comprising the posts below for this date, is available here: Vaccines_The Week in Review_20 February 2012

WHO announced consensus from a technical consultation held last week on H5N1 research and will convene additional meetings on the issue. The WHO media release noted that “…A small group of global public health and influenza experts at a WHO-convened meeting reached consensus on two urgent issues related to the newly created H5N1 influenza viruses: extending the temporary moratorium on research with new laboratory-modified H5N1 viruses and recognition that research on naturally-occurring H5N1 influenza virus must continue in order to protect public health.” The group “also came to a consensus that delayed publication of the entire manuscripts would have more public health benefit than urgently partially publishing.” The announcement noted that “broad issues raised, but not limited to, these research studies will be discussed at future meetings convened by WHO soon with participation by a broader range of experts and interested parties relevant to these issues.”

http://www.who.int/mediacentre/news/releases/2012/h5n1_research_20120217/en/index.html

WHO Technical consultation on H5N1 research issues – consensus points
WHO Headquarters, Geneva
16-17 February 2012

[Full text]
Two recent research studies examining some factors affecting transmissibility of influenza A(H5N1) viruses prompted WHO to convene a technical consultation on 16–17 February 2012. The participants at this meeting reached consensus on the following points.

Recent work discussed at this meeting underscores that influenza A(H5N1) viruses remain an important risk for causing a future pandemic. Therefore, research on these viruses, including on transmissibility and pathogenicity, remains critical to close important gaps in knowledge in order to reduce the danger posed; such research should continue. The PIP Framework, which was adopted by all WHO Member States in 2011 now provides a global framework for the sharing of influenza viruses with human pandemic potential and the sharing of benefits arising from such sharing.     Implementation of this Framework is integral to global pandemic preparedness and response. Future research projects should involve countries from which source material were obtained.

The two studies that were conducted to better understand the transmissibility of H5N1 influenza viruses have shown that these viruses have the potential to become more transmissible among mammals. In light of the continuing evolution of H5N1 viruses, the results of these studies provide an important contribution to public health surveillance of H5N1 viruses and to a better understanding of the properties of these viruses.

At the same time, these studies have raised important and valid concerns about whether they increase risks to the safety of humans. Concerns which have been raised include the potential misuse of the results or methods as well as potential breaches in biosafety and biosecurity related to pathogens. These concerns highlight how important it is that researchers are aware of such issues, exercise judgement about the conduct of their research, dissemination of the results, and for institutional bodies reviewing such studies to identify and address potential concerns about “dual use”. Such safeguards already exist, but continued emphasis should be placed on assuring and reinforcing safety and security.

The laboratory-modified H5N1 viruses are currently stored in well-established research facilities with high security and high safety (BSL3+). There have been no safety breaches related to the storage of the laboratory-modified H5N1 viruses at these facilities. At the same time, the biosafety and biosecurity conditions under which further research is conducted on the laboratory-modified H5N1 viruses should be fully addressed by relevant authorities. This is a matter of urgency and should be achieved as quickly as possible. In the interim, the laboratory-modified H5N1 viruses should remain in their present locations. In addition, the current moratorium on research to enhance the transmissibility of H5N1 influenza viruses and the further research on the laboratory-modified viruses should continue until the conditions have been determined. Other research on H5N1 viruses should not stop.

There is a preference, from a public health perspective, for full disclosure of the information in these papers. However, there are significant social concerns surrounding this research. Two critical issues that must be addressed before publication of the papers are: (1) a focused communications plan to increase public awareness and understanding of the significance of these studies and the rationale for their publication, and (2) a review of the essential biosafety and biosecurity aspects of the newly developed knowledge.

Participants discussed the concept of publication of redacted manuscripts with a mechanism for providing the restricted information to legitimate recipients. The group recognized the difficulty of rapidly creating and regulating such a mechanism in light of the complexity of international and national legislation. A consensus was reached that the redaction option is not viable to deal with the two papers under discussion in view of the urgency of the above mentioned public health needs. The participants noted there may be a need for such a mechanism in the future.

Apart from consideration of these two manuscripts, participants acknowledged the existence of broader issues requiring more detailed exploration and advised that these be considered in subsequent consultations involving other stakeholders.

http://www.who.int/influenza/human_animal_interface/consensus_points/en/index.html

Speech/White Paper: Minister of Foreign Affairs Jonas Gahr Støre
Launch of the Norwegian white paper on global health
Oslo, 15 February 2012

[Full text of speech outline]

The Minister based his presentation on the following points:

Friends, Colleagues, Ladies and Gentlemen,

Great pleasure for me to present the Government’s white paper on global health in the presence of so many distinguished guests. A particularly warm welcome to Margaret Chan, Director General of the World Health Organization (WHO) and to those of you who have travelled a long way to take part in the launch.

First ever white paper on global health. One of the purposes of the Norwegian global health policy is to be better at integrating health goals in foreign and development policies and strategies. Understand globalization through the lens of health.

The new white paper sets out the direction of Norwegian policy on global health for the years to come.

1.  Let me first emphasise Norway’s long traditions in the area of global health.

More than a century ago Norwegian missionaries travelled to many parts of the world. Many of them worked in the field of health. They were later joined by representatives of the labour movement, for example, in Kerala, India, just after the Second World War.

A more recent example of Norway’s commitment to this area, is Dr Gro Harlem Brundtland’s leadership of the WHO at the turn of the millennium. We are pleased that she has agreed to give her perspectives at the end of this event.

2.  Second, the relevance of the white paper in today’s global economy

The white paper sets out 3 priority areas:

(i) Mobilising for women’s and children’s rights and health
(ii) Reducing the burden of disease with emphasis on prevention
(iii) Promoting human security through health

There is a strong link between economic fundamentals and global health. I am therefore happy to see so many leading economists here today, like Professor Bloom, as well as those who have fought for women’s rights in general, like Ms Gumbonzvanda.

Most striking change in Norway last century: women’s participation in the labour market.

I am pleased to launch here today an initiative as a follow-up to the white paper: A project that aims at identifying the economic benefits to be gained from investing in women’s health. So far Dr. Margaret Chan (DG WHO) and President Michelle Bachelet (UN Women) have joined the initiative by taking part in the leadership group of the project.

From experience we know that it is important to secure the involvement of finance ministers and heads of government on the issue of global health as part of our broader efforts to promote equality and human rights.

The initiative will last for 18 months and be led by leading experts in the field.

The identification of economic benefits to be gained from investing in women’s health will culminate in a Lancet report.

Key partners will include Bill and Melinda Gates Foundation, Lancet, the UN, the WHO and the World Bank.

Invite all to participate in the initiative.

3.  Third, role of global health in national, foreign and development policies

No coincidence that Health Minister Anne Grete Strøm-Erichsen is on the podium here today.

Many of the health challenges we are facing in Norway are global and cannot be addressed by Norway alone. International action is needed.

Not primarily a question of development assistance. Also an important area for the Norwegian Ministry of Health as well as a number of other ministries.

We will work actively to enhance collaboration across the various ministries. Coherence key.

Another close colleague present here today is Erik Solheim. He is here in the capacity of minister of the environment as much as in the capacity as minister of international development.

Climate change poses serious threats to people’s health and nutrition, but there are situations where interventions for better health also can have a positive impact on the environment and vice versa.

Clean cookstoves and the reduction in emissions of black carbon and methane are examples of this.

4.  Fourth, civil society and youth

Only partnerships can ensure effective action against the global challenges that characterise our time.

New democratising technologies such as mobile phones and social networks have increased the opportunities for civil society to play an active role and hold governments accountable.

Pleased we have such an outstanding representative like Ms Gumbonzvanda at our panel today to represent the youth (World YWCA). Innovation requires the involvement of young people.

The most revolutionary innovations of our time have been created by college drop-outs like Bill Gates and Mark Zuckerberg.

5.  Fifth, role of the WHO

Last but not least, I should mention the WHO – which is at the core of all our global health efforts.

Like to congratulate Margaret Chan on her nomination for a second term. Will follow with great interest your efforts to address the many challenges we are currently facing during your next five years in office.

The white paper emphasises the central role played by the WHO in relation to the global health agenda.

I congratulate Margaret Chan on the effectiveness of the WHO in recent years in contributing to many other partnerships, not least the UN Secretary-General’s initiative in this area Every Woman Every Child.

Norway will continue to be a strong ally of the WHO. But a demanding ally.

Thank you for your attention.

http://www.regjeringen.no/en/dep/ud/aktuelt/taler_artikler/utenriksministeren/2012/stmeld_helse.html?id=672633

White Paper Citation
Meld. St. 11
(2011–2012)
Melding til Stortinget
Global helse i utenriks- og utviklingspolitikken
Tilråding fra Utenriksdepartementet 3. februar 2012, godkjent i statsråd samme dag. (Regjeringen Stoltenberg II)
Dokumentet i pdf-format (3,7 Mb)

[No English version available]

The Weekly Epidemiological Record (WER) for 17 February 2012, vol. 87, 7 (pp 61–64) includes: Fifth meeting of National Influenza Centres – WHO Western Pacific and South-East Asia Regions

http://www.who.int/entity/wer/2012/wer8707.pdf

Twitter Watch  [accessed 20 February 03:35]
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.

WHO @WHO
Transcript from news conference on WHO preliminary consultation on #H5N1 research available here goo.gl/cdCB8 #birdflu
4:10 AM – 19 Feb 12 via web

HarvardPublicHealth @HarvardHSPH
RT @Harvard: Have efforts to combat bird flu increased the risk to public health? hvrd.me/z2J4kh #fluforum

WHO @WHO
WHO press release on the preliminary consultation on #H5N1 research goo.gl/Pzt4Y #birdflu
1:05 PM – 17 Feb 12 via web · Details

RWJF PublicHealth @RWJF_PubHealth
The role of social media in reporting critical health information: bit.ly/z7EAyI #hcsm #dhcx #sm

Arthur Caplan @ArthurCaplan
Important article on anti-vaccine movemnt slate.me/xT8ju5

Amanda Glassman @glassmanamanda
Systematic review of costs and cost-eff of malaria interventions malariajournal.com/content/10/1/3…

Dagfinn Høybråten @Hoybraten
First White Paper on Global Health from the Norwegian government confirms it’s strong commitment to #GAVI regjeringen.no/nb/dep/ud/dok/…
Retweeted by GAVI Alliance
8:23 AM – 14 Feb 12 via web · Details

Health Evidence @HealthEvidence
Did you know that the @PHAC_GC ‘Parents’ Guide to Immunization’ is available in 11 languages? goo.gl/m6sqy
9:31 AM – 15 Feb 12 via web · Details

British Medical Journal
18 February 2012 (Vol 344, Issue 7844)
http://www.bmj.com/content/current

Editorial
Improving the delivery of safe and effective healthcare in low and middle income countries
BMJ 2012; 344 doi: 10.1136/bmj.e981 (Published 14 February 2012)
Cite this as: BMJ 2012;344:e981

Extract
Research is needed into creating workable systems that can deliver and sustain interventions

Many resource constrained countries are unlikely to attain their millennium development goal targets by 2015,1 despite major global efforts and much progress (figure⇓).2 3 For example, only 23 countries are currently estimated to be on track to achieve the target of a 75% reduction in maternal mortality.4 In addition, the rate of new HIV infections continues to outpace the number of HIV positive patients who start treatment—for every five people newly infected with HIV only two begin treatment each year, and about 5.5 million people needing treatment for HIV in low and middle income countries still do not receive it.5 6

Globalization and Health
[Accessed 20 February 2012]
http://www.globalizationandhealth.com/

Research
Positioning women’s and children’s health in African Union policy-making: A policy analysis
Toure K, Sankore R, Kuruvilla S, Scolaro E, Bustreo F and Osotimehin B Globalization and Health 2012, 8:3 (16 February 2012)

Abstract (provisional) [Open Access]
Background
With limited time to achieve the Millennium Development Goals, progress towards improving women’s and children’s health needs to be accelerated. With Africa accounting for over half of the world’s maternal and child deaths, the African Union (AU) has a critical role in prioritizing related policies and catalysing required investments and action. In this paper, the authors assess the evolution of African Union policies related to women’s and children’s health, and analyze how these policies are prioritized and framed.

Methods
The main method used in this policy analysis was a document review of all African Union policies developed from 1963 to 2010, focusing specifically on policies that explicitly mention health. The findings from this document review were discussed with key actors to identify policy implications.

Results
With over 220 policies in total, peace and security is the most common AU policy topic. Social affairs and other development issues became more prominent in the 1990s. The number of policies that mentioned health rose steadily over the years (with 1 policy mentioning health in 1963 to 7 in 2010). This change was catalysed by factors such as: a favourable shift in AU priorities and systems towards development issues, spurred by the transition from the Organization of African Unity to the African Union; the mandate of the African Commission on Human and People’s Rights; health-related advocacy initiatives, such as the Campaign for the Accelerated Reduction of Maternal Mortality in Africa (CARMMA); action and accountability requirements arising from international human rights treaties, the Millennium Development Goals (MDGs), and new health-funding mechanisms, such as the Global Fund to Fight AIDS, Tuberculosis and Malaria. Prioritization of women’s and children’s health issues in AU policies has been framed primarily by human rights, advocacy and accountability considerations, more by economic and health frames looking at investments and impact. AU policies related to reproductive, maternal, newborn and child health also use fewer policy frames than do AU policies related to HIV/AIDS, tuberculosis and malaria.

Conclusion
We suggest that more effective prioritization of women’s and children’s health in African Union policies would be supported by widening the range of policy frames used (notably health and economic) and strengthening the evidence base of all policy frames used. In addition, we suggest it would be beneficial if the partner groups advocating for women’s and children’s health were multi-stakeholder, and included, for instance, health care professionals, regional institutions, parliamentarians, the media, academia, NGOs, development partners and the public and private sectors.

International Journal of Infectious Diseases
Volume 16, Issue 3 pp. e151-e224 (March 2012)
http://www.sciencedirect.com/science/journal/12019712

Original Reports
Epidemiological analysis of measles and evaluation of measles surveillance system performance in Iraq, 2005–2010
Original Research Article
Pages e166-e171
Jagar Jasem, Kawa Marof, Adnan Nawar, K.M. Monirul Islam

Abstract | Figures/Tables | References
Summary
Objectives
The objectives of this study were to identify the risk factors for measles and low vaccination rates, to evaluate the performance of surveillance, and to calculate vaccine effectiveness and failure in Iraq for the years 2005 to 2010.

Methods
Logistic regression was used on measles surveillance data from Iraq obtained during the period 1 January 2005 to 31 December 2010; adjusted odds ratios were calculated. The performance of surveillance was evaluated according to World Health Organization (WHO) guidelines.

Results
Of 18 746 suspected cases, a measles diagnosis was made for 81.4%. Children aged 1–5 years were the most affected (>48%). The odds of measles were significantly higher in the central and southern provinces than in the northern provinces. Those vaccinated with at least one dose of measles-containing vaccine had a 3.7-times lower risk of contracting measles than those who were not vaccinated. Lower odds of vaccination were noted for adults aged 18 years and older and those living in central and southern provinces, as well as those living outside the capital city of a province. Three WHO performance indicators were lower than the recommended cut-off levels. A vaccine failure rate of 66.1% and effectiveness of 90.03% were estimated.

Conclusions
Measles continues to be an important cause of morbidity in Iraq. Improvements in vaccine coverage, proper vaccine handling, and prompt reporting of suspected cases are all necessary to eliminate measles from Iraq.

International Journal of Infectious Diseases
Volume 16, Issue 3 pp. e151-e224 (March 2012)
http://www.sciencedirect.com/science/journal/12019712

Early impact of pneumococcal conjugate vaccine on invasive pneumococcal disease in Singapore children, 2005 through 2010
Original Research Article
Pages e209-e215
Koh Cheng Thoon, Chia Yin Chong, Nancy Wen Sim Tee

Abstract | Figures/Tables | References
Summary
Background
In a previous study covering the period 1998–2004, we estimated the incidence of invasive pneumococcal disease (IPD) in Singapore to be 13.6 per 105 children aged <5 years, and determined that the 7-valent pneumococcal conjugate vaccine (PCV-7) would provide 78.1% serotype coverage for children aged <5 years. In the present study we sought to determine whether incidence and serotype trends have changed and to estimate pneumococcal vaccine coverage.

Methods
We retrospectively reviewed IPD cases from 2005 to 2010 and calculated separate serotype proportions and population-based incidence rates for 2005–2007 (early PCV period) and 2008–2010 (late PCV period). PCV-7 coverage was obtained from the National Immunisation Registry, and patients with PCV-7 vaccine-type IPD (VT IPD) and non-vaccine-type IPD (non-VT IPD) were compared.

Results
One hundred and eighteen patients, with a mean age of 46 months, were identified during 2005–2010. The incidence rate of IPD increased to 14.8 (for 2005–2007) and 15.2 (for 2008–2010) per 105 children <5 years, despite a gradual increase in PCV-7 coverage to approximately 45% of the birth cohort receiving one or more doses of PCV-7. Although IPD due to serotypes 6B and 19A increased, there was a concomitant reduction in other serotypes. Coverage by PCV-7 progressively declined from 78.6% in 2005–2007 to 64.4% in 2008–2010 for children aged <5 years.

Conclusions
Although population coverage with PCV-7 has risen, it remains suboptimal and the incidence of IPD remains unchanged. Furthermore, significant serotype changes (especially increases in 19A) have occurred. We need to adopt newer PCVs with broader serotype coverage and increase the number of children vaccinated as a matter of urgency.

JAMA   
February 15, 2012, Vol 307, No. 7, pp 637-742
http://jama.ama-assn.org/current.dtl

Viewpoints
The Unintended Consequences of Conflict of Interest Disclosure
George Loewenstein, Sunita Sah,
Daylian M. Cain
JAMA. 2012;307(7):669-670.doi:10.1001/jama.2012.154

[No abstract; Initial language per JAMA convention]
Conflicts of interest, both financial and nonfinancial, are ubiquitous in medicine, and the most commonly prescribed remedy is disclosure. The Medicare Payment Advisory Commission and the Accountable Care Act impose a range of disclosure requirements for physicians, and almost all medical journals now require authors to disclose conflicts of interest (although these requirements may be imperfectly heeded). Given that some relationships between physicians and industry are fruitful and some conflicts are unavoidable, can disclosure correct the problems that arise when economic interests prevent physicians from putting patients’ interests first?

Disclosure has appeal across the political spectrum because it acknowledges the problem of conflicts but involves minimal regulation and is less expensive to implement than more comprehensive remedies. More importantly, even if disclosure is rarely seen as providing a complete solution to the problem, it is broadly perceived to have beneficial effects. There are, however, reasons that disclosure can have adverse …

The Lancet  
Feb 18, 2012  Volume 379  Number 9816  p589 – 684 e33
http://www.thelancet.com/journals/lancet/issue/current

Comment
Prevention of serogroup B meningococcal disease
David S Stephens
Preview
In The Lancet, María Elena Santolaya and colleagues1 describe the immunogenicity and safety in healthy Hispanic adolescents of a new multicomponent vaccine, 4CMenB, a potential breakthrough in protection against meningitis, sepsis, and other infections caused by Neisseria meningitidis serogroup B. With the successful development and use of effective polysaccharide-protein glycoconjugate vaccines for serogroups A, C, Y, and W-135,2,3 serogroup B N meningitidis (distinguished by the expression of an [α2→8]-linked polysialic acid capsule) is now the leading cause of meningococcal disease, especially in infants and young children in many countries.

Articles
Immunogenicity and tolerability of a multicomponent meningococcal serogroup B (4CMenB) vaccine in healthy adolescents in Chile: a phase 2b/3 randomised, observer-blind, placebo-controlled study
María Elena Santolaya, Miguel L O’Ryan, María Teresa Valenzuela, Valeria Prado, Rodrigo Vergara, Alma Muñoz, Daniela Toneatto, Gabriela Graña, Huajun Wang, Ralf Clemens, Peter M Dull, for the V72P10 Meningococcal B Adolescent Vaccine Study group

Summary
Background
Effective glycoconjugate vaccines against Neisseria meningitidis serogroups A, C, W-135, and Y have been developed, but serogroup B remains a major cause of severe invasive disease in infants and adolescents worldwide. We assessed immunogenicity and tolerability of a four-component vaccine (4CMenB) in adolescents.

Methods
We did a randomised, observer-blind, placebo-controlled, study at 12 sites in Santiago and Valparaíso, Chile. Adolescents aged 11—17 years received one, two, or three doses of 4CMenB at 1 month, 2 month, or 6 month intervals. Immunogenicity was assessed as serum bactericidal activity using human complement (hSBA) against three reference strains for individual vaccine antigens, and assessed by ELISA against the fourth strain. Local and systemic reactions were recorded 7 days after each vaccination, and adverse events were monitored throughout the study. Participants were initially randomised to five groups (3:3:3:3:1) during the primary phase to receive either one dose, two doses 1 or 2 months apart, or three doses of 4CMenB, or three doses of placebo, with an additional three groups generated for the booster phase. All subjects received at least one dose of 4CMenB. Geometric mean titres, proportions of participants with serum bactericidal antibody titres of 4 or more, and Clopper-Pearson 95% CIs were calculated. The study is registered with ClinicalTrials.gov, number NCT00661713.

Findings
Overall, 1631 adolescents (mean age 13·8 [SD 1·9] years) received at least one dose of 4CMenB. After two or three doses, 99—100% of recipients had hSBA titres of 4 or more against test strains, compared with 92—97% after one dose (p<0·0145) and 29—50% after placebo. At 6 months 91—100% of participants still had titres of 4 or more for each strain after two or three doses, but only 73—76% after one dose; seroresponse rates reached 99—100% for each strain after second or third doses at 6 months. Local and systemic reaction rates were similar after each 4CMenB injection and did not increase with subsequent doses, but remained higher than placebo. No vaccine-related serious adverse events were reported and no significant safety signals were identified.

Interpretation
On the basis of immunogenicity responses this study provides evidence for an adolescent 4CMenB vaccine schedule of two doses, 1—6 months apart, to provide protection against meningococcal B infection. The extent of this protection against meningococcus B variants circulating worldwide will be determined by national surveys.

Funding
Novartis Vaccines and Diagnostics.

Nature Medicine
February 2012, Volume 18 No 2 pp179-321
http://www.nature.com/nm/journal/v18/n1/index.html

News
India mulling stricter laws to curb unethical trials – p182
Killugudi Jayaraman
doi:10.1038/nm0212-182
Full Text – India mulling stricter laws to curb unethical trials | PDF (188 KB)

Clinicians call for greater transparency in trial recruitment – p186
Rebecca Hersher
doi:10.1038/nm0212-186a
Full Text – Clinicians call for greater transparency in trial recruitment | PDF (108 KB)

Pharmacoeconomics
March 1, 2012 – Volume 30 – Issue 3  pp: 171-256
http://adisonline.com/pharmacoeconomics/pages/currenttoc.aspx

Current Opinion
Population- versus Cohort-Based Modelling Approaches
Ethgen, Olivier; Standaert, Baudouin
Pharmacoeconomics. 30(3):171-181, March 1, 2012.
doi: 10.2165/11593050-000000000-00000

Abstract
While no single type of model can provide adequate answers under all circumstances, any modelling endeavour should incorporate three fundamental considerations in any decision-making question: the target population, the disease and the intervention characteristics.

A target population is likely to be characterized by various types of heterogeneity and a dynamic evolution over time. It is therefore important to adequately capture these population effects on the results of a model. There are essentially two different approaches in modelling a population over time: a cohort-based approach and a population-based approach.

In a cohort-based model, a closed group of individuals who have at least one specific characteristic or experience in common over a defined period of time is run through a state transition process. The cohort is generally composed of a hypothetical number of representative or ‘average’ individuals (i.e. the target population is considered to be a homogeneous group).

The population-based approach projects the evolution of the estimated prevalent target population and intends to reflect as much as possible the demographic, epidemiological and clinical characteristics of the prevalent target population relevant for the decision problem.

A cohort-based approach is generally used in most published healthcare decision models. However, this choice is rarely discussed by modellers. In this article, we challenge this assumption. To address the underlying decision problem, we affirm it is crucial that modellers consider the characteristics of the target population. Then, they could opt for using the most appropriate approach. Decision makers should also understand the impact on the results of both types of models in order to make informed healthcare decisions.

Pharmacoeconomics
March 1, 2012 – Volume 30 – Issue 3  pp: 171-256
http://adisonline.com/pharmacoeconomics/pages/currenttoc.aspx

Commentary
Pricing Human Papillomavirus Vaccines: Lessons from Italy
Garattini, Livio; van de Vooren, Katelijne; Curto, Alessandro
Pharmacoeconomics. 30(3):213-217, March 1, 2012.
doi: 10.2165/11596560-000000000-00000

[No abstract]

Pharmacoeconomics
March 1, 2012 – Volume 30 – Issue 3  pp: 171-256
http://adisonline.com/pharmacoeconomics/pages/currenttoc.aspx

Original Research Articles
Methodological Quality of Economic Evaluations of New Pharmaceuticals in the Netherlands
Hoomans, Ties; Severens, Johan L.; van der Roer, Nicole; Delwel, Gepke O.
Pharmacoeconomics. 30(3):219-227, March 1, 2012.
doi: 10.2165/11539850-000000000-00000

Abstract:
Background: In the Netherlands, decisions about the reimbursement of new pharmaceuticals are based on cost effectiveness, as well as therapeutic value and budget impact. Since 1 January 2005, drug manufacturers are formally required to substantiate the cost effectiveness of drugs that have therapeutic added value in comparison with existing ones through pharmacoeconomic evaluations. Dutch guidelines for pharmacoeconomic research provide methods guidance, ensuring consistency in both the evidence and the decision-making process about drug reimbursement.

Aim: This study reviewed the methodological quality of all 21 formally required pharmacoeconomic evaluations of new pharmaceuticals between 1 January 2005 and 1 October 2008, and verified whether these evaluations complied with pharmacoeconomic guidelines.

Methods: Data on the quality of the pharmacoeconomic evaluations were extracted from the pharmacoeconomic reports published by the Dutch Health Care Insurance Board (CVZ). The Board’s newsletters provided information on the advice to, and reimbursement decisions made by, the Dutch Minister of Health. All data extraction was carried out by two independent reviewers, and descriptive analyses were conducted.

Results: The methodological quality was sound in only 8 of the 21 pharmacoeconomic evaluations. In most cases, the perspective of analysis, the comparator drugs, and the reporting of both total and incremental costs and effects were correct. However, drug indication, form (i.e. cost utility/cost effectiveness) and time horizon of the evaluations were frequently flawed. Moreover, the costs and effects of the pharmaceuticals were not always analysed correctly, and modelling studies were often non-transparent. Twelve drugs were reimbursed, and nine were not.

Conclusions: The compliance with pharmacoeconomic guidelines in economic evaluations of new pharmaceuticals can be improved. This would improve the methodological quality of the pharmacoeconomic evaluations and ensure consistency in the evidence and the decision-making process for drug reimbursement in the Netherlands.

PLoS One
[Accessed 20 February 2012]
http://www.plosone.org/article/browse.action;jsessionid=577FD8B9E1F322DAA533C413369CD6F3.ambra01?field=date

Trends in Notifiable Infectious Diseases in China: Implications for Surveillance and Population Health Policy
Lei Zhang, David P. Wilson
PLoS ONE: Research Article, published 16 Feb 2012 10.1371/journal.pone.0031076

Abstract
This study aimed to analyse trends in notifiable infectious diseases in China, in their historical context. Both English and Chinese literature was searched and diseases were categorised according to the type of disease or transmission route. Temporal trends of morbidity and mortality rates were calculated for eight major infectious diseases types. Strong government commitment to public health responses and improvements in quality of life has led to the eradication or containment of a wide range of infectious diseases in China. The overall infectious diseases burden experienced a dramatic drop during 1975–1995, but since then, it reverted and maintained a gradual upward trend to date. Most notifiable diseases are contained at a low endemic level; however, local small-scale outbreaks remain common. Tuberculosis, as a bacterial infection, has re-emerged since the 1990s and has become prevalent in the country. Sexually transmitted infections are in a rapid, exponential growth phase, spreading from core groups to the general population. Together human immunodeficiency virus (HIV), they account for 39% of all death cases due to infectious diseases in China in 2008. Zoonotic infections, such as severe acute respiratory syndrome (SARS), rabies and influenza, pose constant threats to Chinese residents and remain the most deadly disease type among the infected individuals. Therefore, second-generation surveillance of behavioural risks or vectors associated with pathogen transmission should be scaled up. It is necessary to implement public health interventions that target HIV and relevant coinfections, address transmission associated with highly mobile populations, and reduce the risk of cross-species transmission of zoonotic pathogens.

Science        
17 February 2012 vol 335, issue 6070, pages 765-880
http://www.sciencemag.org/current.dtl

Policy Forum
Public Health and Biosecurity
H5N1 Debates: Hung Up on the Wrong Questions
Daniel R. Perez
Science 17 February 2012: 799-801.
Published online 19 January 2012 [DOI:10.1126/science.1219066]
Information related to influenza transmissibility should be published in its entirety.
Summary  Full Text  Full Text (PDF)

Public Health and Biosecurity
Life Sciences at a Crossroads: Respiratory Transmissible H5N1
Michael T. Osterholm and Donald A. Henderson
Science 17 February 2012: 801-802.
Published online 19 January 2012 [DOI:10.1126/science.1218612]
Release of details of recent research on affecting influenza transmissibility poses far more risk than any good that might occur.
Summary Full Text Full Text (PDF)

Public Health and Biosecurity
The Obligation to Prevent the Next Dual-Use Controversy
Ruth R. Faden and Ruth A. Karron
Science 17 February 2012: 802-804.
Published online 9 February 2012 [DOI:10.1126/science.1219668]
The recent debates over H5N1 experiments highlight current shortcomings in oversight of potential dual-use research.
Summary Full Text Full Text (PDF)

The pdf version of Vaccines: The Week in Review  13 February 2012, comprising the posts below for this date, is available here: Vaccines_The Week in Review_13 February 2012

   GAVI CEO Seth Berkley, MD, speaking in Hyderabad, India, praised India’s emergence as both a global vaccine supplier and a leader in vaccine science. He noted, “India is a prime example of how the vaccine landscape has changed over the past 20 years. Indian manufacturers can produce vaccines that meet high quality standards, are appropriate to specific country settings, and are offered at lower and sustainable prices through a reliable supply over time. (They) also have the capacity to engage in applied vaccine development.” Dr. Berkley’s comments came as he accepted the “Genome Valley Excellence Award,” described as a special award from the Federation of the Asian Biotech Association (FABA). The GAVI announcement noted that Dr. Berkley paid tribute to the contribution of India’s biotech sector to the explosion in vaccine research and development and the number of new vaccines currently in the pipeline for a variety of diseases. He continued, “Never before have we seen such a concentration of scientific innovations for vaccines in such a short period of time…These vaccines are set to contribute to big declines in child mortality and morbidity to allow healthy children to meet their full potential which is what it is all about. We hope to see in the coming years a vaccine against malaria and hopefully not too far in the distant future against HIV, TB and, Dengue.”

http://www.gavialliance.org/library/news/gavi-features/2012/seth-berkley-india-award/