AstroNutrition Health & Fitness Blog

A Food and Drug Administration Public Health Advisory was issued Jan. 17 warning that over-the-counter cough and cold products should not be used to treat infants and very young children because very serious side effects can occur, including death, convulsions, rapid heart rates and decreased levels of consciousness.

"The FDA strongly recommends to parents and caregivers that OTC cough and cold medicines not be used for children younger than 2," said Charles Ganley, MD, director of the FDA's Office of Nonprescription Products. "These medicines, which treat symptoms and not the underlying condition, have not been shown to be safe or effective [for this age group]."

The statement was based on a review of data and the discussions held at an October 2007 joint meeting of the Nonprescription Drugs and Pediatric Advisory committees. The agency is reviewing data regarding use of these medicines in children ages 2 to 11. It will communicate additional recommendations in the near future.

"It's critically important for parents to receive clear information about the risks and lack of benefit from these drugs," said American Academy of Pediatrics President Renee Jenkins, MD, in a statement. The AAP supported the FDA's Jan. 17 action as an important first step. "We urge FDA to continue its analysis of the existing data on these medicines intended for children over age 2 and take appropriate action, including initiation of immediate, rigorous scientific studies as needed to determine the drugs' safety and efficacy."

In the meantime, the agency urges those who choose to use these products for the 2-11 age group to follow the dosing directions on the OTC medication's label; check the "drug facts" label to learn what active ingredients are contained in the products because many contain multiple ones; and use only measuring spoons or cups that are packaged with the medicine or made especially for measuring drugs.

Suggestions on ways to soothe kids with coughs and colds are available on the AAP's Web site (www.aap.org/publiced/br_infections.htm).

Vaccines are hot. "The global vaccine market is set to double by the year 2016, fueled by unprecedented product innovations and global recognition of the benefits of immunization," said Michael D. Decker, MD, MPH, vice president for scientific and medical affairs at vaccine manufacturer Sanofi Pasteur, USA.

"This is one of the very best times to be involved in immunization because of all the excitement," noted Lance Rodewald, MD, director of the Centers for Disease Control and Prevention's Immunization Services Division.

But just a few years ago, the stalwart tetanus vaccine was in short supply, seasonal influenza vaccine was hard to come by, and manufacturers were leaving the field, citing low profits and high production costs.

Now, new vaccines are hitting the market. Shingles, human papillomavirus and rotavirus vaccines were introduced in 2006. In 2005 two Tdap vaccines were approved to help fight pertussis in teens and young adults. Last month, data were published in the Journal of the American Medical Association showing that a meningococcal vaccine protects infants from four types of the meningitis bacteria, and manufacturer Novartis is expected to seek approval to take it to market.

Flu vaccine is also plentiful this year, and last year's National Influenza Vaccine Summit, an annual event sponsored by the AMA and the CDC, attracted representatives from more than 100 groups interested in ensuring this year's smooth flu season.

Not that it's all a rosy picture. Clinical trials for Merck's promising HIV vaccine were halted last fall when the vaccine was found to be ineffective. Also, a current shortage of haemophilus influenzae vaccine type B, or Hib, resulted when Merck recalled the product after production problems.

Nevertheless, excitement is bubbling in the public health world about the renewed interest in vaccines. Experts cite several reasons for this resurgence, ranging from new science to existing policies and changed attitudes.

An assured market

Dr. Rodewald and others credit the Vaccines for Children Program, which was implemented in 1994, with creating consistent demand. The federal entitlement program provides free vaccines for more than half the children in the nation.

The program provides "a large and rather assured market," said William Schaffner, MD, professor and chair of the Dept. of Preventive Medicine at Vanderbilt University in Nashville, Tenn.

The U.S. gives free vaccines to more than half the children in the country.

Although the VFC program capped the prices of existing vaccines at 1993 levels, the cap came off for new vaccines. "So that created a favorable environment for the manufacturers to want to go through the very expensive research and development phase," Dr. Rodewald said.

Of course, he noted, the purchase price for vaccines has risen dramatically as a result, placing a strain on budgets.

But profits from vaccines were virtually nonexistent until recent years, and manufacturers were discouraged from investing the time and money in their development. As recently as the late 1970s, tetanus vaccine cost 17 cents per dose, said Paul Offit, MD, chief of infectious diseases at the Children's Hospital of Philadelphia.

The arrival in 2000 of the pneumonia vaccine for young children, Prevnar, brightened the economic picture for manufacturers when it became the first vaccine to earn more than $1 billion, Dr. Offit said. The HPV vaccine, Gardasil, was launched in 2006 as a nearly $2 billion vaccine. "So there is definitely a sense that there is more money in vaccines than there was previously."

Still, they are not nearly as lucrative as medications that people take daily, such as the statin Lipitor, which has sales of $12 billion a year.

But other advantages to vaccine production have become increasingly evident, Dr. Offit noted. "There is a fairly beaten path in how to make them, and there is, to some extent, protection from liability in children's vaccines," he said. "The third thing is that they are patent independent. Once their patent runs out, there aren't all these generics that hop onto the market, because it is expensive to make a vaccine, and the market isn't big enough to support them."

The lows and highs

Vaccines may have hit a low point in the 1990s, Dr. Offit said. Concerns over the use of the preservative thimerosal resulted in its removal from vaccines. In addition, Rotashield was withdrawn from the market when cases of intussusception were reported. Lastly, the anti-vaccine movement was growing stronger.

Today, new technology and knowledge are helping to fuel the resurgence, Dr. Rodewald said. One big advance has been the ability to produce conjugate vaccines. The process was developed in the 1980s but is paying off now with such vaccines as Prevnar and the meningococcal conjugate vaccine, Menactra, which was licensed in 2005.

The anthrax vaccine in its modern form was developed in the 1940s.

The HPV vaccine uses virus-like particles made with genetic engineering techniques that were refined since their development in the 1980s, he added. Also, "20 years ago we had no idea that cervical cancer was caused by HPV," said Rick Haupt, MD, MPH, executive medical director for Merck Vaccines and Infectious Diseases, which released Gardasil to fight this cancer.

Dr. Schaffner summed up the scenario on the development side: "As the science was moving along, the manufacturing was suddenly a little less risky, and the market was more assured."

At the same time, the country became more interested in health maintenance and the prevention of illness, he added.

Notice was taken by those in public health that, not only were the immunized children healthier, but so were their families, said Myron Levine, MD, director of the Center for Vaccine Development at the University of Maryland School of Medicine in Baltimore. "What this means for public health is that if you vaccinate infants, you have an important extra public health advantage of great economic importance, because you are actually preventing disease in other ages."

The Bill and Melinda Gates Foundation's investment in vaccine development also sparked interest in supplying vaccines to people in the developing world, Dr. Levine said. Half of the money for the public-private group, the Global Alliance for Vaccine and Immunization, was provided by the Gates foundation.

The alliance has brought vaccines to some of the poorest countries in the world and prompted even more support from the Gates foundation. "When the richest guy in the world says this was the best investment he ever made, he provides the antidote to the anti-vaccine lobby in the country," Dr. Levine said.

And new vaccines are showing up in the pipeline. Sanofi Pasteur's dengue vaccine is entering clinical trials this year, just as reports of the mosquito-borne virus's spread along the United States border with Mexico were announced. Meanwhile, work on an HIV/AIDS vaccine continues. But Dr. Rodewald doesn't expect to see any reach market for several years. "For now, I think there will be a little bit of a slowdown in the newly vaccine-preventable diseases, and we are hoping that it will pick up a little later. We have a chance now to catch our breath."

But while doing so, promoters of immunizations can't relax about the need for widespread vaccination to make sure vanquished diseases remain defeated. "We are so successful at using vaccines that many parents aren't aware of these illnesses," Dr. Schaffner said. He related that one mother was confused about why he was talking about polo shirts. He was actually talking about polio, but she had never heard of the disease.

Additional societal issues to resolve include how to successfully integrate the administration of all the new vaccines into the health care schedules of children and, increasingly, teens and adults, and how to pay for them, he said.

Washington -- The Jan. 14 announcement of findings from the Enhance trial, which compared patients on the cholesterol-lowering drug Vytorin -- a combination of ezetimibe and simvastatin -- with a statin alone, sent shockwaves through the medical community. After all, many physicians viewed this as a promising approach in reducing heart disease risk because the drugs it combined work differently to reduce LDL cholesterol.

However, the study results showed no real difference between the two treatment groups in the two-year, randomized trial -- at least when it came to measuring plaque buildup in carotid arteries.

The initial response was to question whether the drug still had a place in physicians' medicine chests. But physician groups, including the American College of Cardiology and the American Heart Assn., soon adopted more measured positions, weighing in to say physicians should stay the course in prescribing Vytorin, and patients now taking the drug should not panic.

The study also found that patients using the combination drug experienced a 58% drop in LDL cholesterol, while those on the statin alone had a 41% drop. Overall, the safety profiles of the drugs were similar.

The data were released by the pharmaceutical companies Merck and Schering-Plough, which make the drugs. They also have been submitted for presentation at the American College of Cardiology's Annual Scientific Session this spring.

"Obviously a positive study would have been more favorable," said Skip Irvine, a spokesman for Merck/Schering Plough Joint Ventures. "This was a very challenging study, given the high hurdle [it] set, the population [people with heterozygous familial hypercholesterolemia], and their very high LDL levels at baseline."

Given the study's two-year duration and doses -- 10 mg of ezetimibe and 80 mg of simvastatin -- "we were very pleased to see that overall the safety profiles of ezetimibe/simvastatin and simvastatin alone were similar and generally consistent with their product labels," he said.

But the study created a stir for another reason. Although the trial concluded in April 2006, Merck and Schering-Plough did not release the results until mid-January -- a span that drew the attention of congressional committees.

The House Committee on Energy and Commerce began an investigation into the trial Dec. 11, 2007. Committee Chair John Dingell (D, Mich.) said in a Jan. 14 statement that the inquiry would continue despite the data's release. The announcement that the study "failed to find any positive benefit from the addition of Zetia to a common, inexpensive, generic therapy raises concerns that attempts were made to mask the minimal value of this new drug," said Dingell.

Irvine said the companies are "fully cooperating with the committee and are in the process of responding to requests for information."

Wait and see

The focus is now shifting to large, ongoing comparison studies of the drugs. Those trials are testing whether the use of the combination simvastatin and ezetimibe will reduce heart attacks or deaths more than the use of simvastatin alone. Results aren't expected for two to three years.

"It will be very important for those larger studies, directed at assessing cardiac outcomes, to be completed so we can fairly assess the potential of ezetimibe," said Daniel W. Jones, MD, the heart association's president.

An American College of Cardiology statement recommends that major clinical decisions not be made on the basis of the Enhance study alone and adds "there should be no reason for patients to panic."

Steven Nissen, MD, chair of cardiovascular medicine at the Cleveland Clinic and immediate past president of the ACC, cautioned that ezetimibe should be used only if a statin fails to reduce cholesterol adequately, since the combination drug demonstrated no added benefit and patients would still be exposed to side effects.

Ezetimibe "is still recommended for patients who cannot meet their cholesterol goals when they are on the highest statin dose they are able to take," said Lisa Martin, MD, director of the Lipid Research Clinic at George Washington University Medical Center in Washington, D.C. "The good news was there were very few cardiac events in either group."

But the whole issue of LDL-cholesterol lowering may need to be reconsidered. "Maybe it's not just lowering LDL," she said, since the lowered cholesterol did not result in lowered arterial plaque. "That's something we will have to find out in the future."

The end point of the Enhance trial, also known as the Effect of Combination Ezetimibe and High-Dose Simvastatin vs. Simvastatin Alone on the Atherosclerotic Process in Patients with Heterozygous Familial Hypercholesterolemia trial, was the change in intima-media thickness measured in three sites in the carotid arteries.

The measures showed no statistically significant change.

Thomas Weida, MD, a family physician in Hershey, Pa., is interested in knowing how the difference in intima thickness translates clinically. "That's going to need a bigger study," said Dr. Weida, who is a board member of the American Academy of Family Physicians.

Dr. Weida also questioned the study population. The 720 people enrolled all had heterozygous familial hypercholesterolemia, a genetic condition that causes high cholesterol at young ages. "They tested this on a fairly rare group, so does their experience translate over to the vast majority of people with high cholesterol that we see?" asked Dr. Weida.

The study really didn't change anything, said James M. Wilson, MD, Hall chair in cardiology at St. Luke's Episcopal Hospital/Texas Heart Institute in Houston. "What we need to say is: It's a negative study. It's not particularly meaningful just yet, but let's see what happens in the clinical trial. Let's see if it shows itself to be a benefit, as we all think it will."

Up to 1% of autism cases may be blamed on too much or too little of a particular strand of an estimated 25 genes on chromosome 16, according to a pair of recent papers. Understanding how this creates the developmental disorder eventually may lead to improved treatment of autistic children, including those who don't carry these mutations.

"Each little piece of the puzzle gets us closer to the fundamental biological mechanisms, and if we understand the specific biological mechanism, we can consider how we might go about developing intelligent therapeutics for this disorder," said Mark J. Daly, PhD, assistant professor at Massachusetts General Hospital and Harvard Medical School.

One paper, published online Jan. 9 in the New England Journal of Medicine and co-authored by Dr. Daly, found that children with one or three copies of the 16p11.2 genetic segment, rather than the normal two, were at significant risk for autism. The other paper, published online Dec. 21, 2007, in Human Molecular Genetics, implicated having only one copy in this disorder.

These are two of the latest studies shedding some light on autism's genetic underpinnings. About 10% of cases can be explained by various genetic syndromes, such as fragile X or Prader-Willi syndromes, but the rest remain a mystery. Experts predict that no single cause will be found to account for a great number of the cases.

"Based on our experience with other human complex disorders, it's relatively infrequent that specific genes are much more than a percent or two of the whole story," Dr. Daly said.

The challenge now facing researchers is to replicate these findings and determine their clinical utility. Genetic testing for this variation is possible and performed at some institutions. Those who conduct the screening say it can help children receive a confirmed autism diagnosis and improve access to educational services. The results also may suggest increased risk in subsequent children and give comfort to parents.

10% of autism cases are caused by genetic syndromes, such as fragile X or Prader-Willi syndromes.

"Mothers wonder, 'Is there something I did while I was pregnant? What could I have done differently?' This tells them that there's nothing that the parent could have done differently, and that's helpful information just in and of itself," said David Miller, MD, PhD, assistant director of the Genetics Diagnostic Laboratory at Children's Hospital Boston, one of the authors of the New England Journal of Medicine paper. He has been testing patients for this deletion or duplication for the past year.

But while there was praise for this study, there also was caution about genetic testing and how these data might be used.

"This study has meaning and significance, but it's still a tiny, little step forward. This is a very small percentage of kids," said Patricia Manning-Courtney, MD, director of the Kelly O'Leary Center for Pervasive Developmental Disorders at Cincinnati Children's Hospital Medical Center. "I'm not sure how we would apply this information clinically or what my next step would be. Everybody wants a biomarker for autism, but we're already learning that there is not going to be one."

Some experts question how specific these chromosomal abnormalities are to autism. For example, not all of the children with this genetic variation in the New England Journal of Medicine study had a diagnosis of autism. They were identified as having developmental delay or mental retardation. Some who had a diagnosis of autism also may have had some intellectual disability, although this is not clear from the paper.

"It would be interesting to know more details about the affected patients," said Scott Myers, MD, a neurodevelopmental pediatrician at the Janet Weis Children's Hospital in Danville, Pa. "I suspect that the more specific and common phenotypic aspect of 16p11.2 microdeletions or microduplications is intellectual disability. ... If the 16p11.2 abnormalities are more specific for the autism phenotype, there should be a substantial number of affected individuals who have autism spectrum disorders without mental retardation."

Doubt also was expressed because autism is considered an inherited genetic disease, and siblings of affected children tend to have a higher risk of developing it. The studies' authors said the deletion and duplication of this genetic material is something that, for the most part, is not passed down by either parent and may occur during the formation of the egg or sperm, at conception or very early in fetal development.

But "it's a pretty big leap to say [autism] is not inherited," Dr. Manning-Courtney said.

Candidate gene for autism identified

But while this genetic variation may not be inherited, another pair of papers, published online Jan. 10 in the American Journal of Human Genetics, reported a genetic factor that is. A variant of CNTNAP2, a gene that makes a protein allowing brain cells to communicate with each other, increases the risk of developing autism, researchers found. Not everyone with this gene variant develops the disorder, but the risk is higher if the gene is inherited from a child's mother.

"CNTNAP2 is an excellent candidate gene for autism," said Aravinda Chakravarti, PhD, senior author on one of the papers and professor of medicine, pediatrics, molecular biology and genetics at Johns Hopkins University School of Medicine in Baltimore. "It encodes a protein that's known to mediate interactions between brain cells and that appears to enable a crucial aspect of brain-cell development. A gene variant that altered either of these activities could have significant impact."

As the list of genetic causes of autism is growing, so are the data against the hypothesis that the vaccine preservative thimerosal could be involved. Researchers with the immunization branch of the California Dept. of Public Health analyzed data collected by the state's Dept. of Developmental Services. Despite the removal of nearly all thimerosal from childhood vaccines between 1999 and 2001, the rate of autism continued to increase, according to the study, published in the January Archives of General Psychiatry. The authors concluded that these data do not support the theory linking thimerosal with this disorder.

Those working to control the spread of methicillin-resistant Staphylococcus aureus say this task is about to get easier. In January, the Food and Drug Administration approved the first blood test that can differentiate it from the methicillin-susceptible variant in two hours, rather than the 24 to 48 hours or longer that currently available technology takes.

"[This] test is good news for the public health community," said Daniel G. Schultz, MD, director of the FDA's Center for Devices and Radiological Health.

The BD GeneOhm StaphSR Assay assesses a blood sample for genetic material specific to the two main forms of these bacteria. Studies leading to the test's approval found that it could identify 100% of MRSA samples and 98% of the susceptible types. According to an FDA statement, this test should be used in patients already suspected of having a staph infection but not to monitor treatment or initially detect it. Doctors still might have to conduct follow-up testing to pin down precisely what will kill particular bacteria, but physicians say the information provided by this product will be enough to narrow down treatment choices early on.

"Compared to what we have now, this is terrific. It's enough information to get you started," said Ed Septimus, MD, a board member of the Infectious Diseases Society of America.

Physicians expect to use it to identify more quickly which antibiotic is most likely to work and which patients need to be isolated from others. Experts hope that this will interrupt MRSA's spread and reduce the use of broad spectrum antibiotics. In turn, this may slow the development of more resistant organisms.

"We will be able to get appropriate treatment to the patient much faster, and we will be able to intervene at a much earlier time so transmission does not occur," said Dr. Septimus, also an infectious disease physician in Houston.

Initially, this test most likely will be used on the sickest, hospitalized patients but also may trickle down to other practice settings for less-critical infections. MRSA has long been a problem in the health care setting, but it is increasingly a community problem as well.

This test previously was given FDA approval to identify colonized patients.

The product's manufacturer, BD (Becton, Dickinson and Co.), is pursuing U.S. approvals for it to be used for nasal swabbing and the detection of MRSA in wounds. These versions were launched in Europe at the end of 2007.

But although there is a lot of hope for the test's potential, there are also concerns. Experts, for instance, expect there may be a lag between this test becoming available and doctors becoming comfortable enough with it to use it for decision-making.

"Having more tools is good, but there's going to be a certain learning curve," said Thomas Fekete, MD, professor of medicine and an infectious disease specialist at Temple University in Philadelphia. "And I don't know if laboratories will be financially prepared to take on this new technology. I'm not saying it's not worth it, but there's a price to pay."

Experts say getting a better handle on MRSA is key, because evidence is accumulating that it may be far more common than previously thought.

A paper in the June 2005 Emerging Infectious Diseases suggested that MRSA could be found in 3.95 of every 1,000 hospitalized patients.

But a study in the December 2007 American Journal of Infection Control found that nationally, 46.3 per 1,000 inpatients carried the bacteria. Of these, at least 34 were infected and 12 were colonized. The remainder of cases were unclassified. Approximately 70% of cases appear to have been contracted in the health care setting.

The authors suspect that the true numbers may be much higher. Only 29% of institutions surveyed actively hunted for these bacteria, and most did not use highly sensitive means to do it.

"This is the minimum estimate, because the majority are not doing screening and [are] testing by less sensitive methods. It's a much bigger problem than anyone had predicted," said William Jarvis, MD, lead author on that paper and a consultant with Jason & Jarvis Associates, a private firm that provides expertise on public health, infection control and patient safety.

Other papers have documented MRSA's impact. One in the Oct. 17, 2007, Journal of the American Medical Association estimated that there were 94,360 cases of invasive MRSA infections and 18,650 deaths in 2005. Patients older than 65 were particularly vulnerable.