With insect-borne viral diseases like Zika, dengue, and Oropouche fever, some insects are better than others at spreading the virus—and it’s important to know which. In a new study, Yale researchers conclude that Oropouche fever is spread chiefly by biting insects called midges, while mosquitoes are unlikely to play much of a role.
“There are a series of barriers that you, as a virus, have to get past to get into a mosquito and to be transmitted by a mosquito, and one very big barrier is that you have to get through the midgut or stomach lining,” said lead author Dr. Colin J. Carlson, PhD, an assistant professor of epidemiology (microbial diseases) at the Yale School of Public Health. “We are reasonably confident that this thing is not getting through the midgut of mosquitoes.”
Carlson studies disease emergence through the lenses of climate change, ecosystems, and biodiversity loss. He is co-founder and executive director of Verena, a collaborative effort among scientists to identify viruses that threaten human health.
A mysterious insect-borne virus
Not much is known about Oropouche virus. Discovered in the 1950s and endemic to South America and the Caribbean, it causes an illness typically featuring fever, headache, and joint pain, usually in small, non-lethal outbreaks. Oropouche fever has received little research attention compared to better-known tropical diseases. Public health authorities have long thought it is spread by midges, but they weren’t sure whether mosquitoes were involved too, as the virus has occasionally been found in mosquitoes.
Our study points very clearly to a need to study these neglected vectors, and this neglected virus, in much greater depth.
Dr. Colin J. Carlson, Yale School of Public Health
Last year, amid a massive epidemic in Central and South America, it became urgent to clarify which insects spread Oropouche. The 2024 outbreak involves a new strain of the virus which has done unprecedented things, including showing up in Cuba for the first time and causing the first known Oropouche deaths. The new strain has also been linked to miscarriage, fetal deaths, and microcephalymiscarriage, fetal deaths, and microcephaly.
Pressing questions arose: Is Oropouche now evading people’s immunity? Might climate change, urbanization, migration, or deforestation be pushing the virus into new territory? Could it reach the United States? Has the virus jumped from midges into mosquitoes?
Carlson and his colleagues combed the research literature for experimental studies testing the ability of various mosquito and midge species to contract Oropouche virus and pass it to other animals or humans—an ability called vector competence. They found only seven studies, all published between 1961 and 2021.
Each study involved collecting mosquitoes and midges, then allowing those insects to feed on Oropouche-infected animals or blood and checking for transmission. In some cases, the insects were injected with Oropouche virus. Then the researchers looked for the virus in the insects’ saliva and tested their ability to spread the virus to other animals during a bite and blood meal.
Based on those experiments, two midge species were clearly competent Oropouche vectors: Culicoides paraensis and C. sonorensis.
Mosquitoes, by contrast, were neither especially susceptible to the virus nor very good at spreading it. Aedes mosquitoes, efficient transmitters of dengue and yellow fever, and Culex mosquitoes, which transmit West Nile, rarely “caught” Oropouche or passed it on.
Carlson’s team concluded that the mosquitoes that transmit dengue and Zika are very unlikely to transmit Oropouche virus and are probably not driving the current epidemic. One caveat: all of the studies predated the 2024 epidemic, and recent strains might interact with insects differently.
Midges' murky role
What might all this mean in terms of Oropouche risk in the United States? Carlson said more experiments and fieldwork are necessary to get a handle on the current outbreak—and on the public health threat Oropouche may pose in future.
That includes basic scientific research on midges. Compared to mosquitoes and ticks, the 1300 known midge species are vastly understudied. Few field studies even look for their presence. Only this spring, a Culicoides midge species was reported in Cuba for the first time.
“We have very limited information on where [midges] are present, how common they are in cities versus rural areas, and how climate and climate change influence their ability to transmit the virus,” Carlson said. “Our study therefore points very clearly to a need to study these neglected vectors, and this neglected virus, in much greater depth.”
The study appeared in PLOS Neglected Tropical Diseases. The authors, including Emily N. Gallichotte and Gregory D. Ebel, both affiliated with Colorado State University, were supported by funding to Verena from the National Science Foundation.