Photo by Harold Ruiz/PAHO-WHO
When Zika virus was suspected of causing birth defects such
as microcephaly, Fogarty-supported scientists who had been
working on Chagas disease and dengue shifted gears.
By Karin Zeitvogel
As more and more babies in Brazil were born with microcephaly in 2015, Fogarty-supported scientists rapidly changed gears on work they'd been doing for years on Chagas disease and dengue, and shifted their focus to the Zika virus, which was suspected of causing the spate of birth defects. By the time researchers had confirmed the link between Zika and microcephaly in infants, scientists in Brazil who had been trained with Fogarty support were using the resources in place for Chagas disease brain research to better understand Zika, and collaborating with other groups to advance knowledge of the disease, said Dr. Jamary Oliveira-Filho of Brazil's Federal University of Bahia. Meanwhile, in Mexico, two Fogarty-supported Ph.D. candidates who were researching different aspects of preventing and controlling dengue - transmitted by the same Aedes aegypti mosquito as Zika - refocused their work on Zika.
Chagas studies inform Zika research
Both Chagas and Zika can cause brain atrophy, which adds to the burden of cognitive defects, including those associated with Alzheimer's and vascular dementia, which affect people in both developed and developing countries. A Fogarty-supported study co-led by Oliveira had already identified that brain involvement, including stroke, can occur in Chagas patients independently of the cardiac disease the chronic illness is most often associated with. Brazilian and American researchers are working together to identify the mechanism that causes stroke, and testing prophylaxis with aspirin in patients identified via a transcranial Doppler scan as being at high risk for stroke. NIH and local agencies helped Brazil to acquire advanced neuroimaging and other equipment to study Chagas and other diseases, and this infrastructure has been put to work to try to better understand Zika.
"We know brain volume is decreased in Chagas because of chronic inflammation, so we're investigating whether part of the damage we see in Zika is also mediated by brain inflammation," said Oliveira. "In Chagas, we think this is primarily due to the activation of the immune system, but in Zika we're early in the research process and we don't know how much of the problem is due to the direct effect of the Zika virus in the brain and how much is due to activation of the immune system."
Recent studies conducted in the United States that have found that babies aren't the only ones affected by Zika, underscore the urgency. One study, published in Cell, found that exposing adult mice to the Zika virus can cause their neural stem cells to become infected, leading to cell death and reduced proliferation. Another study, funded in part by the National Institute of Allergy and Infectious Diseases (NIAID), found that Zika can persist for weeks in the central nervous system and other tissue in infected people, indicating that there may be "more extensive neurologic and lymphoid disease than currently appreciated."
"These studies, like ours, are trying to identify the mechanisms for brain damage in both diseases so that we can target effective treatments and preventive actions," Oliveira said. "Once the mechanism has been identified, we can try to draw conclusions on which treatments would be best to avoid the impairments we're detecting in patients. But to get to that point, we need to do the kind of research that Fogarty and the NIH have made possible."
Dengue, insecticide resistance studies refocused on Zika
In Mexico, Fogarty-supported researchers have "for years worked with different types of intervention strategies to reduce the amount of transmission of dengue, specifically in people's homes," said Dr. Bill Black, a professor of vector biology and parasitology at Colorado State University (CSU) and the principal investigator on a Fogarty training grant in dengue prevention and control. "Since we were already down in Tapachula in southwestern Mexico working on a project on insecticide resistance when the Zika outbreak began," said Black, "It was natural that the trainees should switch their projects to focus on the new threat."
One of CSU's Fogarty-supported trainees, Ph.D. candidate Farah Vera-Maloof, found a sharp increase in recent years of mutations in a gene in mosquitoes, which make an insecticide ineffective. Mosquitoes have built up strong resistance to the pyrethroid family of insecticides, which is the main tool in the Mexican government's arsenal against Aedes aegypti.
Another Fogarty-supported CSU Ph.D. candidate, Selene Garcia-Luna, found that Aedes aegypti is highly efficient at transmitting Zika throughout Mexico, while the other mosquito that carries the virus, Albopictus, is not. Aedes aegypti is also the main vector for Zika in Brazil and in parts of the U.S. - Texas and southern Florida - where local, mosquito-borne transmission of the virus was reported in 2016. Insecticide spraying campaigns were less effective than hoped, according to the CDC, possibly because vectors have developed resistance.
CSU's research points to a simple solution. "The gene mutations have a negative fitness associated with them, so in the absence of an insecticide, they decline in frequency very rapidly," said Black. "So our proposal is to rotate insecticides. The idea behind rotation is, if you switch to an alternative insecticide when you see the one you use is approaching a mutation frequency of 100 percent, and then come back to the usual insecticide a couple of years later, you're likely to find that the mosquitoes are more susceptible to it."
The findings are clearly important to the authorities anywhere that there are Aedes aegypti mosquitoes, including parts of the U.S. "In the southeastern states, mosquitoes are a way of life," said Black. "It's a subtropical area of the U.S. and people there wouldn't have much defense against Zika - and a number of other diseases, including dengue and yellow fever - if insecticides become ineffective and we lose funding for control programs."