Tuberculosis (TB) is a leading cause of infectious disease deaths, claiming over 1 million lives every year. It spreads through the air when an infected person coughs, sneezes, or exhales, and drug-resistant strains and asymptomatic spreading are growing concerns. Curbing TB transmission is an urgent public health challenge, yet scientists still don’t understand how airflow and other environmental factors influence that spread.
One problem is that studies of infectious disease transmission have focused mainly on population-level assessments or individual immune responses. But understanding how airflow and mixing influence transmission in indoor spaces requires expertise in fluid physics and computational modeling.
An interdisciplinary team including researchers at MIT and the University of Texas Southwestern Medical Center has now combined animal transmission experiments with quantitative particle tracking and flow modeling to understand how some lab-based environments can promote the spread of respiratory infectious diseases such as TB, while others mitigate that spread.
A key factor in predicting infectious transmission was not just the total ventilation rate but, more importantly, the local pattern of airflow driven by the design — such as air leakage, inflow and outflow locations, and forces created by an infected individual.
“The local airflow patterns turn out to be pivotal,” says Lydia Bourouiba, the Japan Steel Industry Chair Professor at MIT and faculty lead of the Fluid Dynamics of Disease Transmission Laboratory, part of the Fluids and Health Network within the Institute for Medical Engineering and Science (IMES). “Our team’s findings provide some of the clearest evidence I’m aware of showing the importance of accounting for [airflow] inhomogeneity and its effects when designing for airflow detailed patterns. This insight is critical when building or retrofitting an indoor space to mitigate airborne transmission, or when designing an airborne transmission study.”
The research is an important step toward connecting laboratory infectious disease studies with how people spread such diseases in the real world. The team hopes their insights can extend beyond their model system and show the importance of flow physics in building designs to prevent the spread of airborne diseases indoors.
“Despite recent pandemics and epidemics, there is still resistance to incorporating airflow in routine infectious disease prevention tools,” Bourouiba says. “Infrastructure could be retrofitted at relatively low cost, but the paucity and difficulty of gathering direct evidence prevents broader adoption of flow physics as a tool for indoor health. This study helps provide such evidence.”
Joining Bourouiba on a paper about the work are Yash Kulkarni, a postdoc at IMES, who led the fluid and aerosol physics components; Kubra Naqvi, lead author and a postdoc at UT Southwestern; Michael Shiloh, a professor at UT Southwestern, who led the multiyear effort to reestablish a classic tuberculosis transmission model; Hui Ouyang, an assistant professor of aerosol engineering at UT Dallas; Yuhui Guo, Deepak Sapkota, and Arabella Martin, all UT Southwestern PhD students; Pei Lu and Victoria Ektnitphong, research associates at UT Southwestern; Shibo Wang, a University of Minnesota researcher; Beatriz Dias, a UT Southwestern instructor; Bret Evers, an associate professor at UT Southwestern; and Lenette Lu, assistant professor at UT Southwestern.
Opening the black box
When people exhale, talk, cough, or sneeze, tiny microdroplets and bioaerosols launch from their mouths, carried forward by a cloud. If infected by a respiratory disease, these bioaerosols can contain pathogens that can infect others. Disease transmission depends on pathogen survival in the air, which is influenced by temperature, humidity, and ventilation.
In 1882, German physician and microbiologist Robert Koch first established an animal model for the study of tuberculosis pathogenesis. Decades later, researchers demonstrated airborne transmission of tuberculosis between people and animals.
These early experiments have proven difficult to replicate in today’s modern, biosafety-grade facilities. This new study reveals the difficulty comes from stringent containment and ventilation requirements, which can dramatically influence airflow in experiments.
“Host-to-host transmission is an obligatory evolutionary phase of respiratory pathogens, yet it has been considered too intractable or complex to be amenable to systematic investigation, hence is commonly relegated to a black box. Our work opens that black box,” says Bourouiba, who is professor in MIT’s departments of Mechanical and Civil and Environmental Engineering, and an IMES core faculty member.
To quantify how local airflow patterns impact infectious disease transmission, the researchers redesigned and modelled the early studies for modern high-containment lab facilities — including their seal, inflow, outflow, and exhaust pathways — and quantified particle and bacteria-laden particle release and dispersal. They released tracer particles and bacteria into a compartment and modelled recovery from air sampled on the other side under differing airflow rates, designs, and leak configurations.
The MIT team carried out computations, benchmarked against particle release experiments. The results revealed how important seemingly small details such as leakage paths could be.
“Even a small leak could short-circuit the airflow by drawing fresh air directly toward the exhaust, rather than drawing contaminated air across the containment chambers,” says Kulkarni.
Advancing TB research
To date, uneven indoor airflow patterns have not been fully harnessed as part of a risk mitigation strategy.
“By systematically defining how airflow and design influence biological exposure, we were ultimately able to restore transmission and create a system that can now be used to ask fundamental questions about the bacterial, host, and environmental factors that determine tuberculosis spread,” says Naqvi.
“I began working to reestablish this seminal TB animal transmission model nearly 10 years ago, and it proved far more challenging than I anticipated,” says Shiloh. “I hope this work serves as a reminder that meaningful scientific advances often require patience and perseverance.”
“This work illustrates how crucial it is to support synergistic collaborations integrating complementary disciplines to tackle research bottlenecks — and to standardize reporting norms across laboratories,” Bourouiba says. “If different labs have varying airflow patterns from uncontrolled leaks or seal details, that physical variability can overwhelm the biological signals researchers seek. Beyond its foundational impact for TB transmission studies, our work shows that opening the black box of transmission provides mechanistic insights: Detailed airflow pattern control can enhance or mitigate airborne transmission — making it exploitable as a prevention measure in crowded gathering spaces.”
This work was supported, in part, by the National Institutes of Health, the National Science Foundation, the Burroughs Wellcome Fund, MathWorks, and the Translational Research Institute for Space Health.