The Changing Face of Monkeypox: Evidence of Human-to-Human Transmission

Since 2016, the monkeypox virus has been spreading among humans, marking a significant departure from its historical transmission pattern. While the virus typically spread from small mammals to humans, such as monkeys or rodents, an international team of scientists has discovered evidence of sustained human-to-human transmission outside of African countries with known monkeypox viral reservoirs. Led by epidemiologist Áine O’Toole from the University of Edinburgh, the study’s findings highlight the need for new approaches to outbreak management and control.

Monkeypox, a virus that manifests symptoms similar to smallpox, was first identified in the 1950s when research monkeys in Denmark fell ill. It wasn’t until the 1970s that the first human case was reported in the Democratic Republic of the Congo. For decades, human-to-human transmission was a rare occurrence, with most cases originating from interactions with various mammals in central, east, and west Africa. The original source of the virus, however, remains unknown.

In 2017, an outbreak of monkeypox occurred in Nigeria, spreading internationally by 2022. Genome sequencing of these global cases revealed a lineage of the virus called clade IIb, which is typically less fatal but more severe for individuals with compromised immune systems. Researchers noted that the globally distributed lineage differed from other endemic strains in Africa, potentially indicating human-to-human transmission.

One key factor in understanding the potential shift in human-to-human transmission is the role of the human enzyme APOBEC3. This immune enzyme interacts with the DNA of the monkeypox virus, causing irreversible mutations that alter the viral genome’s base pair sequence in a predictable manner. As more individuals contract the virus, these mutations accumulate. The significance of these mutations is still being studied, but they suggest an increase in viral spread through human hosts.

The accumulation of mutations does not necessarily imply that the virus is adapting to enhance human transmission, but it may be a result of the human body leaving its mark on the virus. Regardless, the rapid accumulation of mutations suggests a high rate of spread. O’Toole and colleagues propose that the human immune system has been contending with this particular lineage of the monkeypox virus for approximately seven years.

While some monkeypox cases continue to originate from animals, the researchers conclude that the majority of cases since 2016 are likely a result of human-to-human transmission. This transmission appears to persist without restraint. There may be ongoing monkeypox epidemics in regions yet to be identified, with the potential to seed outbreaks elsewhere through travel.

The authors stress the importance of global public health efforts, extending equal attention and concern to monkeypox cases in countries with endemic reservoir species. Acknowledging the changing dynamics of monkeypox transmission is vital for effective outbreak management and control measures. Public messaging surrounding monkeypox management must be updated to reflect the newfound evidence of sustained human-to-human transmission.

The discovery of human-to-human transmission of monkeypox since 2016 represents a fundamental shift in our understanding of the virus. The accumulation of mutations and the ongoing spread highlight the need for proactive measures to mitigate the disease’s impact. By recognizing the changing face of monkeypox, public health authorities can better respond to outbreaks and protect vulnerable populations.


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