Tag: Parasitology

A new study challenges the widely held view that mice are the main animal reservoir for Lyme disease in the United States. The paper, published online this week in the Proceedings of the Royal Society B, shows that two shrew species are just as important and that chipmunks play a supporting role. Unless those species are taken into account, say researchers, efforts to control Lyme disease are doomed to fail. Lyme disease can cause anything from rash to arthritic and psychiatric diseases. Borrelia burgdorferi sensu stricto, the bacterium that causes Lyme disease in the United States, is transmitted to humans by blacklegged ticks. Researchers have assumed that the vast majority of ticks become infected when, as larvae, they take their first blood meal from a white-footed mouse. Indeed, lab studies have shown that as many as 90% of ticks feeding on an infected mouse pick up the bug, an “extremely high number,” says disease ecologist Dustin Brisson of the University of Pennsylvania.

But other species that transmit B. burgdorferi to ticks less efficiently might also spread the disease if they are more numerous or if they are bitten by a large number of ticks. And some studies had suggested this to be the case. For instance, a field trial published in 2004 showed that vaccinating mice against Lyme disease and then releasing them led to only a small decrease in the number of infected ticks. To get a fuller picture, Brisson and his colleagues pulled together data from their own studies in the Hudson Valley in New York state and from other papers. The team looked at an outer surface protein of B. burgdorferi found in ticks–which can give clues about the vertebrate host–as well as the probabilities that different host species transmit the microbe during a tick bite, the number of larvae feeding on the animals, and population densities. Then they calculated the importance of each of the host species.

White-footed mice account for only a quarter of the total number of infected ticks, the team found. Short-tailed shrews and masked shrews were responsible for another quarter each, and chipmunks for as much as 13%. That means that mice aren’t the “dominant” host at all, says Brisson, and vaccination strategies aimed at mice alone are unlikely to bring Lyme disease under control. Brisson speculates that mice have received a lot of attention in part because they’re conspicuous, easy to catch, and ideal lab subjects. “It’s a nice paper,” says Durland Fish of Yale University School of Medicine, a co-author of the 2004 vaccination study. However, he believes there are even more culprits. In particular, the team barely looked at birds, he notes, even though one study has shown that robins, which often live close to humans, are very good at transmitting B. burgdorferi to ticks in the lab. “The situation is probably even more complex than we think,” Fish says.

ScienceNow
December 11, 2007

Original web page at ScienceNow

Before venturing into tick-infested territory, you used a topical repellent on exposed skin and outer clothing. When you returned, you did a body check and threw your clothes in the wash. But clean clothes may not be tick-free clothes. When he found a live lone star tick (Amblyomma americanum) on the agitator of his washing machine, Agricultural Research Service (ARS) entomologist John Carroll decided to find out how tough ticks are. So he bagged up nymphs from two species—the lone star tick and the deer tick, (Ixodes scapularis), the creature that transmits Lyme disease—and put them in the washing machine. Carroll used a combination of water temperature settings and detergent types to wash the ticks. The majority of lone star ticks survived all the water-detergent combinations with no obvious side effects. Most of the deer ticks lived through the cold and warm water settings as well. But when one type of detergent was used with a hot water setting, only 25 percent of the deer ticks survived. When it came time to dry, all the ticks of both species died after an hour of tumbling around at high heat. But when the dryer was set to “no heat,” about one-third of the deer ticks and more than half of the lone star ticks survived.

Carroll placed the ticks in mesh bags, which kept them from draining away during the rinse cycle and perhaps increased their odds for survival. However, ticks might also survive a sudsy interlude by sheltering in the folds and crevices of a typical load of laundry. Some tick species have been observed to survive hours of submersion in fresh water. Both adult ticks and nymphs can transmit disease. Carroll’s research reinforces recommendations by the U.S. Centers for Disease Control and Prevention to wash and dry clothes at high temperatures after spending time in areas known to harbor ticks.

Science Daily
October 16, 2007

Original web page at Science Daily

Giardia lamblia, one of the most common human parasites in the United States, causes more than 20,000 intestinal infections a year, often through contact with contaminated drinking or swimming water. In the September 28 issue of Science, an international team led by researchers at the MBL (Marine Biological Laboratory) describe the complete genome (genetic sequence) of Giardia, which could lead to the development of new drugs to combat this persistent infection, called giardiasis. “Even though there are treatments now available, a number of people get chronic giardiasis, which is difficult to eliminate. So there is interest in new treatments,” says Hilary Morrison, Ph.D., of the MBL’s Josephine Bay Paul Center for Comparative Molecular Biology and Evolution, the first author on the paper. The Giardia parasite lives in the human intestine in a swimming and feeding form called a trophozoite, which is eventually expelled through the stools. Outside the body, Giardia takes the form of a highly infectious cyst that can live for weeks in water, soil, food, or on other surfaces.

Giardiasis is most common among children, especially those who are exposed to diaper changing. Swimmers, hikers, campers and others who drink untreated water are also prone to the infection (hence the nickname “backpacker’s disease” or “beaver fever”), as are international travelers. Common symptoms include diarrhea, nausea, stomach cramps and gas, and usually persist two to six weeks. Because the parasite clings to intestinal cells that absorb fats and nutrients, giardiasis can lead to severe complications such as poor nutrient absorption and weight loss.Giardia spends one phase of its lifecycle in the environment and the other in the gut of an infected human or wild animal. To maintain this dual existence, the parasite has two radically different microscopic forms. In water, Giardia exists as a hardy, highly infectious cyst, which can survive for months, even in fresh water devoid of all nutrients. In the gut, Giardia exists in a swimming and feeding form known as a trophozoite.

The awakening of the dormant cyst happens quickly after someone swallows contaminated water or food. After the cysts encounter the warm acidic juices in the stomach, they change into trophozoites. Within about two hours, these trophozoites will be swimming in the intestines. Unlike many other parasites, trophozoites do not invade tissues or cells. Instead they simply attach to cells, drink in nutrients and multiply. The parasite evades the immune system and persists in the intestine by shifting the proteins it displays on its surfaces. Existing drugs can effectively treat people with Giardia infections, the disease known as giardiasis, but most infections resolve on their own. When trophozoites detach from the intestinal wall, they may swim and reattach to new intestinal cells, or they may pass down the digestive tract and into the bowels, transform back into cysts and be passed through the stools.

“Although not life threatening, Giardia is a rather fastidious parasite and quite important from an economical viewpoint worldwide and in the United States, where it constitutes a major cause of diarrheal disease in children in daycare centers,” says Mitchell Sogin, Ph.D., director of the Josephine Bay Paul Center and leader of the Giardia study. Analysis of the Giardia genome revealed several unusual proteins that are promising drug targets, Morrison says. “These proteins are different enough from human proteins that if you affect them with a drug, it’s not going to affect the human counterparts,” she says. “Drugs can be devised that will interfere with the parasite’s ability to replicate, or to move or bind in the small intestine, or to exist at all.”

The team also investigated the evolutionary history of this ancient parasite. Giardia is a single-celled eukaryote, meaning its cell has a nucleus, as do the cells of humans and most other multicellular organisms. But the Giardia genome is compact compared to other eukaryotes, with simplified machinery for several basic processes, such as DNA replication and RNA processing. If the Giardia genome had originally been complex and experienced gene loss over evolutionary time, Morrison says, one would expect to see parts of the machinery intact and parts missing. This, however, wasn’t the case. “It looks like the genome was just simpler to begin with,” she says. The authors hypothesize that Giardia diverged from other eukaryotes more than a billion years ago. “We embarked upon this genome project because of its importance to human health and suggestions from earlier molecular analyses that Giardia represents a very early-diverging lineage in the evolutionary history of eukaryotes,” Sogin says. “Giardia’s genome content and architecture support these theories about the parasite’s ancestral character.”

Eukaryotic organisms are so diverse that they include everything from amoebae to humans. But even within such a wide range, Giardia is unusual. In its trophozoite form, it has two nuclei instead of the more usual one. When it becomes a cyst, it multiplies its genetic material into four identical nuclei. But despite having these multiple copies of its nuclei, Giardia is really a genetic minimalist. It has fewer and simpler genetic components than most other eukaryotes. Why? According to one theory, Giardia is simple because it has lost complexity: evolutionary pressure favors parasites that shed genes coding for functions they can borrow from their infected hosts. An alternative theory holds that the parasite may have always been simple because it diverged from other eukaryotic organisms more than a billion years ago, long before the complex modern eukaryotes emerged.

Science Daily
October 16, 2007

Original web page at Science Daily

Reported cases of Lyme disease have more than doubled since 1991, when Lyme became a nationally notifiable disease, according to a report by the Centers for Disease Control and Prevention (CDC). The report also said 93 percent of reported cases were concentrated in 10 states. “This increase in cases is most likely the result of both a true increase in the frequency of the disease as well as better recognition and reporting due to enhanced detection of cases,” said Dr. Paul Mead, a medical epidemiologist with the CDC Division of Vector-Borne Infectious Diseases. Lyme disease is the most common of all the diseases in the United States transmitted by mosquitoes, ticks and fleas, with approximately 20,000 cases reported each year. It most commonly occurs in the Northeastern, Mid-Atlantic, and North-Central states. Connecticut, Delaware, Maryland, Massachusetts, Minnesota, New Jersey, New York, Pennsylvania, Rhode Island and Wisconsin had the most cases. The report says that during 2003-2005, a total of 64,382 Lyme disease cases were reported to CDC from 46 states and the District of Columbia.

Most illnesses occurred in June, July and August, when the infected ticks that carry the disease are most active. Lyme disease is caused by the spirochete Borrelia burgdorferi which is transmitted to humans by tick bite. From 2003-2005, the incidence of Lyme disease in the cases reported higher rates among two age groups-children aged 5 to 14 years (10 cases per 100,000 population per year) and adults aged 55 to 64 years (9.9 cases per 100,000 population per year). Early symptoms of infection include fever, headache, fatigue, and a characteristic skin rash called erythema migrans. Left untreated, infection can spread to joints, the heart, and the nervous system. People should watch for symptoms especially in these areas with intense Lyme disease transmission, and see a health care provider if these develop. Prompt diagnosis and treatment are important to prevent serious illness and long-term complications. “While this increase is of concern, these rates highlight the need to focus on prevention of this disease. People living in areas where Lyme disease is most frequently reported can take proactive steps to reduce their risk of infection,” Dr. Mead said.

Prevention steps include daily tick checks (self examination for ticks), use of repellent containing 20 percent or more DEET, selective use of insecticides that target ticks, and the avoidance of tick-infested areas. Removing ticks within 24 hours of attachment greatly reduces the likelihood of disease transmission. Tick populations around homes and in recreational areas can be reduced 50 to 90 percent through simple landscaping practices such as removing brush and leaf litter, and creating a buffer zone of wood chips or gravel between forest and lawn or recreational areas.

Science Daily
July 24, 2007

Original web page at Science Daily

A comparison of three parasite species that cause Leishmaniasis has identified a small number of genes, many new to biology, that will provide a framework to target the search for new treatments. Leishmaniasis is a devastating disease that affects about two million people each year and threatens one-fifth of the world’s population and new treatments are desperately needed. In their report in Nature Genetics the researchers compared the genomes of L. infantum and L. braziliensis, which cause life-threatening visceral and disfiguring mucocutaneous leishmaniasis, respectively, with the sequence they produced in 2005 for L. major, which causes a less severe, cutaneous form of the disease. Despite the major differences in disease type, only 200 out of more than 8000 genes present in each genome were found to be differentially distributed between the three species. This exceptionally small variation in gene content has given new insights into those processes that may determine disease severity in humans.

“Identifying factors that allow three closely related organisms to cause vastly different clinical outcomes is a major quest for researchers and in this study we have narrowed the search to a number that can be realistically studied,” commented Dr Matt Berriman, senior author on the paper, from the Wellcome Trust Sanger Institute. The researchers found only five genes in the L. major genome for which no trace could be found in the other two species. By contrast, in Plasmodium, which causes malaria, about 20% of genes differ between related species. “Clearly there must have been considerable evolutionary pressure over time to maintain the structure and sequence of the Leishmania genomes – the degree of similarity between these species was unexpected,” explained Professor Deborah Smith, collaborator on this project at the University of York. “Perhaps only a few parasite genes are important in determining which type of disease develops after infection and the host genome plays a major role in clinical outcome.” The results picked up another surprising finding: the team could assign a function to only one-third of the 200 genes restricted to one or two of the species.

“The genome sequences have given us a short-cut to a small number of largely novel genes,” explained Dr Chris Peacock, first author on the report. “Given their lack of similarity to human genes, they present a limited repertoire of potential targets for drug and vaccine development allowing researchers to optimise the use of limited resources.” Leishmaniasis is one of the neglected diseases that desperately need new research, as WHO/TDR notes: “Treatment of visceral leishmanisis by first-line drugs is long (4 weeks), given systemically, and expensive (US$120–150)”. The affordable drugs have been in use for more than half a century and drug resistance is rife, creating a desperate need for new treatments. Biological studies for the function of 50% of Leishmania genes are lacking, so this comparative genome study provides a route to find those that might be essential to each species.

One potential target is the CFAS gene that codes for cyclopropane fatty acid synthase, an enzyme that may be involved in producing components of the cell membrane. CFAS is present in the genomes of L. braziliensis and L. infantum, but is absent from the human genome. The parasite genes are thought to have been acquired from bacterial species that have very similar sequences. “CFAS is involved in virulence and persistence in Mycobacterium, causative agent of tuberculosis, so the identification of a CFAS gene in Leishmania raises the exciting possibility that some virulence factors are conserved between bacterial and eukaryotic intracellular pathogens,” said Jeremy Mottram, a collaborator on the project who is a Professor in the Wellcome Centre for Molecular Parasitology at the University of Glasgow. Some families of genes that determine the properties of the parasite cell surface have grown in number and some declined among the three species: ‘death’ of genes seems to be a major force for differences between the parasite genomes. Some genes, however, are evolving rapidly, leading the team to suspect they include key genes involved in interacting with the human host – where the battle between parasite and patient is fought and where rapid response is important to both.

Remarkably, L. braziliensis, the most ancient Leishmania species sequenced, contains genes that could provide a working pathway for RNAi, an emerging mechanism for gene regulation. The genome sequences show that components for this pathway are absent from the other two Leishmania species. This pathway might serve as an experimental tool in understanding the role of the many genes whose function is unknown, by using experimentally induced RNAi to ‘knock-down’ gene activity prior to host infection. “In addition to their function with respect to promoting diverse clinical outcomes,” commented David Sacks, PhD, Head of the Intracellular Parasite Biology Section at the National Institute of Allergy and Infectious Diseases, Bethesda, USA, “the remarkably limited number of species-specific genes should lead to the more rapid identification of sequences involved in specialized aspects of Leishmania biology, such as the development of L. braziliensis in the hindgut of its sandfly vector, and the restricted reservoir host range seen with L. infantum infections in dogs.”
Around 350 million people in 88 countries on four continents are at risk of Leishmaniasis and its incidence has risen sharply over the past ten years. It is transmitted by the bite of various species of sandfly: wild and domesticated animals – as well as humans – act as a reservoir for the disease.

Science Daily
July 10, 2007

Original web page at Science Daily

University of Utah biologists invented a chemical-free, hairdryer-like device — the LouseBuster — and conducted a study showing it eradicates head lice infestations on children by exterminating the eggs or “nits” and killing enough lice to prevent them from reproducing. The study — published in the journal Pediatrics — “shows our invention has considerable promise for curing head lice,” says Dale Clayton, a University of Utah biology professor who led the research and co-invented the machine. It is particularly effective because it kills louse eggs, which chemical treatments have never done very well,” he says. “It also kills hatched lice well enough to eliminate entire infestations. It works in one 30-minute treatment. The chemical treatments require multiple applications one to two weeks apart. “The LouseBuster now is in early stages of commercial development by a University of Utah spinoff company, Larada Sciences, for which Clayton is chief scientific officer. Patents are pending on the LouseBuster technology, which Clayton hopes will be on the market within two years for use in schools and clinics.

“Each year, millions of children are infested with head lice, a condition known as pediculosis, which is responsible for tens of millions of lost school days,” the study’s authors write. “Head lice have evolved resistance to many of the currently used pediculicides [insecticide shampoos]. … Hot air is an effective, safe treatment and one to which lice are unlikely to evolve resistance.” The device blows warm air through a flexible hose, which has a rake-like hand piece on the end. It apparently kills lice and nits by drying them out, not by heating them. Clayton urges parents not to use hair dryers to try to kill head lice. “We don’t want kids getting burned by parents who think it’s the heat” that kills lice, he says. “This thing is actually cooler than a hair dryer, but requires twice as much air flow, and the special hand piece is critical because, unless you expose the roots of the hair, it doesn’t work. And it’s difficult to do that with a regular comb.” “The cool thing about the machine is, it works — unlike many other treatments that haven’t been rigorously tested,” Clayton says. “It came out of basic research, completely unplanned.” Clayton’s research focuses on birds and the lice that infest them. But when he moved to the University of Utah in 1996, he couldn’t keep lice alive on laboratory birds because Utah’s air was too dry. He had to humidify bird rooms to keep lice alive.

About the same time, his two children — Mimi and Roger, now 13 and 15, respectively — got head lice, “and we wondered if there was a way to kill head lice by drying them out,” Clayton says. “We started trying different methods of desiccation using hot air like conventional hair dryers, but those didn’t work well.” In the new study, the researchers tested six ways of applying hot air to children’s lice-infested scalps. The tests were conducted during 2001-2005 on 169 infested children who were solicited for the study by flyers distributed in dozens of Salt Lake Valley schools. The study was approved by the university’s Institutional Review Board, which reviews research involving human subjects. Parents and children signed consent forms. Children were excluded from the study if they had used other head lice treatments within the previous two weeks. Clayton dispatched his students in pairs to the homes of infested children to test the various methods. After completion of each treatment trial, each participant was paid $10 and given conventional treatments for lice.

Some 94 percent of the children were girls, who are more likely to have bad infestations because their hair is longer and they have more head-to-head contact on the playground, Clayton says. Before treatment, the researchers combed one side of each child’s head to remove all visible lice and nits, which were placed in an incubator. Then, the entire scalp was treated with one of the six methods being tested. After treatment, the other side of the scalp was combed for the same amount of time as the first side, with removed lice and nits also placed in an incubator. The researchers used a dissecting microscope to count the number of live and dead lice from each side of the scalp. They re-examined them up to 18 hours later to make sure all were dead. Nits were incubated for two weeks to see how many hatched.

“Effectiveness of the different treatment methods was assessed by comparing the percentage of dead lice and non-hatching eggs on the pre- and post-treatment sides of the scalp,” the researchers explain. The researchers measured the temperature and volume of hot air in each method and kept track of any discomfort. No household cleaning measures were taken because they are not considered essential; head lice cannot survive more than 24 hours off a host’s head. Each of the six treatment methods took 30 to 35 minutes and used air at about 140 degrees Fahrenheit. Here are the treatments, from least to most effective:

— Air hoses from two bonnet-style hair dryers fed air into one bonnet. This method killed only 10 percent of hatched lice but 89 percent of eggs.
— A handheld blow dryer was used to apply diffuse heating. Each child’s hair was divided into ten sections using hair clips, and the base of each section was heated three minutes while the dryer was moved to ensure even heating. This method killed only 21 percent of lice but 97 percent of eggs.
— A handheld blow dryer was used to apply directed heating. Hair clips were used to divide each child’s hair into 20 sections. The dryer was held still for 30 seconds to heat one side of each section, then held still another 30 seconds to heat the other side. This method killed 55 percent of lice and 98 percent of eggs.
— A hose was attached to a wall-mounted blow dryer like those in public restrooms. The dryer was put on a table, and the hose used to treat hair divided into 20 sections. The method’s larger air volume killed 62 percent of lice and 97 percent of eggs.
— With the hair divided into 14 to 20 sections, a LouseBuster without a hand piece was used to treat each section with diffuse heat for 60 seconds. Air speed was similar to the wall dryer. This technique killed 76 percent of lice and 94 percent of eggs.
— Aplastic hand piece with 10 coarse teeth (not like fine-toothed nit combs) was attached to the end of the LouseBuster hose and raked through hair while hot air blew the opposite direction. All areas of the scalp were raked and exposed to hot air for at least 30 seconds. The LouseBuster with the handpiece killed 80 percent of hatched lice — a larger proportion than any of the other five methods — and 98 percent of louse eggs.

The 80 percent kill rate was high enough to prevent remaining lice from breeding — possibly due to stress or sterilization — so “virtually all subjects were cured of head lice when examined one week following treatment with the LouseBuster,” the scientists write. Children and their parents reported none of the treatments had adverse effects. Kids reported less discomfort from the LouseBuster than from any other method. Clayton estimates it cost $500,000 to develop and test the LouseBuster, with funding from the Utah Centers of Excellence program, University of Utah, Primary Children’s Medical Center Foundation and the National Pediculosis Association.

Each year, 6 million to 12 million Americans are infested with head lice, making children miss 12 million to 24 million school days, the researchers say. “Although head lice do not produce an illness per se, they are physically and psychologically unpleasant for the child and an exasperating problem for parents and school authorities,” the scientists write. Treatments have been chemical shampoos, louse combs and home remedies. Annual U.S. sales of anti-louse shampoos exceed $160 million, yet the shampoos are not very effective at killing nits, requiring repeat treatment. Many parents dislike using insecticide shampoos on children, and lice rapidly are evolving resistance to chemicals. Louse combs are used to remove the eggs or nits, an effective procedure, but one that requires many hours over several days. “Most parents do not have the time or patience to comb out all the lice and eggs,” Clayton and colleagues write. Some parents resort to home remedies such as bug spray, mayonnaise or kerosene. “These remedies can harm the child and there is little hard evidence that they are effective,” the researchers say. Some of the scientists’ relatives got infested during the study. Clayton’s kids, Mimi and Roger, volunteered to be infested with lice and then were treated successfully. “They like to shock their friends by telling them they served as guinea pigs in their dad’s research,” Clayton says. “I’m waiting for the authorities to show up. They haven’t yet.”

Science Daily
November 21, 2006

Original web page at Science Daily

Universitat Autonoma De Barcelona researchers working in collaboration with the INIA (National Institute of Agricultural and Food Research and Technology) and Germans Trias i Pujol Hospital in Badalona, near Barcelona, are developing the first vaccine against leishmaniasis produced using insect larvae. The new vaccine is based on introducing specific genes and proteins from the protozoan Leishmania infantum into the patient. Although it is currently in the preliminary phase, scientists believe it could be much more effective than conventional vaccines.

Leishmaniasis is one of the biggest global health problems. In our part of the world, it is produced by the protozoan Leishmania infantum, and dogs are the main reservoir. The disease is spread through the bites of the phlebotomy, an insect similar to the mosquito. Clinical manifestations go from light skin lesions to visceral complications and even death. The disease affects more than 12 million people in the world, and 250 million more are at risk. Current treatments are not satisfactory, and although an effective vaccine would be the best way to confront the disease, conventional vaccines have failed.

UAB researchers working in collaboration with the INIA and Germans Trias i Pujol Hospital are working on the development of an unconventional vaccine that could be more effective in treating the disease. In an effort to make the vaccine as specific as possible, the researchers are conducting epidemiological tests on dogs and humans to find out whether the degree of the illness and the differences between regions, species (dog or humans) and infected individual persons are related to the presence of different antibodies against the infectious agent, the protozoan Leishmania infantum.

To create the vaccine and the reagents used in the epidemiological studies, the scientists have isolated the protozoan gene and inserted it into a virus that affects insects (baculovirus) and have infected the larvae of a small worm (Trichoplusia ni) with them. These larvae act as bioreactors and produce large quantities – and at a much lower cost than with conventional reactors involving microorganisms – of the proteins that are codified by these genes and are responsible for the production of antibodies in those affected. Each person would be administered a DNA vaccine with the genes that codify for the proteins of the protozoan that generates most antibodies in the geographical region. Later, the person would be vaccinated again, but this time directly with the proteins associated with the genes (produced cheaply in insect larvae). The aim is to increase effectiveness. The vaccines could be used as prevention or therapeutically.

“Selectivity for each individual and the combination of the vaccination with DNA and protein will probably make this new vaccine much more effective than current ones. Furthermore, the method of producing them in insect larvae would considerably reduce the costs,” explains Jordi Alberola, the main researcher for the project.

Science Daily
August 1, 2006

Original web page at Science Daily

The three main soil-transmitted helminth infections, ascariasis, trichuriasis, and hookworm, are common clinical disorders in man. The gastrointestinal tract of a child living in poverty in a less developed country is likely to be parasitised with at least one, and in many cases all three soil-transmitted helminths, with resultant impairments in physical, intellectual, and cognitive development. The benzimidazole anthelmintics, mebendazole and albendazole, are commonly used to remove these infections. The use of these drugs is not limited to treatment of symptomatic soil-transmitted helminth infections, but also for large-scale prevention of morbidity in children living in endemic areas. As a result of data showing improvements in child health and education after deworming, and the burden of disease attributed to soil-transmitted helminths, the worldwide community is awakening to the importance of these infections. Concerns about the sustainability of periodic deworming with benzimidazole anthelmintics and the emergence of resistance have prompted efforts to develop and test new control tools.

The Lancet
May 23, 2006

Original web page at The Lancet

Since its introduction to the United States in 1999, West Nile virus has become the major vector-borne disease in the U.S., with 770 reported deaths, 20,000 reported illnesses, and perhaps around a million people infected. The virus is transmitted by Culex mosquitoes (the “vector”) and cycles between birds that the mosquitoes feed on. Humans can also be infected with the virus when bitten by these mosquitoes. Scientists have struggled to explain these large outbreaks in the U.S., which stand in stark contrast to the sporadic European infections. In a new study published in the open access journal PLoS Biology, Drs. Marm Kilpatrick, Peter Daszak, and colleagues now present evidence that the major vector of West Nile virus in the USA, Culex pipiens mosquitoes, change their feeding behavior in the fall from their preferred host, American robins, to humans, resulting in large scale outbreaks of disease.

These feeding shifts appear to be a “continent-wide phenomenon,” the researchers conclude, and may explain why West Nile virus outbreaks are so intense in the U.S. compared to Europe and Africa, where the virus originates. From May through September 2005, Dr. Kilpatrick, senior research scientist with the Consortium for Conservation Medicine, and his team collected mosquitoes and caught birds at six sites in Maryland and Washington, D.C. They determined the changes in mosquito populations throughout the West Nile virus transmission season, the abundance and diversity of bird species at these sites, and tested samples for West Nile virus. Dr. Kilpatrick says, “To find out which species mosquitoes favored as hosts, we collected thousands of Culex pipiens mosquitoes and selected those that had just fed and still had bloodmeals in them. We sequenced the DNA in the bloodmeal to identify the species of host they had fed on.”

Their findings showed that from May to June, the American robin, which represented just 4.5% bird population at their sites, accounted for more than half of Culex pipiens’ meals. As the summer wore on and robins left their breeding grounds, the probability that humans were fed on increased sevenfold. Because the overall number of birds increased during this time, Kilpatrick and his team concluded that mosquitoes changed to humans as a result of robin dispersal, rather than a lack of avian hosts. “This feeding shift happened, even though the total number of birds at our site increased as other species’ offspring joined the population,” said Kilpatrick.

With the data collected from the Washington, D.C., area, the researchers presented a model of the risks of infection of the West Nile virus in humans. The model predicted that the risk of human infection peaked in late July to mid-August, declined toward the end of August, and then rose slightly at the end of September. The actual human cases in the area that year, the authors point out, “showed a strikingly similar pattern.” This same pattern was seen in California and Colorado, with numbers of infected Culex tarsalis mosquitoes (the main vectors in the western USA) peaking in June and July, followed by a late-summer spike in human infections, suggesting a continent-wide phenomenon.

Dr. Peter Daszak, Executive Director of the Consortium for Conservation Medicine, comments: “This is a case study in how to understand emerging diseases. Our collaborative team includes ecologists, virologists, and entomologists, and uses state-of-the-art techniques, including DNA sequencing of mosquito blood meals, to piece together what drives a virus to cause outbreaks in people. At the CCM we study the ecology of diseases and develop predictive models that can help us prevent future outbreaks. We are now using this approach to help understand the emergence and spread of other viruses such as SARS, Nipah virus and avian influenza.”

Science Daily Health & Medicine
April 25, 2006

Original web page at Science Daily Health & Medicine

Researchers in Argentina have determined that night blindness is a new clinical symptom of Chagas disease. A team led by Howard Hughes Medical Institute (HHMI) international research scholar Mariano Jorge Levin and Cristina Paveto of the Institute for Genetic Engineering and Molecular Biology (INGEBI), National Research Council, National Council of Scientific Research and Technology in Buenos Aires, found that the immune system of individuals with the tropical disease can shut down a key reaction in the retina, causing night blindness. Triatomine bug, Trypanosoma cruzi vector, defecating on the wound after taking a blood meal. “This is a new observation, a new clinical symptom of Chagas disease,” said Levin, head of the Laboratory of the Molecular Biology of Chagas Disease at the University of Buenos Aires, Argentina. Levin and colleagues report their findings in the March 2006, issue of the FASEB Journal.

Chagas disease affects people living in regions of Latin America where insects carrying the parasite Trypanosoma cruzi thrive in crowded and substandard housing. At night, the insects emerge and bite, transferring the Chagas parasite into a new host. Their victims are often children. After an acute infection characterized by swollen eyelids, those infected usually feel better. But the parasite remains active inside them, in a chronic phase of infection, quietly invading cells and stimulating the immune system. As a result, people can develop heart and gastrointestinal problems months or years after being infected. Some 30,000 people die each year from Chagas disease, according to the World Health Organization, but the number of people who are carrying latent infections is unknown.

“We now know that Chagas patients may have trouble seeing at night,” said Levin. “And this gives us additional motivation to improve conditions for people living in areas where Chagas disease is common.” Silvia Matsumoto, a physician from the Dr. Teodoro Alvarez Hospital in Buenos Aires and first author of the paper, launched the investigation after noticing Chagas patients complaining about vision problems. “This was her idea, that the same antibodies that touch the heart cells might also block rhodopsin,” said Levin.

Matsumoto conducted thorough eye examinations of 45 Chagas disease patients with heart problems. She found that under bright conditions, the Chagas patients performed comparably to 50 healthy control individuals. But in the dark, 37 of 45 (82 percent) Chagas patients had trouble seeing with at least one eye, and 19 of 45 (42 percent) had trouble with both eyes. Matsumoto then approached Paveto, and both contacted Levin, whose laboratory was well-stocked with antibodies from Chagas patients and who had already developed the tests needed to study molecular mimicry. In previous research, Levin and colleagues showed that the immune systems of patients infected by T. cruzi generate antibodies that attack the parasite but also cause damage to heart cells. Levin suspected “molecular mimicry” as the cause of the misguided attack. Molecular mimicry occurs when a molecule that is part of an infectious agent resembles a molecule native to the body. Eventually, the immune system begins to mistake the native molecule for the invader. Levin’s investigations revealed that an intra-cellular T. cruzi protein resembles the beta1-adrenergic receptor on the surface of heart cells, a finding that helped explain why Chagas patients develop certain heart problems.

Now, it turns out, molecular mimicry can also upset the delicate machinery inside retinal cells. Levin and his team found that antibodies geared to attack T. cruzi also block rhodopsin, a molecule that converts light into electrical impulses sent to the brain. “Rhodopsin takes light and transforms it — that’s its function,” said Levin. To demonstrate molecular mimicry in the retina, Paveto extracted rhodopsin from cow’s eyes. Through a series of tests, the team showed that cow rhodopsin, which is similar to the human protein, reacts with antibodies produced by Chagas patients.

“We showed that the same antibodies that attack heart cells can also interfere with rhodopsin,” Levin said. “This is important, because it enlarges the concept of molecular mimicry in Chagas disease.” Rhodopsin and beta1-adrenergic receptors in heart cells belong to the same class of molecules, a subfamily of the G-protein-coupled receptors, he pointed out. Paveto, an independent researcher at INGEBI–an institute that is home to three HHMI international research scholars–conducted much of the painstaking work on the project by developing an original method to test rhodopsin function, said Levin.

Levin said that Chagas patients’ vision problems are caused exclusively by the antibodies that block rhodopsin, and not by inflammation. “In the hearts of Chagas patients, we see scarring because there is a complex reaction that causes inflammation,” he said. “But there are no such scars in the eyes of Chagas patients with reduced vision.” “No one knew about the night blindness, so we don’t know, for instance, if Chagas patients have more accidents at night,” Levin added. “That’s one of many ideas to explore now. The research also points out that we need new drugs or vaccines to stop the parasite, and at a social level, it stresses the need to improve living conditions of Chagas patients, particularly those living in rural areas.”

Science Daily
March 14, 2006

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