Meeting Malaria Where It Lives

Inside Yale’s Laboratory of Epidemiology and Public Health, Dr. Amy Bei unlocks a secure door with mesh curtains behind it. She zips open the curtains and steps into a short hallway where she changes from one white lab coat into another. Through another set of curtains, she enters the ‘mosquito room’. The small insectary resonates with a soft hum as hundreds of mosquitoes swarm in mesh cubes along one wall, waiting for their next meal. At a workstation along another wall, yellow electric bug zappers sit next to electric mosquito traps — extra security should any of the insects escape.

Dr. Bei, PhD, an associate professor of epidemiology (microbial diseases) at the Yale School of Public Health (YSPH), blows into a circular mesh opening on the side of a plastic cube, trying to excite the hundreds of young mosquitoes inside. She points out the drops of blood at the bottom of the enclosure: proof that they are being fed, and it came out the other end.

“Anopheles are notoriously picky; you have to baby them a little bit to get them to take their blood meal,” said Dr. Bei with a knowing smile. She has raised this particular family of mosquitoes for four years, and many more before them. An enclosed incubator chamber in the corner stores more cubes. These are the bug dorms, and the mosquitoes inside them carry the malaria parasite.

As she moves among the cubes, it’s easy to forget that these tiny insects are the deadliest animals on Earth. Each year, the malaria they transmit kills more than half a million people, most of them children under five. After decades of progress, the decline in cases has stalled. “Malaria is a really wily foe,” said Dr. Bei.

To combat it, Dr. Bei is betting on a radical idea. She is testing a new kind of vaccine that stops mosquitoes from transmitting malaria. “It basically becomes a dead end for that infected mosquito,” Dr. Bei explained, “It can no longer transmit malaria to the population.” The vaccines are designed not for the individual, but for the communities in which they live, a new frontier in community-based research.

Her lab works on many different types of malaria vaccines, including those that prevent disease in the human blood stages. This type of vaccine is a transmission blocking vaccine (TBV) where antibodies are generated in the vaccinated human and these block infection in the mosquito (thus preventing mosquito infection and downstream transmission and spread).

The method sounds counterintuitive, and explaining it has become part of Dr. Bei’s job. Transmission-blocking vaccines work very differently from traditional vaccines. “You're still going to get malaria,” Dr. Bei explains, “but the difference is, if you're successfully vaccinated, it'll prevent that transmission to the mosquito and through the population. So ultimately, in the long term, it is protecting you, but it's also protecting your children, and it's protecting your neighbors, and so it's really like an altruistic vaccine."

Dr. Bei's path to malaria began when she was a Harvard student, spending summers as a research assistant in the tropical disease research unit at the University of California, San Francisco. It was her first lab experience, and it changed everything. "This is the kind of work that I want to do," she remembered thinking. "This is the perfect combination for me of scientific interest with my outside-of-science interests."

The lab was a microcosm of the diseases it studied: a multicultural community where everyone came from a different country and spoke a different language. Dr. Bei found herself studying parasites she had never heard of growing up in California, despite them affecting a huge percentage of the world's population. That early exposure led her to a Fulbright fellowship for malaria research in Tanzania after college, and then to Senegal as a Harvard PhD student and later post-doctoral fellow, where she's been working ever since.

Dr. Bei's commitment to Senegal runs deeper than research. She divides her time between Yale and Senegal. Her husband, Sidiya Mbodj, is Senegalese, and they met in 2006 while both were working in the Laboratory of Bacteriology and Virology in Senegal. Two of their three daughters were born there. The family travels together between continents, and Dr. Bei's students often become part of her extended family. "We talk about work every day... sometimes the girls jump into the conversation and ask questions," Mbodj said. When students travel with them for research, "they all know my house, they know my mom's cooking.”

What kept Dr. Bei hooked on malaria wasn’t only the global reach of the disease, but the creature itself. Plasmodium falciparum causes malaria after being transmitted to humans through bites from the Anopheles mosquito. The parasite does not have one definitive structure; instead, it passes through at least five distinct stages as it moves between humans and mosquitoes, transforming shape and function each time. “It has evolved with us,” Dr. Bei said, "These are parasites with all these crazy ways of escaping everything that your body would try and do to control them."

Malaria researchers try to attack the parasite at these different stages, but the parasite can alter its form and its proteins so rapidly that each stage requires a different strategy to target it. That challenge became irresistible to Bei. She has worked on blood-stage vaccine targets since 2005 and in 2018, she began working with transmission-blocking vaccines.

Dr. Albert Ko, MD, Dr. Bei's former department chair at YSPH, recruited her from her post-doc position in 2018 after an hours-long phone call while Dr. Ko was in Geneva, and Dr. Bei, in Dakar. Ko’s interest in recruiting Dr. Bei went beyond her research credentials. For one, Dr. Bei speaks eight languages fluently — English, French, Portuguese, Italian, Amharic, Spanish, Swahili, and Wolof. But it was her motivation that stood out most. "The best parts of Amy have stayed the same," Dr. Ko said. "She's still earnest, sincere. She's the first person to think of others before she thinks of herself."

When they’re in Senegal, Dr. Bei and her students drive up to 11 hours from Dakar to reach the remote region of Kédougou. There, they collect blood samples from patients who have had malaria. Each vial of blood contains both parasites and the antibodies that try to fight them. Dr. Bei’s team brings the blood back to their Kédougou research station: a rented multi-story apartment building, which they’ve converted to have a lab on the first floor, and sleeping quarters on top.

Throughout these weeks in the field, the work is nonstop. Experiments are monitored day and night as the parasites follow their own unpredictable life cycles. Students take overnight shifts to harvest samples at just the right moment. “When they’re ready, you’ve got to go,” Dr. Bei said.

In the summer heat, the building’s limited power forces hard choices. The team often turns off the air conditioning to run their equipment, sleeping instead in the hallways under mosquito tents.

“When you’re doing these beautiful, well-controlled experiments in the lab, you lose a lot of that complexity,” said Dr. Bei, referring to the constantly evolving genetics of humans, mosquitoes, and parasites, “I think this whole approach that we’re doing, this ex vivo testing, right there in the field, using antibodies from vaccines, is really exciting. For us, it feels like a real breakthrough, not only because of the data we’re generating but also because of the teamwork among the students, the speed of the data, and the partnerships with the communities.”

Dr. Bei has supervised over 35 students and trainees, from high-schoolers to PhD-level researchers and fellows, in her two labs at Yale and at the University of Cheikh Anta Diop and Institut Pasteur de Dakar, in Senegal. Her real-world approach resonates with them. Awa Cisse is a Senegalese Yale student who chose to focus on the transmission-blocking vaccines. “My advisor knew I was interested in infectious disease, so he said, ‘You need to meet Dr. Bei.’ It was incredible to find someone working directly with populations from Senegal who also speaks Wolof and understands the culture,” said Cisse.

Dr. Bei believes that malaria science must live where malaria lives. She envisions a future where the Senegalese field lab operates year-round without hauling equipment back and forth and where students on both continents move fluidly between sites.

Her enthusiasm for her work shows most clearly in moments others might find tedious. "My team always teases me because I love to just sit and watch the data coming in," she said with a laugh. "I'll just sit there and watch it, and they're like, aren't you tired? And I'm like, no, this is so exciting."

The vaccine work is moving steadily from theory to practice. In global partnerships, Dr. Bei and other labs are exploring whether combining transmission-blocking vaccines with traditional pre-erythrocytic or blood-stage vaccines can deliver a “win-win,” as Dr. Bei calls it: protecting individuals and curbing transmission simultaneously.

It's her excitement, sustained over two decades, across two continents, through countless overnight shifts and equipment failures, that keeps Dr. Bei flying between Senegal and Yale each year.

In the next five years, data from clinical trials should reveal whether next-generation vaccines, including transmission-blocking vaccines, can finally turn the tide against malaria. Until then, Dr. Bei will keep watching the data come in, one plate at a time, convinced that the answer lies not just in the lab, but in the communities where malaria lives.