KILLER DISEASE IN NORTH AUSTRALIA CARRIED BY MOSQUITO

The Deadly Murray Valley encephalitis

A mosquito-borne virus which killed a Canadian tourist and left a toddler critically ill has prompted a widespread warning for people to cover up and protect themselves from mosquito bites in Australia’s north.

A 19-year-old Canadian woman died after contracting Murray Valley encephalitis following a trip through the Northern Territory this month. She returned home where she became unwell, and yesterday died in a hospital in Calgary, Alberta.

A Northern Territory Health Department spokesman said it was not known where in the NT the Canadian woman had contracted the disease.

In the meantime, a two-year-old remains in Royal Darwin Hospital Australia after also contracting the potentially fatal mosquito-borne virus in the Kimberley region of WA.

A WA police officer who contracted MVE while on a two-week relief stint at an Aboriginal community remains in a Perth hospital.

Constable Ryan Marron, 29, has come out of a coma but is still unable to communicate.

It is not known if the police officer or the toddler will fully recover.

Last month, a man who had been travelling in WA’s northwest became the first person in the state to die from the disease in three years.

So far this year there have been three confirmed cases of MVE in the Northern Territory and one report of the closely related Kunjin virus.

In WA there have been nine reports of MVE, leaving one dead and several hospitalised.

The WA Health Department last week issued its fifth warning in three months, following the death of a man in WA last month.

The viruses, which have no cure and no vaccination, kill 25 per cent of people who contract them while another 25 per cent have residual neurological effects.

People infected in WA so far this year had been travelling through the Kimberley, Pilbara, Gascoyne and eastern Goldfields regions.

Department entomologist Sue Harrington said while there was no suggestion the MVE virus would reach Perth, the fact it had already hit the Wheatbelt and Mid-West regions was of a concern.

“It seems to have activated independently this season,” she said.

“There has been an extension of that area, so a large proportion of West Australia is now affected by MVE.”

The death of a man in the north-west of the state last month and a South Australian man two weeks ago led the Department to issue another stern warning about the virus.

“It causes inflammation of the brain,” she said.

“People have suffered paralysis and brain damage of varying degrees.

“Often people in the north just accept that mosquitoes are a fact of life.

“A lot of people might have been bitten and have developed the antibodies.

“Every year we have activity in the region. It’s still the same disease, with the same drastic symptoms.”

Ms Harrington warned as there was no cure doctors were only able to treat the symptoms of the virus so people living and travelling outside the metropolitan area should take measures to avoid mosquito bites by applying mosquito repellents and wearing long-sleeved clothing.

In addition to MVE and Kunjin viruses, Ross River and Barmah Forest viruses were still causing dramas across the south of the state with more infections reported to the Department.

The latter two viruses cause similar symptoms including painful joints, aching muscles, lethargy, fever, headaches and skin rashes and can last from days to months.

The symptoms of Kunjin and MVE are similar. While the latter is more severe, both cause fever, drowsiness, stiff neck, nausea and dizziness. Young children can experience drowsiness, floppiness, irritability, poor feeding or general distress.

- with AAP

Virus May Act as ‘Evolution-Proof’

Biopesticide Against Malaria

Science (Aug. 21, 2010) — A naturally occurring virus in mosquitoes may serve as a “late-life-acting” insecticide by killing older adult mosquitoes that are responsible for the bulk of malaria transmission. The researchers from Johns Hopkins University and the Johns Hopkins Malaria Research Institute, Baltimore, Maryland, detail their findings in the August 2010 issue of the Journal of Virology.

Malaria infects hundreds of thousands of people each year and is the cause of over a million deaths worldwide. Insecticides are one of the main strategies currently used to control malaria transmission, however, evolving resistance to such therapies continues to impact such efforts. “Late-life-acting” insecticides (LLAIs) are now being examined as a new approach for controlling malaria as they selectively kill older mosquitoes that spread the disease, while younger mosquitoes survive just long enough to reproduce.

“Reproduction allows for relaxation of evolutionary pressures that select for resistance to the agent,” say the researchers. “If resistance alleles exert fitness costs, there are theoretical scenarios under which resistance is not expected to evolve, leading some to provocatively term LLAIs as ‘evolution-proof’.”

Densonucleosis viruses (or densoviruses [DNVs]) are naturally occurring parvoviruses that have been identified in multiple mosquito species. Some DNVs typically infect during the larval stage and are lethal, however, in this study researchers suggest that the Anopheles gambiae densovirus (AgDNV) may infect at low levels during early life and replicate to lethal levels at adult age. Analysis following infection showed that although AgDNV levels increased modestly during larval development they still replicated slower resulting in significantly decreased virus levels during this stage. Additionally, virus levels greatly increased in 7-to-10-day-old adults.

“Ultimately, we expect that a properly engineered LLAI AgDNV can be deployed in the field to significantly modulate malaria transmission,” say the researchers.

Sourced & published  by Henry Sapiecha

New Compound May Be Effective

Against Chagas’ Disease

Science (Aug. 22, 2010) — A new compound may offer an effective drug candidate against the deadly tropical infection, Chagas’ disease say researchers from Brazil. They report their findings in the August 2010 issue of the journal Antimicrobial Agents and Chemotherapy.

Chagas’ disease is an infection caused by the parasite Trypanosoma cruzi and it affects approximately 18 million people and causes up to 50,000 deaths per year in tropical regions of the world. Human infection occurs through contact with contaminated feces or urine from infected insects, blood transfusions, contaminated food, and birth canal transmission. In areas where the disease is endemic, such as Mexico and Argentina, up to 30% of infected patients may develop cardiovascular and gastrointestinal problems.

The current drug used to treat Chagas’ disease, benznidazole, is effective when treating acutely infected patients, however, it is less so when dealing with chronic infections and poses severe side effects in elderly patients.

In this study researchers identified a compound against T. cruzi and found it not only inhibited cell division, but it was also a very effective against T. cruzi even at very low doses. Additionally, it was 340 times more toxic to parasites than mammalian cells as well as more effective than benznidazole in all experiments.

“This compound was demonstrated to have a fast antiparasite effect, decreasing its viability and invasion capacity and leading to an apoptosis-like death,” say the researchers.

First Case Of Insect Transmission Of Chagas Parasite In Louisiana (Jan. 18, 2007) — Loyola biology professor Patricia Dorn, Ph.D., in collaboration with Dawn Wesson, Ph.D., of Tulane University Health Sciences Center and Loyola undergraduate student Leon Perniciaro discovered the …  > read more

Sourced & published by Henry Sapiecha

Deathstalker Scorpion Venom

Could Improve Gene Therapy

for Brain Cancer

Science (Aug. 11, 2010) — An ingredient in the venom of the “deathstalker” scorpion could help gene therapy become an effective treatment for brain cancer, scientists are reporting. The substance allows therapeutic genes — genes that treat disease — to reach more brain cancer cells than current approaches, according to the study in ACS Nano.

Miqin Zhang and colleagues note that gene therapy — the delivery of therapeutic genes into diseased cells — shows promise for fighting glioma, the most common and most serious form of brain cancer. But difficulties in getting genes to enter cancer cells and concerns over the safety and potential side effects of substances used to transport these genes have kept the approach from helping patients.

The scientists describe a new approach that could solve these problems. Key ingredients of their gene-delivery system are chlorotoxin, the substance in deathstalker scorpion venom that can slow the spread of brain cancer, and nanoparticles of iron oxide. Each nanoparticle is about 1/50,000th the width of a human hair. In tests on lab mice, the scientists demonstrated that their venom-based nanoparticles can induce nearly twice the amount of gene expression in brain cancer cells as nanoparticles that do not contain the venom ingredient. “These results indicate that this targeted gene delivery system may potentially improve treatment outcome of gene therapy for glioma and other deadly cancers,” the article notes.

Sourced & published by Henry Sapiecha

Snake Venom Studies Yield Insights

for Development of Therapies

for Heart Disease and Cancer

Science(July 30, 2010) — Researchers seeking to learn more about stroke by studying how the body responds to toxins in snake venom are releasing new findings that they hope will aid in the development of therapies for heart disease and, surprisingly, cancer.

The Japanese team is reporting in a Journal of Biological Chemistry “Paper of the Week” that they are optimistic that inhibiting a protein found on the surface of blood cells known as platelets may combat both irregular blood clotting and the spread of certain cancers throughout the body.

“The finding that platelets not only play a role in blood clotting but also in the development of vessels that allow tumors to flourish was quite unexpected and paves the way for new research on the role or roles of platelets,” says Katsue Suzuki-Inoue, the associate professor at the University of Yamanashi who oversaw the 13-person team’s work in professor Yukio Ozaki’s laboratory.

About platelets, blood clots and stroke

Under normal conditions, platelets are activated to become sticky when blood vessels are injured, and their clumping together (aggregation or clotting) naturally stops bleeding. But, irregular platelet aggregation caused by disease can lead to dangerous clots or even stroke if a clot clogs or bursts in a vessel that carries oxygen and nutrients to the brain.

“When a blood clot, or thrombus, forms during the body’s normal repair process, it’s doing its job,” says Suzuki-Inoue. “But, thrombotic diseases, such as heart attack and stroke, are leading causes of death in developed countries. Understanding and manipulating the underlying chemical reactions could help us save many lives.”

But what does this have to do with snake venom? It’s sort of a long story.

How venom can prevent or cause clotting

“Snake venom contains a vast number of toxins that target proteins in platelets,” says Yonchol Shin, an associate professor at Kogakuin University who specializes in snake toxins. “Some of those toxins prevent platelets from clotting, which can lead to profuse bleeding in snake bite victims. Others, like the one we’ve focused this research on, potently activate platelets, which results in blood clots. Identification of the molecular targets of many of these toxins has made an enormous contribution to our understanding of platelet activation and related diseases.”

Intrigued by the then-recent discovery that elements in snake venom can promote irregular aggregation of platelets — the kind that leads to clots and stroke — Inoue’s and Ozaki’s team set out in 1997 to understand better the molecular underpinnings of those chemical reactions. They hoped that whatever they learned could be applied to the search for new therapies for irregular blood clotting caused by disease.

In 2000, another set of investigators came across a protein on the surface of platelets and dubbed it C-type lectin-like receptor 2, or CLEC-2. At the time, it remained unclear how CLEC-2 was produced or what its job was, but the team suspected it was worth further study.

After six years of research and collaborations with British investigators, the team in 2006 discovered how rhodocytin — a molecule purified from the venom of the Southeast Asia pit viper Calloselasma rhodastoma — binds to the CLEC-2 receptor protein on the platelet surface, spurring the platelet to clot with others like it.

Then, in another JBC “Paper of the Week” in 2007, Suzuki-Inoue and her colleagues reported how a separate molecule, called podoplanin, binds to the CLEC-2 platelet receptor protein very much like the venom molecule does. Discovered in 1990, podoplanin is a protein expressed on the surface of cancer cells, and, when bound to the CLEC-2 receptor on platelets, it spurs blood clotting, too.

“To shield themselves from the immune system, cancer cells send out a chemical, podoplanin, which binds to the CLEC-2 receptor protein on platelets, telling the platelets to get together and form a protective barrier around the cancer cells. Once enveloped, the cancer cells are not detected by the immune system and are able to bind to blood vessels’ inner linings and spread, or metastasize, throughout the body,” she explained.

Using a mouse model, the team in 2008 showed that blocking the tumor protein podoplanin from binding with the platelet receptor protein CLEC-2 could prevent tumors from metastasizing to the lung.

From snake venom to platelets to tumors

The recent investigations by the team, published in the JBC online July 4, hinged on the generation and study of genetically engineered mouse embryos that lacked the platelet receptor protein CLEC-2. In the end, the experiments showed that CLEC-2 is not only necessary for blood clotting but also necessary for the development of a different type of vessel, specifically lymphatic vessels that carry fluid away from tissues and prevent swelling, or edema.

“During fetal development, the CLEC-2 deficiency disturbed the normal process of blood clotting and, in fact, the normal development and differentiation of blood and lymphatic vessels,” says Masanori Hirashima, an associate professor at Kobe University. “They had disorganized and blood-filled lymphatic vessels and severe swelling.”

Podoplanin, Hirashima explains, is also expressed on the surface of certain types of lymphatic cells and is known to play a role in the development of lymphatic vessels: “These findings suggest that the interaction between CLEC-2 and podoplanin in lymphatic vessels is necessary for the separation between blood vessels and lymphatic vessels.”

It has been known that tumors generate blood vessels to promote their growth, and it’s possible that the formation of lymphatic vessels also may contribute to the spread of cancer throughout the body, says Osamu Inoue, an assistant professor at the University of Yamanashi.

“We speculate that the interaction between the platelet’s CLEC-2 protein and the podoplanin molecule in lymphatic cells plays an essential role in the creation of lymphatic vessels, thereby facilitating tumor growth. If this is the case, a drug that blocks that interaction would prevent the spread of tumors through lymphatic vessels,” Inoue said.

By being deemed a “Paper of the Week,” the team’s work is categorized in the top 1 percent of papers reviewed by the JBC editorial board in terms of significance and overall importance. Other contributors included Guo Ding, Satoshi Nishimura, Kazuya Hokamura, Koji Eto, Hirokazu Kashiwagi, Yoshiaki Tomiyama, Yutaka Yatomi and Kazuo Umemura.

Sourced & published by Henry Sapiecha

Disabled man eaten to death

by maggots