Science Drug That Makes Blood Lethal to Mosquitoes In Testing

NPR Article
Imagine this: A pesky mosquito sips some of your blood. Hours later, the blood-sucker drops dead, poisoned by the very blood it just slurped down.

That may sound too good to be true, but it's a tantalizing possibility, according to research published this week in the journal The Lancet Infectious Diseases. The study points to a potential new tool to fight malaria: the medication ivermectin. Studies conducted in the 2000s, including one in 2010, show that malaria-carrying mosquitoes die after feeding on individuals who have ingested the drug.

Malaria is a mosquito-borne infection that affects more than 200 million people worldwide. The disease is transmitted when an infected mosquito bites an individual, spreading a parasite called plasmodium. In humans, the parasite can cause fever, headache, chills and even death. Despite years of eradication efforts in developing countries, growing research shows malaria-carrying mosquitoes are becoming resistant to the insecticides meant to wipe them out.

"Since 2015, the number of annual deaths from malaria has stabilized," says Menno Smit, MD, a Ph.D. candidate at the Liverpool School of Tropical Medicine who led the new study. "We're not making any more progress. We need new tools, and ivermectin could be one."

In their study, the researchers demonstrate that three high doses of ivermectin make human blood deadly to mosquitoes for up 28 days after the third treatment. This high dose of ivermectin was also well-tolerated with few side effects.

"The most exciting result was the fact that even one month after [the subjects took] ivermectin, their blood was still killing mosquitoes," Smit says. "That's much longer than we thought."

To reach these conclusions, researchers at the Jaramogi Oginga Odinga Teaching and Referral Hospital in Kenya gave 47 participants 600 miligrams of ivermectin in tablet form for three days in a row. Blood samples were obtained from these participants six times and then fed to mosquitoes in cages.

"We put the blood in an artificial membrane that mosquitoes could bite on and then watched," Smit explains. "Most died within a week after [drinking] the blood."

Two weeks after feeding, 97 percent of the mosquitoes had died.

Another group of 48 patients were given a dosage of 300 milligrams but the mosquito death rate was not as high.

Either dose is higher than usual. More than 2.5 billion ivermectin treatmentshave been distributed since 1987 for the treatment of parasitic infections, typically one annual dose of up to 200 milligrams.

In this study, Smit says the high dosage of 600 milligrams for three days was well-tolerated. Participants reported few side effects, though he admits everyone in the study was already hospitalized and receiving treatment for malaria.

"The patients may have noticed less side effects because they were already feeling sick," Smit explains. "We have yet to see if the excellent tolerance we saw would be just as good in healthy individuals."

Smit adds that the high dose of ivermectin still needs to be tested in children to ensure that it is safe for all ages.

Dr. Peter Hotez, who was not involved in the study and is dean of the National School of Tropical Medicine at the Baylor College of Medicine, says bigger studies need to be done before ivermectin is seriously considered as part of a national malaria control program.

But "I think ivermectin has potential as a supplemental strategy for malaria control and prevention," Hotez wrote in an email to NPR. "The drug has an excellent safety track record from its use in mass drug administration campaigns in Africa."

Hotez warns that, though ivermectin is an exciting possibility, there is the potential for mosquitoes to build drug resistance. That's why a vaccine is still needed, he says.

Dr. Regina Rabinovich, a malaria scholar at Harvard University who was not involved with the study, agrees that ivermectin is worth pursuing to help fight malaria — as one more "imperfect tool" in the global arsenal against a "tricky" disease.

In a separate commentary on the study, Rabinovich writes that "more than one approach will probably be needed to confront this challenge [of malaria]." Perhaps new drugs that have a similar effect on mosquitoes can be developed that have a longer lasting effect, she says.

In an email to NPR, she stresses the need for trials in an area where malaria is rampant — and reminds people that researchers need to make sure that by killing mosquitoes, ivermectin can also decrease transmission, too.

Nadia Whitehead is a freelance journalist and a science writer. Her work has appeared in Science, The Washington Post and NPR. Find her on Twitter @NadiaMacias.

Editor's note: The original version of this post wrote that ivermectin is used to treat the disease "elephantitis." Several readers noted that a more commonly used term for this condition is "elephantiasis." We have updated the post.
The study done
Summary
Background
Ivermectin is being considered for mass drug administration for malaria due to its ability to kill mosquitoes feeding on recently treated individuals. However, standard, single doses of 150–200 μg/kg used for onchocerciasis and lymphatic filariasis have a short-lived mosquitocidal effect (<7 days). Because ivermectin is well tolerated up to 2000 μg/kg, we aimed to establish the safety, tolerability, and mosquitocidal efficacy of 3 day courses of high-dose ivermectin, co-administered with a standard malaria treatment.

Methods
We did a randomised, double-blind, placebo-controlled, superiority trial at the Jaramogi Oginga Odinga Teaching and Referral Hospital (Kisumu, Kenya). Adults (aged 18–50 years) were eligible if they had confirmed symptomatic uncomplicated Plasmodium falciparum malaria and agreed to the follow-up schedule. Participants were randomly assigned (1:1:1) using sealed envelopes, stratified by sex and body-mass index (men: <21 vs ≥21 kg/m2; women: <23 vs ≥23 kg/m2), with permuted blocks of three, to receive 3 days of ivermectin 300 μg/kg per day, ivermectin 600 μg/kg per day, or placebo, all co-administered with 3 days of dihydroartemisinin-piperaquine. Blood of patients taken on post-treatment days 0, 2 + 4 h, 7, 10, 14, 21, and 28 was fed to laboratory-reared Anopheles gambiae sensu stricto mosquitoes, and mosquito survival was assessed daily for 28 days after feeding. The primary outcome was 14-day cumulative mortality of mosquitoes fed 7 days after ivermectin treatment (from participants who received at least one dose of study medication). The study is registered with ClinicalTrials.gov, number NCT02511353.

Findings
Between July 20, 2015, and May 7, 2016, 741 adults with malaria were assessed for eligibility, of whom 141 were randomly assigned to receive ivermectin 600 μg/kg per day (n=47), ivermectin 300 μg/kg per day (n=48), or placebo (n=46). 128 patients (91%) attended the primary outcome visit 7 days post treatment. Compared with placebo, ivermectin was associated with higher 14 day post-feeding mosquito mortality when fed on blood taken 7 days post treatment (ivermectin 600 μg/kg per day risk ratio [RR] 2·26, 95% CI 1·93–2·65, p<0·0001; hazard ratio
6·32, 4·61–8·67, p<0·0001; ivermectin 300 μg/kg per day RR 2·18, 1·86–2·57, p<0·0001; HR 4·21, 3·06–5·79, p<0·0001). Mosquito mortality remained significantly increased 28 days post treatment (ivermectin 600 μg/kg per day RR 1·23, 1·01–1·50, p=0·0374; and ivermectin 300 μg/kg per day 1·21, 1·01–1·44, p=0·0337). Five (11%) of 45 patients receiving ivermectin 600 μg/kg per day, two (4%) of 48 patients receiving ivermectin 300 μg/kg per day, and none of 46 patients receiving placebo had one or more treatment-related adverse events.

Interpretation
Ivermectin at both doses assessed was well tolerated and reduced mosquito survival for at least 28 days after treatment. Ivermectin 300 μg/kg per day for 3 days provided a good balance between efficacy and tolerability, and this drug shows promise as a potential new tool for malaria elimination.

Funding
Malaria Eradication Scientific Alliance (MESA) and US Centers for Disease Control and Prevention (CDC).


 
I find it hard to believe that animals that eat mosquitos don't dine on other insects too.

They do just not quite in the numbers that Mosquitos are in availability, those little buggers thrive in areas that some other flying insects just are not able to in key parts of the year where access to food is really important like the Mating Season of certain Bird Species.

Scientists haven't deployed it in the wild yet, since they're not sure of the long term impacts (Would it harm their cuteness?), and because it would be unleashing the proverbial genie in a bottle, and to make sure the gene is modified correctly, so that it overwrites any other gene it's paired with.

They are worried about the African Bee issue, last time they tried to genetically modify certain insects in places like South America it ended up with Killer Bee's becoming a thing OK that wasn't done in a Lab and it was done by essentially Blind Cross Breading leading to results that were not as planned.

They don't want to have a stable version that's immune to X but in the wild it encounters X1 then that results in change Y that results in Z but that Z is much worse or unpredictable when compared to X, Say for example the released the Colony into the wild and it worked for a few generations that's all well an good but then they find out that it's removed the ability of the females to detect blood infected with HIV (something they can do and won't feed from people infected with it) and the next thing you know you have Mosquitoes spreading HIV.

While that's pretty much a worse case scenario it's something they are really eager to avoid, it could be something that doesn't spread to humans but to Cattle etc.

There is also a small fringe group of Bioethicists who say that modifying a Creature or Essentially dooming a Virus to extinction or at least curtailing it massively isn't Ethical i.e. what right do we have to do that to a non-sentient species it has just as much right to life as we do etc, etc, etc. I am not saying that there is enough of them to do a protest and march holding signs saying "Give Diptheria a Chance" or anything like that but they are a small minority that has conniptions when they see newspaper articles like this or talking about the eradication of Small Pox, Polio etc and most of them are safely ignored.
 
I have one foot in the "accident waiting to happen" court and the other in the morbidly-curious court.
 
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I mean, it sounds awesome and all but let's be real, nature will simply laugh and the mosquitos will evolve just slightly enough in a few generations to ignore the drug. They'll change faster than we can adapt a new drug to try out again.

Same thing happened with the mosquitos that were genetically altered to be impotent. There was a slight dip in the test batch and then a very fast population rebound showed that they simply ignored the hereditary genes that were supposed keep them from reproducing. Whether we like it or not, we're stuck with the little fuckers.
 
When humans blood is poisonous:

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This is good news, but we still need our old friend DDT to finish the job!
 
It is definitely exciting though; mosquitoes are probably one of the only creatures you can eliminate and actually benefit the ecosystem as a whole. They don't serve any purpose besides being evil. It would certainly help prevent the spread of the more destructive diseases in places like Africa.

Also stink bugs. Fuck stink bugs :mad:
 
It's been used in humans a fair bit, for parasitic infections.

It's also incredibly cheap. You can get enough of the stuff to deworm a herd of horses from your local farm store, and probably get change for a $50 bill.

God, don't tell the pharma industry. One of them will buy the rights for the stupid thing, increase the price 10,000% and charge medicare for it.
 
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