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In a groundbreaking new study, a team of researchers from ÃÛÌÒÓ°Ïñ — led by associate professor Saikat Basu — determined the critical exposure durations for inhaled transmission of pox viruses, including smallpox and mpox, and may have provided key insights into a medical mystery. 

In summer 1978, Janet Parker fell ill and began developing red spore-like rashes on her arms, back and face. Initially, the doctors believed Parker had chicken pox. But Parker's mother had her doubts. Janet had chicken pox as a child, and these spots were much different and far more unsightly.

Roughly a month after falling ill, Parker passed away in Birmingham, England. She  became the last person to die from .

Saikat Basu, associate professor in ÃÛÌÒÓ°Ïñ's Jerome J. Lohr College of Engineering, was browsing through the shelves of books at the Brookings Public Library when he came across Parker's story. He was in the early stages of a research project surrounding the transmission of mpox virus, a closely related virus from the same family as smallpox, and was interested in learning how Parker caught a disease that was thought to be largely eradicated in the developed world.

In the 1970s, Parker worked as a medical photographer at the University of Birmingham's Medical School. The university housed a smallpox research laboratory, led by professor Henry Bedson, in its large medical facility. Initially, investigators assumed that Parker must have visited the lab and contracted the disease. However, access to the lab was heavily restricted, and Parker was never known to have entered.

During the investigation into Parker's death, it was revealed the live smallpox virus was handled in violation of safety protocol. Officials determined this mishandling may have allowed particles carrying the virus to slip into the airstream and up into the telephone room above, through air ducts in the ceiling. Parker visited this room often and a 1980 government report proposed this as the likely route of infection. However, parts of the scientific community objected to the report as they believed this route of infection to be highly unlikely, if not impossible.

Parker's story, while tragic, intrigued Basu and would be the spark needed for his work.

Virus transmission

Before widespread vaccination efforts effectively eradicated the virus in the 1980s, smallpox was widely considered the world's most feared disease and was responsible for killing millions of people. Throughout the 20th century, public health researchers around the world conducted countless studies to mitigate the virus. Research has found the variola virus — the agent responsible for smallpox and other viruses in the Orthopoxvirus family — spreads through direct contact or through the inhalation of virus-laden particles and droplets.

Interestingly, there is a lack of research surrounding the mechanics of what happens inside the human airway after the inhalation of virus-laden droplets. In 2022, Basu, who is the one of the country's leading experts in fluid mechanics, began pivotal research into this question.

In December 2025, he published the results of his team's research in .

"In this work, we explored the microscale mechanics of inhaled transmission within respiratory pathways and then evaluated if Parker’s route of infection could have been possible," Basu explained.

One of the key points from Basu's findings were that airborne inhalation alone can realistically trigger a smallpox infection within a matter of hours and as short as 20 minutes, making Parker's route of infection — through the air ducts — scientifically and logistically feasible.

"This model, merging state-of-the-art fluid dynamics simulations of respiratory physics with crosscutting inputs from virology and immunology, confirms that airborne inhalation alone can realistically trigger smallpox infection within hours," Basu said.

The team was able to determine these findings by both computationally and experimentally tracing microdroplet transmissions inside medical imaging-based digital and 3D-printed human airways that extend down to top of the lungs.

One challenge the team had in this modeling was finding the right type of virological smallpox data to input into their model. While there is a wealth of datasets on smallpox, to model inhalation-based viral particles, Basu's team needed viral concentrations from fresh respiratory secretions — a scarcity, with the emergence of genomic sequencing and since smallpox research is contained to a select few highly secure labs around the world.

"This scarcity is partly due to smallpox no longer being a circulating virus and because genomic sequencing emerged in the late 1970s, coinciding with the eradication of smallpox," Basu explained.

To find this specific type of data, Basu had to unearth a pivotal — but largely forgotten — study from the 1970s. In this work, the researchers collected throat swabs from smallpox patients. The trachea, the bottom half of the throat, is the primary infection site for smallpox. Coincidentally, the study, conducted by a team of researchers from the Calcutta School of Tropical Medicine, took place in a hospital in the same city where Basu grew up, in Kolkata, India.

"I went and visited the hospital during the course of this research," Basu noted.

The research team was able to input this data into their inhalation model. The results were in line with previous research into the critical exposure transmission of smallpox.

"By integrating these simulations with viral concentration and individual immune factors, we estimated the critical exposure durations for infection onset to be between 1-19 hours, aligning with existing smallpox literature," Basu explained.

Mpox 

While smallpox has been eradicated, other viruses from the same family continue to pose a global threat to human health. Monkeypox virus — mpox, as it more widely known in the medical community — has emerged as a public health emergency, per the World Health Organization. When Basu was beginning this research in 2022, mpox was spreading out of Africa, where it is endemic, and into other continents, including Europe. This has created a heightened need to better understand how mpox is transmitted and the critical exposure duration of the virus.

"Current mpox activity reflects overlapping outbreaks involving multiple viral clades and sublineages, with sustained transmission both within Africa and internationally rather than a single geographically contained event," said Julia Port, research group leader at Germany's Helmholtz Center for Infection Research. "Ongoing outbreaks — particularly those driven by clade IIb (a sublineage of mpox virus) — are understood to be transmitted predominantly through direct skin-to-skin and mucosal contact, including intimate and sexual contact, while additional spread may occur through prolonged household or caregiving exposure, contaminated materials, or short-range respiratory droplets during close face-to-face interaction, although the relative contribution of these routes remains uncertain."

Since the team's model validates the virological dataset and past smallpox research, it can be extended to gain insights into other viruses in the Orthopoxvirus family, including mpox.

"The extensive body of research and resulting data on smallpox positions it as the ideal model Orthopoxvirus for testing new mechanistic frameworks aimed at predicting its detailed transmission dynamics," Basu said. "These models may then be prospectively applied toward studying the disease onset mechanisms for other related (and, circulating) pathogens."

The critical exposure duration for mpox, based on the team's modeling, was determined to be substantially longer than smallpox, in the range of 24-40 hours. However, Basu notes this range can vary significantly, from as short as eight hours to as long as 127 hours, depending on the viral concentration in the inhaled particles.

"Predictably longer than the critical exposure durations for smallpox, the mpox findings still strongly suggest the possibility for airborne inhaled transmission during prolonged proximity," Basu said.

Understanding critical exposure duration is essential for public health officials when designing effective mitigation strategies. This time threshold determines who may be infected, who needs to be tested or monitored, who should be quarantined and who qualifies as a close contact. The critical exposure duration can also help model how fast an outbreak will spread.

"Continued human-to-human transmission warrants evolutionary surveillance for potential changes in transmissibility or transmission routes, including shifts in respiratory spread (which could shift the dynamics drastically)," Port said. "This work aims to support a framework for such monitoring."

While the latest mpox outbreak has largely been contained in Africa, the threat remains. The results of this work will be useful to government and public health officials in case of future mpox outbreaks.

Funding for this research was supported by Basu's CAREER Award from the National Science Foundation. Contributing authors include SDSU graduate students Mohammad Yeasin, Abir Malakar and Azadeh Borojeni; Florida State University postdoctoral fellow Mohammad Mehedi Hasan Akash (a former doctoral student in the Basu lab); Harvard University undergraduate student Aditya Tummala (a former high school researcher in the Basu lab); University of North Carolina, Chapel Hill researcher Jihong Wu, professor William Bennett, research associate professor Julia Kimbell and senior scientist Wanda Bodnar; and Fractal Therapeutics CEO Arijit Chakravarty.