HIV vaccine trials and tribulations

The Lancet Infectious Disease
Nov 2009  Volume 9  Number 11  Pages 651 – 718
http://www.thelancet.com/journals/laninf/issue/current

Leading Edge
HIV vaccine trials and tribulations
The Lancet Infectious Diseases

Preview
The results released on Sept 24 of the RV144 trial of a vaccine against HIV offer a glimmer of hope in a field that has experienced many disappointments. The reported vaccine efficacy of 31% for prevention of HIV infection seems promising, but still leaves the prospect of immunisation as a practical public health intervention against HIV tantalisingly out of reach.

Progress towards a dengue vaccine

The Lancet Infectious Disease
Nov 2009  Volume 9  Number 11  Pages 651 – 718
http://www.thelancet.com/journals/laninf/issue/current

Progress towards a dengue vaccine
Daniel P Webster, Jeremy Farrar, Sarah Rowland-Jones

The spread of dengue virus throughout the tropics represents a major, rapidly growing public health problem with an estimated 2.5 billion people at risk of dengue fever and the life-threatening disease, severe dengue. A safe and effective vaccine for dengue is urgently needed. The pathogenesis of severe dengue results from a complex interaction between the virus, the host, and, at least in part, immune-mediated mechanisms. Vaccine development has been slowed by fears that immunisation might predispose individuals to the severe form of dengue infection.

Emerging diseases, zoonoses and vaccines to control them

Vaccine
Volume 27, Issue 46, Pages 6393-6480 (30 October 2009)
http://www.sciencedirect.com/science/journal/0264410X

Advances in Vaccine Technology II 2008: Introduction
Edited by David B. Weiner, Mathura P. Ramanathan, Barry C. Buckland, Kathrin U. Jansen and John G. Auninš

Emerging diseases, zoonoses and vaccines to control them
Pages 6435-6438
Pastoret Paul-Pierre
Abstract
Vaccination, when available, is undoubtedly the most cost-effective means of preventing and controlling, and even eradicating, infectious diseases. In recent years vaccination has also been used for other purposes in animal health, production and welfare, e.g. immunocastration.
Vaccination of animals serves many different purposes, such as controlling animal infections and infestations, thus improving animal health and welfare; controlling anthropozoonoses and food poisoning in humans, thereby protecting public health; solving problems associated with antibiotic and anthelmintic resistance; helping to leave food-producing animals free of chemical residues; protecting the environment and biodiversity and ensuring animal farming sustainability. The problem is nevertheless more complex when facing emerging or re-emerging infections particularly zoonotic ones.

Pandemic (H1N1) 2009 briefing note 13 – 16 Oct 2009: Clinical features of severe cases of pandemic influenza

Pandemic (H1N1) 2009 briefing note 13
Clinical features of severe cases of pandemic influenza

16 OCTOBER 2009 | GENEVA — To gather information about the clinical features and management of pandemic influenza, WHO hosted a three-day meeting at the headquarters of the Pan American Health Organization in Washington, DC on 14–16 October. Findings and experiences were presented by around 100 clinicians, scientists, and public health professionals from the Americas, Europe, Asia, Africa, the Middle East and Oceania.

The meeting confirmed that the overwhelming majority of persons worldwide infected with the new H1N1 virus continue to experience uncomplicated influenza-like illness, with full recovery within a week, even without medical treatment.

Need for intensive care

However, concern is now focused on the clinical course and management of small subsets of patients who rapidly develop very severe progressive pneumonia. In these patients, severe pneumonia is often associated with failure of other organs, or marked worsening of underlying asthma or chronic obstructive airway disease.

Treatment of these patients is difficult and demanding, strongly suggesting that emergency rooms and intensive care units will experience the heaviest burden of patient care during the pandemic.

Primary viral pneumonia is the most common finding in severe cases and a frequent cause of death. Secondary bacterial infections have been found in approximately 30% of fatal cases. Respiratory failure and refractory shock have been the most common causes of death.

Presentations during the meeting explored the pathology of severe disease in detail, with findings supported by work in experimental animals. These findings confirm the ability of the new H1N1 virus to directly cause severe pneumonia.

Clinical picture different from seasonal influenza

Participants who have managed such cases agreed that the clinical picture in severe cases is strikingly different from the disease pattern seen during epidemics of seasonal influenza. While people with certain underlying medical conditions, including pregnancy, are known to be at increased risk, many severe cases occur in previously healthy young people. In these patients, predisposing factors that increase the risk of severe illness are not presently understood, though research is under way.

In severe cases, patients generally begin to deteriorate around 3 to 5 days after symptom onset. Deterioration is rapid, with many patients progressing to respiratory failure within 24 hours, requiring immediate admission to an intensive care unit. Upon admission, most patients need immediate respiratory support with mechanical ventilation. However, some patients do not respond well to conventional ventilatory support, further complicating the treatment.

On the positive side, findings presented during the meeting add to a growing body of evidence that prompt treatment with the antiviral drugs, oseltamivir or zanamivir, reduces the severity of illness and improves the chances of survival. These findings strengthen previous WHO recommendations for early treatment with these drugs for patients who meet treatment criteria, even in the absence of a positive confirmatory test.

In addition to pneumonia directly caused by replication of the virus, evidence shows that pneumonia caused by co-infection with bacteria can also contribute to a severe, rapidly progressive illness. Bacteria frequently reported include Streptococcus pneumoniae and Staphylococcus aureus, including methicillin-resistant strains in some cases. As these bacterial co-infections are more frequent than initially recognized, clinicians stressed the need to consider empiric antimicrobial therapy for community acquired pneumonia as an early treatment.

Groups at greatest risk

Participants agreed that the risk of severe or fatal illness is highest in three groups: pregnant women, especially during the third trimester of pregnancy, children younger than 2 years of age, and people with chronic lung disease, including asthma. Neurological disorders can increase the risk of severe disease in children.

Evidence presented during the meeting further shows that disadvantaged populations, such as minority groups and indigenous populations, are disproportionately affected by severe disease. Although the reasons for this heightened risk are not yet fully understood, theories being explored include the greater frequency of co-morbidities, such as diabetes and asthma, often seen in these groups, and lack of access to care.

Although the exact role of obesity is poorly understood at present, obesity and especially morbid obesity have been present in a large portion of severe and fatal cases. Obesity has not been recognized as a risk factor in either past pandemics or seasonal influenza.

WHO and its partners are providing technical guidance and practical support to help developing countries better detect and treat illness caused by the pandemic virus. Patient care advice that can be applied in resource-limited settings is being rapidly compiled.

http://www.who.int/csr/disease/swineflu/notes/h1n1_clinical_features_20091016/en/index.html

FDA approves Merck’s Gardasil vaccine for the prevention of genital warts in boys and men 9 to 26

The U.S. Food and Drug Administration approved use of Merck’s Gardasil vaccine for the prevention of genital warts (condyloma acuminata) due to HPV types 6 and 11 in boys and men, ages 9 through 26, noting that each year, about 2 out of every 1,000 men in the United States are newly diagnosed with genital warts. Karen Midthun, M.D., acting director of the FDA’s Center for Biologics Evaluation and Research, said, “This vaccine is the first preventive therapy against genital warts in boys and men ages 9 through 26, and, as a result, fewer men will need to undergo treatment for genital warts.” Gardasil’s effectiveness was studied in a randomized trial of 4,055 males ages 16 through 26 years old. The results showed that in men who were not infected by HPV types 6 and 11 at the start of the study, Gardasil was nearly 90 percent effective in preventing genital warts caused by infection with HPV types 6 and 11. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm187003.htm

Balancing Pharma Innovation and Access: Patent Challenges

Science
16 October 2009  Vol 326, Issue 5951, Pages 325-488
http://www.sciencemag.org/current.dtl

Policy Forum
Intellectual Property:
Balancing Innovation and Access: Patent Challenges Tip the Scales
Matthew J. Higgins1,* and Stuart J. H. Graham1,2,*

Improvements in pharmaceutical research and development (R&D) depend on product innovation. But the number of new compounds approved annually by the U.S. Food and Drug Administration (FDA) has fallen from an average of 35 in 1996–2001 to 20 in 2002–07 (1). This decline stems from several factors (2); however, one particular U.S. regulation—the Paragraph IV patent challenge—is increasingly stifling new drug innovation and deserves our attention.

1 College of Management, Georgia Institute of Technology, Atlanta, GA 30308, USA.
2 Berkeley Center for Law and Technology, University of California, Berkeley Law School, Berkeley, CA 94720, USA.
* The authors contributed equally to this work.

ESWI – Third European Influenza Conference Vilamoura, Portugal, 14-17 September 2009

Vaccine
Volume 27, Issue 45, Pages 6269-6392 (23 October 2009)
http://www.sciencedirect.com/science/journal/0264410X

This issue covers presentations made at ESWI – Third European Influenza Conference
Vilamoura, Portugal, 14-17 September 2008.

Influenza vaccination and mortality benefits: New insights, new opportunities
Pages 6300-6304
Lone Simonsen, Cecile Viboud, Robert J. Taylor, Mark A. Miller, Lisa Jackson

Abstract
Influenza vaccination control strategies in most countries rely on vaccination of seniors and other high risk groups. Although placebo-controlled randomized trials show influenza vaccine is effective in younger age groups, few seniors >70 years were studied even though they suffer >90% of influenza-related deaths. Excess mortality studies could not confirm a national decline in influenza-related mortality while vaccine coverage quadrupled. Cohort studies have consistently reported that vaccination reduces all-cause winter mortality by 50%, an astonishing claim given only 5% of all winter deaths are attributable to influenza. This VE overestimation has now been attributed to profound confounding frailty selection bias. A way forward includes a new generation of unbiased studies with laboratory endpoints, and requires an agreement that the evidence base was flawed. The latter may clear the way for more immunogenic vaccines for seniors and exploration of other influenza control strategies

Challenges in evaluating influenza vaccine effectiveness and the mortality benefits controversy
Pages 6305-6311
Kristin L. Nichol

Abstract
Randomized, controlled trials are the gold standard study design. However, ethical constraints and practical considerations may necessitate other types of studies for evaluating influenza vaccine effectiveness in the elderly—a high priority group for annual vaccination in many countries. Observational studies therefore comprise the bulk of the vaccine effectiveness evidence in older persons, but these types of studies can be susceptible to selection bias and residual confounding. All observational studies should utilize strategies to minimize the impact of bias and confounding. Recent studies questioning the plausibility of reported mortality benefits among vaccinated elderly persons may themselves be based on assumptions that are susceptible to important limitations and multiple biases. Future studies that incorporate prospectively collected information on functional status, life expectancy, and other types of data may provide additional insights into these concerns. At present, even after taking into account the potential for residual bias and confounding, most studies confirm the benefits of vaccination among the elderly for reducing hospitalization and death.

Internet-based monitoring of influenza-like illness in the general population: Experience of five influenza seasons in the Netherlands
Pages 6353-6357
I.H.M. Friesema, C.E. Koppeschaar, G.A. Donker, F. Dijkstra, S.P. van Noort, R. Smallenburg, W. van der Hoek, M.A.B. van der Sande

Abstract
Like in most other countries, influenza surveillance in The Netherlands is based upon influenza-like illness (ILI) consultations reported by sentinel general practitioners (GP). In addition, an internet-based monitoring of ILI in the general population started in 2003/2004 (Great Influenza Survey (GIS)). We compared GIS results over 5 influenza seasons with results from the GP system. Weekly ILI incidence from GIS correlated well with ILI incidence from the GP system the same week and even better 1 week later. This suggests that GIS is useful for early detection of trends in influenza activity. However, two important vulnerable groups, children and the elderly, are clearly underrepresented in the GIS. Furthermore, virological confirmation is lacking in the GIS. So, GIS can be a useful addition to the GP system, especially when representativeness can be improved and when participation remains at the current high level.