Schistosomiasis More Debilitating Than Previously Estimated, Study Shows
ScienceDaily (Mar. 7, 2008) — Public health researchers at Brown University have found that the health burden of an Asian strain of schistosomiasis is much more debilitating than previously thought.
The impact of symptoms associated with schistosomiasis japonica is 7 to 46 times greater than current global estimates, the Brown research team found. This is the first strain-specific study of the global disease burden of schistosomiasis and is part of a growing body of evidence that the serious health effects of this common parasitic disease are far greater than previously estimated.
"Schistosomiasis has a detrimental impact on nutrition and growth and development and can lead to major organ damage and death," said lead study author Julia Finkelstein, a graduate of Brown's Program in Public Health who is now a graduate student at the Harvard School of Public Health. "Current measures may severely underestimate its disability-related impact of the infection and need to be revised."
Schistosomiasis is one of the most common infections in the world, infecting an estimated 207 million people in 76 primarily developing countries. Schistosoma parasites are disease-producing flatworms that live in snail-infested fresh water. People get infected from contact with contaminated water through daily activities such as swimming, bathing, fishing or rice farming. The flatworms enter the body through the skin and travel in the blood, causing symptoms ranging from anemia and diarrhea to internal bleeding and organ damage, and, in some cases, death.
Through its Global Burden of Disease project, the World Health Organization (WHO) estimates the incidence, prevalence, severity and duration of more than 130 major causes of illness, injury and death worldwide. This project is based on a statistical measure called the disability-adjusted life year (DALY), which is the number of years of life lost due to premature death and the years lost due to disability. Policy-makers use the data to help determine funding for prevention and treatment programs as well as research.
According to WHO estimates, the disease burden from schistosomiasis is low, with a 0.005 percent DALY score on a scale of 0 (perfect health) to 1 (death). The global burden of schistosomiasis has not been examined in more than a decade. In just the last few years, however, some researchers have published papers showing that the health burden of schistosomiasis may be greater than expected. The Brown team focused on evaluating Schistosoma japonicum, one of the three main forms of schistosomiasis. The strain is found in China and the Philippines and is the subject of intensive study by Brown faculty members over the last 20 years.
The team used data from the scientific literature and a decision-model approach to re-examine the burden of schistosomiasis. Finkelstein and her team arrived at a substantially higher disability impact for schistosomiasis japonica. Instead of a 0.005 score, they arrived at estimates of 0.098 to 0.186. The findings are consistent with the recently published estimates.
Stephen McGarvey, professor of community health and anthropology and director of the International Health Institute at Brown, is senior scientist on the project. McGarvey said the findings have important implications for global health policy. He notes that WHO's Global Burden of Disease program, headquartered at the University of Washington, is currently revising its report on global health -- and that researchers should reevaluate the disability scores for schistosomiasis and other chronic infectious diseases.
"We've got the best evidence yet that the burden of this disease is significantly underestimated," McGarvey said. "So we urgently need new data -- data that can help keep the disease in check by increasing funds for infection control and basic and translational research."
Journal reference: Finkelstein JL, Schleinitz MD, Carabin H, McGarvey ST (2008) Decision-Model Estimation of the Age-Specific Disability Weight for Schistosomiasis Japonica: A Systematic Review of the Literature. PLoS Negl Trop Dis 2(3): e158. doi:10.1371/journal.pntd.0000158
"Ultimately, these new measures of schistosomiasis-associated disability will translate into a greater priority to control schistosomiasis." Incorporating such new approaches and findings with old estimates will, he said, "be essential to providing a balanced and fair assessment of neglected tropical diseases, and for properly setting disease control priorities for these disabling diseases of poverty."
The National Institutes of Health and the National Science Foundation's Ecology of Infectious Diseases Program partly funded the work.
DNA 'Tattoos' Link Adult, Daughter Stem Cells In Planarians
ScienceDaily (Sep. 13, 2008) — Unlike some parents, adult stem cells don't seem to mind when their daughters get a tattoo. In fact, they're willing to pass them along.
Using the molecular equivalent of a tattoo on DNA that adult stem cells (ASC) pass to their "daughter" cells in combination with gene expression profiles, University of Utah researchers have identified two early steps in adult stem cell differentiation—the process that determines whether cells will form muscle, neurons, skin, etc., in people and animals.
The U of U researchers, led by Alejandro Sánchez Alvarado, Ph.D., professor of neurobiology and anatomy, identified 259 genes that help defined the earliest steps in the differentiation of adult stem cells in planarians—tiny flatworms that have the uncanny ability to regenerate cells and may have much to teach about human stem cell biology.
The findings, reported in the Sept. 11 issue of Cell Stem Cell establish planarians as an excellent model for studying adult stem cells in a live animal, rather than a laboratory culture dish.
"This allows us to study an entire stem cell population in its own environment," said Sánchez Alvarado, also an investigator with the Howard Hughes Medical Institute and the study's senior author. "It's likely that what we learned here can be applied to our own stem cell biology."
Planarians share similar biology with humans in many ways. They also, for reasons unknown, regenerate cells unlike any other animal—an entirely new worm can form from just a fragment of another worm. Planarians constantly regenerate new cells to replace those that die naturally or from injury.
The process begins when adult stem cells divide into two new cells (daughter cells): one becomes like its mother (a stem cell), while the other will move on to give rise to the cells that will serve specific functions in planarian life. For example, some cells may form part of the worm's musculature, while others will form part of the brain.
Because daughters and mother cells are indistinguishable from each other in appearance, the researchers devised methods to detect specific differences in gene expression in the BrdU-labeled cells. The researchers identified 259 genes associated with the stem cells and their daughters. When the U team disabled some of these genes, they found that in some cases no defects were observed, while in others deficiencies were detected in the way the cells were patterned in regenerating planarians.
Sánchez Alvarado and two colleagues then marked adult stem cells in the worms by injecting BrdU, a synthetic nucleotide that binds with DNA and leaves an unmistakable mark on it, much like a tattoo. (Nucleotides are the structural units of DNA and RNA.) When the adult stem cells divided into daughter cells as part of the worms' normal cell regeneration, the BrdU was passed to the daughter cells in their DNA, allowing the researchers to track these cells. By detecting which genes were expressed in which BrdU-labeled cells, the collection of identified genes allowed the researchers to work out for the first time the lineage of stem cells in planarians.
They found that the daughter cells that move on to differentiate into different cell types do so by going through at least two steps. Although the daughter cells, which the researchers labeled categories 2 and 3, are indistinguishable by appearance, they play different roles in cell differentiation
"It seems as if category 2 cells make category 3 cells," Sánchez Alvarado said. "We don't know which differentiated cells they make, but category 3 cells likely differentiate into many different cell types."
These findings open a window to understanding how multipotent stem cells take differentiation decisions. "This allows us to begin to understand how adult stem cells decide what their daughter cells will become when they grow up," Sánchez Alvarado said. "These molecular markers will help us identify specific differentiated cells and help us determine how a stem cell population decides how many of each of the differentiated cell types it needs to make."
The next big step for Sánchez Alvarado and his colleagues is to identify the molecules that act to restrict cell types into serving specific functions.
George T. Eisenhoffer is first author on the study and Hara Kang is co-author. Both authors are graduate students in the Department of Neurobiology and Anatomy at the University of Utah School of Medicine.
New Tree Of Life Divides All Lower Metazoans From Higher Animals, Molecular Research Confirms
ScienceDaily (Jan. 27, 2009) — A new and comprehensive analysis confirms that the evolutionary relationships among animals are not as simple as previously thought. The traditional idea that animal evolution has followed a trajectory from simple to complex—from sponge to chordate—meets a dramatic exception in the metazoan tree of life.
New work suggests that the so-called "lower" metazoans (including Placozoa, corals, and jellyfish) evolved in parallel to "higher" animals (all other metazoans, from flatworms to chordates). It also appears that Placozoans—large amoeba-shaped, multi-cellular animals—have passed over sponges and other organisms as an animal that most closely mirrors the root of this tree of life.
"To make inferences about the origin of Bilaterians—animals with a bilateral symmetry, like humans—earlier studies suggested sponges, ctenophores (comb jellies), or a small, interesting group called Placozoa as the most basal or primitive animal," says senior author Rob DeSalle, Curator at the Sackler Institute for Comparative Genomics at the American Museum of Natural History. "But our new analysis implies that the first major event in animal evolution split bilateral animals from all others, and our work firmly places Placozoa as the most primitive of the nonbilaterian animals."
Placozoans were discovered just over 100 years ago, gliding along the glass in laboratory aquariums. Placozoans are simple animals that lack a nervous system and have only four kinds of somatic cells. Because they have never been studied in their oceanic home, however, further characterization of this group has been problematic. The genome of the placozoan species Trichoplax adharens was sequenced in the middle of 2008 by the Trichoplax Genome Consortium team, which was initiated by first author Bernd Schierwater, Director of ITZ, Ecology and Evolution, Tierärztliche Hochschule Hannover in Germany and a research associate at the Museum.
While several previous studies placed Placozoans at the base of the animal tree of life, these results attracted little attention. The current research may provide the final word, since the number of traits considered was very large and the resulting phylogeny was supported very strongly. Researchers lumped data from many different sources, including mitochondrial and nuclear DNA sequences and information about the morphological structure of RNA molecules, to find over 9,400 variable characters that contain parsimony information—the shared, derived traits that help biologists infer the tree of life, or phylogeny.
The phylogeny drawn from the new analysis places Placozoans as basal within the Diptoblasta, a group of animals that includes sponges, comb jellies, jellyfish, corals, and anemones. This means that sponges and comb jellies, both previously considered candidates for the most basal animal, fall within the clade as more derived than Placozoans and as sister taxa to each other. Study results also identify a very deep division between the Diptoblasta and the Bilateria/Triploblasta: when looking at all animals, scientists now see that Placozoans and their relatives are in a separate lineage from all other metazoans (starfish, bivalves, anthropoids, crustaceans and chordates). This means that the nervous system, once thought to have arisen once, must have evolved twice from the DNA that coded for these complex systems (keeping in mind that while Placozoans and sponges do not have nervous systems, many of the taxa related to them do.)
"Some people might initially be shocked to see that nerve cells in cnidarians and higher animals (Bilateria), the group of animals that includes humans, evolved independently," says Schierwater. "But with this new phylogeny, we can take a closer look at the anatomy of these organisms—and we can see that their nervous systems are not all that similar at the morphological level after all."
DeSalle agrees. "It is the underlying genetic tool kit that is similar amongst these basal animals. Placozoa have all of the tools in their genome to make a nervous system, but they just don't do it."