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Johns Hopkins Bloomberg School of Public Health (JHSPH) research articles from Innovation Toronto
Boosting natural ability of mosquito to fight disease could reduce spread of infection
Researchers from the Johns Hopkins Bloomberg School of Public Health have genetically modified mosquitoes to resist infection from dengue virus, a virus that sickens an estimated 96 million people globally each year and kills more than 20,000, mostly children.
The research, published Jan. 12 in PLOS Neglected Tropical Diseases, shows it is possible, in the lab, to boost the Aedes aegypti mosquito’s natural ability to fight the dengue virus as a first step toward suppressing its ability to spread the disease. The findings could be a prelude to developing a strategy to eliminate the threat of dengue. Forty percent of the world’s population live in areas where they are at risk of the virus, which is most common in Southeast Asia and the western Pacific islands and has been rapidly increasing in Latin America and the Caribbean.
“If you can replace a natural population of dengue-transmitting mosquitoes with genetically modified ones that are resistant to virus, you can stop disease transmission,” says study leader George Dimopoulos, PhD, a professor in the Department of Molecular Microbiology and Immunology and a member of the Johns Hopkins Malaria Research Institute. “This is a first step toward that goal.”
While the new mosquitoes significantly suppressed dengue virus infection they did not show any resistance to Zika or chikungunya, two other viruses carried by Aedes aegypti. “This finding, although disappointing, teaches us something about the mosquito’s immune system and how it deals with different viruses. It will guide us on how to make mosquitoes resistant to multiple types of viruses” he says. While being resistant to one disease is a good start, “ideally, you want a mosquito that is resistant to other viruses as well,” he says.
Mosquitoes acquire viruses by feeding on the blood of humans who are sickened with them. Once the mosquitoes are infected, they bite other healthy humans and pass the disease along to them. Many efforts are underway to figure out how to break that cycle, and most scientists agree that the use of multiple methods will be required to eliminate dengue and other mosquito-borne diseases.
Researchers say that Aedes aegypti mosquitoes do mount an immune system response when exposed to the dengue virus, but it appears to be too weak to stop transmission. Knowing this, Dimopoulos and his colleagues were able to manipulate a component of the immune system, the JAK-STAT pathway, that regulates production of antiviral factors. They did this in a part of the mosquito known as the fat body, its version of the liver. Notably, the JAK-STAT pathway is involved in antiviral activity in humans as well.
The genetic modification resulted in fewer mosquitoes becoming infected, and most of those that did had very low levels of dengue virus in their salivary glands, the location from which it gets transmitted to humans. These experiments, however, didn’t lower the level of virus in all mosquitoes to zero, something that puzzled the scientists. They say more research is needed to understand whether this level of virus suppression would be enough to halt disease transmission, and they are working on other experiments to see if they can produce antiviral factors in the gut, which could assist in inducing a stronger immune response and possibly confer resistance to the other viruses.
The researchers found that the dengue-resistant mosquitoes live as long as the wild mosquitoes, though they do produce fewer eggs, most likely because the same mechanism involved in dialing up the immune system to fight dengue also plays a role in egg production.
“It’s likely if we turn this on in the gut we could have a much stronger effect, without compromising egg production,” Dimopoulos says.
Once genetically modified mosquitoes resistant to dengue are developed, scientists would test them in large field cages to see how they compete with wild mosquitoes in very controlled experiments.
The best way to ensure that the genetically modified mosquitoes become the dominant type is for researchers to add something known as a “gene drive” to the new mosquitoes. This essentially makes them genetically superior mosquitoes by ensuring that all offspring of wild- type and genetically modified mosquitoes will be disease resistant.
“In this way, you could convert a disease-transmitting mosquito population to one that does not transmit disease,” Dimopoulos says.
Scientists acknowledge there are concerns with the release of genetically modified mosquitoes in the environment since they can’t be recaptured. They are there to stay.
“This is why extensive lab and semi-field studies are required to get it right,” he says. If the scientists can get this to work, however, it could become a very effective way of controlling disease. It could be done without people having to actively participate. They would get long-lasting protection without having to take medication, get vaccinated or use bed nets or repellants.
Dimopoulos and other researchers are working on similar models in Anopheles mosquitoes which carry the parasite that causes malaria.
The entire process of developing and introducing disease-resistant mosquitoes into the wild could take a decade or more.
ACROSS 94 COUNTRIES, BENEFITS FAR EXCEED THE COSTS, RESEARCHERS FIND
Vaccinations, long recognized as an excellent investment that saves lives and prevents illness, could have significant economic value that far exceeds their original cost, a new study from researchers at the Johns Hopkins Bloomberg School of Public Health has found.
In what is believed to be among the first studies to examine the potential return on investment of vaccinations, the researchers assessed the economic benefits of vaccines in 94 low- and middle-income countries using projected vaccination rates from 2011 to 2020. When looking only at costs associated with illness, such as treatment costs and productivity losses, the return was $16 for every dollar spent on vaccines. In a separate analysis taking into account the broader economic impact of illness, vaccinations save $44 for every dollar spent.
The study appears in the February issue of Health Affairs.
“Vaccines are an excellent investment,” says lead author Sachiko Ozawa, PhD, MHS, an assistant scientist in the Department of International Health at the Bloomberg School. “But to reap the potential economic rewards, governments and donors must continue their investments in expanding access to vaccines.”
Without vaccination, millions of children would die from preventable illnesses and diseases across the decade. While billions of dollars will be spent to try and vaccinate more children, the goal of full coverage — that is, getting every child vaccinated — has not yet been met.
To measure the potential investment returns, researchers used two approaches. The first, known as the “cost-of-illness” approach, measures averted treatment costs, transportation costs, lost caretaker wages and productivity losses. The second, known as the “full-income approach,” estimates the broader economic and social benefits of vaccination and quantifies the value that people place on living longer and healthier lives. With both approaches, the costs of immunization programs were separately modeled to include supply chain, service delivery and vaccine costs.
Between 2011 and 2020, the estimated total cost of immunization programs in the 94 countries studied was $34 billion. Through these programs, an estimated $586 billion would be averted in cost of illness associated with vaccine-preventable diseases. Using the full-income approach, the benefit was estimated at $1.53 trillion dollars.
The study assessed 10 vaccine-preventable infections: Haemophilus influenzae type b, hepatitis B, human papillomavirus, Japanese encephalitis, measles, Neisseria meningitis serogroup A, rotavirus, rubella, Streptococcus pneumoniae and yellow fever.
“Our findings should encourage donors and governments to continue their financial investments in immunization programs. But we must keep in mind that these are estimates that assume immunization coverage continues to expand and improve,” Ozawa says.