Commentary: Ethical Allocation of Preexposure HIV Prophylaxis

JAMA
January 12, 2011, Vol 305, No. 2, pp 123-212
http://jama.ama-assn.org/current.dtl

Commentaries
Ethical Allocation of Preexposure HIV Prophylaxis
Lawrence O. Gostin, Susan C. Kim
JAMA. 2011;305(2):191-192.doi:10.1001/jama.2010.1975

[First 150 words per JASMA convention]

Civil society–led movements transformed global AIDS action from deep skepticism about extending antiretroviral (ARV) treatment in low- and middle-income countries to a historic scaling up of treatment toward universal access. During its first phase (2003-2008), the US President’s Emergency Plan for AIDS Relief (PEPFAR)—the largest national commitment to combat a single disease—supported treatment for more than 2 million people, care for more than 10 million people, and prevention of mother-to-child transmission in 16 million pregnancies. 1 The Global Fund to Fight AIDS, Tuberculosis and Malaria (Global Fund), a unique international financing institution, has committed $19.3 billion in 144 countries to support large-scale prevention, treatment, and care, with most resources devoted to AIDS treatment. 2

The AIDS movement, however, is at an inflection point due to the interplay of key health and economic determinants—the global financial downturn, tight foreign aid budgets, and intense resource competition. Even with historic global engagement, human …

Continuing challenge of infectious diseases in India

The Lancet
Jan 15, 2011  Volume 377  Number 9761  Pages 179 – 270
http://www.thelancet.com/journals/lancet/issue/current

Series
Continuing challenge of infectious diseases in India
T Jacob John, Lalit Dandona, Vinod P Sharma, Manish Kakkar

Summary
In India, the range and burden of infectious diseases are enormous. The administrative responsibilities of the health system are shared between the central (federal) and state governments. Control of diseases and outbreaks is the responsibility of the central Ministry of Health, which lacks a formal public health department for this purpose. Tuberculosis, malaria, filariasis, visceral leishmaniasis, leprosy, HIV infection, and childhood cluster of vaccine-preventable diseases are given priority for control through centrally managed vertical programmes. Control of HIV infection and leprosy, but not of tuberculosis, seems to be on track. Early success of malaria control was not sustained, and visceral leishmaniasis prevalence has increased. Inadequate containment of the vector has resulted in recurrent outbreaks of dengue fever and re-emergence of Chikungunya virus disease and typhus fever. Other infectious diseases caused by faecally transmitted pathogens (enteric fevers, cholera, hepatitis A and E viruses) and zoonoses (rabies, leptospirosis, anthrax) are not in the process of being systematically controlled. Big gaps in the surveillance and response system for infectious diseases need to be addressed. Replication of the model of vertical single-disease control for all infectious diseases will not be efficient or viable. India needs to rethink and revise its health policy to broaden the agenda of disease control. A comprehensive review and redesign of the health system is needed urgently to ensure equity and quality in health care. We recommend the creation of a functional public health infrastructure that is shared between central and state governments, with professional leadership and a formally trained public health cadre of personnel who manage an integrated control mechanism of diseases in districts that includes infectious and non-infectious diseases, and injuries.

Age-Old Struggle against the Antivaccinationists

New England Journal of Medicine
January 13, 2011  Vol. 364 No. 2
http://content.nejm.org/current.shtml

Perspective
The Age-Old Struggle against the Antivaccinationists
Gregory A. Poland, M.D., and Robert M. Jacobson, M.D.
N Engl J Med 2011; 364:97-99  January 13, 2011

[Free full-text]

Since the introduction of the first vaccine, there has been opposition to vaccination. In the 19th century, despite clear evidence of benefit, routine inoculation with cowpox to protect people against smallpox was hindered by a burgeoning antivaccination movement. The result was ongoing smallpox outbreaks and needless deaths. In 1910, Sir William Osler publicly expressed his frustration with the irrationality of the antivaccinationists by offering to take 10 vaccinated and 10 unvaccinated people with him into the next severe smallpox epidemic, to care for the latter when they inevitably succumbed to the disease, and ultimately to arrange for the funerals of those among them who would die (see the Medical Notes section of the Dec. 22, 1910, issue of the Journal). A century later, smallpox has been eradicated through vaccination, but we are still contending with antivaccinationists.

Since the 18th century, fear and mistrust have arisen every time a new vaccine has been introduced. Antivaccine thinking receded in importance between the 1940s and the early 1980s because of three trends: a boom in vaccine science, discovery, and manufacture; public awareness of widespread outbreaks of infectious diseases (measles, mumps, rubella, pertussis, polio, and others) and the desire to protect children from these highly prevalent ills; and a baby boom, accompanied by increasing levels of education and wealth. These events led to public acceptance of vaccines and their use, which resulted in significant decreases in disease outbreaks, illnesses, and deaths. This golden age was relatively short-lived, however. With fewer highly visible outbreaks of infectious disease threatening the public, more vaccines being developed and added to the vaccine schedule, and the media permitting widespread dissemination of poor science and anecdotal claims of harm from vaccines, antivaccine thinking began flourishing once again in the 1970s.

Little has changed since that time, although now the antivaccinationists’ media of choice are typically television and the Internet, including its social media outlets, which are used to sway public opinion and distract attention from scientific evidence. A 1982 television program on diphtheria–pertussis–tetanus (DPT) vaccination entitled “DPT: Vaccine Roulette” led to a national debate on the use of the vaccine, focused on a litany of unproven claims against it. Many countries dropped their programs of universal DPT vaccination in the face of public protests after a period in which pertussis had been well controlled through vaccination2 — the public had become complacent about the risks of the disease and focused on adverse events purportedly associated with vaccination. Countries that dropped routine pertussis vaccination in the 1970s and 1980s then suffered 10 to 100 times the pertussis incidence of countries that maintained high immunization rates; ultimately, the countries that had eliminated their pertussis vaccination programs reinstated them.2 In the United States, vaccine manufacturers faced an onslaught of lawsuits, which led the majority of them to cease vaccine production. These losses prompted the development of new programs, such as the Vaccine Injury Compensation Program (VICP), in an attempt to keep manufacturers in the U.S. market.

The 1998 publication of an article, recently retracted by the Lancet, by Wakefield et al.3 created a worldwide controversy over the measles–mumps–rubella (MMR) vaccine by claiming that it played a causative role in autism. This claim led to decreased use of MMR vaccine in Britain, Ireland, the United States, and other countries. Ireland, in particular, experienced measles outbreaks in which there were more than 300 cases, 100 hospitalizations, and 3 deaths.4

Today, the spectrum of antivaccinationists ranges from people who are simply ignorant about science (or “innumerate” — unable to understand and incorporate concepts of risk and probability into science-grounded decision making) to a radical fringe element who use deliberate mistruths, intimidation, falsified data, and threats of violence in efforts to prevent the use of vaccines and to silence critics.

Antivaccinationists tend toward complete mistrust of government and manufacturers, conspiratorial thinking, denialism, low cognitive complexity in thinking patterns, reasoning flaws, and a habit of substituting emotional anecdotes for data.5 Their efforts have had disruptive and costly effects, including damage to individual and community well-being from outbreaks of previously controlled diseases, withdrawal of vaccine manufacturers from the market, compromising of national security (in the case of anthrax and smallpox vaccines), and lost productivity.2

The H1N1 influenza pandemic of 2009 and 2010 revealed a strong public fear of vaccination, stoked by antivaccinationists. In the United States, 70 million doses of vaccine were wasted, although there was no evidence of harm from vaccination. Meanwhile, even though more than a dozen studies have demonstrated an absence of harm from MMR vaccination, Wakefield and his supporters continue to steer the public away from the vaccine. As a result, a generation of parents and their children have grown up afraid of vaccines, and the resulting outbreaks of measles and mumps have damaged and destroyed young lives. The reemergence of other previously controlled diseases has led to hospitalizations, missed days of school and work, medical complications, societal disruptions, and deaths. The worst pertussis outbreaks in the past 50 years are now occurring in California, where 10 deaths have already been reported among infants and young children.

In the face of such a legacy, what can we do to hasten the funeral of antivaccination campaigns? First, we must continue to fund and publish high-quality studies to investigate concerns about vaccine safety. Second, we must maintain, if not improve, monitoring programs, such as the Vaccine Adverse Events Reporting System (VAERS) and the Clinical Immunization Safety Assessment Network, to ensure coverage of real but rare adverse events that may be related to vaccination, and we should expand the VAERS to make compensation available to anyone, regardless of age, who is legitimately injured by a vaccine. Third, we must teach health care professionals, parents, and patients how to counter antivaccinationists’ false and injurious claims. The scientific method must inform evidence-based decision making and a numerate society if good public policy decisions are to be made and the public health held safe. Syncretism between the scientific method and unorthodox medicine can be dangerous.

Fourth, we must enhance public education and public persuasion. Patients and parents are seeking to balance risks and benefits. This process must start with increasing scientific literacy at all levels of education. In addition, public–private partnerships of scientists and physicians could be developed to make accurate vaccine information accessible to the public in multiple languages, on a range of reading levels, and through various media. We must counter misinformation where it is transmitted and consider using legal remedies when appropriate.

The diseases that we now seek to prevent with vaccination pose far less risk to antivaccinationists than smallpox did through the early 1900s. Unfortunately, this means that they can continue to disseminate false science without much personal risk, while putting children, the elderly, and the frail in harm’s way. We can propose no Oslerian challenge to demonstrate our point but have instead a story of science and contrasting worldviews: on the one hand, a long history of stunning triumphs, such as the eradication of smallpox and control of many epidemic diseases that had previously maimed and killed millions of people; on the other hand, the reality that none of the antivaccinationists’ claims of widespread injury from vaccines have withstood the tests of time and science. We believe that antivaccinationists have done significant harm to the public health. Ultimately, society must recognize that science is not a democracy in which the side with the most votes or the loudest voices gets to decide what is right.

1. Wolfe RM, Sharp LK. Anti-vaccinationists past and present. BMJ 2002;325:430-432
2. Gangarosa EJ, Galazka AM, Wolfe CR, et al. Impact of anti-vaccine movements on pertussis control: the untold story. Lancet 1998;351:356-361
3. Wakefield AJ, Murch SH, Anthony A, et al. Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. Lancet 1998;351:637-41. [Retraction, Lancet 2010;375:445.]

4. McBrien J, Murphy J, Gill D, Cronin M, O’Donovan C, Cafferkey MT. Measles outbreak in Dublin, 2000. Pediatr Infect Dis J 2003;22:580-584
5. Jacobson RM, Targonski PV, Poland GA. A taxonomy of reasoning flaws in the anti-vaccine movement. Vaccine 2007;25:3146-3152
Source Information

From the Mayo Clinic Vaccine Research Group (G.A.P., R.M.J.), the Department of Medicine (G.A.P.), and the Department of Pediatric and Adolescent Medicine (G.A.P., R.M.J.), Mayo Clinic, Rochester, MN.

Estimates of Pandemic Influenza Vaccine Effectiveness in Europe, 2009–2010

PLoS Medicine
(Accessed 16 January 2011)
http://medicine.plosjournals.org/perlserv/?request=browse&issn=1549-1676&method=pubdate&search_fulltext=1&order=online_date&row_start=1&limit=10&document_count=1533&ct=1&SESSID=aac96924d41874935d8e1c2a2501181c#results

Estimates of Pandemic Influenza Vaccine Effectiveness in Europe, 2009–2010: Results of Influenza Monitoring Vaccine Effectiveness in Europe (I-MOVE) Multicentre Case-Control Study
Marta Valenciano, Esther Kissling, Jean-Marie Cohen, Beatrix Oroszi, Anne-Sophie Barret, Caterina Rizzo, Baltazar Nunes, Daniela Pitigoi, Amparro Larrauri Cámara, Anne Mosnier, Judith K. Horvath, Joan O’Donnell, Antonio Bella, Raquel Guiomar, Emilia Lupulescu, Camelia Savulescu, Bruno C. Ciancio, Piotr Kramarz, Alain Moren Research Article, published 11 Jan 2011
doi:10.1371/journal.pmed.1000388

Abstract
Background
A multicentre case-control study based on sentinel practitioner surveillance networks from seven European countries was undertaken to estimate the effectiveness of 2009–2010 pandemic and seasonal influenza vaccines against medically attended influenza-like illness (ILI) laboratory-confirmed as pandemic influenza A (H1N1) (pH1N1).

Methods and Findings
Sentinel practitioners swabbed ILI patients using systematic sampling. We included in the study patients meeting the European ILI case definition with onset of symptoms >14 days after the start of national pandemic vaccination campaigns. We compared pH1N1 cases to influenza laboratory-negative controls. A valid vaccination corresponded to >14 days between receiving a dose of vaccine and symptom onset. We estimated pooled vaccine effectiveness (VE) as 1 minus the odds ratio with the study site as a fixed effect. Using logistic regression, we adjusted VE for potential confounding factors (age group, sex, month of onset, chronic diseases and related hospitalizations, smoking history, seasonal influenza vaccinations, practitioner visits in previous year). We conducted a complete case analysis excluding individuals with missing values and a multiple multivariate imputation to estimate missing values. The multivariate imputation (n = 2902) adjusted pandemic VE (PIVE) estimates were 71.9% (95% confidence interval [CI] 45.6–85.5) overall; 78.4% (95% CI 54.4–89.8) in patients <65 years; and 72.9% (95% CI 39.8–87.8) in individuals without chronic disease. The complete case (n = 1,502) adjusted PIVE were 66.0% (95% CI 23.9–84.8), 71.3% (95% CI 29.1–88.4), and 70.2% (95% CI 19.4–89.0), respectively. The adjusted PIVE was 66.0% (95% CI −69.9 to 93.2) if vaccinated 8–14 days before ILI onset. The adjusted 2009–2010 seasonal influenza VE was 9.9% (95% CI −65.2 to 50.9).

Conclusions
Our results suggest good protection of the pandemic monovalent vaccine against medically attended pH1N1 and no effect of the 2009–2010 seasonal influenza vaccine. However, the late availability of the pandemic vaccine and subsequent limited coverage with this vaccine hampered our ability to study vaccine benefits during the outbreak period. Future studies should include estimation of the effectiveness of the new trivalent vaccine in the upcoming 2010–2011 season, when vaccination will occur before the influenza season starts.

Suppression of Avian Influenza Transmission in Genetically Modified Chickens

Science
14 January 2011 vol 331, issue 6014, pages 117-248
http://www.sciencemag.org/current.dtl

Reports
Suppression of Avian Influenza Transmission in Genetically Modified Chickens
Jon Lyall, Richard M. Irvine, Adrian Sherman, Trevelyan J. McKinley, Alejandro Núñez, Auriol Purdie, Linzy Outtrim, Ian H. Brown, Genevieve Rolleston-Smith, Helen Sang,
and Laurence Tiley
Science 14 January 2011: 223-226.[D

Abstract
Infection of chickens with avian influenza virus poses a global threat to both poultry production and human health that is not adequately controlled by vaccination or by biosecurity measures. A novel alternative strategy is to develop chickens that are genetically resistant to infection. We generated transgenic chickens expressing a short-hairpin RNA designed to function as a decoy that inhibits and blocks influenza virus polymerase and hence interferes with virus propagation. Susceptibility to primary challenge with highly pathogenic avian influenza virus and onward transmission dynamics were determined. Although the transgenic birds succumbed to the initial experimental challenge, onward transmission to both transgenic and nontransgenic birds was prevented.

SAGE November 2010 – summary, conclusions and recommendations.

The WER for 7 January 2011, vol. 86, 1/2 (pp 1–16) includes:

Meeting of the Strategic Advisory Group of Experts on Immunization, November 2010 – summary, conclusions and recommendations.

WHO said the Strategic Advisory Group of Experts (SAGE) recommended at its November 2010 meeting that global measles mortality reduction and regional elimination efforts be carried out in the context of strengthening routine immunization programmes. SAGE “concluded that measles can and should be eradicated but proposed that demonstration of sufficient progress towards regional measles elimination targets be made a precursor to establishing a target date for global eradication. Recognizing the fragility of gains in measles mortality reduction, apparent through outbreaks affecting 28 countries in the African Region since 2009, the Group highlighted the growing risk that the contribution of the reduction in measles mortality to achieving Millennium Development Goal 4 will be lost because of declining political and financial commitment to measles control.” Other topics discussed included: polio eradication; support to lower-middle-income countries; improving the accessibility of affordable vaccines; influenza and typhoid vaccination; optimization of immunization schedules; and epidemiology studies of unimmunized children and gender-related issues.

http://www.who.int/entity/wer/2011/wer8601_02.pdf

National Biodefense Science Board (NBSB) adds experts

HHS said six experts from outside the federal government will join the National Biodefense Science Board (NBSB), a federal advisory committee which provides expert advice and guidance on preventing, preparing for, and responding to adverse health effects of public health emergencies to the Secretary of the U.S. Department of Health and Human Services and the HHS Assistant Secretary for Preparedness and Response (ASPR). The new members replace members whose 3-year terms expire Dec. 31. The ASPR serves as the Secretary’s principal advisor on bioterrorism and other public health emergencies and coordinates the federal public health and medical response to disasters. The board was created under the Pandemic and All-Hazards Preparedness Act in 2006 and chartered in May 2007. Since then, the board has provided recommendations such issues as whether the federal government should encourage stockpiling antibiotics at home for use after a bioterrorism attack and how the department can help protect, preserve, and restore individual and community mental health after a disaster. In addition, the board has provided recommendations on ways to improve the management of the research and development of medicines, vaccines and equipment for pandemic diseases. By statute, the board has 13 voting members with a broad range of expertise in science, medicine, and public health. Additionally, there are non-voting members from federal and state government agencies as deemed appropriate by the Secretary.

http://www.phe.gov/preparedness/mcm/enterprisereview/Pages/default.aspx

Global vaccine market: $34 billion in sales by 2012

[Editor’s Note: We do not endorse or receive any support from any companies that produce market research analysis on the vaccine marketplace. But we are interested in the market growth of vaccines as a dimension of our focus on ethics and policy, so we will occasionally report scaling projections and other data from such reports.]

“The global vaccine market is expected to achieve $34 billion in sales by 2012. With an estimated annual growth rate of 14% during the next five years, vaccines will be the fastest-growing therapeutic area, even outpacing oncology,” according to Research & Markets, a market research firm.

Observations made in the abstract for this report include:
– “…
One of the most striking vaccine advances in recent years is active immunotherapies, including the April 2010 FDA approval of Dendreon’s Provenge, a personalized vaccine targeting prostate cancer. Active immunotherapy stimulates the patient’s immune system to fight cancer while sparing the patient most of the adverse side effects associated with chemotherapy, radiation, and other biologics that target antigens. The anti-cancer activity persists long after a course of treatment. These vaccines feature new modes of action and present opportunities for development of combination therapies to provide exceptional long-term tumor control. Therapeutic vaccines are also being researched for the treatment of HIV, hepatitis C, and more.
– “Novel delivery techniques will help improve access, compliance, and safety, particularly in developing nations. One such system, nanoemulsion, is an oil-based liquid placed in the nose. It has been shown to produce a strong immune response against smallpox and HIV. Virtually any bacterial or viral disease that results in an immune response is a candidate for the development of a nanoemulsion-based vaccine.
– “Innovation among start-up companies is one of the main factors behind the renewed interest in vaccines. Top vaccine manufacturers seek collaboration with academia and small biotech firms in the early phases of development. As the industry continues to evolve, there will be many opportunities for collaboration and public-private partnerships, like the one GlaxoSmithKline established with Brazil’s Oswaldo Cruz Foundation to develop and manufacture vaccines for urgent South American public health priorities. Moving forward, vaccine partners must continue to identify unmet public health needs and accelerate innovative vaccine R&D to create novel solutions.
– “While vaccines are less susceptible to erosion by generic competition because the cost of entry is extremely high, as vaccine formulations become more precise and defined, the vaccines sector will likely follow the lead of the biotech industry toward the production of biosimilar and biobetter vaccines. India and China are emerging as competitors in this area. Both countries have exhibited great skill in copying old vaccines and are becoming increasingly adept at copying new technology, with India having become the largest global producer of copied vaccines.”
http://www.researchandmarkets.com/product/f29684/vaccines_review_and_outlook_2010

Evaluation of Impact of Varicella Vaccination: United States, 1993–2006

Clinical Infectious Diseases
Volume 52 Issue 3 February 1, 2011
http://www.journals.uchicago.edu/toc/cid/current

Jessica Leung, Rafael Harpaz, Noelle-Angelique Molinari, Aisha Jumaan, and Fangjun Zhou
Herpes Zoster Incidence Among Insured Persons in the United States, 1993–2006: Evaluation of Impact of Varicella Vaccination
Clin Infect Dis. (2011) 52(3): 332-340 doi:10.1093/cid/ciq077

Abstract
Background. Herpes zoster (HZ) is caused by reactivation of latent varicella zoster virus and is often associated with substantial pain and disability. Baseline incidence of HZ prior to introduction of HZ vaccine is not well described, and it is unclear whether introduction of the varicella vaccination program in 1995 has altered the epidemiology of HZ. We examined trends in the incidence of HZ and impact of varicella vaccination on HZ trends using a large medical claims database.

Methods. Medical claims data from the MarketScan® databases were obtained for 1993-2006. We calculated HZ incidence using all persons with a first outpatient service associated with a 053.xx code (HZ ICD-9 code) as the numerator, and total MarketScan enrollment as the denominator; HZ incidence was stratified by age and sex. We used statewide varicella vaccination coverage in children aged 19-35 months to explore the impact of varicella vaccination on HZ incidence.

Results. HZ incidence increased for the entire study period and for all age groups, with greater rates of increase 1993-1996 (P < .001). HZ rates were higher for females than males throughout the study period (P < .001) and for all age groups (P < .001). HZ incidence did not vary by state varicella vaccination coverage.

Conclusions. HZ incidence has been increasing from 1993-2006. We found no evidence to attribute the increase to the varicella vaccine program.

Control of Varicella Disease, Version 2.0

Journal of Infectious Diseases
Volume 203 Issue 3 February 1, 2011
http://www.journals.uchicago.edu/toc/jid/current

EDITORIAL COMMENTARIES
David W. Kimberlin
Control of Varicella Disease, Version 2.0
J Infect Dis. (2011) 203(3): 297-299 doi:10.1093/infdis/jiq053

In this issue of the Journal, Shapiro and colleagues present data from a case-controlled study of the effectiveness of 2 doses of varicella vaccine during the first several years after implementation of a routine 2-dose recommended schedule. At 98.3%, the effectiveness of the 2-dose schedule is welcome news indeed. These data validate the calculations of experts from the Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) and the American Academy of Pediatrics (AAP) Committee on Infectious Diseases (COID), made in 2006 when both groups approved a recommendation for routine use of 2 doses of varicella vaccine during childhood. Shapiro and colleagues are to be commended for their forethought in establishing a broad surveillance network in Connecticut in the years after licensure of the varicella vaccine in 1995 and for their careful scientific and statistical evaluation of data generated from this important resource.

In understanding the context within which these new data should be viewed, it is important to reflect on the overall development and implementation of varicella vaccine. The strain that ultimately became the varicella vaccine …

Editorial: The Necessity and Quandaries of Dengue Vaccine Development

Journal of Infectious Diseases
Volume 203 Issue 3 February 1, 2011
http://www.journals.uchicago.edu/toc/jid/current

EDITORIAL COMMENTARIES

Stephen J. Thomas
The Necessity and Quandaries of Dengue Vaccine Development
J Infect Dis. (2011) 203(3): 299-303 doi:10.1093/infdis/jiq060

Dengue is an emerging and reemerging arboviral disease of great global public health importance. Increased transmission and disease outbreaks are being driven by population growth, urbanization, international travel, and unchecked vector populations [ 1]. Southeast Asia, Central and South America, and parts of the Caribbean experience endemic and hyperendemic dengue virus (DENV) transmission while indigenous transmission is being increasingly recognized in areas of Africa, the Middle East and South Asia [ 2– 5]. Reports indicate that southern US border-states and Hawaii can support episodic DENV transmission [ 6– 12]. Dengue poses a risk to traveler and military populations, especially those originating from non-dengue endemic regions [ 13– 18].

Millions of DENV infections, hundreds of thousands of hospitalizations, and tens of thousands of deaths related to dengue occur annually [ 19]. There is no specific, licensed anti-DENV therapeutic or preventative vaccine. The financial, social and individual cost of dengue is significant, underestimated, and underappreciated [ 20– 25]. The strategic administration of a safe and efficacious dengue vaccine, in coordination with efforts to educate about personal protective measures and sustained vector control, is the best hope to reduce the global dengue burden.

There are numerous dengue vaccine candidates in clinical development. Early efforts to develop a dengue vaccine date back more than 70 years, with attempts to prevent virus transmission using infectious human plasma treated with ox bile or virus grown in live mosquitoes and inactivated with formalin [ 26]. Schelsinger and Sabin undertook the first attempts to immunize using mouse-passaged live-attenuated DENV-1 and -2 viruses [ 27– 29]. Halstead and colleagues discovered DENVs were attenuated following passage in primary dog kidney (PDK) cell culture [ 30]. …

Effectiveness of 2 Doses of Varicella Vaccine in Children

Journal of Infectious Diseases
Volume 203 Issue 3 February 1, 2011
http://www.journals.uchicago.edu/toc/jid/current

MAJOR ARTICLES AND BRIEF REPORTS
VIRUSES

Eugene D. Shapiro, Marietta Vazquez, Daina Esposito, Nancy Holabird, Sharon P. Steinberg, James Dziura, Philip S. LaRussa, and Anne A. Gershon
Effectiveness of 2 Doses of Varicella Vaccine in Children
J Infect Dis. (2011) 203(3): 312-315 doi:10.1093/infdis/jiq052

Abstract
Background. Because of ongoing outbreaks of varicella, a second dose of varicella vaccine was added to the routine immunization schedule for children in June 2006 by the Centers for Disease Control and Prevention.

Methods. We assessed the effectiveness of 2 doses of varicella vaccine in a case-control study by identifying children ≥4 years of age with varicella confirmed by polymerase chain reaction assay and up to 2 controls matched by age and pediatric practice. Effectiveness was calculated using exact conditional logistic regression.

Results. From July 2006 to January 2010, of the 71 case subjects and 140 matched controls enrolled, no cases (0%) vs 22 controls (15.7%) had received 2 doses of varicella vaccine, 66 cases (93.0%) vs 117 controls (83.6%) had received 1 dose, and 5 cases (7.0%) vs 1 control (0.7%) did not receive varicella vaccine (P < .001). The effectiveness of 2 doses of the vaccine was 98.3% (95% confidence level [CI]: 83.5%–100%; P < .001). The matched odds ratio for 2 doses vs 1 dose of the vaccine was 0.053 (95% CI: 0.002–0.320; P < .001).

Conclusion. The effectiveness of 2 doses of varicella vaccine in the first 2.5 years after recommendation of a routine second dose of the vaccine for children is excellent. Odds of developing varicella were 95% lower for children who received 2 doses compared with 1 dose of varicella vaccine.

When is research on children ethical?

The Lancet
Jan 08, 2011  Volume 377  Number 9760  Pages 97 – 178
http://www.thelancet.com/journals/lancet/issue/current

Perspectives
When is research on children ethical?
Peter Singer

Preview
Is it ever ethical to do research on human subjects without their consent? The Nuremberg Code, written in the aftermath of the atrocities perpetrated by Nazi doctors, makes the voluntary consent of the human subject “absolutely essential”. Understandable as the desire for so absolute a barrier may be, it comes at a high cost, for it blocks research with the potential to help many children. Hence in 1964 the World Medical Association, in the Declaration of Helsinki, took a different stance, allowing research on human beings without the capacity to consent, if consent can be obtained from a legally authorised representative.

The Origin of the Haitian Cholera Outbreak Strain

New England Journal of Medicine
January 6, 2011  Vol. 364 No. 1
a title=”http://content.nejm.org/current.shtml&#8221; href=”http://content.nejm.org/current.shtml”>http://content.nejm.org/current.shtml

Original Articles
The Origin of the Haitian Cholera Outbreak Strain
C.-S. Chin and Others

Abstract
Background

Although cholera has been present in Latin America since 1991, it had not been epidemic in Haiti for at least 100 years. Recently, however, there has been a severe outbreak of cholera in Haiti.

Methods

We used third-generation single-molecule real-time DNA sequencing to determine the genome sequences of 2 clinical Vibrio cholerae isolates from the current outbreak in Haiti, 1 strain that caused cholera in Latin America in 1991, and 2 strains isolated in South Asia in 2002 and 2008. Using primary sequence data, we compared the genomes of these 5 strains and a set of previously obtained partial genomic sequences of 23 diverse strains of V. cholerae to assess the likely origin of the cholera outbreak in Haiti.

Results

Both single-nucleotide variations and the presence and structure of hypervariable chromosomal elements indicate that there is a close relationship between the Haitian isolates and variant V. cholerae El Tor O1 strains isolated in Bangladesh in 2002 and 2008. In contrast, analysis of genomic variation of the Haitian isolates reveals a more distant relationship with circulating South American isolates.

Conclusions

The Haitian epidemic is probably the result of the introduction, through human activity, of a V. cholerae strain from a distant geographic source. (Funded by the National Institute of Allergy and Infectious Diseases and the Howard Hughes Medical Institute.)

Calibrating Models in Economic Evaluation: A Seven-Step Approach

Pharmacoeconomics
January 1, 2011 – Volume 29 – Issue 1  pp: 1-86
http://adisonline.com/pharmacoeconomics/pages/currenttoc.aspx

Review Articles
Calibrating Models in Economic Evaluation: A Seven-Step Approach
Vanni, Tazio; Karnon, Jonathan; Madan, Jason; White, Richard G.; Edmunds, W. John; Foss, Anna M.; Legood, Rosa
Pharmacoeconomics. 29(1):35-49, January 1, 2011.
doi: 10.2165/11584600-000000000-00000

Abstract:
In economic evaluation, mathematical models have a central role as a way of integrating all the relevant information about a disease and health interventions, in order to estimate costs and consequences over an extended time horizon. Models are based on scientific knowledge of disease (which is likely to change over time), simplifying assumptions and input parameters with different levels of uncertainty; therefore, it is sensible to explore the consistency of model predictions with observational data. Calibration is a useful tool for estimating uncertain parameters, as well as more accurately defining model uncertainty (particularly with respect to the representation of correlations between parameters). Calibration involves the comparison of model outputs (e.g. disease prevalence rates) with empirical data, leading to the identification of model parameter values that achieve a good fit.

This article provides guidance on the theoretical underpinnings of different calibration methods. The calibration process is divided into seven steps and different potential methods at each step are discussed, focusing on the particular features of disease models in economic evaluation. The seven steps are (i) Which parameters should be varied in the calibration process? (ii) Which calibration targets should be used? (iii) What measure of goodness of fit should be used? (iv) What parameter search strategy should be used? (v) What determines acceptable goodness-of-fit parameter sets (convergence criteria)? (vi) What determines the termination of the calibration process (stopping rule)? (vii) How should the model calibration results and economic parameters be integrated?

The lack of standards in calibrating disease models in economic evaluation can undermine the credibility of calibration methods. In order to avoid the scepticism regarding calibration, we ought to unify the way we approach the problems and report the methods used, and continue to investigate different methods.

Vaccine studies show advances in health economic research

Pharmacoeconomics & Outcomes News
January 8, 2011 – Volume – Issue 619 pp: 1-11
http://adisonline.com/pecnews/pages/currenttoc.aspx

Vaccine studies show advances in health economic research
PharmacoEconomics & Outcomes News. (619):5, January 8, 2011.

Abstract
Using steady-state population-based analyses has the “advantage of helping policy makers understand the impact of their policy decisions on a population level in the year that the decision has reached its full effect” says Dr Lieven Annemans, of the medical faculties at Ghent and Brussels Universities. Dr Annemans was commenting on two vaccine studies that used steady-state population model included in a supplement entitled “Progress in vaccines, progress in health economics” published in Vaccine. The supplement, sponsored by GlaxoSmithKline, included articles on the economic and health consequences of vaccinating against pneumococcal and haemophillus infections.

In the first study, the researchers used national estimates in order to determine the residual economic burden of pneumococcal and haemophilus infections following pneumococcal 7-valent CRM197 vaccine conjugate (PCV-7) vaccination in children under 10 years old in Canada, Germany, Mexico and Norway.2 They estimated direct and indirect costs (at 2008 values; converted to $US) and assumed full herd effect over 1 year.

The current annual national costs ranged from $2.59/capita in Mexico up to $7.89/capita in Canada. They found that because of the high incidence of otis media it accounted for up to 88% of national direct costs and up to 96% of caregiver costs for pneumococcal or haemophilus infections.

The researchers say that a strength of this study was that they included both direct medical and caregiver productivity loss costs for the diseases across each of the different countries, and that estimating these costs separately “gives decision makers a better understanding of how much of the cost burden is attributable” to these different factors.

The second study evaluated the cost effectiveness of haemophilus influenzae pneumococcal vaccine (PHiD-CV) compared with PCV-7 across the same four countries.3 This study used an adapted static population model in order to determine the costs and QALYs associated with each vaccine (2008 values were used in the local currency). The investigators also conducted a short-term analysis, with a separate module from the underlying population, where vaccination of a single birth cohort each year for 10 years was simulated.

They found that, when price parity was assumed, “routine vaccination with PHiD-CV resulted in lower costs compared with PCV-7 in both the short term and the steady-state year”. The cost savings were not so pronounced in the short-term analysis “but cost savings increased quickly after multiple birth cohorts were vaccinated”.

Dr Annemans says that analyses like these “illustrate well what country-specific data really mean”, highlighting that the differences observed between countries not only pertain to the epidemiology but the “management style, unit costs and quality-of-life impact”.

FDA approves Gardasil for prevention of anal cancer/precancerous lesions: males & females

The U.S. Food and Drug Administration approved Gardasil “for the prevention of anal cancer and associated precancerous lesions due to human papillomavirus (HPV) types 6, 11, 16, and 18 in people ages 9 through 26 years.” Gardasil is already approved for the same age population for the prevention of cervical, vulvar, and vaginal cancer and the associated precancerous lesions caused by HPV types 6, 11, 16, and 18 in females.  It is also approved for the prevention of genital warts caused by types 6 and 11 in both males and females. Karen Midthun, M.D., director of the FDA’s Center for Biologics Evaluation and Research, commented, “Treatment for anal cancer is challenging; the use of Gardasil as a method of prevention is important as it may result in fewer diagnoses and the subsequent surgery, radiation or chemotherapy that individuals need to endure.” The FDA said that Gardasil’s ability to prevent anal cancer and the associated precancerous lesions [anal intraepithelial neoplasia (AIN) grades 1, 2, and 3] caused by anal HPV-16/18 infection was studied in a randomized, controlled trial of men who self-identified as having sex with men (MSM). This population was studied because it has the highest incidence of anal cancer. At the end of the study period, Gardasil was shown to be 78 percent effective in the prevention of HPV 16- and 18-related AIN.  Because anal cancer is the same disease in both males and females, the effectiveness data was used to support the indication in females as well, the FDA said.

http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm237941.htm

Emergent BioSolutions announces Phase I trial for third generation anthrax vaccine

Emergent BioSolutions announced the initiation of a Phase I clinical trial for NuThraxTM (Anthrax Vaccine Adsorbed with CPG 7909 Adjuvant), described as a third generation vaccine being developed as part of Emergent’s anthrax franchise consisting of BioThrax (Anthrax Vaccine Adsorbed) in combination with a novel immunostimulatory compound, CPG 7909. Daniel J. Abdun-Nabi, president and chief operating officer of Emergent BioSolutions, commented, “We believe this third generation anthrax vaccine has the potential to exhibit advanced characteristics such as requiring fewer doses, generating an enhanced immune response, and having a favorable shelf life. If successful, this could be an attractive candidate for the government’s growing arsenal of medical countermeasures.”

http://www.businesswire.com/news/home/20101227005257/en/Emergent-BioSolutions-Starts-Phase-Clinical-Trial-Generation

Implementation of Cocooning against Pertussis in a High-Risk Population

Clinical Infectious Diseases
http://www.journals.uchicago.edu/toc/cid/current
Volume 52 Issue 2 January 15, 2011

ARTICLES AND COMMENTARIES
Implementation of Cocooning against Pertussis in a High-Risk Population
C. Mary Healy, Marcia A Rench, and Carol J. Baker
Clin Infect Dis. (2011) 52(2): 157-162 doi:10.1093/cid/ciq001

Abstract
Despite logistical barriers, tetanus, diphtheria, acellular pertussis cocooning (vaccination of all caregivers of infants <1 year of age) was successfully implemented in a high-risk, predominantly Hispanic, medically underserved, uninsured population at a Houston hospital using standing orders and providing vaccinations on-site.

Projected Impact and Cost-Effectiveness of a Rotavirus Vaccination Program in India, 2008

Clinical Infectious Diseases
http://www.journals.uchicago.edu/toc/cid/current

Projected Impact and Cost-Effectiveness of a Rotavirus Vaccination Program in India, 2008
Douglas H. Esposito, Jacqueline E. Tate, Gagandeep Kang and Umesh D. Parashar

Abstract
Background. To assess the value of rotavirus vaccination in India, we determined the potential impact and cost-effectiveness of a national rotavirus vaccination program.

Methods.  We compared the national rotavirus disease and cost burden with and without a vaccination program and assessed the cost-effectiveness of vaccination. Model inputs included measures of disease and cost burden, vaccine performance, and vaccination coverage and cost. We measured the annual number of health-related events and treatment costs averted, as well as the cost-effectiveness in US dollars per disability-adjusted life-year (DALY) and cost per death averted. One-way sensitivity analyses were performed by individually varying each model input.

Results. With use of a vaccine that has an estimated effectiveness of 50%, a rotavirus vaccination program in India would prevent approx 44,000 deaths, 293,000 hospitalizations, and 328,000 outpatient visits annually, which would avert $20.6 million in medical treatment costs. Vaccination would be cost-saving at the GAVI Alliance price of $0.15 per dose. At $1.00 per dose, a vaccination program would cost $49.8 million, which would result in an expenditure of $21.41 per DALY averted or $662.94 per life saved. Even at $7.00 per dose, vaccination would be highly cost-effective. In sensitivity analyses, varying efficacy against severe rotavirus disease and vaccine price had the greatest impact on cost-effectiveness.

Conclusions. A national rotavirus vaccination program in India would prevent substantial rotavirus morbidity and mortality and would be highly cost-effective at a range of vaccine prices. Public health officials can use this locally derived data to evaluate how this highly cost-effective intervention might fit into India’s long-term health care goals.

EDITORIAL: Reaching MDG 4 in India: A Role for Rotavirus Vaccine?

Clinical Infectious Diseases
http://www.journals.uchicago.edu/toc/cid/current

EDITORIAL COMMENTARY: Reaching MDG 4 in India: A Role for Rotavirus Vaccine?
Edmund Anthony S. Nelson and Damian G. Walker
Clin Infect Dis. (2011) 52(2): 178-179 doi:10.1093/cid/ciq095

Abstract
A new health intervention can be either more or less expensive than existing intervention(s) (usually more). It can also be more or less effective (again, usually more). Thus, improving the health of a population usually costs more money (for governments, taxpayers, and/or individuals). Occasionally, the situation arises when a new and better intervention costs less and is cost-saving. In this case, the decision should be to introduce the intervention, and a failure to do so would require a very detailed explanation.

The economic evaluation by Esposito et al of the introduction of rotavirus vaccine to India’s National Immunization Programme reports that if the Government of India applies to the GAVI Alliance and is approved to receive funds to support its introduction, it could pay the heavily discounted copay price of US$ .15 per dose (US$ .30 for a 2-dose course); at such a price per dose, it would be in the fortunate position of saving both lives and money. Of importance, however, the contribution of the Government of India to the cost of the vaccine would be expected to steadily increase over time until the full cost was borne by the government; thus, the potential cost-saving scenario would not last forever. Nevertheless, even at higher prices, purchasing the rotavirus vaccine would be considered to still be a very sound investment. What is the likely eventual …

H1N1 School Closings: New York City

Clinical Infectious Diseases
Volume 52 supplement 2 January 15, 2011

Special Supplement: The 2009 H1N1 Influenza Pandemic: Field and Epidemiologic Investigations
Closing Schools in Response to the 2009 Pandemic Influenza A H1N1 Virus in New York City: Economic Impact on Households
Rebekah H. Borse, Casey Barton Behravesh, Tamara Dumanovsky, Jane R. Zucker, David Swerdlow, Paul Edelson, Julia Choe-Castillo, and Martin I. Meltzer

Abstract
Understanding the effectiveness of a school closure in limiting social interaction and the economic impact of school closure on households is critical when developing guidelines to prevent spread of pandemic influenza. A New York City survey conducted in June 2009 in 554 households affected by the 2009 pandemic influenza H1N1–related school closures showed that, during closure, 30% of students visited at least 1 locale outside their homes. If all the adults in the home were employed, an ill child was less likely to leave home. In 17% of the households, at least 1 adult missed some work because of the closure. If all adults in the home were employed, someone was more likely to take time off work. If other children were in the household, it was less likely that an adult took time off work. The findings of our study will be important when developing future pandemic school-closure guidance.

Completeness of Communicable Disease Reporting, North Carolina, USA

Emerging Infectious Diseases
Volume 17, Number 1–January 2011
http://www.cdc.gov/ncidod/EID/index.htm

Research
Completeness of Communicable Disease Reporting, North Carolina, USA, 1995–1997 and 2000–2006
Emily E. Sickbert-Bennett, David J. Weber, Charles Poole, Pia D.M. MacDonald, and Jean-Marie Maillard

Abstract
Despite widespread use of communicable disease surveillance data to inform public health intervention and control measures, the reporting completeness of the notifiable disease surveillance system remains incompletely assessed. Therefore, we conducted a comprehensive study of reporting completeness with an analysis of 53 diseases reported by 8 health care systems across North Carolina, USA, during 1995–1997 and 2000–2006. All patients who were assigned an International Classification of Diseases, 9th Revision, Clinical Modification, diagnosis code for a state-required reportable communicable disease were matched to surveillance records. We used logistic regression techniques to estimate reporting completeness by disease, year, and health care system. The completeness of reporting varied among the health care systems from 2% to 30% and improved over time. Disease-specific reporting completeness proportions ranged from 0% to 82%, but were generally low even for diseases with great public health importance and opportunity for interventions.

Second National Immunization Congress 2010: Addressing vaccine financing in U.S.

Human Vaccines
Volume 7, Issue 1 January 2011
http://www.landesbioscience.com/journals/vaccines/toc/volume/6/issue/12/

Meeting Report
Second National Immunization Congress 2010: Addressing vaccine financing for the future in the United States
Angela K. Shen, Sarah Duggan-Goldstein, Elizabeth Sobzcyk, Anna Buchanan and Lauren Wu

At the 2nd National Immunization Congress held in Chicago, IL, from August 31-September 2, 2010, partners from government, provider groups, academia, and manufacturers gathered to discuss the progress made and the future of financing child, adolescent, and adult vaccines. The meeting is a continuation of a solution-oriented vaccine financing dialogue held in February 2007 at the 1st Immunization Congress. The need for this forum arose from concerns that increased costs of immunization could hinder the ability of current financing and delivery systems to maintain access without financial barriers. Preventive care and additional financial coverage for vaccines are key points in federal health reform but some populations, especially adolescents and adults, could continue to experience challenges in accessing vaccines. Congress participants discussed adequate reimbursement in the public and private sectors for vaccine delivery and the potential financial resources, data, and infrastructure needed to increase vaccine uptake in the United States. Participants agreed that partners from all sectors – manufacturers, providers, public health, employers, payors, insurers, and consumers – will collectively need to leverage their efforts to address financial gaps not covered by health care reform law to ensure the preventive benefits of vaccines are fully realized for all Americans.

Recommended adolescent vaccine uptake: adolescent females North Carolina

Human Vaccines
Volume 7, Issue 1 January 2011
http://www.landesbioscience.com/journals/vaccines/toc/volume/6/issue/12/

Research Papers
Correlates of receiving recommended adolescent vaccines among adolescent females in North Carolina
Paul L. Reiter, Annie-Laurie McRee, Sami L. Gottlieb and Noel T. Brewer

Background. Immunization is a successful and cost-effective method for preventing disease, yet many adolescents do not receive recommended vaccines. We assessed correlates of uptake of three vaccines (tetanus booster, meningococcal, and human papillomavirus [HPV] vaccines) recommended for adolescent females.

Methods. We examined cross-sectional data from 647 parents of 11-20 year-old females from North Carolina who completed the Carolina HPV Immunization Measurement and Evaluation (CHIME) Project follow-up survey in late 2008. Analyses used ordinal and binary logistic regression.

Results. Only 17% of parents indicated their daughters had received all three vaccines. Eighty-seven percent of parents indicated their daughters had received tetanus booster vaccine, 36% reported vaccination against meningococcal disease, and 36% reported HPV vaccine initiation. Daughters aged 13-15 years (OR=1.70, 95% CI: 1.09–2.64) or 16-20 years (OR=2.28, 95% CI: 1.51–3.44) had received a greater number of these vaccines compared to daughters aged 11-12 years. Daughters who had preventive care visits in the last year (OR=4.81, 95% CI: 3.14–7.34) or whose parents had at least some college education (OR=1.90, 95% CI: 1.29–2.80) had also received a greater number of these vaccines.

Conclusions. Few daughters, particularly 11-12 years olds, had received all three vaccines recommended for adolescent females. Ensuring annual preventive care visits and increasing concomitant administration of adolescent vaccines may help increase vaccine coverage.

Influenza: barriers to vaccination among secondary school teachers and staff

Human Vaccines
Volume 7, Issue 1 January 2011
http://www.landesbioscience.com/journals/vaccines/toc/volume/6/issue/12/

Seasonal and 2009 H1N1 influenza vaccine uptake, predictors of vaccination, and self-reported barriers to vaccination among secondary school teachers and staff
Lisa M. Gargano, Julia E. Painter, Jessica M. Sales, Christopher Morfaw, LaDawna M. Jones, Dennis Murray, Gina M. Wingood, Ralph J. DiClemente and James M. Hughes

Objective: Teachers, like healthcare workers, may be a strategic target for influenza immunization programs. Influenza vaccination is critical to protect both teachers and the students they come into contact with. This study assessed factors associated with seasonal and H1N1 influenza vaccine uptake among middle- and high-school teachers. Methods: Participants were recruited from two counties in rural Georgia. Data were collected from surveys in September 2009 and May 2010. Multivariate logistic regression was used to assess the association between teachers’ attitudes toward seasonal and H1N1 influenza vaccination and vaccine uptake. Results: Seventy-eight percent of teachers who planned to receive seasonal influenza vaccine and 36% of those who planned to receive H1N1 influenza vaccine at baseline reported that they did so. Seasonal vaccine uptake was significantly associated with perceived severity (odds ratio [OR] 1.57, P=0.05) and self-efficacy (OR 4.46, P=0.006). H1N1 vaccine uptake was associated with perceived barriers (OR 0.7, P=0.014) and social norms (OR 1.39, P=0.05). The number one reason for both seasonal and H1N1 influenza vaccine uptake was to avoid getting seasonal/H1N1 influenza disease. The number one reason for seasonal influenza vaccine refusal was a concern it would make them sick and for H1N1 influenza vaccine refusal was concern about vaccine side effects. Conclusions: There is a strong association between the intention to be vaccinated against influenza (seasonal or 2009 H1N1) and actual vaccination uptake. Understanding and addressing factors associated with teachers’ influenza vaccine uptake may enhance future influenza immunization efforts.

Non-specific and sex-differential effects of routine vaccines: low-income countries

Human Vaccines
Volume 7, Issue 1 January 2011
http://www.landesbioscience.com/journals/vaccines/toc/volume/6/issue/12/

Non-specific and sex-differential effects of routine vaccines: What evidence is needed to take these effects into consideration in low-income countries?
Peter Aaby and Christine S. Benn

None of the original vaccines used in the child immunization programmes in low-income countries, including BCG, diphtheria-tetanus-pertussis (DTP), oral polio vaccine (OPV), and measles vaccine (MV), were tested for their overall effect on child mortality before being introduced. It was assumed that the effect on overall child mortality would be equivalent to the proportion of deaths caused by the targeted disease(s) (1). However, this is no longer a tenable assumption. Many studies have shown that these routine vaccines may have more general effects on the immune system than merely protecting against the targeted disease, i.e. so-called non-specific effects (NSE) (2). The NSE may well be more important for overall child survival than the lives saved by specific disease prevention (2-4). The WHO´s Global Advisory Committee on Vaccine Safety (GACVS) has recently stated that it will keep a watch on the non-specific effects (NSE) of vaccination. GACVS indicated that “conclusive evidence for or against non-specific effects of vaccines on mortality, including a potential deleterious effect of DTP vaccination on children’s survival as has been reported in some studies, was unlikely to be obtained from observational studies” (5). By insisting on new RCTs to provide conclusive evidence, GACVS is making it very difficult if not impossible to test the NSEs of the currently recommended vaccines. It would usually be considered unethical to test currently recommended vaccines as part of a trial withholding these vaccines from some children (6).

Measuring impact in the Millennium Development Goal era and beyond

The Lancet
Jan 01, 2011 Volume 377 Number 9759 Pages 1 – 96
http://www.thelancet.com/journals/lancet/issue/current

Health Policy
Measuring impact in the Millennium Development Goal era and beyond: a new approach to large-scale effectiveness evaluations
Cesar G Victora, Robert E Black, J Ties Boerma, Jennifer Bryce

Summary
Evaluation of large-scale programmes and initiatives aimed at improvement of health in countries of low and middle income needs a new approach. Traditional designs, which compare areas with and without a given programme, are no longer relevant at a time when many programmes are being scaled up in virtually every district in the world. We propose an evolution in evaluation design, a national platform approach that: uses the district as the unit of design and analysis; is based on continuous monitoring of different levels of indicators; gathers additional data before, during, and after the period to be assessed by multiple methods; uses several analytical techniques to deal with various data gaps and biases; and includes interim and summative evaluation analyses. This new approach will promote country ownership, transparency, and donor coordination while providing a rigorous comparison of the cost-effectiveness of different scale-up approaches.

Effectiveness of inactivated influenza vaccine in children aged 9 months to 3 years

The Lancet Infectious Disease
Jan 2011  Volume 11 Number 1 Pages 1 – 72
http://www.thelancet.com/journals/laninf/issue/current

Articles
Effectiveness of inactivated influenza vaccine in children aged 9 months to 3 years: an observational cohort study
Santtu Heinonen, Heli Silvennoinen, Pasi Lehtinen, Raija Vainionpää, Thedi Ziegler, Terho Heikkinen

Summary
Background
Few prospectively collected data are available to support the effectiveness of inactivated influenza vaccines in children younger than 2 years. We aimed to establish the effectiveness of trivalent inactivated influenza vaccine against laboratory-confirmed influenza A and B infections in a cohort of children younger than 3 years.

Methods
In a prospective cohort study during the influenza season of 2007—08 in Turku, Finland, between Jan 14 and April 9, 2008, we assessed the effectiveness of trivalent inactivated influenza vaccine against laboratory-confirmed influenza A and B infections in children aged 9 months to 3 years. Our study was part of a clinical trial on antiviral treatment of influenza in children (ClinicalTrials.gov, number NCT00593502). The vaccine was given as part of the Finnish vaccination programme as a 0·5 mL injection. Children enrolled into our study through mailed announcements and local advertisements were examined every time they had fever or signs of respiratory infection. No exclusion criteria were used for enrolment. Influenza was diagnosed with viral culture, antigen detection, and RT-PCR assays of nasal swab specimens. Vaccination status of children was determined by parental report. We calculated the primary effectiveness of influenza vaccination by comparing the proportions of infections in fully vaccinated and unvaccinated children in the follow-up cohort.

Findings
We enrolled 631 children into our study with a mean age of 2·13 years (range 9—40 months). Seven (5%) of 154 fully vaccinated children and 61 (13%) of 456 unvaccinated children contracted influenza during the study (effectiveness 66%, 95% CI 29—84; p=0·003). In the subgroup of children younger than 2 years, four (4%) of 96 fully vaccinated children and 21 (12%) of 172 unvaccinated children contracted influenza (66%, 9—88, p=0·03). We were unable to record any adverse events associated with the vaccination of the children in our study.

Interpretation
Trivalent inactivated influenza vaccine was effective in preventing influenza in young children, including those younger than 2 years. Our findings suggest that influenza vaccine recommendations should be reassessed in most countries.

Funding
F Hoffmann-La Roche Ltd.

Antimalarial drug resistance of Plasmodium falciparum in India

The Lancet Infectious Disease
Jan 2011  Volume 11 Number 1 Pages 1 – 72
http://www.thelancet.com/journals/laninf/issue/current

Review
Antimalarial drug resistance of Plasmodium falciparum in India: changes over time and space
Naman K Shah, Gajender PS Dhillon, Adtiya P Dash, Usha Arora, Steven R Meshnick, Neena Valecha

After the launch of the National Malaria Control Programme in 1953, the number of malaria cases reported in India fell to an all-time low of 0·1 million in 1965. However, the initial success could not be maintained and a resurgence of malaria began in the late 1960s. Resistance of Plasmodium falciparum to chloroquine was first reported in 1973 and increases in antimalarial resistance, along with rapid urbanisation and labour migration, complicated the challenge that India’s large geographical area and population size already pose for malaria control.

HPV vaccination and trends in genital warts in Australia

The Lancet Infectious Disease
Jan 2011  Volume 11 Number 1 Pages 1 – 72
http://www.thelancet.com/journals/laninf/issue/current

Quadrivalent human papillomavirus vaccination and trends in genital warts in Australia: analysis of national sentinel surveillance data
Basil Donovan, Neil Franklin, Rebecca Guy, Andrew E Grulich, David G Regan, Hammad Ali, Handan Wand, Christopher K Fairley

Preview
The decrease in frequency of genital warts in young Australian women resulting from the high coverage of HPV vaccination might provide protective effects in heterosexual men through herd immunity.

The Remaining Challenge of Pneumonia: The Leading Killer of Children

The Pediatric Infectious Disease Journal
January 2011 – Volume 30 – Issue 1 pp: A9-A10,1-94,e1-e17
http://journals.lww.com/pidj/pa     ges/currenttoc.aspx

The Remaining Challenge of Pneumonia: The Leading Killer of Children
Dagan, Ron; Bhutta, Zulfiqar A.; de Quadros, Ciro A.; Garau, Javier; Klugman, Keith P.; Khuri-Bulos, Najwa; Levine, Orin; Saha, Samir K.; Sow, Samba; Were, Fred; Yang, Yonghong
Pediatric Infectious Disease Journal. 30(1):1-2, January 2011.
doi: 10.1097/INF.0b013e3182005389

[No abstract available]

Vaccine Preventable Community-acquired Pneumonia in Hospitalized Children: Northwest China

The Pediatric Infectious Disease Journal
January 2011 – Volume 30 – Issue 1 pp: A9-A10,1-94,e1-e17
http://journals.lww.com/pidj/pa     ges/currenttoc.aspx

Vaccine Preventable Community-acquired Pneumonia in Hospitalized Children in Northwest China
Zhang, Qingli; Guo, Zhongqin; MacDonald, Noni E.
Pediatric Infectious Disease Journal. 30(1):7-10, January 2011.
doi: 10.1097/INF.0b013e3181ec6245

Abstract:
Background: Community-acquired pneumonia (CAP) is a major cause of morbidity in industrialized countries and morbidity/mortality in developing countries. In China, comprehensive studies of the etiology of CAP in children aged between 2 months and 14 years who are serious enough to require hospitalization are lacking. Previous studies have been limited in child age range, focused on fatal cases, and/or limited in etiologies sought. An understanding of the etiologies is needed for development of best prevention and management practices.

Objective: The aim of this study was to prospectively determine during a 12-month period the etiology of CAP in hospitalized children in a center in Northwest China.

Design/Methods: A prospective 12-month study (2004–2005) of CAP cases in children who were 2 months to 14 years of age admitted to the Second Hospital of Lanzhou University, China. Testing included admission and 1-month postdischarge serum for viral and bacterial serologic analyses (respiratory syncytial virus, influenza A and B, paraflu 1–3, adenovirus; Streptococcus pneumoniae, Haemophilus influenza B, Mycoplasma, and Moraxella. catarrhalis), blood culture, a nasopharyngeal aspirate for viral antigen testing, and a chest radiograph on admission and 1 month postdischarge. The study was funded by Lanzhou University. The study was performed in compliance with the guidelines of the institutional review board of the Second Hospital of Lanzhou University.

Results: CAP was the admitting diagnosis for 29% of all admissions during the 12-month study. Of the 884 CAP cases, 821 (93%) were enrolled and completed the study. The age range was 2 months to 14 years; mean age was 2.3 years; 40% were <1 year. The average length of stay was 9.2 days (range, 6–20) but varied by age and etiology. Fourteen percent had received antibiotics before admission and 14% had underlying illnesses; 12% required intensive care unit treatment and 5 died. A microbial etiology for CAP was identified in 547 (67%); viral 535 (43%), bacterial 228 (27%), mixed viral bacterial 107 (13%), mixed viral in 1%, and mixed bacterial in 1%. The etiology varied by age; respiratory syncytial virus was most common in <1 year, S. pneumoniae and Hib 1–3 years, and Mycoplasma >5 years. Three potentially vaccine preventable etiologies accounted for 35% of the cases: influenza 9%, Hib 12%, and S. pneumonia 14%.

Conclusions: CAP is a major cause of childhood admission in China. Given the etiologic findings in this study, potentially 25% to 35% of cases could be prevented if seasonal influenza vaccine and conjugated H. influenza b and conjugated pneumococcal vaccines were introduced into routine practice

Adherence to the HPV Vaccine Dosing Intervals

Pediatrics
January 2011 / VOLUME 127 / ISSUE 1
http://pediatrics.aappublications.org/current.shtml

Adherence to the HPV Vaccine Dosing Intervals and Factors Associated With Completion of 3 Doses
Lea E. Widdice, David I. Bernstein, Anthony C. Leonard, Keith A. Marsolo, and Jessica A. Kahn
Pediatrics 2011; 127: 77-84.

Abstract
OBJECTIVE The objectives of this study were to determine (1) adherence to the immunization schedule for the human papillomavirus quadrivalent vaccine and (2) factors associated with completion of the 3-dose series.

METHODS This was a retrospective review of health information records from an academic medical center. The sample included all 9- to 26-year-old female patients who initiated vaccination within 2 years after quadrivalent vaccine availability. Multivariable logistic regression models were estimated to determine associations with completion of the 3-dose series within 7 and 12 months.

RESULTS Among the 3297 female patients who initiated vaccination with human papillomavirus quadrivalent vaccine, 67% self-identified as black and 29% self-identified as white. Fewer than 3% of vaccine doses were received earlier than recommended, but >50% of doses were received late. Completion rates were 14% by 7 months and 28% by 12 months. Independent predictors of completion by 7 months included white versus black race (odds ratio [OR]: 2.04 [95% confidence interval (CI): 1.64–2.56]; P < .001), use of contraception that required intramuscular injections every 3 months (OR: 1.53 [95% CI: 1.12–1.95]; P < .001), and private versus public insurance (OR: 1.31 [95% CI: 1.06–1.63]; P < .05). Age and clinic type were not independent predictors of completion.

CONCLUSIONS Adherence to recommended intervals and completion of the vaccine series were low. Lower rates of completion in black patients compared with white patients raises concern that disparities in vaccine completion could exacerbate existing disparities in cervical cancer.

Toward a Consensus on Guiding Principles for Health Systems Strengthening

PLoS Medicine
(Accessed 2 January 2011)
http://medicine.plosjournals.org/perlserv/?request=browse&issn=1549-1676&method=pubdate&search_fulltext=1&order=online_date&row_start=1&limit=10&document_count=1533&ct=1&SESSID=aac96924d41874935d8e1c2a2501181c#results

Toward a Consensus on Guiding Principles for Health Systems Strengthening
Robert C. Swanson, Annette Bongiovanni, Elizabeth Bradley, Varnee Murugan, Jesper Sundewall, Arvind Betigeri, Frank Nyonator, Adriano Cattaneo, Brandi Harless, Andrey Ostrovsky, Ronald Labonté Policy Forum, published 21 Dec 2010
doi:10.1371/journal.pmed.1000385

Summary Points
– Despite the expanding consensus about the need for health systems strengthening (HSS), there is a lack of a common definition and set of guiding principles that can inform strategic frameworks used to develop policy, practice and evaluations.

– Without a set of agreed-upon principles, these frameworks may be unclear and inconsistent, limiting the ability for collective learning, innovation, and improvement.

– A set of ten guiding principles for HSS is proposed in this paper that is based upon a systematic review and consultation with experts in three countries.

– They are: holism, context, social mobilization, collaboration, capacity enhancement, efficiency, evidence-informed action, equity, financial protection, and satisfaction.

– The authors welcome and encourage further discussion of these findings at all levels so that a broad consensus on HSS principles is obtained.

Congo Polio Outbreak Breaks the Rules

Science
24 December 2010 vol 330, issue 6012, pages 1717-1852
http://www.sciencemag.org/current.dtl

News of the Week: Infectious Disease
Polio Outbreak Breaks the Rules
Leslie Roberts

Summary
Polio is a horrendous disease, but it is seldom fatal—except now. An explosive outbreak in the Republic of Congo is writing another chapter in the book on how this ancient scourge behaves. The new outbreak tearing through this West African country has so far killed an estimated 42% of its victims, who, in another unusual twist, are mostly adult males between the ages of 15 and 25. Since it began in early October, the outbreak has paralyzed more than 476 people and killed at least 179, according to World Health Organization estimates from early December, making this one of the largest and deadliest polio outbreaks in recent history. And one of the most mystifying, too, polio experts say.

What’s Next for Disease Eradication?

Science
24 December 2010 vol 330, issue 6012, pages 1717-1852
http://www.sciencemag.org/current.dtl

News Focus: Global Public Health
What’s Next for Disease Eradication?
Martin Enserink

Summary
Two days after the 30th anniversary of the eradication of smallpox, 30 scientists and public health experts from around the world gathered for a weeklong meeting in the German city of Frankfurt am Main to try to chart a new path for disease eradication in the 21st century. Their meeting was triggered by several developments. Interest in tackling global health problems has surged the past decade, as has funding, but the two ongoing eradication campaigns—against guinea worm disease and polio—have proven far more difficult than predicted. Meanwhile, a key rationale for past eradication efforts—the promised financial windfall from stopping all control measures once a disease is gone—all but disappeared as a result of 9/11 and the 2001 anthrax letters. Wealthy countries in particular are determined never to let their guard down against diseases like smallpox, polio, or measles. Meanwhile, developing countries have their own questions: Why should they keep spending inordinate amounts of time and money on a disease such as polio—now down to fewer than 2000 cases a year—while their health systems are struggling with far more devastating diseases such as AIDS and TB?

Civil society: A critical new advocate for vaccination in Europe

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 29, Issue 4 pp. 613-864 (17 January 2011)

Review Article
Civil society: A critical new advocate for vaccination in Europe

Pages 624-628
Vanina Laurent-Ledru, Angus Thomson, Joseph Monsonego

Abstract
The vaccinology landscape has changed, with national authorities now being increasingly accountable to new stakeholders such as health insurers, regional regulatory bodies, the media, and civil society. Here, we discuss how civil society organisations (CSOs), such as patient and women’s groups, have become important drivers in the introduction and sustainability of new vaccination programs. This shift in public implication in vaccine policy has been well illustrated in the recent introduction of human papillomavirus (HPV) vaccination in Europe. Patient and women’s groups which were traditionally focused on advocacy of treatments have also become advocates for prevention with the advent of HPV vaccination. Civil society advocacy at the European level supported key resolutions and white papers which in turn informed national recommendations on cervical cancer vaccination. CSOs were also active at the national level, supporting national policy makers. These organisations may bring innovative and effective new approaches to communication on vaccination benefits, using public events, celebrities and various social media. Working with experts, CSOs can also be an important bridge from the science to the lay public. This may provide a vital counterbalance to media hype and antivaccination groups, although CSOs may also be active and vocal opponents of immunization. The successful implementation and sustainability of future vaccination programs against infections such as HIV will be dependent upon the active participation of civil society to inform, to reassure and to maintain public trust.

Participant perspectives in the aftermath of an early HIV vaccine trial termination

Vaccine
Volume 29, Issue 3 pp. 363-612 (10 January 2011)
“Once Bitten, Twice Shy”: Participant perspectives in the aftermath of an early HIV vaccine trial termination

Original Research Article
Pages 451-458
P.A. Newman, S. Yim, A. Daley, R. Walisser, R. Halpenny, W. Cunningham, M. Loutfy

Abstract
The Step Study phase IIb HIV-1 vaccine trial was terminated early due to futility; subsequent analyses revealed increased susceptibility to HIV infection among a subset of test vaccine recipients. We conducted a mixed methods investigation, including a brief, self-administered baseline questionnaire and in-depth, semi-structured, 1-h interviews after unblinding, to explore experiences and perspectives among trial participants and key informants. Interviews were digitally recorded, transcribed, and analyzed using NVivo and thematic techniques. Forty-eight trial participants (46 gay/bisexual men) completed baseline surveys; 15 (14 gay/bisexual men) engaged in post-trial interviews. Participants indicated surprise and disappointment about the early trial termination and unexpected risks. Some articulated understanding the uncertainties of clinical trials, steadfast support and willingness to participate in the future; others reported greater risks than they deemed acceptable and unlikelihood of volunteering again. A few indicated mistrust of trial sponsors and ethics. Participants’ most profound criticism was not about unexpected results, but perceived delays in unblinding and gaps in post-trial dissemination of information. Future HIV vaccine trials may benefit from increased emphasis on: (1) communication mechanisms among participants, investigators and trial sponsors, and (2) post-trial dissemination of information and psychosocial support.

Economic evaluation of infant and adolescent hepatitis B vaccination in the UK

Vaccine
Volume 29, Issue 3 pp. 363-612 (10 January 2011)
Economic evaluation of infant and adolescent hepatitis B vaccination in the UK

Original Research Article
Pages 466-475
M. Ruby Siddiqui, Nigel Gay, W. John Edmunds, Mary Ramsay

Abstract
A Markov model of hepatitis B virus (HBV) disease progression in the UK estimated that 81% of predicted HBV-associated morbidity and mortality could be prevented by universal infant vaccination at a cost of approximately £260,000 per QALY gained.

Universal adolescent vaccination would be less effective (45% prevented) and less cost-effective (£493,000 per QALY gained). Higher HBV incidence rates in males and intermediate/high risk ethnic populations meant it was approximately 3 times more cost-effective to vaccinate these groups. At current vaccine costs a selective infant vaccination programme, based on vaccinating intermediate/high risk ethnic populations would not be considered cost effective.

The threshold cost per vaccinated child at which the programme would be considered cost-effective was investigated. Universal infant vaccination would be cost-effective if the average cost of vaccinating each child against HBV, including vaccine and administration costs of all doses, was less than £4.09. Given the low cost of vaccination required to make a universal programme cost-effective the most feasible policy in the UK would be to use a suitably priced combined vaccine that included the other antigens in the current infant vaccination schedule.

Worsening disparities in HPV vaccine utilization among 19–26 year old women

Vaccine
Volume 29, Issue 3 pp. 363-612 (10 January 2011)
Worsening disparities in HPV vaccine utilization among 19–26 year old women

Original Research Article
Pages 528-534
Amanda Dempsey, Lisa Cohn, Vanessa Dalton, Mack Ruffin

Abstract
We evaluated the characteristics associated with uptake of HPV vaccine by 19–26 year old women seen in primary care university-based clinics. Of the 11,545 women analyzed only 18% had initiated the 3-dose vaccine series. Series completion among the sample overall was only 10% in the 30 month study period. Decreased series initiation was associated with older age, public insurance, white race and non-family medicine specialty. Decreased series completion was associated with public insurance and African American race. Utilization disparities by race and insurance worsened over time suggesting that the highest risk populations of women were not getting vaccinated.