The genome of Plasmodium simium, a species of malaria parasite that mostly infects monkeys on the coast of Brazil, was found to be extremely similar to that of Plasmodium vivax, the most common cause of recurrent malaria in the Americas, strongly suggesting a recent jump between humans and nonhuman primates that could result in new outbreaks of the disease.

The study, published April 19 in The Journal of Infectious Diseases, proposes that the flexibility of malaria parasites to adapt to different hosts could result in future malaria outbreaks in urban areas that do not see nearly the same rates of infection as the Amazon region, where the vast majority of malaria cases occur in South America. 

"Humans may be a source of parasites that can infect wild animals," said senior author Marcelo Ferreira, a professor of parasitology at the University of São Paulo. "And because these parasites can still infect humans, this is important from a public health perspective."

Malaria is a significant public health burden around the world. In 2019, there were 229 million malaria infections and 409,000 deaths. And while the majority of these occurred in Africa, factors such as climate change, high numbers of the mosquitoes that transmit malaria and low funding for malaria-control programs have made the Amazon a vulnerable region over the last several decades, despite efforts to eradicate the disease.

The movement of malaria parasites from humans to nonhuman primates is a unique example of a reverse zoonosis, a human disease that moves to other animals. 

Zoonoses, diseases that move from nonhumans to humans, are well studied, and thee are over 200 documented types, including Ebola, rabies and even COVID-19, though there is some disagreement about which animal the latter disease originated in. Reverse zoonosis, on the other hand, is less common and less understood.

P. vivax has proved to be an exception to this rule. While it is less deadly than the strains of malaria common across Africa, P. vivax causes about 72% of malaria cases in the Americas.

On the other hand, P. simium does not frequently infect people but runs rampant in monkeys. In 2017, this species was first found to move from monkeys to humans. The concern at the time was establishing whether malaria cases could actually be caused by this species or whether the monkeys were acting as a reservoir, a host where a pathogen can live and reproduce before moving on to a primary host.

"So we have few human cases, but lots of infections in monkeys very close to big cities in Brazil, including São Paulo, which is the largest city in South America," Ferreira said. "From a public health perspective, this is very scary."

While it may not immediately appear that diseases transmitting from humans to other animals should be a cause for alarm, the formation of reservoirs for malaria is dangerous. If monkeys can act as a reservoir for malaria in South America, this will make it more difficult to eradicate the disease in humans because there will be more parasites waiting in the wings.

Upon sequencing genetic material from parasites found in the blood of monkeys in the forests around São Paulo to that from parasites in the blood of humans living in a similar region, the researchers found "meagre genetic diversity," suggesting that P. simium originated as a P. vivax lineage, only recently making the jump from humans to monkeys.

The team hypothesizes that malaria in South America originated with Portuguese colonists, and that the ability to go back and forth between hosts in this way was an adaptation that helped malaria survive by having a greater number of possible hosts. This is particularly true because the mosquitoes that transmit the disease in South America are very different from those the parasite would have encountered on the other side of the world and would have presented a great challenge to the parasites.

"Adapting to these new vertebrate hosts was a huge advantage for them," said Ferreira. "And it's amazing that the prevalence of malaria infection in some monkeys, in some species of monkeys, especially in howler monkeys, may be as high as 30% or 40%."

Ferreira also explained that there is an "interesting parallel" between the malaria situation in South America and yellow fever, a viral disease that also uses monkeys as a reservoir. However, there is less to fear from yellow fever being reserved by the monkeys, because there is a vaccine for it. Unfortunately, there is no vaccine for malaria, though recent developments in biotechnology brought about by the pandemic are bringing researchers closer to this goal.  

Until that day, the researchers maintain that addressing the monkey reservoir of malaria will remain a challenge for South America. However, they are also optimistic that the malaria outbreaks that could be seen in these urban areas will be less severe than those seen in Africa or even the Amazon.

"I think it's important to remember that we do have malaria close to big cities, but this doesn't mean that we are very close to a huge outbreak in the next few years and everyone will die from malaria," Ferreira said. "We still have thousands of malaria cases in the Amazon. We should keep a balance."

The study, "Plasmodium simium: population genomics reveals the origin of a reverse zoonosis," published April 19 in The Journal of Infectious Diseases, was authored by Thaís C. de Oliveira, Priscila T. Rodrigues, Marina G. Bueno, José L Catão-Dias and Marcelo U. Ferreira, University of São Paulo; Angela M. Early and Daniel E. Neafsey, Broad Institute of MIT and Harvard; Ana Maria R. C. Duarte, Superintendency for the Control of Endemics; Julyana C. Buery and Crispim Cerutti Jr., Federal University of Espírito Santo; and Luísa D. P. Rona, Federal University of Santa Catarina.