As global concerns about mpox rise, straightforward questions about its risks and variant differences remain unclear.
In July, the World Health Organization (WHO) declared an international health emergency over mpox, a disease that first emerged in humans around 1970 in the Democratic Republic of Congo (DRC).
For decades, known as "monkeypox," the illness was confined to a few African countries, with mortality estimates ranging from 1% to 10% of those infected.
The uncertainty grew in 2022 when mpox spread to Western countries. Cases in these newly affected regions had a very low mortality rate of around 0.2%.
Such differences likely stem from several factors. First, individuals in the U.S. or Europe are more likely to receive swift, appropriate medical treatment compared to patients in many African nations.
"The danger mpox presents strongly depends on the quality of basic care," said Antoine Gessain, a virologist specializing in the disease.
The mortality rate in the current outbreak – around 3.6% – would likely be lower if it were not primarily confined to the DRC.
Other factors affecting the mortality rate include patient vulnerability. In the DRC, where over 500 of more than 15,000 mpox cases resulted in death, most victims were children, many suffering from malnutrition.
In contrast, during the DRC's 2022-23 epidemic, the small number of deaths – around 200 out of 100,000 cases – were primarily adults whose immune systems were weakened by HIV infection.
Mortality outcomes can also vary based on how a disease spreads. In 2022-23, most transmissions occurred through sexual contact among homosexual or bisexual men.
Another complicating factor is the clade, or family, of the virus causing the outbreak. Scientists are still determining the health risks and transmission differences between clades.
The 2022-23 mpox epidemic was caused by Clade 2 mpox, primarily found in western Africa but also present in South Africa. The current deadly outbreak in the DRC is linked to Clade 1 mpox, found mostly in central Africa.
A separate epidemic in the DRC affecting mostly adults is associated with variant 1b, a derivative of Clade 1 that has emerged recently.
Some media outlets have claimed that variant 1b is more dangerous than previous mpox varieties. However, Dutch virologist Marion Koopmans cautions against such claims due to limited evidence.
"There are rather big claims in the popular media for which evidence is limited, both about severity and transmissibility of the new sublineage 1b," Koopmans told the UK-based Science Media Centre. "What we do know is that Clade 1 is associated with more severe disease than Clade 2."
Historically, Clade 1 outbreaks have been linked to higher mortality rates than Clade 2. Researchers urge caution before drawing conclusions, even with seemingly clear data.
The urgency of understanding mpox variants is heightened by the detection of Clade 1 in Sweden in mid-July – the first occurrence outside Africa.
"It's very difficult to compare between different clades given that the context and the type of at-risk population are so important," virologist Gessain said. "How can you compare children suffering from malnutrition and HIV-positive adults?"
