One of the most persistent mysteries in medical science is why certain infections appear to cause more severe symptoms in men than they do in women.
Men infected with tuberculosis are 1.5 times more likely to die than women, and five times more likely to develop cancer when infected with human papillomavirus (HPV). And now scientists think they know why - women are more valuable as hosts, so pathogens have evolved to keep them alive longer than men.
"Viruses may be evolving to be less dangerous to women, looking to preserve the female population," says one of the team, Francisco Úbeda, from the Royal Holloway University of London.
"The reason why these illnesses are less virulent in women is that the virus wants to be passed from mother to child, either through breastfeeding, or just through giving birth."
The basic premise is that, while illness is the most obvious sign that we’ve been infected by a virus or bacterium, its main 'objective' is to proliferate and spread from host to host - not make them sick.
The illness that often comes with an infection is an unfortunate side effect, both for the host and the pathogen, because if the host is bedridden or dies, they can no longer help it spread.
"[Illness] is not something a pathogen particularly sets out to do, because it’s shooting itself in the foot, should it have one," one of the researchers, Vincent Jansen, explained to New Scientist.
That means if you were a virus or bacterium capable of being spread from person to person - including from mother to child - you’d opt to infect a woman, because there’s a chance she'll either spread the infection to people she comes into contact with in daily life, or her own children though childbirth.
Men, on the other hand, only have one possible mode of transmission, because they can’t spread a pathogen through pregnancy, childbirth, or breastfeeding.
Úbeda and his team decided to figure out why some pathogens appear to favour women over men by looking not at the patients' response, but at the pathogen's strategy.
Instead of focussing on differences in male and female immune systems, and how those could play into the severity of symptoms, they wanted to figure out if it was something the pathogen was doing to achieve such results.
"We were surprised that all potential explanations to the observed differences in virulence between men and women were centred on the patient, and that the pathogen had largely been ignored," he told Michelle Kuepper at ResearchGate.
"We took the 'pathogen's eye view', and researched whether natural selection would favour a different behaviour in each sex."
They came up with a mathematical model for the transmission of pathogens between men and women, and used that to figure out which strategy would best favour a given virus.
The virus they focussed on was human T-cell lymphotropic virus type 1 (HTLV-1), found in Japan, the Caribbean, and West Africa.
Their results showed that HTLV-1 was up to 3.5 times more likely to cause Adult T-cell Leukaemia (ATL) - which is lethal - in Japanese men than women, but in the Caribbean, the likelihood of the virus progressing to leukaemia was roughly equal between the sexes.
Considering that HTLV-1 is spread by either sexual transmission or from mother to child during the lactating period, the researchers suggest that differences in breastfeeding trends in Japan and the Caribbean could explain the result.
"This could be because a higher proportion of Japanese women breastfeed their children, and for longer, when compared to women in the Caribbean," Úbeda said. "This provides the disease more of chance to be passed on to children."
There are plenty of examples to support the hypothesis that viruses and bacteria that can be passed on from mother to child favour women as more valuable hosts, and have evolved strains that keep them alive longer than men.
Men infected with Epstein-Barr virus are twice as likely to develop Hodgkin’s lymphoma as women, and men have a higher risk for a severe case of chickenpox than females. Both viruses are able to be transmitted from mother to child.
But the hypothesis can't explain one important detail: how the virus or bacterium can tell if it's infecting a man or a woman.
As Jansen explained to New Scientist, it's not out of the question that they could, seeing as there are all sorts of hormonal cues and other chemical pathways that are slightly different between men and women, but it's now up to the researchers to prove it.
"We could try to make the virus think it’s in a female body rather than a male body and therefore take a different course of action," he suggested.
The team wants to investigate further by looking at how different sexes in animals respond to certain viruses, and plan to start with retroviruses that cause cancer in chickens.
"When flocks of chickens are infected with a particular virus, we see that more of the male chickens develop tumours than females," he says.
The research has been published in Nature Communications.