UC Davis Entomologist Receives $1.3 Million NIH Grant to Study Sand Flies

DAVIS—Medical entomologist Gregory Lanzaro, director of the University of California Mosquito Research Program and the UC Davis Center for Vectorborne Diseases, based at the School of Veterinary Medicine, has received a four-year $1.3 million grant from the National Institutes of Health to study the role of saliva in a blood-sucking sand fly that transmits the deadly parasitic disease, visceral leishmaniasis (VL). This is the first-ever study focusing on the effects of sand fly salivary proteins on VL, also known as kala azar or “black fever,” Lanzaro said. The Leismania parasites, transmitted by infected female sand flies, attack the internal organs, including the spleen and liver. “The disease is almost always fatal unless treated,” he said.

Previous studies on sand fly saliva have targeted the more common cutaneous leishmaniasis (CL), characterized by skin lesions that result in permanent scarring, but is rarely fatal. Globally, an estimated 500,000 new cases of VL and 1.5 million cases of CL occur annually. World Health Organization statistics indicate that leishmaniasis infects 12 million people, but more than 350 million people in 88 countries, primarily tropical and sub-tropical, are at risk.  In the United States, the disease occasionally occurs in states bordering Mexico and among travelers to Latin America and soldiers returning from the Middle East. Like female mosquitoes, female sand flies need blood meals for protein to develop their eggs. A single bite of an infected female sand fly can discharge as many as 1000 Leishmania parasites into the human bloodstream. The sand fly usually becomes infected after feeding on an infected dog or other domestic animal. The grant, “The Role of Sand Fly Saliva in Visceralization of Leishmania Parasites,” runs through March 2010. The findings could be a step toward the development of a human vaccine. Earlier studies, including those by Lanzaro, showed that certain substances in the sand fly saliva enhance and exacerbate the development of the parasites. “These findings have had a profound effect on our understanding of the relationship between insect vectors, the parasites they transmit and the diseases they cause,” he said.

Salivary proteins affect the blood flow and modulate the immune response of the host.  Of special interest is the salivary protein, maxidilan, which suppresses white blood cells that destroy the invading parasites.  

Lanzaro and his research team are targeting  Leishmania chagasi, a New World parasite that causes VL in the Americas.  “The parasite is known to cause only visceral leishmaniasis in South America,” he said. “However, in Central America, the identical parasite, transmitted by the same vector species, causes a benign atypical cutaneous disease.”

 The federally funded grant has three aims:

• Analyze the pathology of L. chagasi in hamsters infected via the bites of sand flies from Costa Rican and Brazilian strains
• Determine if immunization with a salivary gland extract or a synthetic maxadilan will protect hamsters from developing visceral disease
• Evaluate the immune functions of maxadilan variants found in natural populations of sand flies (Lutzomyia longipalpis) from Brazil and Costa Rica.  

Co-principal investigator is Lynn Soong, an associate professor, Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, who will be involved in tissue evaluation.

Stephen Barthold, director of the Center for Comparative Medicine, UC Davis School of Veterinary Medicine and a veterinary pathologist with 35 years of experience in experimental pathology of  infectious diseases, is a collaborator. Others working on the grant include Peter Melby of the University of Texas Health Sciences Center; assistant specialist Claudio Meneses and graduate students Melody Malpass and Heather Malka, all of the Lanzaro Lab; and associate researcher Emir Hodzic, Center for Comparative Medicine.

Lanzaro said the disease can cause large-scale epidemics with high fatality rates. More than 90 percent of the world's cases of VL are in India, Bangladesh, Nepal, Sudan and Brazil. VL is endemic in 66 countries and is found in some parts of 88 countries within Central America, South America, Africa, India, the Middle East, Asia, southern Europe and the Mediterranean.

The Leishmania parasite incubates for weeks to months in the host before the disease becomes clinically apparent. Symptoms of VL include bouts of fever, hemorrhaging, weight loss, swollen glands, anemia and darkening of the skin. 

Leishmaniasis usually is more common in rural areas, Lanzaro said, but it is found in the outskirts of some cities. The risk for leishmaniasis is highest from dusk to dawn, when sand flies are the most active. At increased risk are military, adventure travelers, Peace Corps volunteers, missionaries, ornithologists and researchers who work outdoors at night.

How to Decrease the Risk of Getting Leishmaniasis

Vaccines and drugs for preventing leishmaniasis, a parasitic disease spread by the bite of infected sand flies, are not yet available, so it’s important to “know the enemy” and take precautions, says UC Davis medical entomologist Gregory Lanzaro.

Sand flies are about one-third the size of mosquitoes. They are difficult to see and make no noise when they fly. The insects become infected by biting an infected dog, rodent or person.

Cutaneous leishmaniasis (CL), characterized by skin lesions resulting in permanent scarring, is found in parts of 88 countries, including the United States (in southern rural Texas). Ninety-percent of the global cases of visceral leismaniasis (VL), which attacks the organs, are in India, Bangladesh, Nepal, Sudan and Brazil. The settings range from rain forests to deserts. Leishmaniasis is not found in Australia or Oceana (islands in The Pacific that include Melanesia, Micronesia and Polynesia). 

Symptoms of CL (skin sores) usually appear within a few weeks after the sand fly bite. With VL, people usually become sick within several months of being bitten.

To decrease the risk of being bitten by sand flies: 

• Stay in well-screened areas as much as possible or use a bed net soaked with permethrin. Use a fine-mesh netting (at least 18 holes to the inch) to guard against  sand flies
• Avoid outdoor activities, especially from dusk to dawn, when sand flies are the most active.
• Wear long-sleeved shirts, long pants and socks. Tuck your shirt into your pants.
• Apply insect repellent on uncovered skin and under the ends of sleeves and pant legs. The most effective repellents are those that contain the chemical DEET.
• Spray clothing with permethrin-containing insecticides. The insecticide should be reapplied after every five washings.
• Spray living and sleeping areas with an insecticide to kill insects. Bed nets, repellents containing DEET and permethrin should be purchased before traveling. They can be found in hardware, camping and military surplus stores

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Media contact:

Kathy Keatley Garvey, UC Statewide Mosquito Research Program, (530) 754-6894

This press release was originally distributed June 14, 2006 by the UC Statewide Mosquito Research Program.