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A Measles Mystery: How Could the Vaccine Prevent Deaths from Other Diseases Too?

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By Michael Mina, Postdoctoral researcher at Princeton University and MD/PhD candidate at Emory University

If infectious diseases were a monarchy, measles might be king. Not only does measles reign among the most contagious diseases known to man – likely to infect any non-vaccinated individual who stands in the same room as an infected person – measles has long been known to be one of the great killers of children. Before vaccination, measles was responsible for millions of childhood deaths. Today it remains a cause of great illness and death in low-resource countries, killing over 140,000 children worldwide every year. [Read more…]

The Ebola outbreak highlights shortcomings in disease surveillance and response – and where we can do better

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By Grant Hill-Cawthorne, Lecturer in Communicable Disease Epidemiology at University of Sydney

At this time last year, Ebola Virus Disease (EVD) was rapidly spreading through West Africa, and the outbreak is rightly a major item on this year’s assembly agenda. Attention will be paid to the decisions made in response to the outbreak and what this tells us about how best to respond to the next one, including for advance preparation and early warning. [Read more…]

Flu Prevention for Children and Teens – Report

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Although children and teenagers rarely die from flu–related causes, many of the deaths could have been prevented if the children had been vaccinated against the flu, according to a report by the Centers for Disease Control and Prevention.

The study reports 115 influenza–associated deaths of people younger than 18, from September 2010 through August 2011 and highlights the importance of both annual vaccination and rapid antiviral treatment.

“It′s vital that children get vaccinated,” said Dr. Lyn Finelli, chief of the CDC′s Surveillance and Outbreak Response Team. “We know the flu vaccine isn′t 100 percent effective, especially not in children with high risk medical conditions. That′s why it′s essential that these two medical tools be fully utilized. Vaccinate first; then use influenza antiviral drugs as a second line of defense against the flu. Right now we aren′t fully using the medical tools at our disposal to prevent flu illnesses and deaths in children.”

The study in CDC′s Morbidity and Mortality Weekly Report provides details on the deaths. Since 2004, states have been required to report influenza-associated deaths in children and teenagers, giving the CDC a chance to look closely at factors that can increase risk.

Among the most notable findings was the infrequent use of the most important influenza prevention measure – vaccination. Despite a recommendation for vaccination of all children 6 months of age and older having been in place since 2008, only 23 percent of the 74 children older than six months with a known vaccination history had received their flu vaccine last season.

While many people believe that healthy children can withstand a bout of flu, this is not always the case. About half of the children who died last season were previously healthy and did not have a medical condition that would put them at risk for flu complications. However, the report underscores the fact that young age in itself is a risk factor. The report identified that 46 percent of the children who died were younger than 5 years and 29 percent were younger than 2 years.

The other half of the children who died did have a medical condition that predisposed them to being at greater risk of flu complications. Of 57 children with a medical condition, 54 percent had a neurological disorder, 30 percent had pulmonary disease, 25 percent had a chromosome or genetic disorder and 19 percent had congenital heart disease or other cardiac disease.

The report also identified issues with the use of antiviral drugs, which provide effective treatment for influenza. Of the 94 children who died in a hospital or emergency department, only 50 percent were prescribed antiviral drugs. Since the 2009 H1N1 pandemic especially, CDC has recommended immediate treatment with influenza antiviral medications in severely ill patients with suspected flu.

Another report in the Sept. 16 MMWR provides a summary of influenza activity from mid–May to the beginning of September. “If trends in that report continue,” Finelli says, “we should have a vaccine that will offer good protection against the viruses we expect will circulate this season.”

This season′s influenza vaccine protects against three influenza viruses, the 2009 influenza A (H1N1) virus, an influenza A (H3N2) virus, and an influenza B virus. These are the same three flu virus strains that were circulating in 2010–2011 – just the eighth time since 1969 this phenomenon has occurred. Moreover, it is important to note that vaccine immunity wanes over time so CDC is recommending that everyone get vaccinated this season, even if they got vaccinated last season, in order to be optimally protected.

Source: CDC

Antimicrobial Resistance a Growing Health Threat, Says CDC

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Millions of Americans take antimicrobial drugs each year to fight illness, trusting they will work. However, the bacteria, viruses and other pathogens are fighting back.

Within the past couple of years alone, new drug-resistant patterns have emerged and resistance has increased – a trend that demands urgent action to preserve the last lines of defense against many of these germs.

Today, the Centers for Disease Control (CDC) joined the World Health Organization and other health partners in recognizing World Health Day, which this year spotlights antimicrobial resistance. [Read more…]

ICU Bloodstream Infections Decline Dramatically

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The number of bloodstream infections in intensive care unit patients with central lines decreased by 58 percent in 2009 compared to 2001, according to the Centers for Disease Control (CDC). During these nine years, the decrease represented up to 27,000 lives saved and $1.8 billion in excess health care costs. Bloodstream infections in patients with central lines can be deadly, killing as many as 1 in 4 patients who gets one.

A central line is a tube usually placed in a large vein of a patient’s neck or chest to deliver treatment in an intensive care unit, elsewhere in the hospital, and during dialysis. A bloodstream infection can happen when germs enter the blood through a central line, often because proper procedures were not used while the central line was placed or maintained. In recent years, studies have proven that health care providers can prevent most bloodstream infections in patients with central lines by following CDC infection control recommendations, which include removing central lines as soon as medically appropriate. In hemodialysis patients, central lines should only be used when other options are unavailable.

“Preventing bloodstream infections is not only possible, it should be expected. Meticulous insertion and care of the central line by all members of the clinical care team including doctors, nurses and others at the bedside is essential. The next step is to apply what we’ve learned from this to other health care settings and other health care-associated conditions, so that all patients are protected,” said Thomas R. Frieden, M.D., M.P.H., CDC director. [Read more…]

48 Million Americans Sickened by Food-Borne Illness Each Year

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About sixteen percent of Americans, or 48 million people get sick each year from food-borne illness. Of those, 128,000 are hospitalized, and 3,000 die each year from the disease, according to a recent report from the Centers for Disease Control CDC).

“We’ve made progress in better understanding the burden of foodborne illness and unfortunately, far too many people continue to get sick from the food they eat,” said CDC Director Thomas Frieden, M.D, M.P.H. “These estimates provide valuable information to help CDC and its partners set priorities and further reduce illnesses from food.” [Read more…]

H1N1 Vaccine Boosts Immune Response in Asthmatics

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A single dose of H1N1 vaccine is safe and induces a strong immune response predictive of protection, according to a clinical trial of inactivated H1N1 flu vaccine in people with asthma.

The findings also suggest that individuals over the age of 60 who have severe asthma may require a larger dose of vaccine.

“Asthma was the most common underlying health condition among those hospitalized in the United States with 2009 H1N1 influenza infection during the 2009-2010 influenza season,” says NIAID Director Anthony S. Fauci, M.D. “The results of this clinical trial show that the 2009 H1N1 influenza vaccine was safe and led to adequate production of antibodies thought to be protective against the virus. This is important because the H1N1 vaccine is one component of the seasonal influenza vaccine currently being distributed for the 2010-2011 influenza season.” [Read more…]

Scientists Discover How Dengue Virus Infects Cells

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How does the dengue virus infect cells? To infect a cell, the dengue virus (counterclockwise, from upper left), binds to the cell membrane. The virus is then enveloped in the membrane, which coalesces around the virus, forming a pouch-like structure called an endosome. Deep inside the cell, the endosome membrane acquires a negative charge, which allows the virus to fuse with the endosomal membrane and release genetic material into the cell’s interior.

Researchers have discovered a key step in how the dengue virus infects a cell. The discovery one day may lead to new drugs to prevent or treat the infection.

Researchers from the National Institutes of Health discovered how the dengue virus releases itself from the protective membrane that shields it as it penetrates deep inside the cell. The discovery allows researchers to study the invasion process in the laboratory and provides a means to test potential treatments for the virus.

Dengue, which is transmitted by mosquitoes, infects up to 100 million people each year. People bitten by an infected mosquito first develop a fever, followed by other symptoms such as joint pain, rash and nausea. Without treatment, symptoms may become more severe. Patients with the severe form of the disease, dengue hemorrhagic fever, may develop difficulty breathing, bruising, bleeding from the nose or gums, and breakdown of the circulatory system. Each year, 22,000 people — most of them children — die from dengue, according to the World Health Organization.

To infect a cell, the virus binds to the cell membrane. The cell membrane engulfs the virus, enveloping it in a pouch-like structure known as an endosome. To begin the infection process, the virus delivers its hereditary material into the cytosol, the fluid interior of the cell, where it begins reproducing itself. To do so, however, it must first release itself from the endosome. The virus does this by fusing its membrane with the endosomal membrane. When the two membranes come together, they form a pore through which the virus’ genetic material is released.
Graphic shows how the virus is taken into the cell and releases its DNA in the presence of a negative charge.

To infect a cell, the dengue virus (counterclockwise, from upper left), binds to the cell membrane. The virus is then enveloped in the membrane, which coalesces around the virus, forming a pouch-like structure called an endosome. Deep inside the cell, the endosome membrane acquires a negative charge, which allows the virus to fuse with the endosomal membrane and release genetic material into the cell’s interior.

Scientists have used their understanding of HIV to develop drugs that block the fusion process and infection. To study the fusion stage of viral entry, researchers have typically observed viral fusion at the cell surface and fusion of a virus with an artificial membrane. Researchers working with dengue, however, were unable to get the virus to fuse under either of these conditions. Why dengue, unlike other viruses, would not readily fuse with these membranes had puzzled researchers for years.

The current study was undertaken by Leonid V. Chernomordik, Ph.D., of the Section on Membrane Biology at the NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development and his colleagues, Elena Zaitseva, Sung-Tae Yang, Kamran Melikov, and Sergei Pourmal.

The researchers discovered that two conditions are necessary for dengue virus fusion—an acidic environment and the presence of a negatively charged membrane. They also discovered that these conditions are present at only certain points in the endosome’s journey within the cell.

“We spent several years trying to understand how the dengue virus fuses with its target membrane,” said Dr. Chernomordik. “The findings will now enable us to test new ways to disrupt the fusion process and prevent infection.”

Their research was published online in PLoS Pathogens.

To conduct their study, the researchers tagged dengue virus and cell membranes with molecules that would glow when the virus and membranes fused. They also exposed samples of the virus to an artificial membrane under various conditions, to identify factors that would allow fusion to take place.

The researchers first confirmed that a protein controlling fusion is active only under acidic conditions. However, conditions in the endosome are always acidic, and this alone was not enough to guarantee fusion, they found.

In additional experiments using artificial and cell membranes along with fluorescent markers, they discovered that fusion occurred only when the membranes were negatively charged. When the endosome begins its journey, the endosomal membrane has a neutral charge. The negative charge is present only after the endosome has been taken deep within the cell.

“The confluence of acidity and a negative charge deep in the cell’s interior ensures that the virus is safe within the endosome early in its journey, when it is most vulnerable, but can release its genome when it reaches its destination,” Dr. Chernomordik said.

Dr. Chernomordik and his colleagues plan to test various compounds to learn whether they can prevent the virus from fusing with cell and artificial membranes, in order to identify potential new treatments for dengue infection.

Source: NIH, October 12, 2010

Study Models H1N1 Flu Spread

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As the United States prepares for the upcoming flu season, a group of researchers continues to model how H1N1 may spread.

The work is part of an effort  called the Models of Infectious Disease Agent Study (MIDAS), to develop computational models for conducting virtual experiments of how emerging pathogens could spread with and without interventions. The study, supported by the National Institutes of Health, involves more than 50 scientists with expertise in epidemiology, infectious diseases, computational biology, statistics, social sciences, physics, computer sciences and informatics.

As soon as the first cases of H1N1 infections were reported in April 2009, MIDAS researchers began gathering data on viral spread and affected populations. This information enabled them to model the potential outcomes of different interventions, including vaccination, treatment with antiviral medications and school closures. The work built upon earlier models the MIDAS scientists developed in response to concerns about a different potentially pandemic influenza strain H5N1 or avian flu.

“Computational modeling can be a powerful tool for understanding how a disease outbreak is unfolding and predicting the implications of specific public health measures,” said Jeremy M. Berg, Ph.D., director of the National Institute of General Medical Sciences, which supports MIDAS. “During the H1N1 pandemic, MIDAS scientists applied their models to see what they could do to help in a real situation.”

Because the H1N1 flu strain is still circulating, a MIDAS group based at the University of Washington in Seattle is now studying the impact the virus could have this fall and winter. Its model, which represents the world population, includes information about immunity — how many people are protected by vaccination or prior infection—and the other circulating flu strains. Using the model, the scientists may be able to predict how H1N1 evolves and the possible role of the H3N2 strain, which historically has been the dominant seasonal flu virus. The results also may help forecast the potential effectiveness of the new flu vaccine that includes both the H1N1 and H3N2 viral strains.

Estimating Severity

To predict the likely severity of H1N1 in the fall and winter months following the initial outbreaks, the MIDAS group led by Marc Lipsitch, D.Phil., of the Harvard School of Public Health in Boston analyzed patient care data from Milwaukee and New York City. The researchers estimated that about 1 in 70 symptomatic people were admitted to the hospital, 1 in 400 required intensive care and 1 in 2,000 died. They predicted H1N1 to be no more and possibly even less severe than the typical seasonal flu strain. The work, which factored in local differences in flu detection and reporting, also showed that it’s possible to make predictions about severity using data from the early stages of an outbreak.

Vaccinating Children

Ira Longini, Ph.D., at the University of Washington and his MIDAS colleagues developed a simulation model to evaluate the effectiveness of different strategies to vaccinate school-aged children, who are known to play a key role in transmitting the flu virus. They modeled a range of scenarios that varied the type of vaccine, the percentage of children vaccinated and the infectiousness of the virus. For each situation, the modeling results indicated that vaccinating this age group substantially reduced overall disease spread and prevented up to 100 million additional cases in the general population. These effects, however, were less strong when the virus was more contagious or when fewer children were vaccinated. Based on these results, Longini’s group concluded that vaccine distribution strategies should depend on a number of factors, including vaccine availability and viral transmission rates.

Cost-Benefit of Employee Vaccination Programs

In one of the first analyses of the economic value of work-sponsored seasonal and pandemic flu vaccine programs, the MIDAS group led by Donald Burke, M.D., at the University of Pittsburgh developed a model that estimated the employer cost to be less than $35 per vaccinated employee with a potential savings of $15 to $1,494 per employee, depending on the infectiousness of the virus.

Interventions and Local Demographics

To determine if a vaccination strategy would likely have the same effect in different locations, a team led by MIDAS investigator Stephen Eubank, Ph.D., of the Virginia Bioinformatics Institute at Virginia Tech in Blacksburg developed models representing the demographics of Miami, Seattle and each county in Washington. The models indicated that while vaccinating school-aged children was the best strategy in each place, the optimal timing and overall effectiveness of the approach varied due to specific characteristics of the local population, such as age, income, household size and social network patterns. These differences, Eubank concluded, suggest that vaccination and probably other intervention strategies should take local demographics into account.

Antiviral Medications

Lipsitch’s collaborators Joseph Wu, Ph.D., and Steven Riley, D.Phil., at the University of Hong Kong used mathematical modeling to predict the likelihood that the H1N1 strain would develop resistance to the widespread use of antiviral medications taken to lessen flu symptoms. Their work showed that giving a secondary antiviral flu drug either prior to or in combination with a primary antiviral could mitigate the emergence of resistant strains in addition to slowing the spread of infection. The results, the researchers concluded, point to the value of stockpiling more than one type of antiviral drug.

School Closures

A public health measure under consideration was closing schools, which previous MIDAS pandemic flu models identified as a potentially effective intervention. According to Burke’s model of Allegheny County, Penn., closing individual schools after they identified cases may work as well as closing entire school systems. When strictly maintained for at least 8 weeks, both types of school closure could delay the epidemic peak by up to 1 week, allowing additional time to develop and implement other interventions. However, the model also indicated that school closures lasting less than 2 weeks could actually facilitate flu spread by returning susceptible students to school in the middle of an outbreak.

“Models like the ones MIDAS has developed help us understand not only trends in disease spread, but also how different factors can influence those trends,” said Irene A. Eckstrand, Ph.D., who directs the MIDAS program. “MIDAS research is leading to new tools and approaches that can aid in making public health decisions at a range of levels, from local to national.”

Source: National Institutes of Health (NIH), September 21, 2010

World Health Organization Declares End to H1N1 Influenza Pandemic

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The World Health Organization (WHO) International Health Regulations (IHR) Emergency Committee and the WHO Director-General, Dr. Margaret Chan, today declared an end to the 2009 H1N1 influenza pandemic. This declaration was based on strong indications that influenza, worldwide, is transitioning toward seasonal patterns of transmission.

In the majority of countries, out-of-season 2009 H1N1 outbreaks are no longer being observed, and the intensity of 2009 H1N1 influenza virus transmission is lower than that reported during 2009 and early 2010. Members of the Emergency Committee further noted that the 2009 H1N1 viruses will likely continue to circulate for some years to come, taking on the behavior of a seasonal influenza virus.

This does not mean that the H1N1 virus has disappeared. Rather, it means current influenza outbreaks including those primarily caused by the 2009 H1N1 virus, show an intensity similar to that seen during seasonal epidemics. Pandemics, like the viruses that cause them, are unpredictable. WHO noted that continued vigilance is extremely important, and it is likely that the virus will continue to cause serious disease in younger age groups and pregnant women, at least in the immediate post-pandemic period.

The WHO Director-General ended the Public Health Emergency of International Concern in accordance with the International Health Regulations (2005).

Implications for United States
This is a formal WHO declaration regarding the end of the pandemic at the global level. The U.S. Public Health Emergency determination for 2009 H1N1 Influenza expired on June 23, 2010.

The only impact on the United States resulting from the WHO declaration will be a cessation in weekly reporting under the International Health Regulations (IHR) to the Pan American Health Organization and the World Health Organization. CDC has reported weekly to IHR since early in the pandemic.

There are no changes for the United States in terms of CDC’s recommendations for the upcoming influenza season and the United States is already proceeding with the understanding that the 2009 H1N1 virus is now part of seasonal influenza virus circulation.

Protecting Yourself and Others from Influenza
CDC recommends a three-step approach to fighting flu: vaccination, everyday preventive actions and the correct use of antiviral drugs if your doctor recommends them. The first and most important step in protecting against the flu is to get a flu vaccine each season.

The U.S. 2010-2011 influenza vaccine will protect against an H3N2 virus, an influenza B virus, and the 2009 H1N1 influenza virus that caused the first global pandemic in more than 40 years and resulted in substantial illness, hospitalizations and deaths. In the United States, the CDC’s Advisory Committee on Immunization Practices recently recommended that everyone 6 months of age and older be vaccinated against influenza each season. Pregnant women, young children, and anyone with underlying health conditions like asthma, diabetes and neuromuscular diseases are at especially high risk for influenza-related complications and, therefore, should be vaccinated as soon as vaccine becomes available. Vaccine manufacturers are predicting an ample supply of influenza vaccine for the upcoming 2010-2011 U.S. influenza season.

Source: CDC, August 10, 2010