Jacinta Bowler
This article was first published on 2 May 2023. It’s just been commended by the Universities Australia Higher Education Media Awards.
A promising treatment for anaemia in the developing world has failed in a landmark trial, instead uncovering “the hard way” that adding iron can’t always fix anaemia. Failures like this are rarely reported but this case is special.
“We’ve learnt the hard way that anaemia is complex in sub-Saharan Africa and in women in pregnancy,” WEHI leading anaemia researcher Professor Sant-Rayn Pasricha told Cosmos Science.
“I think we expected it, but we maybe hoped that just the dose of iron would be able to overcome it.”
Most of us will know someone who has had anaemia – those who menstruate, and pregnant women are particularly at risk. But in many regions and developing nations, like sub-Saharan Africa, these things are amplified by a mix of malaria, HIV, and less access to healthcare. In Africa this culminates in anaemia affecting almost 50% of pregnancies.
Iron deficiency is one of the most common reasons people get anaemia, but the two are not the same disease. While iron deficiency is a low count of the essential mineral in the body, anaemia is when the blood doesn’t contain enough red blood cells.
The new research, published in The Lancet undertaken by Australian and Malawian researchers, had set out to investigate if an iron infusion called ferric carboxymaltose would be more effective than the standard of care – 90 days of iron tablets – at stopping anaemia in the small African nation of Malawi.
“Prior to doing this, it was completely unknown if it would be dangerous to deliver intravenous iron or intravenous ferric carboxymaltose in such remote settings where healthcare resources are limited,” said Pasricha.
“Also, there’s always been a concern that iron could actually promote infection by giving iron for pathogens to feed off.”
In that regard the trial of 862 women was a complete success. They were able to give FCM with no increase in infections or adverse reactions. But it just didn’t work to stop anaemia.
“The drug was better than oral iron in reducing iron deficiency,” Pasricha told Cosmos Science. “But it was not better than oral iron, in our study, in reducing anaemia – at least not statistically significantly.”
It also didn’t increase the birthweight of the babies in the study – an important measure that the women are able to give enough nutrients to their unborn children.
In science journalism, it’s pretty rare to hear about research that has failed. But that’s not to say that research always succeeds. In fact, if you asked any scientist, they’d probably tell you they’ve failed much more often than they’ve got something to work.
But sometimes these failures can still reveal something important or allow efforts to be redirected into a new area. Rarely do these stories make it out of the university and into the newsroom, but this new study is one of those important failures that bucks the trend.
So, why didn’t a huge infusion of iron stop anaemia in these Malawian women?
The team knew already that at least some of the anaemia wasn’t just because of low iron levels.
The team had screened out all of those who tested positive for malaria at the start of the study, as malaria causes red blood cells to rupture, and no amount of iron can fix that. HIV and malaria also cause systemic inflammation, which blocks iron from being used by the body.
However, malaria has two forms – regular and a ‘hidden form’ in which the infection has dormant ‘hypnozoites’ in the liver, and which is much more difficult to test for. The high amount of inflammation seen in the women studied suggests that this might be more common than previously realised.
But sometimes iron can be helpful, even when inflammation is present. For example, patients in high income countries with inflammatory anaemia due to heart or liver failure can still benefit from FCM.
“Among the treatments, we give ferric carboxymaltose – it works. So, that’s why we reasoned that it might also work in this setting, but that’s not what we saw,” said Pasricha.
“We’ll need a more comprehensive solution.
“We do have samples here in Australia that allow us to understand some of these processes better, and that work is in progress.”
This is the first of three studies from the team of researchers.
While the first trial gave the iron injection during the second trimester of pregnancy, the second trial will intervene at the third trimester. This would give the women a huge boost of iron when the baby is only a few weeks or days away, which could lower anaemia when the women need it most.
The third trial is in Bangladesh, where there isn’t any malaria, and although anaemia is still a problem, the epidemiology is different. This could give a firmer answer on whether this hidden malaria is what is stopping the iron from working as it should.
“This is the first study, and like any field it’s rare that the first study is also the last,” Pasricha added.
“This study has opened a door to this research field.”