Mosquitoes, diseases and the “natural” delusion

Mosquitoes have always been a major problem in the tropical regions. There are few things as unpleasant as a mosquito bite. That, however, is nothing compared to the very real threat mosquitoes pose to humans as disease vectors. Mosquitoes are known to be carriers of a variety of diseases such as malaria, dengue, filariasis and chikungunya, among others.  Zika , a viral disease spread by mosquito bites, that otherwise presents very mild symptoms, has of late become another reason for major concern worldwide. It has been found that the virus that causes the disease can be sexually transmitted, and that if a pregnant woman has zika, her child is very likely to be born with microcephaly and neurological problems that may lead to severe mental and physical handicaps or even death. And the virus, which was confined mainly to certain parts of Africa and Asia in the past, saw an outbreak in Brazil recently, and has since been spreading worldwide, because the Aedes mosquitoes that carry the virus are spreading, with a little help from their human friends. It is important, then, to stop the mosquitoes from doing any harm, and steps have to be taken to prevent them from spreading.

The traditional way of dealing with mosquitoes has been the use of insecticides, mainly DDT. But with prolonged use of DDT, newer generations of mosquitoes came to be resistant to it. Resistance led to a massive resurgence of the mosquitoes -whose numbers had plummeted earlier- and hence led to spikes in the number of malaria cases. It was also found to be toxic to humans, so that the cost-benefit ratio had become just too high to be sustainable:

In Sri Lanka, for instance, malaria was all but wiped out with the help of DDT, but by the end of the 1960s, when resistance was widespread, cases surged to more than half a million a year. By that time, Rachel Carson had highlighted the toxic effects of DDT in Silent Spring, and many nations banned its use.

DDT has since been replaced by their less toxic alternatives, a class of compounds called pyrethroids, which have been greatly successful in their repellent action against mosquitoes as well:

In a Nature paper last year, a group led by Simon Hay at the University of Oxford in the United Kingdom estimated that between 2000 and 2015, some 633 million malaria deaths were averted, with 68% of that decline due to insecticide-treated bed nets and 10% to IRS. (Treating people with antimalarial drugs accounted for the remaining 22%.) Pyrethroids have also played a role in the fight against Aedes aegypti, the main mosquito transmitting the yellow fever, dengue, and Zika viruses, even though bed nets are less effective against A. aegypti because it predominantly bites people outdoors and during the day.

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Transfluthrin – a pyrethroid, meant to be delivered in vapor form

However, starting from 1993 in Ivory Coast, mosquitoes have been found to become increasingly resistant to pyrethroids, and this trend is fast becoming a global one, causing concern. Quite a few African countries have been among the worst hit by pyrethroid resistance. Malaria cases have been on the rise, and that is becoming a big problem once again, after decades of having been under control. New alternatives to pyrethroids are being offered and put to experimental use in some places, but they are not cost-effective or safe enough to be viable. Also there is another challenge that they cannot overcome:

Finding replacement insecticides for bed nets is far trickier. Any insecticide used in a bed net “has to be safe enough that a child can put it in their mouth,” says Ranson, and only pyrethroids fit the bill. Pyrethroids also have a trait scientists call excito-repellency: They stimulate mosquitoes to leave the net. [Alternatives to pyrethroids don’t do] that.

Not only are bed nets the best weapon in the fight against malaria-carrying mosquitoes, in many countries they are the only one.

Other solutions, which don’t have to do with insecticides, are also being explored. Some mosquitoes are being genetically modified so that the females, which are the ones that bite mammals, die before they reach maturity and mate with males. This serves to massively bring down the number of mosquitoes, because they cannot reproduce. Some techniques also introduce new microbes that compete with the viruses and drastically reduce their numbers in transmission while themselves not transmitting to the host. They instead, find their way into the eggs of the mosquitoes, which is how it gets transmitted to the next generation of mosquitoes. These are currently being researched even as the preliminary pilot studies in places like Brazil are showing encouraging results. Any large scale implementation, is however, at least a decade away -as does happen with any new medical intervention- and likely to be expensive because of the sophisticated biotechnology involved, and the difficulty in acquiring and provide adequate numbers of the desired mosquitoes.

Mosquitoes usually breed in moist environments, laying their eggs in standing water. The females of hematophagic (literally, “blood eating”) mosquito species need blood proteins, mainly the heme protein, which is hydrolysed in the gut of the mosquito, helping to form egg yolk proteins during the completion of their gonadotrophic cycle, and to ensure the fertility of their eggs. Mosquitoes mainly detect the presence of humans using certain cues, major among them being our body odors and CO2 gas that is exhaled by us. A 2015 review of all studies researching mosquitoes’ susceptibility to various cues stated:

In recent work, McMeniman et al. were able to assess if a female mosquito’s reactions to heat and skin odor were modulated by contact with CO2 by comparing the responses of normal mosquitoes with ones engineered to lack a subunit of the CO2 receptor (and therefore to be insensitive to CO2). In a screened-cage assay, mosquitoes exposed to a 20 second pulse of CO2 landed on a heated target, whereas mutated mosquitoes were insensitive to this stimulus. Similarly, in a port-entry assay, normal mosquitoes were more apt to enter a port releasing human odor plus CO2 over human odor alone, but mutated mosquitoes were not influenced by added CO2. Thus, in these trials, CO2 seemed to gate the response to heat and skin odor. In a semi-field setting, however, these mutated mosquitoes had only marginally impaired (about 15%) orientation to humans compared to wild-type mosquitoes, indicating that, the in absence of CO2 detection, other combinations of odorants and cues can induce orientation to a host and landing.

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Flowchart model for mosquito location of host and effects of various cues on locating behaviour of mosquitoes (Source: http://www.cell.com)

A further study published in a recent issue of Current Biology by van Breugel et al. using a wind-tunnel setting found that the presence of a CO2 plume gated highly directed flights to, and landings on, an otherwise unattractive 20-cm-diameter black dot placed against the white background of the tunnel’s floor. Evidently, the dark object’s contrast with background was important in this reaction, because, in another wind-tunnel study, a dark visual target that was not highly contrasted with background failed to induce landing in the presence of a CO2 plume. In the work of van Breugel et al., this mosquito only oriented to a thermal mimic of human in close proximity and this salience, in contrast to findings of McMeniman et al., seemed independent of recent contact with the CO2 plume. The differences evidenced in these three studies suggest that the context of stimulus presentation can determine behavioral outcomes and interpretation of stimulus integration and valence.

This means that mosquitoes are most likely to be attracted to us because of the CO2 gas we exhale, in addition to our body odors. Apart from that, objects that have darker hues are likely to attract more mosquitoes. As a result, people wearing clothes of dark colors are likely to attract mosquitoes more than those wearing clothes of lighter shades. The review concludes that:

From the perspective of preventing this dangerous mosquito from biting, the adage of wearing lightly colored clothing stands, and the use of a repellent to interfere with response to skin odorants remains the most practical tactic.

Hence, we can see that the other way in which we can keep mosquitoes away is by using insect repellents which we can wear on our clothes or body. The standard and most effective such repellent is N,N-Diethyl-3-methylbenzamide, or DEET. Many people have raised health concerns regarding DEET, suggesting other alternatives, and which are touted as “safe” and “natural,” among other things. Most of these alternatives are derived from plant products. One of the most popular, and most effective, such alternatives is citronella. However, the problem with citronella is that it evaporates fast, so that the user is left unprotected once concentration of citronella has dropped below the critical level needed to maintain repellency. Certain techniques can be used to prolong the repellency of citronella, but with variations of weather conditions, the availability of citronella also varies. In most practical cases, standard doses of citronella last, on an average, for about 3-4 hours. Then too, they are not as effective in outdoor conditions as they are in indoor conditions. But what about safety? DEET, after years of stringent testing for safety and effectiveness, has proved to be both safe and effective, if used in right doses and care is taken to avoid ingestion or contact with mucous membranes. The alternative repellents, whose effectiveness is always lesser than DEET, or at most the same, are never tested for their safety because they are sold with the “natural” tag. The fallacy involved in popular thinking, that “natural” essentially translates to “safe,” is obvious here, and is called “appeal to nature fallacy.” As a review evaluating plant-based mosquito repellents suggests:

…it must be emphasised that many other plant produce compounds that are highly toxic to mammals and / or irritating to the skin, and natural does not equate to safe.

If being plant-based alone is the criterion for a product to be labeled “natural,” then plants produce chemicals that are both beneficial and harmful to us. In fact, the same chemical can be harmful, beneficial or neutral, depending on a multitude of factors. Beta-carotenes are a good example, acting as provitamins for vitamin A, and to some extent vitamin E, but in higher concentrations than required, or dietary supplementation that is lacking in specificity, has also been found to increase the risk of lung cancer in smokers and asbestos workers. Therefore, it is imperative that every single chemical be rigorously tested for safety before it is okayed for human use. Until controlled and methodologically sound trials for safety of a chemical are done and their results published and verified, there is no reason to trust it at face value just because it is plant-based and is being touted as “natural.” Although citronella is safe and effective alone -if applied every 3-4 hours and if the subject is situated indoors- the best safety-efficacy profile appears to be found in the citronellal-citronellol-geraniol blend, but more research needs to be done to be done in this regard.

But nothing can supplement good outreach programs and targeted public health policy. Political will is one of the most crucial factors in realization of any public health achievement, as Sri Lanka’s recent eradication of malaria would testify. Mosquitoes are pretty much an intractable species, unless you take the best measures you can to keep them from reproducing and spreading. Greater the population, greater the challenges. Apart from instituting measures for speedy diagnosis and treatment of mosquito-transmitted diseases, early identification of disease hotspots and organized diversion of resources to such areas in order to combat the spread of disease are also important. Special care needs to be taken to protect children and pregnant women from such diseases as well. People need to be made aware of STDs like zika and encouraged to adopt safe sex practices. As long as mutant mosquitoes that don’t spread malaria, dengue, yellow fever and zika are elusive, we need to take every single tried and tested step to keep these and other mosquito-transmitted diseases at bay.

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