Scientists have been studying the oddball lifestages and sexual peculiarities of malaria parasites for more than a century now. The newest discovery is as bizarre as any that came before it: Human-infecting Plasmodium falciparum protozoa appear to burrow into bone marrow to undergo a kind of parasitic puberty, their sexual coming of age.
The finding could prove essential in developing drugs that interfere with P. falciparum reproduction. That might help health workers cut transmission rates of a disease that infects millions of people every year, claiming more than 600,000 lives annually—most of them in sub-Saharan Africa.
Human-infecting Plasmodium falciparum protozoa appear to burrow into bone marrow to undergo a kind of parasitic puberty, their sexual coming of age.
When mosquitoes drink infected blood, they suck up sexualized P. falciparum specimens, which are known as gametocytes. Male and female gametocytes fuse inside malaria-spreading species of mosquitoes to produce oocysts, which churn out thousands of baby parasites known as sporozoites. Perhaps 60 to 100 of these sporozoites are injected through an infected mosquito's proboscis into each new human victim.
The sporozoites migrate through the human bloodstream in a quest to reach the liver, where they overtake liver cells, multiply, and mature before streaming into the bloodstream as microbes that can infect red blood cells. These so-called merozoites rapidly clone themselves and infect additional red blood cells as they spread through the bloodstream. They ride the infected blood cells into organs. If they invade the brain, the victim risks slipping into a fatal coma.
Somewhere along the way, some of the merozoites divide and develop into gametocytes—that sexual stage that must be sucked out by an Anopheles species of mosquito if the whole cycle is to repeat. It has always been a mystery where this sexual development happens. They aren't found in the bloodstream until they've matured to the point where they're ready for transmission to a mosquito, so scientists figured they develop deep inside infected organs. But which ones?
New research published in Science Translational Medicine appears to confirm a hypothesis that these changes occur in bone marrow.
The parasites are highly specialized, making it impossible to use lab rats in studies that could determine which tissues are sheltering the parasites as they produce their wicked seeds. So a research team led by Matthias Marti, an associate professor of immunology and infectious diseases at the Harvard School of Public Health, turned to grim but critical autopsy work underway in Malawi for answers.
The team examined tissues collected from different organs of child victims of malaria, finding high levels of gametocytes in spleen, brain, gut, and bone marrow tissue. The highest ratios of sex-stage parasites to adult stages were found in bone marrow. Further experiments showed that the parasites could both divide and develop into sexual stages outside the blood stream in the fleshy marrow. Marti says some gametocytes might be produced in other organs, then matured in bone marrow.
"Bone marrow is a complex organ," Marti says. "Penetration of drugs into the extravascular system of the bone marrow would be important to make sure the drugs can reach where the sexual stages develop."