GPEI Update: Polio this week – As of 17 July 2013

Update: Polio this week – As of 17 July 2013
Global Polio Eradication Initiative
http://www.polioeradication.org/Dataandmonitoring/Poliothisweek.aspx
[Editor’s extract and bolded text]

:: The outbreak in the Horn of Africa is expanding, with 21 newly-reported cases (one from Kenya, 20 from Somalia). In Somalia, two immunization campaigns have been conducted since the most recent case occurred. Outbreak response activities are continuing, and planning and approaches continue to be strengthened. See ‘Horn of Africa’ section for more.

:: Update on WPV in environmental samples in Israel: WPV1 has now been isolated in 30 sewage samples from 10 sampling sites in Israel. The samples were collected between February and June 2013. All viruses have been detected in sewage only – no cases of paralytic polio have been reported. Health authorities in Israel are continuing to conduct a full epidemiological and public health investigation. The Government of Israel is planning supplementary immunization activities (SIAs) with OPV, to boost mucosal immunity levels to rapidly interrupt virus circulation. More.

Pakistan
:: Three new WPV cases were reported in the past week (WPV1s from Khyber Agency and North Waziristan, Federally Administered Tribal Areas – FATA, and in Peshawar, Khyber Pakhtunkhwa – KP), bringing the total number of WPV cases for 2013 to 21. The case from Peshawar is the most recent WPV in the country, and had onset of paralysis on 30 June…

:: …FATA is the major WPV1 reservoir in Pakistan at the moment. Bara in Khyber Agency is particularly affected. This outbreak is threatening progress achieved elsewhere in the country and in neighbouring Afghanistan.

:: In 2011 and 2012, Bara was the epicentre of a major outbreak which also spread to other areas.

:: The new case in North Waziristan is particularly concerning, as it is in an area where immunizations have been suspended by local leaders since last June. Immunizations in neighbouring high-risk areas are being intensified, to further boost population immunity levels in those areas and prevent further spread of this outbreak. North Waziristan is also affected by cVDPV2 cases.

:: Confirmation of these latest cases underscores the risk ongoing polio transmission (be it due to WPV or cVDPV) in the country continues to pose to children everywhere, and in particular to children living in areas where access has not been possible for extended periods of time.

Central Africa: Chad and Cameroon
:: In Chad, no new WPV cases were reported in the past week. The most recent WPV case had onset of paralysis on 14 June 2012 (WPV1 from Lac). No new cVDPV2 cases were reported in the past week. The total number of cVDPV2 cases for 2013 remains four (the most recent cVDPV2 case had onset of paralysis on 12 May from Ennedi).

:: In Cameroon, one new cVDPV2 case was reported in the past week, bringing the total number of cVDPV2 cases for 2013 to two. This latest case had onset of paralysis on 27 May, from Extreme-Nord. The first case had onset of paralysis on 9 May, also from Extreme-Nord.

:: Emergency outbreak response plans are currently being finalized in both countries. In Chad, nationwide campaigns were held on 23-26 June with trivalent OPV, with further campaigns planned in late July and in August. Cameroon will conduct its first round in the north of the country on 26-29 July with trivalent OPV, with further activities in August and September.

Horn of Africa
:: 21 new WPV1 cases were reported in the past week (one from Dadaab, Kenya, and 20 from Somalia), bringing the total number of WPV1 cases in the region to 73 (65 WPV1s from Somalia and eight WPV1s from Kenya). The most recent case in the region had onset of paralysis on 14 June (the newly-reported case from Kenya).

:: In Somalia, two immunization campaigns have been conducted since the most recent case occurred.

:: Some of the new cases are from inaccessible areas of south-central Somalia. More than 600,000 children are particularly vulnerable to polio in this area. Vaccination posts are being set up in areas bordering inaccessible areas to immunize all populations entering/leaving such areas (including targeting older age groups). Assessments of high-risk areas and populations continue to be conducted, including mapping chronic conflict-areas and major population movement routes. Local-level access negotiations have intensified, to increase access to populations in inaccessible areas.

:: Outbreak response across the Horn of Africa continues to be implemented. In Somalia, campaigns were held on 1-6 July. Planning is under way for NIDs during Ramadan on 21-24 July. Specific radio messages are being developed with the involvement of the Ministry of Religious Affairs.

WHO Report: Priority medicines for Europe and the World 2013 – update

WHO Report: Priority medicines for Europe and the World 2013 – update
Joint news release WHO/Geneva & WHO/EURO

Excerpt
16 July 2013 | GENEVA/COPENHAGEN – For the first time, EU countries have more people over 65 years of age than under 15 years of age. Echoing the trend seen in Europe, much of the rest of the world, including low-and middle-income countries, is moving in a similar direction. A new WHO report calls for pharmaceutical researchers to adjust their research and development efforts to account for this shifting demographic…

…The report, emphasizes that this shift in EU countries is ‘bell weather’ for the rest of the world as globally more people will be ageing and face similar health challenges in the future.

The report focuses on pharmaceutical ‘gaps’, where treatments for a disease or condition may soon become ineffective, are not appropriate for the target patient group, does not exist, or are not sufficiently effective.

“Despite an over three-fold rise in spending on pharmaceutical research and development in Europe since 1990, there is an increasing mismatch between people’s real needs and pharmaceutical innovation. We must ensure that industry develops safe, effective, affordable and appropriate medicines to meet future health needs,” says Nina Sautenkova, Health Technologies and Pharmaceuticals, WHO/Europe.

From a public health view, the trend of an increasing population over 65 leads to greater prevalence of diseases and conditions associated with ageing, such as heart disease, stroke, cancer, diabetes, osteoarthritis, low-back pain, hearing loss, and Alzheimer disease. In combination with health promotion and disease prevention initiatives, these conditions also require more investment in research and innovation to bridge the pharmaceutical gaps.

:: Master document – 2013 Update Report
pdf, 5.09Mb

:: Presentation, Brussels, July 9th 2013

http://www.who.int/medicines/areas/priority_medicines/en/index.html

Can informal social distancing interventions minimize demand for antiviral treatment during a severe pandemic?

BMC Public Health
(Accessed 20 July 2013)
http://www.biomedcentral.com/bmcpublichealth/content

Research article
Can informal social distancing interventions minimize demand for antiviral treatment during a severe pandemic?
Amy L Greer
BMC Public Health 2013, 13:669 doi:10.1186/1471-2458-13-669
Published: 18 July 2013
http://www.biomedcentral.com/1471-2458/13/669/abstract

Abstract (provisional)
Background
In the case of a pandemic, individuals may alter their behaviour. A dynamic model incorporating social distancing can provide a mechanism to consider complex scenarios to support decisions regarding antiviral stockpile size while considering uncertainty around behavioural interventions. We have examined the impact of social distancing measures on the demand for limited healthcare resources such as antiviral drugs from a central stockpile during a severe pandemic.

Methods
We used an existing age-structured model for pandemic influenza in Canada and biologically plausible scenarios for severe influenza transmission within the population. We incorporated data from published reports regarding stated intentions to change behaviour during a pandemic as well as the magnitude and duration of time that individuals expected to maintain the behavioural change. We ran simulations for all combinations of parameter values to identify the projected antiviral requirements in each scenario.

Results
With 12 weeks of distancing, the effect is relatively small for the lowest R0 of 1.6 with a projected stockpile to treat 25.6% being required (IQR = 21.7 — 28.7%) unless the proportion of people involved (81%) and magnitude of the behaviour change is large (69% reduction in contacts). If 24 weeks of distancing occurs, with only a low to moderate reduction in contacts (38% or less), it is not possible to bring treatment requirements below 20% regardless of what proportion of the population engages in distancing measures when transmissibility is high (R0 = 2.0; stockpile size = 31%, IQR = 29.2 — 33.5%).

Conclusions
Our results demonstrate that the magnitude and duration of social distancing behaviours during a severe pandemic have an impact on the need for antiviral drugs. However, significant investments over a long period of time (>16 weeks) are required to decrease the need for antiviral treatment to below 10% of the total population for a highly transmissible viral strain (R0 > 1.8). Encouraging individuals to adopt behaviours that decrease their daily contact rate can help to control the spread of the virus until a vaccine becomes available however; relying on these measures to justify stockpiling fewer courses of treatment will not be sufficient in the case of a severe pandemic.

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

JAMA: West Nile Virus

JAMA   
July 17, 2013, Vol 310, No. 3
http://jama.ama-assn.org/current.dtl

The 2012 West Nile Encephalitis Epidemic in Dallas, Texas FREE
Wendy M. Chung, MD, SM; Christen M. Buseman, PhD, MPH; Sibeso N. Joyner, MPH; Sonya M. Hughes, MPH; Thomas B. Fomby, PhD; James P. Luby, MD; Robert W. Haley, MD
Includes: Supplemental Content

Review
West Nile Virus: Review of the Literature
Lyle R. Petersen, MD, MPH; Aaron C. Brault, PhD; Roger S. Nasci, PhD

Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study

The Lancet  
Jul 20, 2013  Volume 382  Number 9888  p181 – 284  e1
http://www.thelancet.com/journals/lancet/issue/current

Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study
Karen L Kotloff, James P Nataro, William C Blackwelder, Dilruba Nasrin, Tamer H Farag, Sandra Panchalingam, Yukun Wu, Samba O Sow, Dipika Sur, Robert F Breiman, Abu SG Faruque, Anita KM Zaidi, Debasish Saha, Pedro L Alonso, Boubou Tamboura, Doh Sanogo, Uma Onwuchekwa, Byomkesh Manna, Thandavarayan Ramamurthy, Suman Kanungo, John B Ochieng, Richard Omore, Joseph O Oundo, Anowar Hossain, Sumon K Das, Shahnawaz Ahmed, Shahida Qureshi, Farheen Quadri, Richard A Adegbola, Martin Antonio, M Jahangir Hossain, Adebayo Akinsola, Inacio Mandomando, Tacilta Nhampossa, Sozinho Acácio, Kousick Biswas, Ciara E O’Reilly, Eric D Mintz, Lynette Y Berkeley, Khitam Muhsen, Halvor Sommerfelt, Roy M Robins-Browne, Myron M Levine
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2813%2960844-2/abstract

Summary
Background
Diarrhoeal diseases cause illness and death among children younger than 5 years in low-income countries. We designed the Global Enteric Multicenter Study (GEMS) to identify the aetiology and population-based burden of paediatric diarrhoeal disease in sub-Saharan Africa and south Asia.

Methods
The GEMS is a 3-year, prospective, age-stratified, matched case-control study of moderate-to-severe diarrhoea in children aged 0—59 months residing in censused populations at four sites in Africa and three in Asia. We recruited children with moderate-to-severe diarrhoea seeking care at health centres along with one to three randomly selected matched community control children without diarrhoea. From patients with moderate-to-severe diarrhoea and controls, we obtained clinical and epidemiological data, anthropometric measurements, and a faecal sample to identify enteropathogens at enrolment; one follow-up home visit was made about 60 days later to ascertain vital status, clinical outcome, and interval growth.

Findings
We enrolled 9439 children with moderate-to-severe diarrhoea and 13 129 control children without diarrhoea. By analysing adjusted population attributable fractions, most attributable cases of moderate-to-severe diarrhoea were due to four pathogens: rotavirus, Cryptosporidium, enterotoxigenic Escherichia coli producing heat-stable toxin (ST-ETEC; with or without co-expression of heat-labile enterotoxin), and Shigella. Other pathogens were important in selected sites (eg, Aeromonas, Vibrio cholerae O1, Campylobacter jejuni). Odds of dying during follow-up were 8·5-fold higher in patients with moderate-to-severe diarrhoea than in controls (odd ratio 8·5, 95% CI 5·8—12·5, p<0·0001); most deaths (167 [87·9%]) occurred during the first 2 years of life. Pathogens associated with increased risk of case death were ST-ETEC (hazard ratio [HR] 1·9; 0·99—3·5) and typical enteropathogenic E coli (HR 2·6; 1·6—4·1) in infants aged 0—11 months, and Cryptosporidium (HR 2·3; 1·3—4·3) in toddlers aged 12—23 months.

Interpretation
Interventions targeting five pathogens (rotavirus, Shigella, ST-ETEC, Cryptosporidium, typical enteropathogenic E coli) can substantially reduce the burden of moderate-to-severe diarrhoea. New methods and accelerated implementation of existing interventions (rotavirus vaccine and zinc) are needed to prevent disease and improve outcomes.

Funding
The Bill & Melinda Gates Foundation.

Nature Editorial: Parents should vaccinate their children against human papillomavirus.

Nature   
Volume 499 Number 7458 pp253-374  18 July 2013
http://www.nature.com/nature/current_issue.html

Editorial
Active protection
Parents should vaccinate their children against human papillomavirus.
17 July 2013

Scientists at the US Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, announced good news last month. The prevalence of key strains of disease-causing human papilloma­virus (HPV) fell by 56% in US girls aged 14–19 years in the years after 2006, when a vaccine was added to the routine US immunization schedule for girls (L. E. Markowitz et al. J. Infect. Dis. 208, 385–393; 2013).

This is a clear-cut vaccine success story. The decline represents a drop from more than 1 in 10 girls in this age range carrying the relevant strains of the virus to just 1 in 20. This is a significant result. About 14 million people in the United States, most in their late teens and early 20s, become infected with HPV each year. The two most dangerous strains — those targeted by vaccines made by both Merck and GlaxoSmithKline — cause cervical cancer, other anogenital cancers and throat cancer. Merck’s vaccine also protects against two further strains that cause genital warts.

The vaccine is given in three doses over six months. The CDC first recommended that all girls aged 11 and 12 be vaccinated. In 2011, it said the same for boys, for whom only the Merck vaccine is licensed. The idea is to immunize children before they become sexually active. Given that HPV is the most common sexually transmitted disease, waiting longer only increases the odds that the protection will be provided too late. The vaccine has been shown to be both safe and highly effective, and continuing experience — as of March, about 56 million doses had been distributed in the United States — reinforces that.

Yet proportional uptake in the United States has been poor. In 2010, a national survey found that only 49% of girls aged 13 to 17 had received at least one dose of vaccine, and only 32% had received all three doses. By comparison, Rwanda has achieved more than 80% vaccination coverage and several Canadian provinces have reached 85%.

“HPV is an equal-opportunity infectious agent.”

It is possible that unvaccinated girls in the United States are already benefiting from the compliance of the parents who have stepped up to have their children immunized. When the CDC scientists explored whether the decrease in HPV prevalence among 14–19-year-old girls might be due to herd immunity, they found that vaccinated sexually active girls showed a striking 88% decrease in prevalence of the relevant HPV strains, compared with the pre-vaccine era. But they also found a 28% decrease in prevalence among unvaccinated girls. The finding was not statistically significant, and was difficult to interpret owing to differences in the reported sexual behaviour of the two groups — for instance, the unvaccinated girls reported fewer sexual partners. Nevertheless, herd immunity is a possible explanation, and other studies have indicated that it is at play.

It is worth noting that cervical cancer, almost all of which is caused by HPV, disproportionately affects black and Hispanic women in the United States, possibly because they have reduced access to screening. And among women who do contract cervical cancer, black women have proportionally the highest death rate.

But neither white people nor parents of boys of any race or ethnicity should be complacent when considering whether to vaccinate. The vaccine is not only about preventing cervical cancer, nor even only about preventing anal cancer in males who have sex with males. Consider that the proportion of US throat cancers associated with HPV has exploded in recent decades among white men and women. (Similar increases have occurred in Canada and some European countries.) As the actor Michael Douglas was frank enough to acknowledge in an interview published last month, throat cancer of the type that he was treated for in 2010 is caused by HPV contracted through oral sex. (Douglas’s representatives later denied that he had intended the statement to refer to his own particular case.)

The take-home message is that HPV is an equal-opportunity infectious agent. As the CDC noted when it announced the findings last month, cervical cancer is simply the most common among about 19,000 cases of cancer caused by HPV in US women each year, and throat cancer is the most frequent among 8,000 cases of such cancers in men. The costs are sobering: the CDC calculates, for instance, that 50,000 girls alive today who will get cervical cancer during their lifetimes would not have done so had the country quickly reached 80% vaccination rates.

Squeamishness among parents being asked to vaccinate 11-year-olds against a sexually transmitted disease is understandable. But in the face of such a clearly effective means of protecting our young people, ducking the issue, hoping for the best or relying on the responsible actions of others is not.

http://www.nature.com/news/active-protection-1.13387

Perspective: Communicating and Promoting Comparative-Effectiveness Research Findings

New England Journal of Medicine
July 18, 2013  Vol. 369 No. 3
http://www.nejm.org/toc/nejm/medical-journal

Perspective
Communicating and Promoting Comparative-Effectiveness Research Findings
Peter J. Neumann, Sc.D.
N Engl J Med 2013; 369:209-211July 18, 2013DOI: 10.1056/NEJMp1300312
http://www.nejm.org/doi/full/10.1056/NEJMp1300312
[Full text]

The comparative-effectiveness research (CER) movement has sparked an important debate about who may communicate research findings, for what purposes, and using what methodologic standards.1-3 CER is intended to inform discussions about what works in health care. Much of the information comes from research using retrospective databases and quasi-experimental designs rather than randomized clinical trials. The Food and Drug Administration (FDA) prohibits drug companies from using such information to promote pharmaceuticals, requiring that promotions be supported by “substantial evidence” of purported effects (which generally means evidence from two well-controlled trials, though one randomized, controlled trial is permitted in certain circumstances).1,2

Pharmaceutical companies have complained about “asymmetry” between the strict rules for their industry and the absence of restrictions for other organizations — including public and private payers and agencies such as the new Patient-Centered Outcomes Research Institute (PCORI) — which are increasingly conducting CER and communicating its results.3 The counterargument is that permitting drug companies to freely promote CER findings, including those that don’t meet the substantial-evidence standard, opens the door for industry to mislead physicians and patients, potentially harming public health and safety.2 It would also remove incentives for companies to conduct confirmatory trials, effectively allowing them to circumvent the FDA requirements for drug approval.2 Moreover, there are existing channels for manufacturers to communicate CER findings, even if the data do not meet the substantial-evidence standard. For example, manufacturers can write letters to the editor in defense of public challenges, distribute peer-reviewed articles discussing unapproved uses (with certain restrictions), and respond to unsolicited requests for information.2 Industry representatives, however, respond that the rules for communication outside of the substantial-evidence standard are vague and that the lack of formal FDA guidance has restricted their actions.3

In part, the issue can be addressed with better standards for the conduct and translation of CER. FDA officials recently noted that such standards are a necessary prerequisite to ensuring that comparative-effectiveness information from observational studies will provide credible evidence.1 Several groups are developing standards for using observational data in CER and, more generally, for including nonrandomized studies in systematic reviews. Eventually, the FDA might be able to determine when such studies meet substantial-evidence requirements.2 But standards alone are unlikely to suffice. Though the field is improving, judging whether a study based on observational data is of high quality will always be challenging, given unmeasured confounders and investigator choices in design and analysis that can affect results.2 The advent of CER organizations such as the PCORI, which has a specific mandate to disseminate CER findings, calls for a more immediate response.

A possible step forward would be for Congress to broaden the scope of a legislative provision — Section 114 of the Food and Drug Administration Modernization Act of 1997 — that enables drug companies to promote information related to health care economics that conforms to a broader “competent and reliable scientific evidence” standard rather than the substantial-evidence criterion, as long as the targets of that promotion are restricted to formulary committees or similar entities and the information is directly related to approved indications (see tableEvidentiary Standards and Intended Audiences under Current Law and Proposed Expansion.).3,4 Extending Section 114 to include CER findings would permit pharmaceutical companies to promote the information using the competent-and-reliable standard, though only to organizations such as health plans. The FDA could use the Federal Trade Commission’s definition of competent and reliable scientific evidence, which encompasses evidence based on the expertise of relevant professionals using generally accepted procedures, rather than requiring two well-controlled trials.3

Expanding Section 114 in this way would reflect a grand bargain of sorts, providing a more flexible evidentiary framework for business-to-business communication of CER findings while retaining key protections. It would open the door to promotion of results from a wider range of CER studies, including those using observational data to draw inferences about patients, settings, and end points (e.g., adherence, hospitalizations) that are of interest to payers and are difficult or impossible for drug companies to include in registration trials.

Of course, the plan is not without risks. There remain concerns that allowing drug companies to promote information about end points that have not been adequately studied could still deceive intended audiences and remove incentives for companies to conduct randomized trials.    Historical examples of misleading industry marketing and selective reporting of clinical data are warnings to proceed with caution.2 The proposal presumes that health plans have the expertise and wherewithal to judge CER information, and the situation should be monitored. In addition, Section 114 has proved to be challenging to regulate and interpret. To date, the FDA has never released any guidance or taken any regulatory action on the matter.5

However, the plan would preserve key guardrails for public health. Promotion would be restricted to organizations that retain strong incentives to be informed and wary consumers of drug-company promotions and that increasingly employ their own experts, mine their own data, and request CER evidence from companies, sometimes in the form of dossiers using the Academy of Managed Care Pharmacy Format for Formulary Submissions.4 The substantial-evidence standard would remain in place for industry promotion targeting physicians or consumers. Product manufacturers would retain powerful incentives to conduct trials on appropriate indications, populations, and comparators, because such research would provide them with labeled claims for general promotion. Furthermore, the new legislation requiring the FDA to regulate CER promotions according to the competent-and-reliable standard could include a directive to the agency to issue guidance about when such promotions amounted to non-misleading information, which would help advance the creation of standards for CER.

Other mechanisms for exchanging trusted information, such as peer-reviewed publications, would continue to exist, and the creation of additional ones should be encouraged, including government-supported academic detailing of CER findings and the development of ClinicalTrials.gov-type models for observational research (ideally, with FDA- and journal-imposed requirements that designs for observational studies be posted publicly before initiation of a study).2 The new law could also require disclaimer or disclosure statements when information does not constitute substantial evidence.3

The entire debate over the promotion of CER findings has also been thrown for a loop by a series of recent court decisions, including the December 2012 ruling in United States v. Caronia, in which the Second Circuit court overturned a conviction of a drug company sales representative for off-label promotion on the grounds that FDA prohibitions of such promotion infringed the individual’s First Amendment right to free speech. Caronia continues a judiciary trend toward broadening the definition of protected speech and holds that the government cannot restrict truthful, non-misleading off-label promotion. Conceivably, the FDA will have to establish on a case-by-case basis whether any CER promotion, regardless of its intended audience, is “truthful.” However, a great deal of uncertainty prevails, and it may be some time before there is clarity around the issue. In the meantime, expanding Section 114 to include CER could help Congress, the FDA, and perhaps even the Courts to consider and define more clearly the circumstances and audiences for which CER promotion can be truthful and non-misleading.

Varicella Disease in Beijing in the Era of Voluntary Vaccination, 2007 to 2010

The Pediatric Infectious Disease Journal
August 2013 – Volume 32 – Issue 8  pp: A15-A16,e314-e347,805-929
http://journals.lww.com/pidj/pages/currenttoc.aspx

Varicella Disease in Beijing in the Era of Voluntary Vaccination, 2007 to 2010
Lu, Li; Wang, Chengbin; Suo, Luodan; Li, Juan; Liu, Weixiang; Pang, Xinghuo; Seward, Jane F.
Pediatric Infectious Disease Journal. 32(8):e314-e318, August 2013.
doi: 10.1097/INF.0b013e31828d948b

Abstract:
Background: In China, varicella vaccine has been available in the private sector to children ≥12 months of age since 1998 with a single-dose indication. In December 2006, varicella became a notifiable disease in Beijing. We used surveillance data to describe varicella vaccine uptake from 2005 to 2010 and varicella epidemiology in Beijing from 2007 to 2010.

Methods: Limited sociodemographic and clinical information was available from the passive surveillance system. Varicella vaccine coverage was estimated for each year for children born between 2004 and 2008 using the number of children in the immunization registry of each birth year as the denominator without adjustment for history of varicella.

Results: Vaccine coverage increased within each birth cohort between 2005 and 2010. The coverage at 2 years of age increased from 62.4% in 2005 to 74.1% in 2010 and was 80.4% in children 3–6 years of age in 2010. Between 2007 and 2010, 15,544 to 18,256 varicella cases were reported annually with stable overall incidence (range: 1.0–1.1/1000 persons), but the incidence in children 1–4 years of age decreased significantly from 6.2 per 1000 children in 2007 to 4.4 per 1000 children in 2010 (P < 0.001). Among adults (≥20 years of age), there were significant increases in the number and proportion of cases from 2557 (16.5%) in 2007 to 4277 (23.4%) in 2010 (P < 0.001).

Conclusions: Moderately high 1-dose vaccine coverage in young children has been achieved with declining disease incidence, but varicella remains a common, seasonal disease in the population. Current epidemiology suggests that a government-funded varicella vaccine program that includes catch-up vaccination for older children, adolescents and adults needs consideration.

Infectious Disease Burden Related to Child Day Care in the Netherlands

The Pediatric Infectious Disease Journal
August 2013 – Volume 32 – Issue 8  pp: A15-A16,e314-e347,805-929
http://journals.lww.com/pidj/pages/currenttoc.aspx

Infectious Disease Burden Related to Child Day Care in the Netherlands
Enserink, Remko; Ypma, Rolf; Donker, Gé A.; Smit, Henriette A.; van Pelt, Wilfrid
Pediatric Infectious Disease Journal. 32(8):e334-e340, August 2013.
doi: 10.1097/INF.0b013e318290601e

Abstract:
Background: Studying day-care–associated infectious disease dynamics aids in formulating evidence-based guidelines for disease control, thereby supporting day-care centers in their continuous efforts to provide their child population with a safe and hygienic environment. The objective of this study was to estimate the (excess) infectious disease burden related to child day-care attendance in the Netherlands.

Methods: A Dutch surveillance network of child day-care centers (DCCs) prospectively reported on infectious disease episodes and related use of health care among their child population on a daily basis from March 2010 to March 2012.

Results: Gastroenteritis (387 per 1000 child-years) and influenza-like illness (247 per 1000 child-years) were the most frequently reported infectious diseases. DCCs reported these infectious diseases to occur twice as often among children aged 0–2 years compared with children aged 2–4 years. Antibiotic treatment was required in 6%, a general practitioner visit in 29% and hospitalization in 2% of infectious disease episodes. DCC incidences of gastroenteritis and influenza-like illness requiring children to visit a general practitioner were approximately twice as high as general population estimates for this age group. Part of the DCCs indicated to not always wash the hands of children before eating (34%) or after a toilet visit (15%) or to not always clean the toilet and kitchen areas (17%) on a daily basis.

Conclusion: The infectious disease risk associated with child day-care attendance is substantial, particularly among the very young attendees, in excess of general population estimates for this age group and potentially partly preventable.

Undervaccination of Perinatally HIV-infected and HIV-exposed Uninfected Children in Latin America and the Caribbean

The Pediatric Infectious Disease Journal
August 2013 – Volume 32 – Issue 8  pp: A15-A16,e314-e347,805-929
http://journals.lww.com/pidj/pages/currenttoc.aspx

Undervaccination of Perinatally HIV-infected and HIV-exposed Uninfected Children in Latin America and the Caribbean
Succi, Regina C. M.; Krauss, Margot R.; Harris, D. Robert; Machado, Daisy M.; de Moraes-Pinto, Maria Isabel; Mussi-Pinhata, Marisa M.; Ruz, Noris Pavia; Pierre, Russell B.; Kolevic, Lenka; Joao, Esau; Foradori, Irene; Hazra, Rohan; Siberry, George K.; for the NISDI Pediatric Study Group 2012
Pediatric Infectious Disease Journal. 32(8):845-850, August 2013.
doi: 10.1097/INF.0b013e31828bbe68

Abstract:
Background: Perinatally HIV-infected (PHIV) children may be at risk of undervaccination. Vaccination coverage rates among PHIV and HIV-exposed uninfected (HEU) children in Latin America and the Caribbean were compared.

Methods: All PHIV and HEU children born from 2002 to 2007 who were enrolled in a multisite observational study conducted in Latin America and the Caribbean were included in this analysis. Children were classified as up to date if they had received the recommended number of doses of each vaccine at the appropriate intervals by 12 and 24 months of age. Fisher’s exact test was used to analyze the data. Covariates potentially associated with a child’s HIV status were considered in multivariable logistic regression modeling.

Results: Of 1156 eligible children, 768 (66.4%) were HEU and 388 (33.6%) were PHIV. HEU children were significantly (P < 0.01) more likely to be up to date by 12 and 24 months of age for all vaccines examined. Statistically significant differences persisted when the analyses were limited to children enrolled before 12 months of age. Controlling for birth weight, sex, primary caregiver education and any use of tobacco, alcohol or illegal drugs during pregnancy did not contribute significantly to the logistic regression models.

Conclusions: PHIV children were significantly less likely than HEU children to be up to date for their childhood vaccinations at 12 and 24 months of age, even when limited to children enrolled before 12 months of age. Strategies to increase vaccination rates in PHIV are needed.

Vaccination of Healthy Children Against Seasonal Influenza: A European Perspective

The Pediatric Infectious Disease Journal
August 2013 – Volume 32 – Issue 8  pp: A15-A16,e314-e347,805-929
http://journals.lww.com/pidj/pages/currenttoc.aspx

Vaccination of Healthy Children Against Seasonal Influenza: A European Perspective
Heikkinen, Terho; Tsolia, Maria; Finn, Adam
Pediatric Infectious Disease Journal. 32(8):881-888, August 2013.
doi: 10.1097/INF.0b013e3182918168

Abstract:
Despite ample evidence for the great burden that annual influenza epidemics place on children and society in general, few European countries currently recommend influenza vaccination of healthy children of any age. The most frequently cited reasons for reluctance to extend general vaccine recommendations to children include the view that influenza is a mild illness of limited clinical importance, lack of country-specific data on disease burden, uncertainty about the efficacy and safety of influenza vaccines in children and inadequate evidence of cost-effectiveness of vaccinating children. In recent years, several clinical studies have provided new and important information that help address many of these areas of question and concern. In light of this newly available scientific evidence, influenza vaccine recommendations for children should be properly reevaluated in all European countries. Furthermore, to allow for variation in costs and patterns of healthcare delivery between different countries, cost-effectiveness analyses of influenza vaccination of healthy children should be performed in each country or region. Finally, increased efforts should be made to educate both healthcare professionals and the great public about recent findings and advances in the field of pediatric influenza.

Predicting Seasonal Influenza Vaccination among Healthy Chinese Adults in Hong Kong: A Prospective Longitudinal Study

PLoS One
[Accessed 20 July 2013]
http://www.plosone.org/

Comparison of Different Risk Perception Measures in Predicting Seasonal Influenza Vaccination among Healthy Chinese Adults in Hong Kong: A Prospective Longitudinal Study
Qiuyan Liao, Wing Sze Wong, Richard Fielding
Research Article | published 19 Jul 2013 | PLOS ONE 10.1371/journal.pone.0068019

Abstract
Background
Risk perception is a reported predictor of vaccination uptake, but which measures of risk perception best predict influenza vaccination uptake remain unclear.

Methodology
During the main influenza seasons (between January and March) of 2009 (Wave 1) and 2010 (Wave 2),505 Chinese students and employees from a Hong Kong university completed an online survey. Multivariate logistic regression models were conducted to assess how well different risk perceptions measures in Wave 1 predicted vaccination uptake against seasonal influenza in Wave 2.

Principal Findings
The results of the multivariate logistic regression models showed that feeling at risk (beta=0.25, p=0.021) was the better predictor compared with probability judgment while probability judgment (beta=0.25, p=0.029 ) was better than beliefs about risk in predicting subsequent influenza vaccination uptake. Beliefs about risk and feeling at risk seemed to predict the same aspect of subsequent vaccination uptake because their associations with vaccination uptake became insignificant when paired into the logistic regression model. Similarly, to compare the four scales for assessing probability judgment in predicting vaccination uptake, the 7-point verbal scale remained a significant and stronger predictor for vaccination uptake when paired with other three scales; the 6-point verbal scale was a significant and stronger predictor when paired with the percentage scale or the 2-point verbal scale; and the percentage scale was a significant and stronger predictor only when paired with the 2-point verbal scale.

Conclusions/Significance
Beliefs about risk and feeling at risk are not well differentiated by Hong Kong Chinese people. Feeling at risk, an affective-cognitive dimension of risk perception predicts subsequent vaccination uptake better than do probability judgments. Among the four scales for assessing risk probability judgment, the 7-point verbal scale offered the best predictive power for subsequent vaccination uptake.

Evidence Review to Support Influenza Vaccine Introduction in WHO’s Western Pacific Region

PLoS One
[Accessed 20 July 2013]
http://www.plosone.org/

A Review of the Evidence to Support Influenza Vaccine Introduction in Countries and Areas of WHO’s Western Pacific Region
Gina Samaan, Michelle McPherson, Jeffrey Partridge
Research Article | published 16 Jul 2013 | PLOS ONE 10.1371/journal.pone.0070003

Abstract
Background
Immunization against influenza is considered an essential public health intervention to control both seasonal epidemics and pandemic influenza. According to the World Health Organization (WHO), there are five key policy and three key programmatic issues that decision-makers should consider before introducing a vaccine. These are (a) public health priority, (b) disease burden, (c) efficacy, quality and safety of the vaccine, (d) other inventions, (e) economic and financial issues, (f) vaccine presentation, (g) supply availability and (h) programmatic strength. We analyzed the body of evidence currently available on these eight issues in the WHO Western Pacific Region.

Methodology/Principal Findings
Studies indexed in PubMed and published in English between 1 January 2000 and 31 December 2010 from the 37 countries and areas of the Western Pacific Region were screened for keywords pertaining to the five policy and three programmatic issues. Studies were grouped according to country income level and vaccine target group. There were 133 articles that met the selection criteria, with most (90%) coming from high-income countries. Disease burden (n = 34), vaccine efficacy, quality and safety (n = 27) and public health priority (n = 27) were most frequently addressed by studies conducted in the Region. Many studies assessed influenza vaccine policy and programmatic issues in the general population (42%), in the elderly (24%) and in children (17%). Few studies (2%) addressed the eight issues relating to pregnant women.

Conclusions/Significance
The evidence for vaccine introduction in countries and areas in this Region remains limited, particularly in low- and middle-income countries that do not currently have influenza vaccination programmes. Surveillance activities and specialized studies can be used to assess the eight issues including disease burden among vaccine target groups and the cost-effectiveness of influenza vaccine. Multi-country studies should be considered to maximize resource utilization for cross-cutting issues such as vaccine presentation and other inventions.

Single-dose vaccine against tick-borne encephalitis

PNAS – Proceedings of the National Academy of Sciences of the United States of America
(Accessed 20 July 2013)
http://www.pnas.org/content/early/recent

Single-dose vaccine against tick-borne encephalitis
Alexander A. Rumyantsev, Maryann Giel-Moloney, John Catalan, Yuxi Liu, Qing-sheng Gao, Jeff Almond, Harry Kleanthous, and Konstantin V. Pugachev
PNAS 2013 ; published ahead of print July 15, 2013, doi:10.1073/pnas.1306245110
http://www.pnas.org/content/early/2013/07/11/1306245110.abstract

Abstract
Tick-borne encephalitis (TBE) virus is the most important human pathogen transmitted by ticks in Eurasia. Inactivated vaccines are available but require multiple doses and frequent boosters to induce and maintain immunity. Thus far, the goal of developing a safe, live attenuated vaccine effective after a single dose has remained elusive. Here we used a replication-defective (single-cycle) flavivirus platform, RepliVax, to generate a safe, single-dose TBE vaccine. Several RepliVax-TBE candidates attenuated by a deletion in the capsid gene were constructed using different flavivirus backbones containing the envelope genes of TBE virus. RepliVax-TBE based on a West Nile virus backbone (RV-WN/TBE) grew more efficiently in helper cells than candidates based on Langat E5, TBE, and yellow fever 17D backbones, and was found to be highly immunogenic and efficacious in mice. Live chimeric yellow fever 17D/TBE, Dengue 2/TBE, and Langat E5/TBE candidates were also constructed but were found to be underattenuated. RV-WN/TBE was demonstrated to be highly immunogenic in Rhesus macaques after a single dose, inducing a significantly more durable humoral immune response compared with three doses of a licensed, adjuvanted human inactivated vaccine. Its immunogenicity was not significantly affected by preexisting immunity against WN. Immunized monkeys were protected from a stringent surrogate challenge. These results support the identification of a single-cycle TBE vaccine with a superior product profile to existing inactivated vaccines, which could lead to improved vaccine coverage and control of the disease.

Influenza: Prioritizing Homeless and Hard-to-Reach Populations

Public Health Ethics
Volume 6 Issue 2 July 2013
http://phe.oxfordjournals.org/content/current

Influenza: Prioritizing Homeless and Hard-to-Reach Populations
Kristy Buccieri
http://phe.oxfordjournals.org/content/6/2/185.abstract
Abstract
The manner in which limited vaccines are distributed during a pandemic is an ethical issue. The utility principle has been used to argue priority be given to certain individuals based on factors such as the epidemiology of the spread of disease and maintaining the functioning of society. The equity principle has been used to encourage fair practices that account for the economic and social costs of all decisions made. We argue that both principles are met through priority vaccination of homeless individuals, as this strategy protects a medically vulnerable population while reducing the chances of transmission to others as they move through populated urban spaces. We begin by reviewing debates around ethical vaccine distribution. We then argue the homeless are a medically high-risk population who may contribute to the spread of disease through their mobility. As immunization rates are generally lower among the homeless and many do not access mainstream health care, we argue that community vaccine clinics must be used to reach these individuals. We provide support by analyzing Toronto Public Health’s operation of vaccine clinics in shelters and drop-in centres during pH1N1 and conclude that this strategy is effective for immunizing homeless individuals, bringing together the equity and utility principles.

Enhancing Children against Unhealthy Behaviors—An Ethical and Policy Assessment of Using a Nicotine Vaccine

Public Health Ethics
Volume 6 Issue 2 July 2013
http://phe.oxfordjournals.org/content/current

Enhancing Children against Unhealthy Behaviors—An Ethical and Policy Assessment of Using a Nicotine Vaccine
Ori Lev, Benjamin S. Wilfond, and Colleen M. McBride
Public Health Ethics (2013) 6 (2): 197-206 doi:10.1093/phe/pht006
http://phe.oxfordjournals.org/content/6/2/197.abstract

Abstract
Health behaviors such as tobacco use contribute significantly to poor health. It is widely recognized that efforts to prevent poor health outcomes should begin in early childhood. Biomedical enhancements, such as a nicotine vaccine, are now emerging and have potential to be used for primary prevention of common diseases. In anticipation of such enhancements, it is important that we begin to consider the ethical and policy appropriateness of their use with children. The main ethical concerns raised by enhancing children relate to their impact on children’s well-being and autonomy. These concerns are significant, however they do not appear to apply in the case of the nicotine vaccine; indeed the vaccine could even further these goals for children. Nevertheless, concerns about broadly applying this enhancement may be more challenging. The vaccine may be less cost-effective than alternative public efforts to prevent tobacco use, utilizing it could distract from addressing the foundational causes of smoking and it might not be publically acceptable. Empirical research about these concerns is needed to ascertain their likelihood and impact as well as how they could be minimized. This research could help determine whether behavior-related enhancements hold promise for improving children’s health.

Intradermal delivery for vaccine dose sparing: Overview of current issues

Vaccine
Volume 31, Issue 34, Pages 3389-3460 (25 July 2013)
http://www.sciencedirect.com/science/journal/0264410X
Skin Vaccination Summit 2011
Gallaudet University, Washington, DC, USA
12–14 October 2011

Intradermal delivery for vaccine dose sparing: Overview of current issues
Original Research Article
Pages 3392-3395
Darin Zehrung, Courtney Jarrahian, Amy Wales
Abstract
There is a wide range of methods and technologies aimed at improving human vaccine products and the way they are delivered. Some of these have the potential to increase vaccine effectiveness in specific populations and may furthermore help to increase vaccine access, reduce costs, and ease the logistical burdens of immunization programs, especially in low-resource settings. One strategy under evaluation is the use of intradermal (ID) delivery of vaccines, which has been shown to result in dose sparing with some vaccines. Novel ID delivery devices could enable needle-free and therefore safer and more reliable ID administration than current ID injection methods, facilitating ID delivery and dose sparing with existing or new vaccines. There are promising clinical data with some vaccines that highlight the potential of reduced-dose immunization via the ID route. And more studies are under way. However, a number of clinical and technical research as well as operational challenges exist, including establishing the optimal doses for different vaccines, reformulating to adjust antigen concentration or add preservatives, matching vaccine vial volume to session size, working with vaccine manufacturers to achieve regulatory clearance for ID delivery, and developing ID delivery devices suitable for the varying scenarios of use of different vaccines. These will need to be addressed before the benefits of ID delivery and the impact of novel ID delivery technologies on human health are fully realized.

Rotavirus vaccine administered by skin vaccination using a microneedle patch

Vaccine
Volume 31, Issue 34, Pages 3389-3460 (25 July 2013)
http://www.sciencedirect.com/science/journal/0264410X
Skin Vaccination Summit 2011
Gallaudet University, Washington, DC, USA
12–14 October 2011

Dose sparing and enhanced immunogenicity of inactivated rotavirus vaccine administered by skin vaccination using a microneedle patch
Original Research Article
Pages 3396-3402
Sungsil Moon, Yuhuan Wang, Chris Edens, Jon R. Gentsch, Mark R. Prausnitz, Baoming Jiang
Abstract
Skin immunization is effective against a number of infectious diseases, including smallpox and tuberculosis, but is difficult to administer. Here, we assessed the use of an easy-to-administer microneedle (MN) patch for skin vaccination using an inactivated rotavirus vaccine (IRV) in mice. Female inbred BALB/c mice in groups of six were immunized once in the skin using MN coated with 5 μg or 0.5 μg of inactivated rotavirus antigen or by intramuscular (IM) injection with 5 μg or 0.5 μg of the same antigen, bled at 0 and 10 days, and exsanguinated at 28 days. Rotavirus-specific IgG titers increased over time in sera of mice immunized with IRV using MN or IM injection. However, titers of IgG and neutralizing activity were generally higher in MN immunized mice than in IM immunized mice; the titers in mice that received 0.5 μg of antigen with MN were comparable or higher than those that received 5 μg of antigen IM, indicating dose sparing. None of the mice receiving negative-control, antigen-free MN had any IgG titers. In addition, MN immunization was at least as effective as IM administration in inducing a memory response of dendritic cells in the spleen. Our findings demonstrate that MN delivery can reduce the IRV dose needed to mount a robust immune response compared to IM injection and holds promise as a strategy for developing a safer and more effective rotavirus vaccine for use among children throughout the world

Measles vaccination using a microneedle patch

Vaccine
Volume 31, Issue 34, Pages 3389-3460 (25 July 2013)
http://www.sciencedirect.com/science/journal/0264410X
Skin Vaccination Summit 2011
Gallaudet University, Washington, DC, USA
12–14 October 2011

Measles vaccination using a microneedle patch
Original Research Article
Pages 3403-3409
Chris Edens, Marcus L. Collins, Jessica Ayers, Paul A. Rota, Mark R. Prausnitz
Abstract
Measles vaccination programs would benefit from delivery methods that decrease cost, simplify logistics, and increase safety. Conventional subcutaneous injection is limited by the need for skilled healthcare professionals to reconstitute and administer injections, and by the need for safe needle handling and disposal to reduce the risk of disease transmission through needle re-use and needlestick injury. Microneedles are micron-scale, solid needles coated with a dry formulation of vaccine that dissolves in the skin within minutes after patch application. By avoiding the use of hypodermic needles, vaccination using a microneedle patch could be carried out by minimally trained personnel with reduced risk of blood-borne disease transmission. The goal of this study was to evaluate measles vaccination using a microneedle patch to address some of the limitations of subcutaneous injection. Viability of vaccine virus dried onto a microneedle patch was stabilized by incorporation of the sugar, trehalose, and loss of viral titer was less than 1 log10(TCID50) after storage for at least 30 days at room temperature. Microneedle patches were then used to immunize cotton rats with the Edmonston-Zagreb measles vaccine strain. Vaccination using microneedles at doses equaling the standard human dose or one-fifth the human dose generated neutralizing antibody levels equivalent to those of a subcutaneous immunization at the same dose. These results show that measles vaccine can be stabilized on microneedles and that vaccine efficiently reconstitutes in vivo to generate a neutralizing antibody response equivalent to that generated by subcutaneous injection.

From Google Scholar+ [to 20 July 2013]

From Google Scholar & other sources: Selected Journal Articles, Dissertations, Theses, Commentary

Receipt of human papillomavirus vaccine among privately insured adult women in a US Midwestern Health Maintenance Organization
EO Kharbanda, E Parker, JD Nordin, B Hedblom… – Preventive Medicine, 2013
Objectives To describe human papillomavirus (HPV) vaccine coverage among adult privately insured women including variation in coverage by race/ethnicity. Methods This cross-sectional, observational study included women 18–26 years of age with continuous …

O10. 2 A Community-Randomised Phase IV Human Papillomavirus (HPV) Vaccination Trial of Vaccination Strategy
J Paavonen – Sexually Transmitted Infections, 2013
… Abstract. High-risk human papillomavirus (hrHPV) is the 2nd leading cause of cancer in women Bivalent Cervarix™ vaccine is highly efficacious against hrHPVs and associated precancers. Mathematical models disagree about the best vaccination strategy. …

Novel HIV vaccine strategies: overview and perspective
Yehuda Z. Cohen, Center for Virus and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, USA; Raphael Dolin, Beth Israel Deaconess Medical Center, Boston, USA
Published online before print July 15, 2013, doi: 10.1177/2051013613494535 Therapeutic Advances in Vaccines July 15, 2013 2051013613494535
http://tav.sagepub.com/content/early/2013/07/14/2051013613494535.abstract
Abstract
A human immunodeficiency virus (HIV) vaccine remains a central component in the quest to control the worldwide epidemic. To examine the status of the development of HIV vaccines, we review the results of the efficacy trials carried out to date and the immunologic principles that guided them. Four vaccine concepts have been evaluated in HIV-1 vaccine efficacy trials, and the results of these trials have provided significant information for future vaccine development. While one of these trials demonstrated that a safe and effective HIV vaccine is possible, many questions remain regarding the basis for the observed protection and the most efficient way to stimulate it. Novel HIV vaccine strategies including induction of highly potent broadly neutralizing antibodies, use of novel homologous and heterologous vector systems, and vectored immunoprophylaxis seek to expand and build upon the knowledge gained from these trials.

Immunogenicity of Quadrivalent Human Papillomavirus Vaccine in Organ Transplant Recipients
D Kumar, ER Unger, G Panicker, P Medvedev… – American Journal of Transplantation…, 2013
Abstract Solid organ transplant recipients are at risk of morbidity from human papillomavirus
(HPV)-related diseases. Quadrivalent HPV vaccine is recommended for post- transplant patients but there are no data on vaccine immunogenicity. We determined the …

Vaccines: The Week in Review 13 July 2013

Vaccines: The Week in Review is a weekly digest — summarizing news, events, announcements, peer-reviewed articles and research in the global vaccine ethics and policy space. Content is aggregated from key governmental, NGO, international organization and industry sources, key peer-reviewed journals, and other media channels. This summary proceeds from the broad base of themes and issues monitored by the Center for Vaccine Ethics & Policy in its work: it is not intended to be exhaustive in its coverage. You are viewing the blog version of our weekly digest, typically comprised of between 30 and 40 posts below all dated “29 June 2013″
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Email Summary: Vaccines: The Week in Review is published as a single email summary, scheduled for release each Saturday eveningbefore midnight (EDT in the U.S.). If you would like to receive the email version, please send your request to david.r.curry@centerforvaccineethicsandpolicy.org.
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pdf version: A pdf of the current issues is available here: Vaccines_The Week in Review_13 July 2013
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Twitter: Readers can also follow developments on twitter: @vaxethicspolicy.
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Links: We endeavor to test each link as we incorporate it into any post, but recognize that some links may become “stale” as publications and websites reorganize content over time. We apologize in advance for any links that may not be operative. We believe the contextual information in a given post should allow retrieval, but please contact us as above for assistance if necessary.
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Support: If you would like to join the growing list of individuals who support this service and its contribution to their roles in public health, clinical practice, government, IGOs/NGOs, research, industry and academia, please visit this page at The Wistar Institute, our co-founder and fiduciary. Thank you…
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David R. Curry, MS
Executive Director
Center for Vaccine Ethics and Policy
a program of the
– Division of Medical Ethics, NYU Medical School
– The Wistar Institute Vaccine Center
– Children’s Hospital of Philadelphia Vaccine Education Center
Associate Faculty, Division of Medical Ethics, NYU Medical School

– email: david.r.curry@centerforvaccineethicsandpolicy.org
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Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Update: IHR Emergency Committee, CDC Recommendations

WHO: Middle East Respiratory Syndrome Coronavirus (MERS-CoV) – Statement by WHO Director-General, Dr Margaret Chan
9 July 2013
“Cases of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) have been reported regularly to WHO since 2012. In order to take an independent expert view of the situation and to be prepared for any further action, should it be required, the Director-General convened a meeting of the International Health Regulations Emergency Committee. The Emergency Committee is composed of international experts from a variety of relevant disciplines and all Regions of WHO, their task is to provide expert technical advice to the Director-General in accordance with the IHR (2005) [see link to list of members below].

“The first meeting of the Committee was held on Tuesday, 9 July 2013, from 12:00 to 15:00 Geneva time (CET).

“After reviewing data on the current situation provided by the Secretariat, and information presented to the Committee by officials of several States Parties which have, or have had, cases of MERS-CoV, and after further deliberation, the Committee considered that additional information was needed in a number of areas.

“The Committee also considered it needed time for further discussion and consideration. In this regard, it noted that a second Committee meeting is set to be held Wednesday, 17 July 2013, at 12:00 Geneva time (CET).
http://www.who.int/ihr/procedures/statements_20130709/en/index.html

List of Members of the International Health Regulations (2005) Emergency Committee concerning Middle East Respiratory Syndrome Coronavirus (MERS-CoV)
http://www.who.int/ihr/procedures/emerg_comm_members_2013/en/index.html

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WHO: Global Alert and Response (GAR) – Disease Outbreak News
http://www.who.int/csr/don/2013_03_12/en/index.html
Middle East respiratory syndrome coronavirus (MERS-CoV) – update 11 July 2013  Excerpt
The Ministry of Health (MoH) in Saudi Arabia has announced an additional laboratory-confirmed case of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in the country.

The patient is a 66 year-old man from Asir region with an underlying health condition. He is currently in critical but stable condition.

In addition, a Qatari patient earlier confirmed with MERS-CoV infection, who was being treated in the United Kingdom died on 28 June 2013.

Globally, from September 2012 to date, WHO has been informed of a total of 81 laboratory-confirmed cases of infection with MERS-CoV, including 45 deaths.

Based on the current situation and available information, WHO encourages all Member States to continue their surveillance for severe acute respiratory infections (SARI) and to carefully review any unusual patterns…

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CDC/MMWR Watch – July 12, 2013 / Vol. 62 / No. 27
http://www.cdc.gov/mmwr/mmwr_wk.html
Update: Recommendations for Middle East Respiratory Syndrome Coronavirus (MERS-CoV)
Weekly
July 12, 2013 / 62(27);557-557
On June 11, 2013, CDC issued interim infection prevention and control recommendations for hospitalized patients with known or suspected Middle East respiratory syndrome coronavirus (MERS-CoV) infection in U.S. hospitals (1). To date, no MERS-CoV cases have been reported in the United States; however, cases have been reported in eight other countries (2). Recent published reports (3,4) have described limited health-care transmission of MERS-CoV, including cases among health-care personnel in international settings. These published reports highlight the need for rapid detection of infectious patients and adherence to correct infection prevention measures to prevent transmission of the virus among patients, health-care personnel, and visitors.

In coming months, the U.S. health-care system might be called upon to provide care to patients infected with MERS-CoV. Front-line providers and health-care organizations should be prepared to care for MERS-CoV patients as part of routine operations. To aid providers and facilities, CDC has developed checklists that identify key actions that can be taken now to enhance preparedness for treating persons with MERS-CoV infection and compiled a list of preparedness resources (available at http://www.cdc.gov/coronavirus/mers/preparedness).

Additional information, including guidance on case definitions, infection control, case investigation, and specimen collection and testing, is available at the CDC MERS website (2).         The MERS website contains the most current information and guidance, which is subject to change. State and local health departments with questions should contact the CDC Emergency Operations Center at telephone, 770-488-7100.

References

    1. CDC. Interim infection prevention and control recommendations for hospitalized patients with Middle East respiratory syndrome coronavirus (MERS-CoV). Atlanta, GA: US Department of Health and Human Services, CDC; 2013. Available at http://wwwdev.cdc.gov/coronavirus/mers/infection-prevention-control.html.
    2. CDC. Middle East respiratory syndrome (MERS). Atlanta, GA: US Department of Health and Human Services, CDC; 2013. Available at http://www.cdc.gov/coronavirus/mers/index.html.
    3. Assiri A, McGeer A, Perl TM, et al. Hospital outbreak of Middle East respiratory syndrome coronavirus. N Engl J Med 2013. Epub June 19, 2013.
    4. Mailles A, Blanckaert K, Chaud P, et al. First cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infections in France, investigations and implications for the prevention of human-to-human transmission, France, May 2013. Euro Surveill 2013;18(24).

http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6227a4.htm?s_cid=mm6227a4_w

Lions Clubs International committed to raise US$30 million for GAVI

 Lions Clubs International committed to raise US$30 million for GAVI through “a unique partnership designed to protect tens of millions of children in the world’s poorest countries against measles, a highly infectious disease that kills an estimated 430 people every day, mostly in developing countries.” Under the partnership, Lions Clubs will deploy its network of 1.35 million volunteers to raise US$30 million for the GAVI Alliance by 2017, when Lions Clubs celebrates its 100th anniversary. The funds raised by the Lions will be matched by the UK’s Department for International Development (DFID) and the Bill & Melinda Gates Foundation, bringing the total to US$60 million. Lions Clubs and GAVI “will work with ministries of health in developing countries to ensure children are vaccinated against measles and rubella. Lions will also play a key role in social mobilization efforts by working work with local leaders, coordinating community-level publicity and serving as volunteers at vaccination centers.”

Full media release: HAMBURG, Germany, July 8, 2013 /PRNewswire-USNewswire:  http://www.prnewswire.com/news-releases/lions-clubs-international-and-gavi-alliance-partner-to-protect-children-from-measles-214616501.html

Global Fund announces support HIV, malaria programs in Namibia; seeks Technical Review Panerl nominees

   The Global Fund to Fight AIDS, Tuberculosis and Malaria signed agreements with Namibia for US$91.6 million to further support the national HIV response and US$8.5 million for malaria programs. Dr. Richard Kamwi, Minister of Health, said, “We are very pleased to be signing these grants, which will allow us to continue to improve the quality of health of our people in Namibia. The Global Fund continues to be an important partner in our country, and we are committed to continue investing in this fight. Our government is currently funding 75 percent of ARV treatment and we thank the Global Fund for funding the remaining 25 percent. Thanks to this support we were able to reach 85 percent coverage in March last year.”
Full media release: 9 July 2013  WINDHOEK, Namibia:  http://www.theglobalfund.org/en/mediacenter/newsreleases/2013-07-09_Namibia_and_the_Global_Fund_Sign_USD_100_Million_Grant_Agreement/

Global Fund Seeks Applicants for Technical Review Panel
02 July 2013
Excerpt
The Global Fund said it is seeking new members for a Technical Review Panel, an independent group of experts convened to assess the technical merit of funding requests to the Global Fund. The Panel also plays a role in guiding the strategic focus of Global Fund investments, by looking at effective program design and implementation strategies, so that the greatest impact can be achieved…

Senior level HIV experts, tuberculosis experts, and malaria experts as well as experts on health systems, community systems, and cross cutting development are all encouraged to consider applying. Applicants will be evaluated on their technical qualifications, interpersonal skills and other qualities. We seek qualified experts who bring a range of technical skills and experience from the public and private sectors and civil society. Significant experience working in a developing country is a key requirement.

The closing date for applications is Wednesday, 31 July 2013, at 12 Noon (GMT). For more information on how to apply, please visit: http://www.theglobalfund.org/en/trp/recruitment/
http://www.theglobalfund.org/en/mediacenter/announcements/2013-07-02_Global_Fund_Seeks_Applicants_for_Technical_Review_Panel/

Prevenar 13 receives European approval for an expanded indication to include adults aged 18 to 49 years

    Pfizer announced that Prevenar 13* received European approval for an expanded indication to include adults aged 18 to 49 years for active immunization for the prevention of invasive disease caused by vaccine-type Streptococcus pneumoniae (S. pneumoniae). With previously approved use in infants, young children and adolescents aged 6 weeks to 17 years, as well as adults 50 years of age and older, Prevenar 13 is now the only pneumococcal vaccine in the EU that offers protection against invasive disease from infancy through adulthood. Pfizer noted that the European Commission’s decision to approve this label expansion for Prevenar 13 followed the submission and review of data from an open-label Phase 3 trial of the vaccine in healthy adults aged 18 to 49 years.2 The study – which met all primary and secondary objectives – showed that Prevenar 13 is at least as immunogenic in this age group as it is in adults 60 to 64 years of age, as measured one month after vaccination.

Full media release: July 10, 2013  NEW YORK–(BUSINESS WIRE)– http://www.businesswire.com/news/home/20130710005477/en/Pfizer-Receives-European-Approval-Expand-Prevenar-13*

Global Good to commercialize vaccine storage invention for use in developing countries

   Global Good and AUCMA announced an agreement to commercialize Global Good’s vaccine storage invention for use in developing countries. Under the agreement, AUCMA, described as a leading refrigeration company, “will manufacture and distribute the device to help strengthen the vaccine supply chain in underserved regions. The agreement marks the first commercialization deal for Global Good, which is a collaboration between Intellectual Ventures (IV) and Bill Gates to invent technology that improves life in developing countries.” Global Good’s vaccine storage device uses “a combination of super-insulation techniques to hold vaccines at the appropriate temperature for more than a month with no external power. Originally unveiled by IV CEO Nathan Myhrvold at TED 2010, the device was developed at IV Lab and recently completed field trials in Senegal.” The vaccine storage device will undergo additional field testing in Africa before broader manufacturing and distribution in 2014. “With only a single batch of ice, it can store up to 300 doses of vaccines, enough to serve a community of 6,000 for more than a month. The device is also equipped with technology to monitor its location, internal temperature and the number of times vaccines have been retrieved from it. This information can be communicated via daily SMS transmissions and downloaded via a USB port to inform future vaccination campaign planning.”

Full Media Release: BELLEVUE, Wash. and QINGDAO, China, July 9, 2013 /PRNewswire/ http://www.prnewswire.com/news-releases/global-good-and-aucma-partner-to-commercialize-vaccine-storage-invention-for-developing-countries-214733141.html

PATH names Dr. David C. Kaslow vice president of product development; Ashley Birkett as deputy director of Malaria Vaccine Initiative.

PATH named Dr. David C. Kaslow to the newly created position of vice president of product development, and Ashley Birkett as deputy director of PATH’s Malaria Vaccine Initiative. In his new role, Dr. Kaslow, currently director of PATH’s Malaria Vaccine Initiative (MVI), “will oversee the activities of all five of PATH’s product development programs, as well as PATH’s China programs, which also focus heavily on product development activities.”  PATH’s five product development programs consist of MVI, Drug Development, Technology Solutions, Vaccine Development, and Vaccine Access and Delivery. These programs represent PATH’s work in community-based interventions, devices, diagnostics, drugs, and vaccines. Dr. Kaslow “is a physician-scientist with 25 years of vaccine research and development experience whose professional career encompasses the academic, governmental, and private sectors. He served as vice president and head of vaccine project leadership and management at Merck Research Laboratories and worked for more than a decade as a tenured scientist at the National Institutes of Health, where he founded the Malaria Vaccine Development Unit. He became director of MVI in early 2012 and, prior to that, served for three years as chair of MVI’s Vaccine Science Portfolio Advisory Council.”

PATH also announced that Ashley Birkett, PhD, a five-year veteran of MVI and current director of research and development (R&D), has been appointed to the new position of deputy director at MVI, effective immediately. In his previous position as director of R&D at MVI, Ashley has led MVI’s efforts to support the development of transmission-blocking vaccines; guided MVI’s portfolio of evaluation technology projects, which are developing and refining ways to assess vaccine efficacy prior to large-scale field trials; and provided technical support to MVI’s two additional program areas: next-generation vaccines and the RTS,S program. Prior to joining MVI, he was senior director of preclinical research at Acambis (now part of Sanofi Pasteur Biologics Co.).

Full media release: Seattle, July 12, 2013 http://www.path.org/news/pr130712-kaslow.php

Gates Foundation names Keith Klugman as Director, Pneumonia Program

   The Bill & Melinda Gates Foundation announced that Keith Klugman has been named director of its Pneumonia program. Dr. Klugman was previously the William H. Foege Professor of Global Health and Professor of Epidemiology in the Rollins School of Public Health at Emory University, as well as Professor of Medicine in the Division of Infectious Diseases at the Emory School of Medicine. He will continue to serve as Honorary Professor in the Respiratory and Meningeal Pathogens Research Unit at the University of the Witwatersrand in South Africa. Klugman has chaired or served on numerous expert committees for the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC). He trained in South Africa and completed his post-doctoral research at Rockefeller University in New York.

http://www.gatesfoundation.org/Media-Center/Press-Releases/2013/08/Klugman

IAVI announces appointment of Dr. Robin Weiss as Chair, Scientific Advisory Committee

   The International AIDS Vaccine Initiative (IAVI) announced the appointment of Dr. Robin Weiss as Chair of its Scientific Advisory Committee (SAC) effective July 1, 2013, to June 30, 2016. In this capacity, Dr. Weiss will also serve as the SAC representative to the IAVI Board of Directors. Dr. Weiss is Emeritus Professor of Viral Oncology at University College London (UCL) and will be the fourth SAC Chair since IAVI was established in 1996. Margaret McGlynn, President and CEO of IAVI, commented, “We are delighted that Dr. Weiss, a pioneer in HIV research whose laboratory made seminal findings on the pathogenesis of HIV infection, is rejoining IAVI’s Scientific Advisory Committee to serve as its Chairman. In this capacity, Dr. Weiss will lead a newly reconstituted SAC to provide scientific and strategic advice and counsel to IAVI’s research and development efforts aimed at accelerating global efforts in HIV vaccine development.”

Full media release: July 09, 2013 – http://www.iavi.org/Information-Center/Press-Releases/Pages/HIV-Research-Pioneer-Dr-Robin-Weiss-Appointed-Chair-of-IAVI-Scientific-Advisory-Committee.aspx

GPEI Update: Polio this week – As of 10 July 2013

Update: Polio this week – As of 10 July 2013
Global Polio Eradication Initiative
http://www.polioeradication.org/Dataandmonitoring/Poliothisweek.aspx

[Editor’s extract and bolded text]
:: In the Horn of Africa, an outbreak of WPV1 is continuing, centred around Banadir, Somalia. The majority of cases associated with this outbreak developed paralysis before the start of the comprehensive emergency outbreak response activities.
:: WPV3 continues to be at the lowest ever recorded levels. Globally, WPV3 has not been detected anywhere since November 2012, from Yobe state, Nigeria. In Asia, the strain the strain has not been detected in over a year (since April 2012, from Khyber Agency in Pakistan)… For more, please click here: http://www.polioeradication.org/Mediaroom/Newsstories/Newsstories2013/tabid/488/iid/290/Default.aspx

Nigeria
:: Nine new WPV cases were reported in the past week, bringing the total number of WPV cases for 2013 to 35. The most recent WPV case had onset of paralysis on 18 June (WPV1 from Bauchi).

Pakistan
:: FATA is the major WPV1 reservoir in Pakistan at the moment. Of 18 WPV1 cases reported in the country in 2013, more than half are from FATA. Bara in Khyber Agency is particularly affected. This outbreak is threatening progress achieved elsewhere in the country and in neighbouring Afghanistan.

:: In 2011 and 2012, Bara was the epicentre of a major outbreak which also spread to other areas.

Horn of Africa
:: Four new WPV cases were reported in the past week (all from Banadir, Somalia), bringing the total number of WPV1 cases in the region to 52 (45 WPV1s from Somalia and seven WPV1s from Kenya). The most recent case in the region had onset of paralysis on 8 June (from Banadir).

:: Banadir remains the epicentre of the outbreak.

:: Outbreak response across the Horn of Africa continues to be implemented. In Somalia, campaigns were held on 1-6 July. In Kenya, activities were conducted on 3-7 July. In Ethiopia on 5-8 July, and in Yemen the next campaigns are planned for late August.

IOM Report: Health Literacy – Improving Health, Health Systems, and Health Policy Around the World – Workshop Summary

Report: Health Literacy – Improving Health, Health Systems, and Health Policy Around the World – Workshop Summary
July 12, 2013
IOM: Board on Population Health and Public Health Practice

“From the first use of the term health literacy in 1974 – described as “health education meeting minimal standards for all school grade levels” – the definition of health literacy has evolved into a common idea that involves both the need for people to understand information that helps them maintain good health and the need for health systems to reduce their complexity. Since the 1990s, health literacy has taken two different approaches; one oriented to clinical care and the other to public health. The public health approach is more prominent in developing nations, where organizations not only work to improve health for large groups of people but also provide educational opportunities. There are many opportunities for international research collaboration between the United States, European countries, and developing nations.

“In September 2012, the IOM Roundtable on Health Literacy hosted a workshop focused on international health literacy efforts. The workshop featured presentations and discussions about health literacy interventions from various countries as well as other topics related to international health literacy. This document summarizes the workshop.”

http://iom.edu/Reports/2013/Health-Literacy-Improving-Health-Health-Systems-and-Health-Policy-Around-the-World.aspx?utm_medium=etmail&utm_source=Institute%20of%20Medicine&utm_campaign=07.12.13+New+Report+-+Health+Literacy&utm_content=&utm_term

Measles Vaccination Before the Measles-Mumps-Rubella Vaccine

American Journal of Public Health
Volume 103, Issue 8 (August 2013)
http://ajph.aphapublications.org/toc/ajph/current

Measles Vaccination Before the Measles-Mumps-Rubella Vaccine
Jan Hendriks, MSc, and Stuart Blume, PhD, M
http://ajph.aphapublications.org/doi/abs/10.2105/AJPH.2012.301075

ABSTRACT
At the beginning of the 1960s, it was clear that a vaccine against measles would soon be available. Although measles was (and remains) a killer disease in the developing world, in the United States and Western Europe this was no longer so. Many parents and many medical practitioners considered measles an inevitable stage of a child’s development. Debating the desirability of measles immunization, public health experts reasoned differently. In the United States, introduction of the vaccine fit well with Kennedy’s and Johnson’s administrations’ political commitments. European policymakers proceeded cautiously, concerned about the acceptability of existing vaccination programs. In Sweden and the Netherlands, recent experience in controlling polio led researchers to prefer an inactivated virus vaccine. Although in the early 1970s attempts to develop a sufficiently potent inactivated vaccine were abandoned, we have argued that the debates and initiatives of the time during the vaccine’s early history merit reflection in today’s era of standardization and global markets.

Policies to Reduce Influenza in the Workplace: Impact Assessments Using an Agent-Based Model

American Journal of Public Health
Volume 103, Issue 8 (August 2013)
http://ajph.aphapublications.org/toc/ajph/current

Policies to Reduce Influenza in the Workplace: Impact Assessments Using an Agent-Based Model
Supriya Kumar, PhD, MPH, John J. Grefenstette, PhD, David Galloway, MS, Steven M. Albert, PhD, and Donald S. Burke, MD
http://ajph.aphapublications.org/doi/abs/10.2105/AJPH.2013.301269

Abstract
Objectives. We examined the impact of access to paid sick days (PSDs) and stay-at-home behavior on the influenza attack rate in workplaces.

Methods. We used an agent-based model of Allegheny County, Pennsylvania, with PSD data from the US Bureau of Labor Statistics, standard influenza epidemic parameters, and the probability of staying home when ill. We compared the influenza attack rate among employees resulting from workplace transmission, focusing on the effects of presenteeism (going to work when ill).

Results. In a simulated influenza epidemic (R0  = 1.4), the attack rate among employees owing to workplace transmission was 11.54%. A large proportion (72.00%) of this attack rate resulted from exposure to employees engaging in presenteeism. Universal PSDs reduced workplace infections by 5.86%. Providing 1 or 2 “flu days”—allowing employees with influenza to stay home—reduced workplace infections by 25.33% and 39.22%, respectively.

Conclusions. PSDs reduce influenza transmission owing to presenteeism and, hence, the burden of influenza illness in workplaces.

Effectiveness of Border Screening for Detecting Influenza in Arriving Airline Travelers

American Journal of Public Health
Volume 103, Issue 8 (August 2013)
http://ajph.aphapublications.org/toc/ajph/current

Effectiveness of Border Screening for Detecting Influenza in Arriving Airline Travelers
Patricia C. Priest, DPhil, MPH, MBChB, Lance C. Jennings, PhD, MSc, BSc, Alasdair R. Duncan, MPH, BSc, Cheryl R. Brunton, MBChB, DipComH, and Michael G. Baker, MBChB, DPH
http://ajph.aphapublications.org/doi/abs/10.2105/AJPH.2012.300761

Abstract
Objectives. We measured symptom and influenza prevalence, and the effectiveness of symptom and temperature screening for identifying influenza, in arriving international airline travelers.

Methods. This cross-sectional study collected data from travelers to Christchurch International Airport, New Zealand, in winter 2008, via a health questionnaire, temperature testing, and respiratory sampling.

Results. Forms were returned by 15 976 (68%) travelers. Of these, 17% reported at least 1 influenza symptom, with runny or blocked nose (10%) and cough (8%) most common. Respiratory specimens were obtained from 3769 travelers. Estimated prevalence of influenza was 1.1% (4% among symptomatic, 0.2% among asymptomatic). The sensitivity of screening criteria ranged from 84% for “any symptom” to 3% for a fever of 37.8 °C or greater. The positive predictive value was low for all criteria.

Conclusions. Border screening using self-reported symptoms and temperature testing has limitations for preventing pandemic influenza from entering a country. Using “any symptom” or cough would lead to many uninfected people being investigated, yet some infected people would remain undetected. If more specific criteria such as fever were used, most infected people would enter the country despite screening.

Longitudinal Predictors of Human Papillomavirus Vaccination Among a National Sample of Adolescent Males

American Journal of Public Health
Volume 103, Issue 8 (August 2013)
http://ajph.aphapublications.org/toc/ajph/current

Longitudinal Predictors of Human Papillomavirus Vaccination Among a National Sample of Adolescent Males
Paul L. Reiter, PhD, Annie-Laurie McRee, DrPH, Jessica K. Pepper, MPH, Melissa B. Gilkey, PhD, Kayoll V. Galbraith, BSN, BA, and Noel T. Brewer, PhD
http://ajph.aphapublications.org/doi/abs/10.2105/AJPH.2012.301189

Abstract
Objectives. We conducted a longitudinal study to examine human papillomavirus (HPV) vaccine uptake among male adolescents and to identify vaccination predictors.

Methods. In fall 2010 and 2011, a national sample of parents with sons aged 11 to 17 years (n = 327) and their sons (n = 228) completed online surveys. We used logistic regression to identify predictors of HPV vaccination that occurred between baseline and follow-up.

Results. Only 2% of sons had received any doses of HPV vaccine at baseline, with an increase to 8% by follow-up. About 55% of parents who had ever received a doctor’s recommendation to get their sons HPV vaccine did vaccinate between baseline and follow-up, compared with only 1% of parents without a recommendation. Fathers (odds ratio = 0.29; 95% confidence interval = 0.09, 0.80) and non-Hispanic White parents (odds ratio = 0.29; 95% confidence interval = 0.11, 0.76) were less likely to have vaccinated sons. Willingness to get sons HPV vaccine decreased from baseline to follow-up among parents (P < .001) and sons (P = .003).

Conclusions. Vaccination against HPV remained low in our study and willingness to vaccinate may be decreasing. Physician recommendation and education about HPV vaccine for males may be key strategies for improving vaccination.

Prevalence of Anogenital Warts Among Participants in Private Health Plans in the United States, 2003–2010: Potential Impact of Human Papillomavirus Vaccination

American Journal of Public Health
Volume 103, Issue 8 (August 2013)
http://ajph.aphapublications.org/toc/ajph/current

Prevalence of Anogenital Warts Among Participants in Private Health Plans in the United States, 2003–2010: Potential Impact of Human Papillomavirus Vaccination
Elaine W. Flagg, PhD, MS, Robert Schwartz, BS, and Hillard Weinstock, MD, MPH
http://ajph.aphapublications.org/doi/abs/10.2105/AJPH.2012.301182

Abstract
Objectives. We estimated anogenital wart prevalence from 2003 to 2010 by gender and age group in a large US cohort with private insurance to detect potential decreases among people most likely to be affected by human papillomavirus (HPV) vaccination.

Methods. We restricted health care claims to those from individuals aged 10 to 39 years with continuous insurance within a given year. We derived anogenital wart diagnoses from a diagnosis of condyloma acuminata, or either a less specific viral wart diagnosis or genital wart medication combined with either a benign anogenital neoplasm or destruction or excision of a noncervical anogenital lesion.

Results. Prevalence increased slightly in 2003 to 2006, then significantly declined in 2007 to 2010 among girls aged 15 to 19 years; increased in 2003 to 2007, remained level through 2009, and declined in 2010 among women aged 20 to 24 years; and increased through 2009 but not in 2010 for women aged 25 to 39 years. For males aged 15 to 39 years, prevalence for each 5-year age group increased in 2003 to 2009, but no increases were observed for 2010.

Conclusions. These data indicate reductions in anogenital warts among US females aged 15 to 24 years, the age group most likely to be affected by introduction of the HPV vaccine.

Reasons for and against receiving influenza vaccination in a working age population in Japan: a national cross-sectional study

BMC Public Health
(Accessed 13 July 2013)
http://www.biomedcentral.com/bmcpublichealth/content

Research article
Reasons for and against receiving influenza vaccination in a working age population in Japan: a national cross-sectional study
Tsubasa Iwasa and Koji Wada
http://www.biomedcentral.com/1471-2458/13/647/abstract

Abstract (provisional)
Background
To improve influenza vaccination coverage in the working age population, it is necessary to understand the current status and awareness of influenza vaccination. This study aimed to determine influenza vaccination coverage in Japan and reasons for receiving the vaccine or not.

Methods
An anonymous internet-based survey was performed in September 2011. Our target study size was 3,000 participants between 20 and 69 years of age, with approximately 300 men and 300 women in each of five age groups (20–29, 30–39, 40–49, 50–59, and 60–69). We asked the history of influenza vaccine uptake in the previous year, and reasons for having vaccination or not.

Results
There were 3,129 respondents, of whom 24.2% of males and 27.6% of females received influenza vaccination between October 2010 and March 2011. Among those who were vaccinated, the main reasons for receiving the influenza vaccine were “Wanted to avoid becoming infected with influenza virus” (males: 84.0%; females: 82.6%) and “Even if infected with influenza, wanted to prevent the symptoms from becoming serious” (males: 60.7%; females: 66.4%). Among those not vaccinated, the most frequent reasons for not receiving the influenza vaccine included “No time to visit a medical institution” (males: 32.0%; females: 22.4%) and “Unlikely to become infected with influenza” (males: 25.1%; females: 22.7%).

Conclusions
The reasons for receiving the influenza vaccine varied between age groups and between sexes. To heighten awareness of influenza vaccination among unvaccinated working age participants, different intervention approaches according to sex and age group may be necessary.

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

Debate: Towards the eradication of HPV infection through universal specific vaccination

BMC Public Health
(Accessed 13 July 2013)
http://www.biomedcentral.com/bmcpublichealth/content

Debate
Towards the eradication of HPV infection through universal specific vaccination
Piergiorgio Crosignani, Antonella De Stefani, Gaetano Maria Fara, Andrea M Isidori, Andrea Lenzi, Carlo Antonio Liverani, Alberto Lombardi, Francesco Saverio Mennini, Giorgio Palu¿, Sergio Pecorelli, Andrea P Peracino, Carlo Signorelli and Gian Vincenzo Zuccotti
http://www.biomedcentral.com/1471-2458/13/642/abstract

Abstract (provisional)
Background
The Human Papillomavirus (HPV) is generally recognized to be the direct cause of cervical cancer. The development of effective anti-HPV vaccines, included in the portfolio of recommended vaccinations for any given community, led to the consolidation in many countries of immunization programs to prevent HPV-related cervical cancers. In recent years, increasing evidence in epidemiology and molecular biology have supported the oncogenic role of HPV in the development of other neoplasm including condylomas and penile, anal, vulvar, vaginal, and oro-pharyngeal cancers. Men play a key role in the paradigm of HPV infection: both as patients and as part of the mechanisms of transmission. Data show they are affected almost as often as women. Moreover, no screening procedures for HPV-related disease prevention are applied in men, who fail to undergo routine medical testing by any medical specialist at all. They also do not benefit from government prevention strategies.

Discussion
A panel of experts convened to focus on scientific, medical, and economic studies, and on the achievements from health organizations’ intervention programs on the matter. One of the goals was to discuss on the critical issues emerging from the ongoing global implementation of HPV vaccination. A second goal was to identify contributions which could overcome the barriers that impede or delay effective vaccination programs whose purpose is to eradicate the HPV infection both in women and men.

Summary
The reviewed studies on the natural history of HPV infection and related diseases in women and men, the increasing experience of HPV vaccination in women, the analysis of clinical effectiveness vs economic efficacy of HPV vaccination, are even more supportive of the economic sustainability of vaccination programs both in women and men. Those achievements address increasing and needed attention to the issue of social equity in healthcare for both genders.

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

Social equity in Human Papillomavirus vaccination: a natural experiment in Calgary Canada

BMC Public Health
(Accessed 13 July 2013)
http://www.biomedcentral.com/bmcpublichealth/content

Research article
Social equity in Human Papillomavirus vaccination: a natural experiment in Calgary Canada
Richard Musto1,2*, Jodi E Siever1, J C Johnston1,2, Judy Seidel1,2, M S Rose3 and Deborah A McNeil1,4
http://www.biomedcentral.com/1471-2458/13/640/abstract

Abstract
Background
The Alberta Immunization Program offers a vaccine against the Human Papillomavirus (HPV) free of charge to all girls in Grades 5 and 9. The vaccine is provided in two different service delivery models depending upon the acceptance of the program by the local school board. Vaccinations may be provided “in-school” or in “community” through appointments at Public Health Clinics. The purpose of this study was to determine whether there was a difference in vaccine uptake in Calgary between the two service delivery models, “in-school” and “community”, and to examine if socioeconomic status (SES) was a contributing factor.

Methods
Individual data from the Calgary Zone Public Health vaccination database for all grade 5 and 9 girls in Calgary for school years 2008–2011 were analyzed using descriptive statistics. These data included vaccination records for 35,592 girls. Logistic regression was used to examine the effect of delivery system and SES status on being vaccinated, controlling for school type.

Results
HPV vaccination completion rates were 75% (95% confidence interval = 74.7%, 75.8%) for girls with an “in-school” compared to 36% (95% confidence interval = 35.3%, 37.2%) for girls in schools with a “community” service delivery model. A girl’s neighbourhood SES was related to the likelihood of being HPV vaccinated depending on the service delivery model available to her. For girls attending a Public school with an “in-school” delivery model, the proportion completing vaccination increased as SES decreased (high SES = 79%; medium SES = 79%; low SES = 83%; p-value<0.001). For girls attending Calgary Catholic School District schools with the “community” delivery model there was a decrease in immunization rates from high and mid to low SES (high SES = 41%; medium SES = 42%; low SES = 34%; p-value<0.001). These results show that those with lower SES were differentially disadvantaged by not having access to an “in-school” vaccination delivery model.

Conclusion
Service delivery models make a difference in HPV vaccination completion rates and create inequities for health protection and disease prevention based on socioeconomic status.

Detection of mild to moderate influenza A/H7N9 infection by China’s national sentinel surveillance system for influenza-like illness: case series

British Medical Journal
13 July 2013 (Vol 347, Issue 7916)
http://www.bmj.com/content/347/7916

Research
Detection of mild to moderate influenza A/H7N9 infection by China’s national sentinel surveillance system for influenza-like illness: case series
Dennis KM Ip, clinical assistant professor1, Qiaohong Liao, public health officer 2, Peng Wu, post doctorate fellow1, Zhancheng Gao, professor and respiratory physician3, Bin Cao, professor and infectious disease physician4, Luzhao Feng, public health officer2, Xiaoling Xu, respiratory physician5, Hui Jiang, public health officer2, Ming Li, public health officer2, Jing Bao, respiratory physician3, Jiandong Zheng, public health officer2, Qian Zhang, public health officer2, Zhaorui Chang, public health officer2, Yu Li, public health officer2, Jianxing Yu, public health officer2, Fengfeng Liu, public health officer2, Michael Y Ni, clinical assistant professor1, Joseph T Wu, associate professor1, Benjamin J Cowling, associate professor1, Weizhong Yang, medical epidemiologist and deputy director6, Gabriel M Leung, professor1, Hongjie Yu, medical epidemiologist and director2
http://www.bmj.com/content/346/bmj.f3693

Abstract
Objective  To characterise the complete case series of influenza A/H7N9 infections as of 27 May 2013, detected by China’s national sentinel surveillance system for influenza-like illness.

Design  Case series.

Setting  Outpatient clinics and emergency departments of 554 sentinel hospitals across 31 provinces in mainland China.

Cases  Infected individuals were identified through cross-referencing people who had laboratory confirmed A/H7N9 infection with people detected by the sentinel surveillance system for influenza-like illness, where patients meeting the World Health Organization’s definition of influenza-like illness undergo weekly surveillance, and 10-15 nasopharyngeal swabs are collected each week from a subset of patients with influenza-like illness in each hospital for virological testing. We extracted relevant epidemiological data from public health investigations by the Centers for Disease Control and Prevention at the local, provincial, and national level; and clinical and laboratory data from chart review.

Main outcome measure  Epidemiological, clinical, and laboratory profiles of the case series.

Results  Of 130 people with laboratory confirmed A/H7N9 infection as of 27 May 2013, five (4%) were detected through the sentinel surveillance system for influenza-like illness. Mean age was 13 years (range 2-26), and none had any underlying medical conditions. Exposure history, geographical location, and timing of symptom onset of these five patients were otherwise similar to the general cohort of laboratory confirmed cases so far. Only two of the five patients needed hospitalisation, and all five had mild or moderate disease with an uneventful course of recovery.

Conclusion  Our findings support the existence of a “clinical iceberg” phenomenon in influenza A/H7N9 infections, and reinforce the need for vigilance to the diverse presentation that can be associated with A/H7N9 infection. At the public health level, indirect evidence suggests a substantial proportion of mild disease in A/H7N9 infections.

Brazil’s Conditional Cash Transfer Program Associated With Declines In Infant Mortality Rates

Health Affairs
July 2013; Volume 32, Issue 7
http://content.healthaffairs.org/content/current
Theme: States, Medicaid & Countdown To Reform

Brazil’s Conditional Cash Transfer Program Associated With Declines In Infant Mortality Rates
Amie Shei1]
http://content.healthaffairs.org/content/32/7/1274.abstract

Abstract
Conditional cash transfer programs are innovative social safety-net programs that aim to relieve poverty. They provide a regular source of income to poor families and are “conditional” in that they require poor families to invest in the health and education of their children through greater use of educational and preventive health services. Brazil’s Bolsa Família conditional cash transfer program, created in 2003, is the world’s largest program of its kind. During the first five years of the program, it was associated with a significant 9.3 percent reduction in overall infant mortality rates, with greater declines in postneonatal mortality rates than in mortality rates at an earlier age and in municipalities with many users of Brazil’s Family Health Program than in those with lower use rates. There were also larger effects in municipalities with higher infant mortality rates at baseline. Programs like Bolsa Família can improve child health and reduce long-standing health inequalities. Policy makers should review the adequacy of basic health services to ensure that the services can respond to the increased demand created by such programs. Programs should also target vulnerable groups at greatest risk and include careful monitoring and evaluation.

Exempting Schoolchildren From Immunizations: States With Few Barriers Had Highest Rates Of Nonmedical Exemptions

Health Affairs
July 2013; Volume 32, Issue 7
http://content.healthaffairs.org/content/current
Theme: States, Medicaid & Countdown To Reform

Exempting Schoolchildren From Immunizations: States With Few Barriers Had Highest Rates Of Nonmedical Exemptions
Nina R. Blank1,*, Arthur L. Caplan2 and Catherine Constable3
http://content.healthaffairs.org/content/32/7/1282.abstract

Abstract
Rates of nonmedical exemptions from school immunizations are increasing and have been associated with resurfacing clusters of vaccine-preventable diseases, such as measles. Historically, state-level school immunization policies successfully suppressed such diseases. We examined state immunization exemption regulations across the United States. We assessed procedures for exempting schoolchildren and whether exemption rates were associated with the complexity of the procedures. We also analyzed legal definitions of religious objections and state legislatures’ recent modifications to exemption policies. We found that states with simpler immunization exemption procedures had nonmedical exemption rates that were more than twice as high as those in states with more-complex procedures. We also found that the stringency of legal definitions of religious exemptions was not associated with exemption procedure complexity. Finally, we found that although there were more attempts by state legislatures to broaden exemptions than to tighten them in 2011–13, only bills tightening exemptions passed. Policy makers seeking to control exemption rates to achieve public health goals should consider tightening nonmedical exemption procedures and should add vaccine education components to the procedures by either mandating or encouraging yearly educational sessions in schools for parents reluctant to have their children vaccinated.

In Memoriam: Hilary Koprowski, 1916–2013 [by Stanley Plotkin]

Journal of Virology
August 2013, volume 87, issue 15
http://jvi.asm.org/content/current

In Memoriam: Hilary Koprowski, 1916–2013
Stanley A. Plotkin
+ Author Affiliations
University of Pennsylvania, Philadelphia, Pennsylvania, USA

Koprowski, who died this year at the age of 96, was an extraordinary person. He excelled as an innovative scientist, a director of a research institute, a classical pianist, a composer of music, a connoisseur of art, and a polyglot world traveler. Born in Warsaw, Poland, where he obtained a medical degree, the Nazi invasion forced him and his wife, Irena, to flee to Italy, where he studied piano at the Accademia Nazionale di Santa Cecilia in Rome. During the Second World War, he managed to emigrate to Brazil, where he became a research assistant in the Rockefeller Foundation Laboratories. There, his work on yellow fever and several arboviruses so impressed the senior staff that a position was found for him at the Lederle Laboratories in Pearl River, New York. At Lederle, he began work leading to improved rabies vaccines and on attenuation of polio virus, the work for which he will be most remembered.

In the early 1950s, there was pessimism about the development of a polio vaccine subsequent to disastrous clinical trials of two experimental vaccines. Koprowski set out to attenuate the virus through adaptation to mouse brain. Starting with what later was identified as a type 2 strain, he achieved attenuation of neurovirulence in monkeys. After ingesting the orally administered vaccine himself, he arranged to vaccinate 20 mentally disabled children in collaboration with the physician in charge of the institution in which they resided, although it is said that his superiors at Lederle were unaware of this step. The ethical justification was the fear of poliovirus entering the institution, a common occurrence at the time. Although this first trial showed safety and immunogenicity of the strain, the presentation of the results at a later scientific meeting was greeted with shock because of the audacity of the work (1).

In the mid-1950s, cell culture became available, and Koprowski and Albert Sabin separately began to attenuate polioviruses by passage in monkey kidney cells. Both succeeded, and the Koprowski strains were tested extensively in the former Belgian Congo, his native Poland, and elsewhere (2). Nevertheless, because the Sabin strains were less neurovirulent in monkeys and were given successfully to millions of children in the former Soviet Union, they achieved licensure in the United States and adoption by the WHO for use throughout the world. During the battle between the oral polio vaccines, the atmosphere between Sabin and Koprowski became quite heated, with many colorful exchanges of insults, but afterwards they reestablished a friendship.

In 1957, Koprowski left Lederle to become Director of the Wistar Institute on the campus of the University of Pennsylvania in Philadelphia, a position he held for 35 years. The Wistar, established in 1892, was somewhat sleepy when he arrived, but he proceeded to convert it into a flourishing institution where there were no departments or walls between laboratories and where both fundamental and applied biology were at the leading edge. I also arrived in 1957, and like many others, I consider him to be my scientific father. Although the emphasis at Wistar was on virology and cancer, other areas, such as atherosclerosis, were investigated. The Wistar was a marvelous place to work in those years because of the international scientists Koprowski recruited and the stimulating atmosphere that he fostered. The lingua franca of Wistar was said to be broken English.

After losing the battle with Sabin over the polio vaccine, Koprowski switched to studies of fusion between somatic cells and eggs, subacute sclerosing encephalitis caused by measles, and “slow” viruses in the central nervous system (3, 4, 5). In that period, his laboratory also adapted rabies virus to human diploid cell culture, leading to a new and highly immunogenic rabies vaccine for humans (6). The gene for the rabies glycoprotein was also inserted into poxvirus vectors for immunization of wild animals, a technique that has successfully controlled wildlife rabies in parts of the world. It is no exaggeration to say that not since Pasteur had one person made more progress in preventing rabies than Koprowski. In addition, while Koprowski was director of Wistar, vaccines were also developed against rubella and rotaviruses.

A curious late sequel of polio vaccination in the Belgian Congo between 1957 and 1960 was the accusation in the late 1990s by certain journalists that Koprowski’s experimental vaccine had been made in chimpanzee cells contaminated by a simian immunodeficiency virus (SIV) that mutated to human immunodeficiency virus (HIV) and thus had introduced the virus into humans. Characteristically, Koprowski rejected the accusation with disdain, but in any case the accusation was refuted by a search of historical records, PCR of the supposed contaminated lot, and studies of SIV and HIV sequences and evolution which showed that HIV entered humans from wild chimpanzees early in the 20th century (7). Nevertheless, setting the matter to rest required international meetings and considerable work by his colleagues (8).

Koprowski’s scope in virology was breathtaking: his bibliography includes articles on at least 25 different viruses, including polio virus, rabies virus, simian virus 40 (SV40), parainfluenza virus type 1, herpes simplex virus, and many flaviviruses. His publication record includes over 900 articles.

When the technology to make monoclonal antibodies became available in the late 1970s, Koprowski founded the Centocor biotechnology company to make antibodies that could be used practically to treat viral infections and cancer. Late in his career, Koprowski set up the Biomedical Foundation to channel research toward making vaccine antigens in plants. Despite his age, he was actively promoting this field until the last year of his life.

Naturally, Koprowski received many awards in his lifetime, locally in the United States but also from Poland, France, Belgium, and Finland. He was a member of the National Academy of Sciences.

However, this recounting of his life does not fully convey the combination of charm, brilliance, and roguishness that struck anyone who came into contact with Hilary. He could converse in many languages about science, art, or music and had a sense of humor that included playing practical jokes. His piano concerts at Wistar and compositions, including short stories, plays, and an opera, were legendary. For his 70th birthday party, he came disguised as a disgruntled gentleman who was angry at the director of the Wistar Institute. Hilary could be an enfant terrible, but he was never boring, always full of ideas, and always stimulating. He left no one who met him unmoved, and none of us, friend or critic, will see his like again.

References available here: http://jvi.asm.org/content/87/15/8270.full

Comment: Timely estimates of influenza A H7N9 infection severity [Articles]

The Lancet  
Jul 13, 2013  Volume 382  Number 9887  p101 – 180
http://www.thelancet.com/journals/lancet/issue/current

Comment
Timely estimates of influenza A H7N9 infection severity
Cécile Viboud, Lone Simonsen
Preview |
WHO guidance, released in May, 2013, established that estimates of disease severity are key for risk assessment of novel influenza viruses.1 Unfortunately, epidemiological assessment of severity is difficult in the context of an emerging disease, when estimates are most needed to guide pandemic response. The case fatality risk is an estimate of the proportion of patients with a specific disease who have died; however, both the numerator and denominator of this estimator are elusive.2–4 Case detection is typically skewed towards patients with severe disease; laboratory-based case ascertainment can vary geographically and temporally; and there are delays between onset, death, and reporting, potentially leading to overestimation or underestimation of fatality risk.

Comparative epidemiology of human infections with avian influenza A H7N9 and H5N1 viruses in China: a population-based study of laboratory-confirmed cases
Benjamin J Cowling, Lianmei Jin, Eric HY Lau, Qiaohong Liao, Peng Wu, Hui Jiang, Tim K Tsang, Jiandong Zheng, Vicky J Fang, Zhaorui Chang, Michael Y Ni, Qian Zhang, Dennis KM Ip, Jianxing Yu, Yu Li, Liping Wang, Wenxiao Tu, Ling Meng, Joseph T Wu, Huiming Luo, Qun Li, Yuelong Shu, Zhongjie Li, Zijian Feng, Weizhong Yang, Yu Wang, Gabriel M Leung, Hongjie Yu
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2813%2961171-X/abstract
Preview |
The sex ratios in urban compared with rural cases are consistent with exposure to poultry driving the risk of infection—a higher risk in men was only recorded in urban areas but not in rural areas, and the increased risk for men was of a similar magnitude for H7N9 and H5N1. However, the difference in susceptibility to serious illness with the two different viruses remains unexplained, since most cases of H7N9 were in older adults whereas most cases of H5N1 were in younger people. A limitation of our study is that we compared laboratory-confirmed cases of H7N9 and H5N1 infection, and some infections might not have been ascertained.

Human infection with avian influenza A H7N9 virus: an assessment of clinical severity
Hongjie Yu, Benjamin J Cowling, Luzhao Feng, Eric HY Lau, Qiaohong Liao, Tim K Tsang, Zhibin Peng, Peng Wu, Fengfeng Liu, Vicky J Fang, Honglong Zhang, Ming Li, Lingjia Zeng, Zhen Xu, Zhongjie Li, Huiming Luo, Qun Li, Zijian Feng, Bin Cao, Weizhong Yang, Joseph T Wu, Yu Wang, Gabriel M Leung
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2813%2961207-6/abstract
Preview |
Human infections with avian influenza A H7N9 virus seem to be less serious than has been previously reported. Many mild cases might already have occurred. Continued vigilance and sustained intensive control efforts are needed to minimise the risk of human infection.

Editorial: A brighter future in the fight against hepatitis Article: Current progress in development of hepatitis C virus vaccines

Nature Medicine
July 2013, Volume 19 No 7 pp791-945
http://www.nature.com/nm/journal/v19/n7/index.html

Editorial
A brighter future in the fight against hepatitis
doi:10.1038/nm.3269

Public health and research efforts directed at managing and targeting viral hepatitis have borne fruit in recent decades. However, more work is necessary to meet the goals of preventing transmission and treating infection to eliminate the enormous burden of hepatitis worldwide.

In 2012, the World Health Organization (WHO) established a Global Hepatitis Program with the goal of fully preventing and treating viral hepatitis. This month, the WHO hopes to increase public awareness through the official World Hepatitis Day, on 28 July. In this issue, Nature Medicine features a series of Review and Perspective articles that discuss promising research and clinical efforts and continuing challenges in viral hepatitis.

Hepatitis B virus (HBV) and HCV are primarily responsible for the high global prevalence of hepatitis disease and for the morbidity and mortality associated with chronic infection. A key challenge for the management of hepatitis is its silent progression, as acute hepatic failure rarely occurs. Infection is often asymptomatic, causing liver scarring and damage decades later in up to 30% of people infected with HCV, and the proportion is even higher in those infected with HBV at birth or during early childhood. Inadequate recognition of infection and region-specific variation in prevalence and risk groups hinders diagnosis and precludes timely treatment. The lack of sufficiently widespread antibody screening to identify all exposed individuals and of follow up with RNA testing, a technique not yet available for routine medical use, to distinguish people with active virus, results in incorrect estimates of infection and increased transmission. In the case of hepatitis C, recent human studies showed that less than half of the infected people in the United States knew they carried the virus (Hepatology 55, 1652–1661, 2012), a number that may be higher in areas with limited disease-control tools. Moreover, the harsh side effects of pegylated interferon-α and ribavirin force many infected people to opt out of this standard therapy, contributing to viral persistence in the community and prevalence of chronic disease.

The advent of effective antivirals is changing the therapeutic landscape, and the goal for eradicating hepatitis viruses may not be as distant as it seemed five years ago, high treatment costs notwithstanding. Current antiviral therapies do not cure chronic hepatitis B, which affects about 210 million people worldwide. At the 2013 International Liver Congress, new approaches to eliminate the HBV replication template, which persists inside liver cells, by modulating host processes such as epigenetic mechanisms and hepatocyte regeneration showed promise and may offer the potential of a cure in the future. For HCV, which affects about 150 million individuals worldwide, there have been rapid advances in drugs. Two protease inhibitors approved in 2011 greatly improved responses in patients infected with the predominant genotype 1; however, host genetic variability affecting antiviral efficacy, evolving drug resistance and the lack of coverage to inhibit all existing HCV genotypes are major drawbacks. Also, these new drugs must be given with the standard therapy, which exacerbates side effects. Second-generation antivirals with different viral targets are under development, and combination strategies should improve efficacy and may even eradicate the virus. Although these therapies are promising, resistance may still develop, and monitoring the emergence of resistant variants will be necessary for guiding treatment choices.

An interferon-free therapy for hepatitis C may also soon exist. In April, a triple combination of direct-acting antivirals without interferon showed efficacy in treatment-naive individuals and in nonresponders to standard of care. And in May, four clinical trials tested an inhibitor of viral polymerase, sofosbuvir, in patients infected with HCV (N. Engl. J. Med. 368, 1867–1887, 2013). In combination with ribavirin, sofosbuvir showed increased efficacy against genotypes 2 and 3 compared to both standard of care and placebo, and adding pegylated interferon alpha-2a to the combination achieved broad genotype coverage. Patients with unacceptable side effects to standard therapy or who were unresponsive to previous therapies may therefore benefit from these new approaches. Research on host factors required for the HCV life cycle has also yielded targets that may overcome virus-acquired resistance and circumvent side effects. A recent example is the targeting of microRNA-122, which is liver specific and necessary for viral replication (N. Engl. J. Med. 368, 1685–1694, 2013) Although long-term studies are necessary to address their safety and toxicity in the long run, interferon-free strategies may become the future of hepatitis C therapy.

But the holy grail for eradicating and decreasing the burden of any infectious disease is a prophylactic vaccine. Prevention of infection with the effective HBV vaccines and with improved medical and lifestyle practices has reached impressive levels in developed countries, and continuing efforts to improve testing and implement mass vaccination programs in low-income countries should achieve similar results in these regions. A working vaccine for HCV, however, still remains elusive, in part because of the lack of experimental systems to study the virus and the lack of animal models to test vaccine candidates. Moreover, because this virus has developed mechanisms of persistence and has an enormous genetic diversity, vaccines will need to induce both neutralizing antibodies and T cell–mediated responses to achieve broad, lasting cross-protection. Unraveling how the host immune response clears the virus during the course of natural infection and prevents persistence will help us understand what constitutes protective immunity and provide a rationale to develop an effective pan-genotype vaccine.

The goals of preventing infection, slowing disease progression and curing chronic hepatitis will undoubtedly require continuing research and clinical efforts. Pharmaceutical companies should be encouraged to keep investigating future compounds to overcome the existing therapeutic barriers, and public awareness efforts should be intensified to underscore to funding and public health agencies that, although we are closer, we are still far from achieving the goals proposed to tackle these silent elusive killers.
http://www.nature.com/nm/journal/v19/n7/full/nm.3269.html

Current progress in development of hepatitis C virus vaccines – pp869 – 878
T Jake Liang
doi:10.1038/nm.3183
Ongoing investigational studies aim to uncover new strategies to develop an effective vaccine to prevent hepatitis C infection. Advances have moved forward vaccine candidates, but technical and biological barriers posed by the virus still exist. This Review discusses how to better design vaccine trials and evaluate key components of protective immunity to achieve a working preventive vaccine.
Abstract – | Full Text – Current progress in development of hepatitis C virus vaccines | PDF (1,514 KB)

U.S. Hospitalizations for Pneumonia after a Decade of Pneumococcal Vaccination

New England Journal of Medicine
July 11, 2013  Vol. 369 No. 2
http://www.nejm.org/toc/nejm/medical-journal

Original Article
U.S. Hospitalizations for Pneumonia after a Decade of Pneumococcal Vaccination
Marie R. Griffin, M.D., M.P.H., Yuwei Zhu, M.D., Matthew R. Moore, M.D., M.P.H., Cynthia G. Whitney, M.D., M.P.H., and Carlos G. Grijalva, M.D., M.P.H.
N Engl J Med 2013; 369:155-163July 11, 2013DOI: 10.1056/NEJMoa1209165
http://www.nejm.org/doi/full/10.1056/NEJMoa1209165

Background
The introduction of 7-valent pneumococcal conjugate vaccine (PCV7) into the U.S. childhood immunization schedule in 2000 has substantially reduced the incidence of vaccine-serotype invasive pneumococcal disease in young children and in unvaccinated older children and adults. By 2004, hospitalizations associated with pneumonia from any cause had also declined markedly among young children. Because of concerns about increases in disease caused by nonvaccine serotypes, we wanted to determine whether the reduction in pneumonia-related hospitalizations among young children had been sustained through 2009 and whether such hospitalizations in older age groups had also declined.

Methods
We estimated annual rates of hospitalization for pneumonia from any cause using the Nationwide Inpatient Sample database. The reason for hospitalization was classified as pneumonia if pneumonia was the first listed diagnosis or if it was listed after a first diagnosis of sepsis, meningitis, or empyema. Average annual rates of pneumonia-related hospitalizations from 1997 through 1999 (before the introduction of PCV7) and from 2007 through 2009 (well after its introduction) were used to estimate annual declines in hospitalizations due to pneumonia.

Results
The annual rate of hospitalization for pneumonia among children younger than 2 years of age declined by 551.1 per 100,000 children (95% confidence interval [CI], 445.1 to 657.1), which translates to 47,000 fewer hospitalizations annually than expected on the basis of the rates before PCV7 was introduced. The rate for adults 85 years of age or older declined by 1300.8 per 100,000 (95% CI, 984.0 to 1617.6), which translates to 73,000 fewer hospitalizations annually. For the three age groups of 18 to 39 years, 65 to 74 years, and 75 to 84 years, the annual rate of hospitalization for pneumonia declined by 8.4 per 100,000 (95% CI, 0.6 to 16.2), 85.3 per 100,000 (95% CI, 7.0 to 163.6), and 359.8 per 100,000 (95% CI, 199.6 to 520.0), respectively. Overall, we estimated an age-adjusted annual reduction of 54.8 per 100,000 (95% CI, 41.0 to 68.5), or 168,000 fewer hospitalizations for pneumonia annually.

Conclusions
Declines in hospitalizations for childhood pneumonia were sustained during the decade after the introduction of PCV7. Substantial reductions in hospitalizations for pneumonia among adults were also observed. (Funded by the Centers for Disease Control and Prevention.)

Policy Forum: A Comparison of Frameworks Evaluating Evidence for Global Health Interventions

PLoS Medicine
(Accessed 13 July 2013)
http://www.plosmedicine.org/

Policy Forum
A Comparison of Frameworks Evaluating Evidence for Global Health Interventions
Jill Luoto, Margaret A. Maglione, Breanne Johnsen, Christine Chang, Elizabeth S. Higgs, Tanja Perry, Paul G. Shekelle
PLoS Med 10(7): e1001469. doi:10.1371/journal.pmed.1001469
Published: July 9, 2013

Summary Points
:: Evidence-based decision-making is critical to informing policy in global health interventions and programs.

:: Existing frameworks for evaluating evidence that were developed or recommended for community or public health decision-making vary in their criteria and application.

:: We compared how different community or public health evidence frameworks assessed the same body of evidence for three advocated global health interventions and find there can be substantial differences in the rating of evidence, which could contribute to differences in policy recommendations.

:: All current frameworks emphasize effectiveness, and have shortcomings on other important factors into policy decision-making such as costs, implementation issues, context, and sustainability.

:: As global health policymakers move towards evidence-based approaches, we find a gap between what is currently available and the needs for an evidence framework appropriate for application to a global health setting in a low- and middle-income country context. More work is needed to either adapt one or more existing frameworks, or to develop an entirely new framework to meet the needs of policymakers and others responsible for implementing global health interventions.

Introduction
A major movement in global health and development in the past 10 years has been the enthusiastic adoption by many of randomized controlled trials (RCTs) from the field of medicine to represent the most rigorous method to evaluate a program’s causal impact [1][4]. More recently, this movement has brought about a conceptual debate in global health and development about the proper role for RCTs in informing policy, with increasing efforts to “mind the gap” [5] between the evidence generated by RCTs (which focus on internal consistency) and the larger policy questions at the level of communities or populations (which require, among other things, generalizability) [4],[6][10]. The field of medicine that developed the RCT also developed the concept of “evidence-based” medicine that aims to improve health policy decision making by encouraging policymakers to base their policies on the best available evidence. Large international policy-making bodies appear set on applying a similar concept to global health and health systems research [4],[11]. In order to be evidence-based, decisions about global health interventions must consider the available evidence in terms of its quantity, quality, and relevance. Rather than use implicit judgment or other ad hoc methods, in evidence-based medicine it is now advocated and common practice to use a formal framework for considering the evidence as part of a systematic review, the advantages of which include increased transparency and better decision-making. Formal frameworks for evaluating evidence about community-level public health interventions have been proposed and advocated for similar reasons [12][17]. These frameworks differ in the degree to which they weight the importance of data from RCTs as compared to data from other study designs, the magnitude of potential benefits and harms, the role of context and implementation, and other factors. At present, there are no commonly accepted guidelines within global public health for how to evaluate evidence, and there is scant evidence to guide policymakers when selecting a framework to use for assessing a body of evidence about a global health intervention. We sought to assess how summary conclusions about the evidence for interventions or programs currently in use or proposed for wide adoption could be influenced by the choice of framework. Consistent results across frameworks would increase policymakers’ confidence in using and applying evidence frameworks, and may thereby help to narrow the gap between the questions asked by global health researchers and policymakers. Inconsistent results would call for a re-examination of current frameworks in terms of the domains they assess and the ways in which they are applied.

From Google Scholar+ [to 13 July 2013]

From Google Scholar & other sources: Selected Journal Articles, Dissertations, Theses, Commentary

H7N9 Avian Influenza A Virus and the Perpetual Challenge of Potential Human Pandemicity
David M. Morensa, Jeffery K. Taubenbergerb, Anthony S. Faucia
mBio 4(4):e00445-13. doi:10.1128/mBio.00445-13.
Published 9 July 2013
http://mbio.asm.org/content/4/4/e00445-13
ABSTRACT
The ongoing H7N9 influenza epizootic in China once again presents us questions about the origin of pandemics and how to recognize them in early stages of development. Over the past ~135 years, H7 influenza viruses have neither caused pandemics nor been recognized as having undergone human adaptation. Yet several unusual properties of these viruses, including their poultry epizootic potential, mammalian adaptation, and atypical clinical syndromes in rarely infected humans, suggest that they may be different from other avian influenza viruses, thus questioning any assurance that the likelihood of human adaptation is low. At the same time, the H7N9 epizootic provides an opportunity to learn more about the mammalian/human adaptational capabilities of avian influenza viruses and challenges us to integrate virologic and public health research and surveillance at the animal-human interface.

A Comprehensive, Model-Based Review of Vaccine and Repeat Infection Trials for Filariasis
CP Morris, H Evans, SE Larsen, E Mitre – Clinical Microbiology Reviews, 2013
SUMMARY Filarial worms cause highly morbid diseases such as elephantiasis and river blindness. Since the 1940s, researchers have conducted vaccine trials in 27 different animal models of filariasis. Although no vaccine trial in a permissive model of filariasis has …

Vaccine adjuvants: the future is bright
R Rappuoli – Expert Review of Vaccines, 2013
Interview by Jenaid Rees, Commissioning Editor Rino Rappuoli is the Global Head of Vaccines Research at Novartis Vaccines & Diagnostics (Siena, Italy). Previously, he was Head of R&D (Sclavo, Italy), and then Head of Vaccine Research and Chief Scientific …

[PDF] Should acellular pertussis vaccine be recommended to healthcare professionals? A vacina pertússis acelular deve ser recomendada a profissionais de saúde?¿ La …
JC de Moraes, T Carvalhanas, LF Bricks – Cad. Saúde Pública, 2013
Page 1. Cad. Saúde Pública, Rio de Janeiro, 29(7):1277-1290, jul, 2013 Should acellular
pertussis vaccine be recommended to healthcare professionals? A vacina pertússis
acelular deve ser recomendada a profissionais de saúde? …

CURRENT OPINION Immunization in transplantation: review of the recent literature
LF Pittet, KM Posfay-Barbe – Curr Opin Organ Transplant, 2013
… CONCLUSION Despite an increasing number of interesting studies evaluating immunization in SOT patients, many questions remain unanswered and research should continue, aiming at elaborating the best immunization strategies in this vulnerable population. …