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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.

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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

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May Persist on Feathers

Fallen from Domestic Ducks

ScienceDaily (Aug. 22, 2010) — Highly pathogenic avian influenza virus (H5N1) may persist on feathers fallen from the bodies of infected domestic ducks and contribute to environmental contamination. Researchers from the National Institute of Animal Health, Tsukuba, Ibaraki, Japan report their findings in the August 2010 issue of the journal Applied and Environmental Microbiology.

Since the emergence of Asian avian influenza virus in 1997, it has spread to Europe, the Middle East and Africa causing significant mortality and economic loss in the poultry industry. Although the virus is mainly found in waterfowl and transmitted through fecal contamination in water, humans as well as other mammalian species have contracted the virus through close contact with infected birds.

A prior study showed that H5N1 could replicate in the skin cells of feathers and further suggested that those that drop off the body could potentially contaminate the environment. Here, researchers evaluated the environmental risk posed by contaminated feathers by inoculating domestic ducks with H5N1, collecting feathers, feces and drinking water three days following, and then storing them at 39 degrees and 68 degrees Fahrenheit for 360 days. Results showed that H5N1 persisted the longest in feathers at both temperatures.

“These results indicate that feathers detached from domestic ducks infected with highly pathogenic avian influenza virus (H5N1) can be a source of environmental contamination and may function as fomites with high viral loads in the environment,” say the researchers.

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.

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Appears to Keep Cancer in Check

in Majority of CLL Patients

Science (June 4, 2010) — An extract of green tea appears to have clinical activity with low toxicity in chronic lymphocytic leukemia (CLL) patients who used it in a phase II clinical trial, say researchers at Mayo Clinic.

The findings were presented June 7 during the annual meeting of the American Society of Clinical Oncology (ASCO). They are the latest in a series of Mayo studies to show promise for use of the chemical epigallocatechin gallate (EGCG) — the major component of green tea — in reducing the number of leukemia cells in patients with CLL. Mayo first tested EGCG in a variety of laboratory assays about eight years ago, and it was found to reduce the survival of CLL leukemic cells. This laboratory finding was followed by a successful phase I clinical trial — the first time green tea extract had been studied in CLL patients.

“Although only a comparative phase III trial can determine whether EGCG can delay progression of CLL, the benefits we have seen in most CLL patients who use the chemical suggest that it has modest clinical activity and may be useful for stabilizing this form of leukemia, potentially slowing it down,” says Tait Shanafelt, M.D., a Mayo Clinic hematologist and lead author of the study.

“These studies advance the notion that a nutraceutical like EGCG can and should be studied as cancer preventives,” says Neil Kay, M.D., a hematology researcher whose laboratory first tested the green tea extract in leukemic blood cells from CLL patients. “Using nontoxic chemicals to push back cancer growth to delay the need for toxic therapies is a worthy goal in oncology research — particularly for forms of cancer initially managed by observation such as CLL.”

Drs. Shanafelt and Kay caution that EGCG is not a substitute for chemotherapy. All of the patients Mayo tested with EGCG were early stage, asymptomatic CLL patients who would not otherwise be treated until their disease progressed. The extract was supplied by the National Cancer Institute (NCI) and Polyphenon E International for these initial clinical trials.

CLL is a blood cancer that is a hybrid between leukemia and lymphoma. Progression of the disease is measured by the quantity of leukemia cells in the blood and bone marrow as well as enlargement of lymph nodes due to infiltration by the leukemia cells. In the phase I study, published in May 2009 in the Journal of Clinical Oncology, researchers found that the blood lymphocyte (leukemia cell) count was reduced in one-third of participants, and that the majority of patients who entered the study with enlarged lymph nodes due to involvement by CLL saw a 50 percent or greater reduction in their lymph node size.

Using the highest dose tested in the phase I study, the researchers launched their phase II clinical trial in an additional 36 patients. The results presented at the ASCO meeting evaluate the effects in these 36 patients as well as the six patients from the phase I trial treated at the same dose (total 42 patients). Results from 41 patients who have completed the study show that 31 percent of patients had a 20 percent or greater sustained reduction in blood leukemia count, and 69 percent of patients with enlarged lymph nodes saw a reduction of node size of 50 percent or greater.

In all, 69 percent of CLL patients had a biological response to EGCG as evidenced by a 20 percent or greater sustained reduction in blood lymphocyte count and/or a 50 percent or greater reduction in lymph node size, the researchers say.

Because EGCG was being studied in patients who did not otherwise need treatment, the researchers took a rigorous approach toward studying side effects. Most clinical trials of therapeutic agents only report grade 3 and higher side effects, but the researchers looked at and reported grade 1 and grade 2 as well. While a number of patients had transient grade 1 or 2 side effects, only three of 42 experienced a grade 3 side effect during their six months of treatment.

“All in all, the treatment was well tolerated with very mild side effects in most patients,” Dr. Shanafelt says.

The researchers say that the prior publications on the effects of EGCG on CLL leukemia cells in the laboratory and the data from the published phase I study have been widely disseminated via the Internet by patient advocacy groups. Based on information from patients and colleagues throughout the country, the Mayo researchers have become aware that many CLL patients nationwide have started to use EGCG supplements, which are readily available over the counter.

“Without a phase III clinical trial, we cannot make a recommendation that EGCG be used by CLL patients, but those who want to take supplements should consult with their oncologists and need to receive appropriate monitoring using laboratory tests,” Dr. Kay says.

The study was funded by grants from the NCI, the Mayo Comprehensive Cancer Center and from donors and patient advocacy foundations.

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