How smallpox eradication cleared the way for new threats

Encouragingly, there is a key difference between smallpox and its viral cousins that makes the latter far less dangerous to populations at large.

Unlike most orthopoxviruses, which require close skin-to-skin contact to spread, smallpox was highly adapted to respiratory transmission.

This allowed infected individuals to shed large amounts of virus in droplets and aerosols during coughing, speaking or just breathing, particularly early on in infection, when they were still mobile and mixing with other people.

In 1520, a single Spanish soldier infected with smallpox inadvertently brought the virus to the Aztec Empire during the Spanish conquest of the Americas.

Within a year, the virus had killed five to eight million people, including the Aztec emperor Cuitláhuac, and wiped out at least 90 per cent of the population. The virus is considered to be a major factor behind the collapse of the empire.

“Smallpox is transmitted via the respiratory route, which enabled efficient transmission and its pandemics in the past,” said Dr Albarnaz. “In contrast, other orthopoxviruses that can infect humans, such as cowpox virus and mpox virus, are transmitted via close contact with an infected individual or animal, or contaminated objects.”

“This means that despite the international reach of mpox since 2022 and 2024, these viruses are unlikely to cause a pandemic like Covid-19,” he added.

While evidence suggests mpox can sometimes spread through respiratory droplets, a major review published in The Lancet in 2023 concluded that although respiratory transmission is possible, it is not the primary mode of spread and is unlikely to play a substantial role in current outbreaks.

Some experts, however, fear this could change – particularly with the emergence of the newer clade 1b strain.

Recent outbreaks show the virus accumulating mutations faster than expected. Certain genetic changes appear to improve its ability to transmit between people, for example by increasing viral shedding or survival outside the body.

The combination of rapid mutation and a growing reservoir of human infection is why some experts believe newer strains carry pandemic potential.

“There were multiple studies during the mpox epidemic in 2022 that tested air samples in clinics where infected men were being assessed,” Dr MacIntyre said. “You could find traces in the air – and there is now plenty of evidence that some strains of mpox can spread respiratorily.”