Today in the News (17 May 10)

And a few more news articles for today. And snarky comments because I am in a snarky mood.

(Can't be stopping 500,000 deaths with an evil vaccine, can we?)

Rotavirus Vaccine Greatly Reduces Hospitalizations for Acute Gastroenteritis in Children. Study Finds

ScienceDaily (May 14, 2010) — Vaccinating infants against rotavirus, a leading cause of severe diarrhea and dehydration among babies and young children, was associated with a dramatic decline in U.S. hospitalization rates for acute gastroenteritis. The findings appear in a study, now available online, published in the June 1 issue of The Journal of Infectious Diseases.

Worldwide, rotavirus infection is estimated to cause more than 500,000 deaths each year. Before a vaccine was introduced, the virus led to an estimated 55,000 to 70,000 hospitalizations in the U.S. annually. A vaccine, RotaTeq, was licensed for use in the U.S. and recommended for routine use in infants in 2006.

In this study, Aaron T. Curns, MPH, and colleagues at the Centers for Disease Control and Prevention (CDC) and the Agency for Healthcare Research and Quality examined hospitalization rates for acute gastroenteritis during the typical rotavirus season among U.S. children under 5 years of age. They compared these rates over two periods: from 2000 to 2006, before the rotavirus vaccine was introduced; and after, from 2007 to 2008.

Using hospital discharge data from 18 states accounting for almost 50 percent of the U.S. population, researchers compared the median hospitalization rate for gastroenteritis from all causes during the two time periods. Researchers considered the months January through June to be the rotavirus season.

Hospitalization rates for gastroenteritis were 16 percent lower in 2007 and 45 percent lower in 2008 compared with rates before the vaccine was introduced. During 2008, infants aged 0-2 months had a 28 percent reduction, while those 6-23 months of age had a 50 percent reduction. Rates among children aged 3-5 months and 24-59 months declined between 42 percent and 45 percent. The researchers estimated that approximately 55,000 acute gastroenteritis hospitalizations were prevented during the 2008 rotavirus season because of vaccination. Hospitalization rates during this season were substantially diminished with rates one-half to two-thirds lower at peak activity compared to previous seasons.

The researchers noted that the observed declines in hospitalizations exceeded their estimates and also occurred among age groups that were too young or too old to receive the vaccine, suggesting that these children may have been protected by the "herd immunity" caused by their peers being vaccinated.

In an accompanying editorial, Geoffrey A. Weinberg, MD, and Peter G. Szilagyi, MD, MPH, of the University of Rochester School of Medicine & Dentistry in New York, highlighted the importance of such vaccine effectiveness studies, which provide a real-world view that can improve the planning of public health initiatives. An advantage of the study design is its analysis of how well vaccination works within a population, they wrote.

"These encouraging findings are important for emphasizing the benefits and increasing the acceptance of rotavirus vaccination in the United States and will also help other countries assess the value of rotavirus vaccines for their children," the researchers said. In light of the study's results, "it remains essential to continue monitoring acute gastroenteritis hospitalization rates during subsequent rotavirus seasons to fully understand and document the impact of vaccination as the program matures in this country."

Fast Facts:

1. Rotavirus infection leads to more than 500,000 deaths worldwide each year. Before a vaccine was introduced in 2006, rotavirus resulted in an estimated 55,000 to 75,000 hospitalizations in the U.S. annually.
2. Hospitalization rates for acute gastroenteritis among children were 16 percent lower during the 2007 rotavirus season and 45 percent lower in 2008, compared with rates before rotavirus vaccine was introduced.
3. An estimated 55,000 acute gastroenteritis hospitalizations were prevented during the 2008 rotavirus season in the U.S. Reductions also occurred in other age groups that did not receive the vaccine, probably due to "herd immunity."

(Oh, but we all know the Amish don't have these diseases, right?)

Rare Disease in Amish Children Sheds Light on Common Neurological Disorders

ScienceDaily (May 12, 2010) — So often the rare informs the common. Penn researchers investigating a regulatory protein involved in a rare genetic disease have shown that it may be related to epileptic and autistic symptoms in other more common neurological disorders.

A team of researchers from the University of Pennsylvania School of Medicine, led by Peter B. Crino, MD, PhD, associate professor of Neurology and director of the Penn Epilepsy Center, demonstrate how mutations in the STRAD-alpha gene can cause a disease called PMSE (polyhydramnios, megalencephaly, and symptomatic epilepsy) syndrome, found in a handful of Amish children. PMSE is characterized by an abnormally large brain, cognitive disability, and severe, treatment-resistant epilepsy.

Specifically, in an animal model, they found that the lack of the STRAD-alpha protein due to genetic mutations causes activation of the signaling pathway involving another protein called mTOR. In humans, this in turn may promote abnormal cell growth and cognitive problems in the developing brains of children. STRAD-alpha and mTOR proteins are part of a complex molecular network implicated in other, more common neurological disorders, many of which have autism-like symptoms as a component.

"The identification of a new gene that regulates mTOR provides fascinating insights into how mTOR pathway dysfunction may be associated with neurological disorders," says Crino. "Each new mTOR regulatory protein that is identified provides a new possible therapeutic target for drug development and treatment."

The research on PMSE -- published in the Journal of Clinical Investigation -- reveals clues about more common neurological disorders characterized by benign tumors and malformations of the brain, the most common of which is tuberous sclerosis complex (TSC). The root cause of TSC also lies in mutations in proteins along the mTOR pathway, however a different protein is affected compared to PMSE.

"It is quite compelling that TSC, a relatively common disorder, and PMSE, a rare disorder, are linked by a common cellular pathway, and exhibit similar severe neurological features," notes Crino. "In our study, we found that we could reverse some of the cellular features that result from STRAD-alpha deficiency in cell culture models of PMSE. This provides important conceptual support for more widespread treatment approaches that modify mTOR signaling in neurological disorders associated with epilepsy, autism, and cognitive disability."

Current estimates place tuberous sclerosis complex-affected births at one in 6,000. Nearly 1 million people worldwide are known to have TSC, with approximately 50,000 in the United States.

PMSE, on the other had, has only been described in 25 people in Lancaster County, PA. It's incidence among other Amish populations, let alone the rest of the country, is unknown. PMSE is also known as pretzel syndrome in the Amish community, because the lax joints of patients fold over easily. PMSE was identified in an Amish, or Old Order Mennonite pediatric population in 2007 by researchers from Penn and the Clinic for Special Children in Lancaster, PA, a genetic clinic devoted to the needs of the Amish.

The mTOR pathway normally controls cell growth, but in PMSE uncontrolled mTOR signaling leads to increases in brain size and areas in which the cerebral cortex is malformed. To prove this, the researchers knocked down the activity of the STRAD-alpha protein in a mouse model and caused malformations of the developing brain. The structure of these malformations was similar to what is seen in human PMSE and TSC and supports the conclusion that normal brain development in part depends on normal STRAD-alpha function. Localized brain malformations are among the most common causes of epilepsy and neurological disability in children.

This research was funded by the National Institute of Neurological Diseases and Stroke.

Ksenia Orlova, PhD, a graduate student in the Crino lab and Kevin Strauss, MD, Medical Director at the Clinic for Special Children, were also co-authors on the JCI paper.

(That pesky science, always refining our understanding!)

New Insights Into Genomics of Speciation

ScienceDaily (May 12, 2010) — A new study by a team of researchers led by University of Notre Dame biologist Jeffrey Feder could herald an important shift in thinking about the genomics of speciation.

The paper appears in the Proceedings of the National Academy of Sciences.

The prevailing assumption among scientists about how the genomes of newly forming species should differ during the earliest stages of divergence with gene flow speciation is that it will be characterized by a few regions of strong differentiation, amidst a remainder of the genome that remains unaffected by natural selection and thus relatively undifferentiated. This analogy of "genomic islands of speciation" has come to dominate the evolutionary genetics community.

"The island concept has crystallized around an attractive hypothesis termed 'divergence hitchhiking,' in which selection on one or a few genomic regions drives speciation," Feder said.

In the new paper, Feder and his colleagues report experimental and genomic evidence that contrary to the prevailing assumption, speciation in the classic apple maggot fly system Rhagoletis pomonella involves genome-wide differentiation driven by natural selection.

"Our result in Rhagoletis conflicts with the current thinking about how the genomes of newly forming species could differ during the earliest stages of divergence-with-gene-flow speciation," Feder said. "Rather than finding just isolated 'genomic islands' of genetic divergence, we instead discovered 'continents' of divergence encompassing large swaths of the genome."

He points out that past work on the genomics of speciation lacked experimental data and thus may have been unable to detect genomic regions under weaker natural selection, establishing a view of speciation involving genetic divergence in just a few, isolated genomic islands.

Rhagoeitis pomonella fruit flies originally attacked the fruit of hawthorn trees. But about 150 years ago, a portion of the hawthorn fly population shifted and began to feed on apples. In ecologically adapting to apples as a new host plant, apple flies are becoming genetically distinct and reproductively isolated from hawthorn flies. Apple and hawthorn flies are therefore considered to represent "host races" in the early stages of actively diverging into species. As such, the apple and hawthorn races of Rhagoeitis pomonella provided Feder and his fellow researchers a unique opportunity to conduct a direct experimental test of the island versus continents hypotheses.

"This type of comprehensive data, particularly the experimental results, are missing from the bevy of genome scan studies performed in the last few years lending support to the island hypothesis," Feder said. "Without experimental data on responses to selection, these genome scan studies alone can be biased toward identifying isolated outer loci, supporting the island hypothesis.

"We foresee that as mass genotyping techniques continue to advance, it will be these types of inquires and questions that come to dominate the emerging field of population genomics and speciation. We hope our study offers a glimpse of what the future may look like."

The research was funded by the National Science Foundation and the United States Department of Agriculture.