Valenzuela Creates Test that Could Detect Exposure of Disease-Causing Insects
Diagnostic tests might one day show whether a person was bitten by a sand fly or a tick, and help determine increased risk of the disease transmitted by these vectors, said Dr. Jesus Valenzuela.
“The test uses recombinant salivary protein of insects to measure insect exposure,” said Valenzuela, a senior investigator in the vector molecular biology section of the National Institute of Allergy and Infectious Diseases (NIAID).
When an insect bites a person, proteins in its saliva interact with the host’s initial immune response to help pathogens evade the host’s disease defenses. These salivary proteins also induce an antibody response and therefore can be used for biomarkers.
“We know we mount antibodies against insect bites or to the components that insects inject when they bite us,” he explained. “We just need to identify what salivary proteins we have antibodies to.” Valenzuela came up with the idea more than two decades ago. However, the technology to turn the idea into a reality didn’t exist. Advances have brought the concept he envisions closer to fruition. Eventually, he believes these test kits will be available for clinical or home use.
Dr. Shaden Kamhawi and Dr. Eva Iniguez, both members of his lab, recently deployed this technology for elimination campaigns of leishmaniasis in India. Leishmaniasis is a parasitic disease found in parts of the tropics, subtropics and southern Europe. It’s caused by infection with Leishmania parasites, which are spread by the bite of sand flies.
There are several forms of leishmaniasis. The most common forms are cutaneous leishmaniasis, which causes skin sores, and visceral leishmaniasis, which affects several internal organs. Left untreated, visceral leishmaniasis is almost always fatal.
The test identifies where people are being exposed to sand fly bites. Researchers use this data to decide where to deploy insecticides and then test whether they were effective in controlling sand flies and consequently leishmaniasis.
“We take blood from individuals before and after insecticide treatment in the area and use a recombinant protein from insect saliva to see if antibodies recognize that molecule,” Valenzuela said. “This directly measures whether a sand fly has bitten a person.”
If fewer people have antibodies against sand flies, the treatment is effective. This is different than the current procedure they use in the field. Right now, researchers put out traps to collect insects before and after an insecticide treatment. The standard procedure does not measure the contact between the person and the insect.
Valenzuela has turned his attention to developing a test to detect the exposure in humans to the tick Ixodes scapulairs, the vector of Borrelia burgdorferi that causes Lyme disease, using the same approach. Lyme disease is the most common vector-borne disease in the United States. It’s transmitted by the blacklegged tick, also known as the deer tick. Common symptoms include fever, headache, fatigue and a bulls-eye skin rash called erythema migrans. The disease can spread to joints, the heart and the nervous system if left untreated.
“We want to know more about how many people are exposed to the tick that transmits Lyme disease,” he said. Right now, they are working on identifying the molecules that most accurately predict whether a person has been bitten by this tick.
His lab and Dr. Lucas Tirloni’s lab in NIAID’s Rocky Mountain Laboratories are working with a pharmaceutical company to develop the test. The company has produced a Lyme disease vaccine; Valenzuela’s and Tirloni’s diagnostic tool will help to determine where people are most bitten by ticks and initially administer the vaccine candidate to that population.
In the future, the tests could also alert the public to Lyme disease hotspots and the risk of contracting Lyme from a tick bite.
His lab and Tirloni’s lab also are working to develop a test to measure exposure to the brown dog tick Rhipicephalus sanguineous, which transmits Rickettsia rickettsii in Arizona and Northern Mexico. This bacteria is responsible for Rocky Mountain Spotted Fever, a potentially fatal disease.
In addition to developing test kits for insect bites, Valenzuela’s lab has also produced two potential vaccines against leishmaniasis. It took years of research to identify the right candidate.
“We demonstrated that specific sand fly saliva proteins can induce an immune response that’s protective against leishmaniasis,” he said.
Valenzuela first came to NIH after he graduated from the University of Arizona with a Ph.D in biochemistry. In 2009, he became a senior investigator in NIAID’s Laboratory of Malaria and Vector Research. When he arrived at NIH, there were almost no Latinos. During his time here, he’s seen an increase in diversity, something he appreciates.
“The environment here is very supportive,” he concluded. “There are a lot of smart people who can answer your questions and you can collaborate with. It’s very conducive to great science.”