The malaria parasite is well known for hijacking red blood cells in its potentially deadly quest to spread to its next unsuspecting victim via a mosquito bite.
But scientists have discovered it has another surprising trick up its sleeve: it can lurk undetected in the spleen, which filters blood.
The discovery, reported today in the journals New England Journal of Medicine and PLOS Medicine, not only rewrites what we know about the biology of this insidious disease, but it has important implications for malaria elimination programs, researchers say.
“What we found is that there are some people walking around that have malaria parasites in their spleen and not in their [circulating] blood,” said lead author Steven Kho, of the Menzies School of Health Research.
This means they may not be picked up by screening programs, which look for evidence of the parasite in the circulating blood.
One of the other problems, Dr Kho says, is people with infected spleens have no symptoms, so they are unlikely to seek medical treatment.
“Which means they are carriers and they are able to transmit the disease within the population if a mosquito bites them [once the parasite moves back into the bloodstream],” he said.
The life cycle of malaria — as we knew it
The malaria parasite is transmitted from person to person through the saliva of the blood-sucking female Anopheles mosquito.
Within days, the parasite travels through the bloodstream until it invades the liver, where it transforms into the next stage that infects red blood cells.
Once in the red blood cells, the second generation of parasites reproduce over and over again, killing off the cells as they go.
It is during this phase that the symptoms of headache, fever and nausea appear.
As the disease progresses it can cause severe anaemia, respiratory distress, organ failure, coma and death.
Some of the earliest references to malaria’spresence are found in 5,000-year-old Egyptian mummies.
Today, it is found across 40 per cent of the world, mainly in sub-Saharan Africa, South-East Asia, the eastern Mediterranean and the Western Pacific.
In 2019, there were 229 million cases of malaria and 409,000 deaths — mostly children and pregnant women — worldwide.
Scientists had long suspected that the second generation of malaria parasites that cause disease may have hung out in other organs such as the spleen, but until this point, no direct evidence had been found, Dr Kho said.
“No-one has actually ever done a study to actually show that’s where these parasites are hiding,” he said.
The spleen and malaria
Lying in the left-hand side of the body, the spleen plays a critical role in the immune system.
As blood flows in and out of the fist-sized organ, abnormal and dead blood cells are removed.
This process puts the spleen under a lot of pressure and it is common to see people with enlarged spleens in areas where malaria is endemic.
“If the spleen only removes parasites, we should only see parasite remnants or evidence of dead parasites [in the spleen],” Dr Kho said.
However, when the international team of scientists examined spleen tissue, they were surprised.
“We actually saw [live] malaria parasites in 95 per cent of the spleens we got.”
Tissue was collected from spleens removed from 22 people living in Timika, in the Indonesian province of Papua.
These were people without symptoms, but their spleens had been removed after being ruptured during an accident.
“We didn’t expect [to see malaria parasites] because these were just individuals living in Timika that had happened to have an accident,” Dr Kho said.
Although these people had no malaria parasites in their blood, large amounts of the two most common species — Plasmodium vivax and Plasmodium falciparum — were found in their spleen.
“Some individuals only had malaria parasites detectable in the spleen, which were true hidden reservoirs of infection,” Dr Kho said.
Although the people in the study didn’t have any symptoms of malaria, Dr Kho said many had had malarial infections in the past, suggesting they had developed a level of immunity.
“After multiple times of getting malaria, you get this build-up of immunity but somehow the parasites can survive in your spleen.”
Closer examination of the spleen tissue also showed a higher number of young red blood cells, known as reticulocytes.
These young blood cells provide the perfect breeding ground for P. vivax, the dominant species of parasite in this area.
A game-changing discovery
The discovery of a hidden reservoir of malaria parasites in the spleen was a “game changer”, said Justin Boddey of the Walter and Eliza Hall Institute.
“We always think we understand everything, then something like this comes along and it’s completely not what one would expect.”
Dr Boddey, who was not involved in this research, studies the malaria parasite particularly in liver cells, which provide a hiding place for the first stage of the parasites before they enter blood cells and cause disease.
“[This new work] explains now there are two reservoirs. Not just the first phase of infection in the liver, but there’s this other reservoir in the spleen after the parasites come out of the liver,” he said.
“This whole lifecycle [of the parasite] they are describing has been missed.”
In particular, Dr Boddey said, the finding that the spleen contained blood cells with active parasites still growing normally was striking.
“I was like ‘woah’, this is super cool.
“That shows if they are viable, they can come out again, so there’s a possibility for reseeding an infection that makes someone feel sick, but also to transmit it onward.”
He said the next step would be to find out if the results in this one region were also true of other parts of South-East Asia where P. vivax dominates, and in Africa where P. falciparum is the main disease culprit.
“I can see this [discovery] having a huge influence in the way we understand malaria transmission into the mosquito and back out of the mosquito, and the disease itself,” Dr Boddey said.
Originally published at Abc news