Do our medicines boost pathogens?

Vanaerschot studies the Leishmania parasite, a unicellular organism that has amazed scientists before. Leishmania is an expert in adaptation to different environments, and the only known organism in nature disregarding a basic rule of biology: that chromosomes ought to come in pairs. (The latter was also discovered by ITG-scientists recently.)

The parasite causes Leishmaniasis, one of the most important parasitic diseases after malaria. It hits some two million people, in 88 countries – including European ones – and yearly kills fifty thousand of them. The parasite is transmitted by the bite of a sand fly. The combined resistance against a medicine and the human immune system emerged in Leishmania donovani, the species causing the deadly form of the disease.

On the Indian subcontinent, where most cases occur, the disease was treated for decades with antimony compounds. As was to be expected, the parasite adapted to the constant drug pressure, and evolved into a form resisting the antimonials. In 2006 the treatment was switched to another medicine, because two patients out of three did not respond to the treatment. The antimonials closely work together with the human immune system to kill the parasite. This probably has given Leishmania donovani the opportunity to arm itself against both. It not only became resistant against the drug, but also resists better to the macrophages of its host. Macrophages are important cells of our immune system.

There is no absolute proof yet (among other things, because one obviously cannot experiment on humans) but everything suggests that resistant Leishmania not only survive better in humans – have a higher "fitness" – but also are better at making people ill – have a higher "virulence" – than their non-resistant counterparts.

Superbug?

It is the first time that science finds an organism that always benefits from its resistance. Normally resistance is only useful when a pathogen is bombarded by drugs; the rest of the time it is detrimental to the organism.

Resistant organisms are a real problem to medicine. More and more pathogens become resistant to our drugs and antibiotics – to a large extend because you and I use them too lavishly and improperly. For several microbes, the arsenal of available drugs and antibiotics has so diminished that people may die again from pneumonia, or even from ulcerating wounds.

Luckily for us, resistance helps pathogens only in a drug-filled environment. In the open field their resistance is a disadvantage to them, because they have to invest energy and resources into a property with no use there. Just like a suit of armour is quite useful on the battle field, but a real nuisance the rest of the time.

So the propagation of resistant organisms is substantially slowed down because they are at a disadvantage outside of sick rooms. But this rule, too, is violated by Leishmania: even in absence of the drug, the resistant parasite survives better, instead of worse, and it is more virulent than a non-resistant parasite.

Did our medicines create a superbug? A legitimate question, and the phenomenon has to be investigated, but this sole case doesn't imply we better stop developing new medicines (as a matter of fact, the antimony-resistant Leishmania are still susceptible to a more recent drug, miltefosine). On the contrary, we should develop more new drugs, to give new answers to the adaptive strategies of pathogens, and we should protect those drugs, for instance by using them in combination therapies. In this never-ending arms race we should use our drugs wisely, to minimise the chances for pathogens to develop resistance.

Provided by Institute of Tropical Medicine Antwerp