MALARIA uses a gender-bending trick to ensure that enough parasites of each sex survive to infect new hosts and reproduce. This discovery may suggest new ways to control the disease by altering the balance of the sexes.
Initially, malaria parasites reproduce asexually in an animal鈥檚 bloodstream, destroying red blood cells and causing anaemia. The body produces more red blood cells to compensate, and also mounts an increasingly effective immune response.
Soon, however, individual asexual parasites change to a sexual form, known as a gametocyte. Each asexual parasite is capable of becoming either a male or a female gametocyte. Once ingested by a mosquito, gametocytes spawn male and female gametes that reproduce sexually within the mosquito, completing the malaria life cycle.
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But in all species of malaria, the asexual parasites at first tend to become female gametocytes rather than male ones. There have also been hints that later in an infection, the production of male gametocytes increases so that the sex ratio in the population evens out. 鈥淲e noticed they changed to males, which was strange,鈥� says Richard Paul of the Pasteur Institute in Paris.
He and his colleagues investigated this effect using the chicken malaria parasite Plasmodium gallinaceum. They confirmed that more male gametocytes appeared later in an infection, and that the numbers of males correlated with the numbers of fresh red blood cells. So the team wondered whether the hormones that trigger the production of red blood cells might also bump up the male parasite population.
To test this, they placed newly infected chickens in a chamber containing lower concentrations of oxygen than normal鈥攕imilar to the levels at the top of a high mountain. This made the chickens produce new red blood cells earlier in the infection than usual. As expected, more male gametocytes appeared than in control infected birds kept at normal oxygen levels. The team also found that the parasites that were tricked into altering their sex ratio too early reproduced poorly in mosquitoes, indicating that the normally timed change in sex ratio helps successful reproduction.
The researchers then tested whether the mammalian hormone erythropoietin (EPO), which some professional cyclists take illicitly to increase their red blood cell count, prompts a sex ratio change in mouse malaria, Plasmodium vinckei. Sure enough, it did.
Paul thinks that the reason the normal change in sex ratio is useful to the malaria parasite is that the mounting immune reaction in the warm-blooded host affects the male gametocytes in a way that subsequently hinders the ability of male gametes to swim and find female gametes in the mosquito gut. The increase in numbers of males may compensate for this, he says.
He plans to find out whether EPO or similar hormones trigger the parasite sex change in people and animals. If so, extra EPO might be a useful natural weapon against them. 鈥淚f we can push all the gametocytes to being male, and not female, they can鈥檛 sexually reproduce in mosquitoes,鈥� he says.
David Baker, a malaria expert at the London School of Hygiene and Tropical Medicine in London, says this is a real insight into sex determination in malaria. 鈥淭here鈥檚 no doubt that in human malaria, manipulating the sex ratio could lower transmission.鈥� But he cautions that it is still unclear whether EPO would work on Plasmodium falciparum, which causes most human deaths from the disease.