Antibiotics Are Helping Mosquitos Spread Malaria More Effectively

Antibiotic therapy is the closest medical science has ever come to having a magic bullet. People generally don't die of scarlet fever or lose limbs to staph anymore, and getting syphilis today is embarrassing but unlikely to erode your skull.

But new research from a group at Imperial College London shows that we might not be the only ones benefiting from antibiotic prescriptions. The researchers found that mosquitos feeding on the blood of malaria patients taking antibiotics were healthier, lived longer, and were likely more effective at spreading malaria than those feeding on unmedicated hosts.

The mosquitos—Anopheles gambiae—were essentially taking our drugs for their benefit.

The paper, published this week in Nature Communications, detailed further unintended consequences of antibiotic use, and suggests that many global health initiatives may be facing a new, complicating factor in their battle against infectious diseases in areas also affected by malaria.

Over-prescription and improper use of antibiotics has already been blamed for creating so-called "superbugs"—highly drug resistant bacteria that affect millions worldwide. Scientists are also just beginning to understand the importance of the human microbiome, the countless bacteria that colonize our bodies to our benefit. Indiscriminately killing bacteria with antibiotics can clear out these beneficial organisms and may have serious consequences.

The key to the hyper-malarial mosquitos described in the study lies in their guts. Just as the human gut is home to a diverse array of helpful native bacteria—as demonstrated by icky but effective fecal transplant therapy—mosquitos have their own beneficial bowel dwellers that protect them from infection.

When a typical mosquito ingests a blood meal containing Plasmodium falciparum—the parasite responsible for malaria—its native microbes compete with the parasite for resources while emitting free radicals that are toxic to P. falciparum too. But while the parasite is weakened by the native bacteria, the group theorized that stripping the mosquitos of their native bacterial populations would allow P. falciparum to take over. The resulting mosquitos would carry more of the parasite than normal, increasing infectivity.

"We knew that without a gut microbiota the mosquitos had a higher rate of Plasmodium infection," said Dr. Mathilde Gendrin, lead author of the paper. "We decided to look at blood containing antibiotics. That is, if someone takes an antibiotic treatment, what is the effect on malaria?"

The scientists fed mosquitos blood containing penicillin and streptomycin, antibiotics in common use. They observed a 70 percent decrease in the native microbiota and a significant increase in both the number of mosquitos carrying P. falciparum, and the total amount of the parasite in infected mosquitos.

With the native bacteria depleted by antibiotics, P. falciparum began to reproduce unchecked. The researchers confirmed their initial laboratory observations using blood donated by malarial patients in Burkina Faso, and the effect was the same. The incidence and intensity of P. falciparum infection spiked when there were antibiotics in the blood.

The group had proved their hypothesis correct, but the mosquitos were benefitting in other ways, too. "A new thing we hadn't planned on was that [the mosquitos] were healthier on the antibiotics. They survived better, lived longer, and laid more eggs," said Dr. Gendrin, noting that the effect was independent of P. falciparum.

The scientists believe it is possible that after a blood rich meal the mosquito gut microbiota surge in number due to the abundant nutrients, provoking a low level immune response and weakening the mosquito. In other words, the native bacteria become too much of a good thing. This effect no longer happens in mosquitos who have ingested antibiotics.

Whatever the reason, as Dr. Gendrin notes in the paper, anything that increases mosquito's survival rate increases their ability to spread disease. That malaria patients on antibiotics may aid the spread of the parasite adds a further wrinkle to the already hugely complex task of combating diseases in the equatorial regions where malaria is prevalent.

The paper notes that epidemiological studies will be needed to confirm that the effect they see on the individual level holds true for entire populations. But if the results bear out, entire global health strategies may need to be re-thought.

One of the antibiotics used in the study, streptomycin, is also used against tuberculosis which is by most accounts the most prevalent infection in the world. The Mycobacterium responsible for the disease is notoriously resilient and slow growing, with antibiotic treatment courses lasting from six months to years in some cases.

Add to this leprosy (also a Mycobacteria), antibiotic prescriptions for the large portions of sub-saharan African residents dealing with HIV/AIDS related infections, and a whole host of so-called "neglected tropical diseases" with various active initiatives to eradicate them via antibiotic therapy, and the picture starts to look bleak.

However, despite the outcome of the study, Dr. Gendrin insisted that no-one is suggesting abandoning the use of antibiotics in malaria affected areas. "It's more complicated. When we are designing large drug administration programs we need to know which drugs may increase malaria transmission and direct patients on antibiotics according to risks," she said, noting that they are working on additional antibiotics that restrict the malaria parasite directly.

The solution may be as simple as different drugs. P. falciparum is a microscopic parasite, but it's not a bacteria, and it avoids being killed by many antibiotics that target bacteria specifically. There are compounds that are active against organisms like P. falciparum, and there may be antibiotics that work against their intended disease targets without enhancing malaria infection in mosquitos.

As it stands this research has revealed a potentially serious issue with the way antibiotic drugs are prescribed and used in areas of the world where malaria is endemic. When the first antibiotics went into mass production in the mid twentieth century the response in the western world was jubilant; medicine had conquered bacterial infection. The city of Madrid even built a statue featuring a bronze matador raising his cap to Sir Alexander Fleming, thanking him for discovering penicillin and saving their beloved bullfighters from long and painful post-goring deaths by sepsis.

Antibiotics are still rightly seen as a triumph today. But nature likes to remind us that nothing is simple—the interplay between parasites, hosts, medicines, and disease is incredibly complex, and our magic bullets aren't as precise or accurate as we once thought.