Good-Guy Fungi

Mosquitoes: itch givers, whine makers, and malaria bringers. Anopheles stephensi is the species of mosquito that acts as the vector of transmission and the vessel for sexual replication of Plasmodium, the malaria parasite. While there is a large amount of blood (literally), sweat and tears being used in the effort to develop a vaccine to kill this abominable parasite, there is some research going on in the background that is looking for different ways to make a positive impact on malaria transmission by killing off the mosquito instead, using an unlikely organism.

Amidst all the flashy Bill and Melinda Gates headlines, we can easily become blinded to anything but the vaccine that they purport will save the world from malaria. Indeed, a vaccine may be the final step in eliminating malaria from the planet. However we need novel initiatives to stem malaria now as even the most promising vaccine candidates are weak and slow-progressing, and drug resistance is spreading.

Insecticide-treated bednets have been heralded by many as the new essential tool for reducing malaria transmission. Insecticide spraying on the walls of dwellings (as mosquitoes like to rest on the walls after taking a blood meal) is also very effective at killing mosquitoes. But just as was seen in the late 1960s and 1970s, the mosquito can rapidly develop resistance to chemical insecticides if they are used at sublethal doses. And so there is some fear that the re-introduction of widespread DDT spraying in malaria-endemic regions will encourage the spread of DDT resistance once more [1].

This was the picture that Andrew Read (University of Edinburgh) and Matt Thomas (Imperial College, London) were faced with. Thus, in the search for a new practical alternative to insecticides, they turned to the recent literature on biological control of mosquitoes. As they discover in their brief report published in Science, fungal entomopathogens (i.e. a pathogen of insects) may prove to be the next best option in the fight against malaria [2].

If Spores Could Kill (wait… they can!)

For their first experiment, they simply tested a variety of fungi on how effective they were at killing mosquitoes. Choosing fungal isolates that have already been shown to have pathogenic effects on insects, they applied the fungi in an oil-based spray to the inside of cardboard "pots," and placed blood-fed mosquitoes inside the sprayed pots for 14 days.


© AAAS

The first figure shows that six of the eight fungal isolates were able to kill 80% of the mosquitoes by day 14 (day 14 is key timespan, as it is the amount of time the malaria parasite needs in order to develop from the ingested form in the gut of the mosquito into the infectious form that will pass malaria onto an uninfected individual). Notably, 70% of the cadavers had fungus spores growing on them.

They moved forward choosing Beauveria bassiana isolate IMI 391510 for the remainder of the paper, as this particular isolate is already presently being used as a biopesticide for agricultural purposes (and so it has already jumped through most of the hoops needed to prove that it is not pathogenic to humans). In their second experiment, they simulated a treated bednet situation, exposing the mosquitoes to impregnated nettings over 14 days. Once again, the fungus killed over 90% of the mosquitoes by day 14 (compared with only 38% that died from the only-oil-treated netting without fungus). Exposing the mosquitoes to the fungus every three days for six-hour periods (in the attempt to better mimic the three-day feeding cycle of the mosquito) did not reduce the killing efficacy of the fungus.

The Malaria Test

Of course, the next question is whether the lethal fungus can have any impact on malaria transmission. You can indeed make the argument that less mosquitoes means less malaria, but wouldn’t you like to see the data to back it up? The research group therefore tested what would happen if the mosquitoes contracted malaria (they used the murine species Plasmodium chabaudi) as well as the B. bassiana fungal infection.


© AAAS

The second figure shows similar mortality trends for the Beauveria-only and the Beauveria+Malaria treatments. However the authors comment that during the last 3 days (days 12, 13 and 14), the mortality rate of the Beauveria-only treatment appeared to slow, while the Beauveria+Malaria treatment kept its pace (note how the line is not as steep during days 12-14 for the Beauveria-only group). Therefore by day 14, the Beauveria-only treatment killed 90% of the mosquitoes while the Beauveria+Malaria treatment killed 95%.


© AAAS

Finally, the kicker experiment was when the group dissected a small sub-sample of the Beauveria-only and Beauveria+Malaria mosquitoes, looking whether they had oocysts in their midguts and sporozoites in their salivary glands.

When you compare the Malaria-only and the Beauveria+Malaria treated mosquitoes, there is no difference between the two groups when you look at the percentage of mosquitoes that have oocysts in their midgut. When you look at the proportion of mosquitoes that have sporozoites in their salivary glands, 35% of the Malaria-only treated mosquitoes had sporozoites, while only 8% of the Beauveria+Malaria treated mosquitoes had sporozoites in their salivary glands.

Figure 3 basically takes the above oocyst/sporozoite numbers and incorporates the mosquito mortality data (Figure 2), thereby illustrating what proportion of the starting population was capable of transmitting malaria. Remarkably, this re-interpretation of the data demonstrated that 31% of the starting population for the Malaria-only treatment would be able to transmit malaria to a new individual, while only 0.4% (1 out of 200) of the combined Beauveria+Malaria treated mosquitoes would be able to pass on the disease. Exposure to the fungal pathogen B. bassiana therefore reduced transmission of malaria 80-fold!

A Fungus Soon to be Among Us?

As I’ve already mentioned, these fungal biopesticides are already currently being used in agricultural practices. Therefore translating their use for ultra-low volume spraying inside houses will definitely be faster than designing a whole new chemical pesticide. Better yet, as you are much less likely to have a mosquito that is resistant to both chemical and fungus, combined spraying of both chemical and fungal-based pesticides would be an extraordinarily powerful weapon in the mosquito control arsenal.

And what about the human health risks of fungal spores in houses? Well first, Beauveria is a very common fungus found in the soil. So most individuals are probably regularly exposed to it. Moreover, there is very little evidence that this species of fungus is pathogenic to humans (most likely because it likes to grow at 25ºC, and is unable to survive at our sweltering 37ºC body temperature). So hopefully this demonstration for a new application for fungal biopesticides will inspire pesticide manufacturers to get involved in global health. With industry on board, indeed the possibilities just may mushroom...

References:

1. DDT. (2006, September 12). In Wikipedia, The Free Encyclopedia. Retrieved 04:13, September 12, 2006, from http://en.wikipedia.org/wiki/DDT
   
2. S. Blanford et al. (2005). Fungal pathogen reduces potential for malaria transmission. Science 308:1638-41.