Protein Is Highly Effective Against an Intestinal Roundworm in Mice
Intestinal parasitic nematode (roundworm) diseases infect well over 1 billion people worldwide and cause significant illness, especially in children and pregnant women. To date, there is only one drug, albendazole, which is widely used in administering single-dose treatments to large populations as an antihelminthic (a substance to destroy or eliminate parasitic worms, especially intestinal helminths).
Given the large numbers of people to be treated, and the threat of parasites developing resistance to the current drug, another drug called tribendimidine has been developed, and appears to be as good as albendazole in clinical trials. Scientists are also studying new treatment options.
NIAID-funded biologists at the University of California, San Diego, have identified a protein that could potentially be a new treatment for parasitic roundworm infections, including ascariasis, trichuriasis, and hookworm. The crystal protein (Cry5B) is found in a soil bacterium used to kill insects naturally on organic crops. The scientists report that the protein is better at killing parasitic roundworms than the drugs currently being used. In their study in mice, the Cry5B protein was found to be three times better than tribendimidine and, by extension, albendazole.
The challenge researchers now face is to protect the protein from gastric juices. If scientists can solve this issue of delivering the treatment to the gut, it will likely become a superior anthelmintic used to treat parasitic infections.
Hu Y, Georghiou SB, Aroian, RV. Bacillus thuringiensis Cry5B Protein Is Highly Efficacious as a Single-Dose Therapy against an Intestinal Roundworm Infection in Mice. PLoS Negl Trop Dis. 4(3): e614, 2010.
Using Bacteria To Prevent the Transmission of Lymphatic Filariasis
Lymphatic filariasis, commonly known as elephantiasis, affects more than 120 million people in 80 countries. It is caused by Wuchereria bancrofti, a filarial worm, which is transmitted to humans through the bite of an infected mosquito. Disease control efforts through drug therapy and the use of insecticides has had limited success. Scientists are now looking to the use of novel vector control strategies to provide an additional tool to break the cycle of disease transmission.
Dr. Steven Dobson from the University of Kentucky and his collaborators in Tahiti are studying an innovative approach to vector control. If successful, the target mosquito population will be suppressed to the point where transmission of worms to humans will not occur or will be minimal. Dr. Dobson and his team are studying Aedes polynesiensis mosquitoes infected with the bacteria Wolbachia to suppress the mosquito population in French Polynesia. The bacteria alter the reproductive capabilities of insects they infect, often causing sterility in females. By encouraging Wolbachia infection among mosquito populations, Dr. Dobson’s team hopes to decrease and eventually reduce the population of A. polynesiensis, lowering the number of infected mosquitoes capable of transmitting the disease-causing worm.
Brelsfoard CL, Séchan Y, Dobson SL. Interspecific Hybridization Yields Strategy for South Pacific Filariasis Vector Elimination. PLoS Negl Trop Dis. 2(1): e129, 2008.
Understanding How DEET Insecticide Works
DEET (chemical name, N,N-diethyl-meta-toluamide) has been used for more than 50 years as an effective insect repellent. However, the mechanisms behind how the insecticide repels insects have not been well understood. Until recently, the hypothesis has been that DEET masks the odors that insects find attractive, such as lactic acid and carbon dioxide, resulting in the insect being unable to find its host.
NIAID-supported researchers, led by Dr. Gregory Lanzaro of the University of California, Davis, examined how DEET works on Culex quinquefasciatus mosquitoes. This species of mosquito is a vector of arboviruses and filarial worms, which cause disease in humans. The team found that DEET does not, as previously thought, interfere with attractive odors, but rather, that mosquitoes are able to directly detect DEET, which subsequently causes the mosquitoes to avoid any surface where DEET has been applied. Improved knowledge about how DEET repels mosquitoes may result in more effective use of this repellent for improved protection against disease-transmitting insects.
Syed Z, Leal WS. Mosquitoes smell and avoid the insect repellent DEET. Proc Natl Acad Sci.& 105: 13598, 2008.
New Metabolic Pathway Discovered in Mosquitoes
Novel control strategies for mosquitoes are needed to effectively control the diseases they transmit. One promising approach is through better understanding the unique metabolic pathways of mosquitoes. Such improved understanding may lead to the development of novel control strategies that do not affect non-target organisms, including humans.
NIAID-supported researchers, led by Dr. Roger Miesfeld from the University of Arizona, have discovered a second, previously unknown, metabolic pathway in female Aedes aegypti mosquitoes, the primary vector of dengue. The newly discovered process metabolizes uric acid into urea in a pathway that may provide a target for novel insecticides. This discovery could lead to control efforts that uniquely affect mosquitoes.
Scaraffia PY, Tan G, Isoe J, Wysocki VH, Wells MA, Miesfeld RL. Discovery of an alternate metabolic pathway for urea synthesis in adult Aedes aegypti mosquitoes. Proc Natl Acad Sci. 105: 518, 2008.