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Fighting drug resistance by switching to environmental management of mosquito habitats

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William Jobin
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Fighting drug resistance by switching to environmental management of mosquito habitats

Drug resistance can be fought by engineering methods.

I share the concern of WHO and others about preventing the spread of drug resistance from Burma (or Myanmar as it is called by a few dictators) to the rest of the world (See Oped piece of 29 March in International Herald Tribune). But there is a better way to prevent it, by using environmental management of mosquito habitats and reducing the dependency on drugs and their increasing use. However the response of the malaria people in Burma and in WHO Geneva to growing drug resistance of the malaria parasite has simply been "More of the Same." It is incredible that the failure of malaria control in Burma is occurring right next door to the success of malaria control in Malaysia, but WHO is not exploring the reason for this huge difference. The reason for the difference in these two countries is that the base for the fight against malaria in Malaysia has always been environmental management of the malaria mosquito habitats, whereas in Burma the malaria people don’t even know which mosquito is causing their problem; they simply look for another combination of drugs. I call it chemical dependency, and it weakens not only the fight against malaria in Burma, but also in Africa.

Malaysia started their long history of successful suppression of malaria in the 1920’s when they discovered that the responsible mosquitoes lived along the edge of small streams, needed shade, and could breed in coastal swamps. So they developed ways to flush the streams with permanent siphon structures, remove the shade manually, and control the salinity in coastal swamps with tide gates. I visited the island of Penang in Malaysia a few years ago and saw that these measures are still in place and still working, after decades. Penang is just south of Burma. They also pioneered the use of underground drainage channels, filled with coconut husks to maintain the flow channel. This eliminates the problem of "hoofprint" breeding sites by lowering the local water table. I have covered these engineering approaches to mosquito control in my book "A realistic strategy to fight malaria in Africa" by Boston Harbor Publishers 2011. But Please check out the Malaysia vector control website, especially the last section, on environmental management of mosquito habitats. Note that the current number of cases of malaria in Malaysia is down to a few thousand per year. http://www.actmalaria.net/IRW/IRW_Malaysia.pdf Or simply look up malaysia and malaria.

I was interested to see this successful program in Malaysia because I have worked on environmental management of tropical disease transmission for about 50 years. I learned that long before chloroquine or DDT came on the scene, the malaria had been reduced to a manageable prevalence in Malaysia by these kinds of environmental measures. Their success has endured. Currently only a few thousand cases of malaria are found in Malaysia in an average year, whereas in Burma the number is in the millions, and growing. But in Burma you have been swamped by drug resistance, first to chloroquine, and now to the supposed answer to chloroquine resistance; artemisinin in combination therapy. So in 2011 WHO proposed the strategy to fight drug resistance which is basically more of the same, adding more drugs to the mix and looking for new ones. What do they call it when you keep doing the same thing over and over but expect different results?

The way to get out of the treadmill of drug resistance is to broaden the fight in Burma to add environmental mangagement of mosquito habitats, and to get off the dependency on drugs. It is a fairly simple process.

The first step is to find out which mosquitoes are transmitting malaria locally and where they live.

The second step is to modify their habitats so that the habitats and mosquitoes are drastically reduced in numbers. As transmission is reduced by control of mosquito breeding, then limited and careful use of drugs can help to achieve suppression of malaria prevalence for generations, without causing more drug resistance.

David Warhurst
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control of drug-resistance spread
<P>I agree with William Jobin that the origin of&nbsp;drug-resistance lies in the use of drugs, which select for random, generally unfit, mutations,&nbsp;or for, also unfit, copy number variations which happen to&nbsp;&nbsp;enable the parasite to grow in the presence of that drug.</P> <P>It is nevertheless also clear we&nbsp;cannot not stop treating clinically ill persons for their infections.</P> <P>So why, when mutations are random,&nbsp;does drug-resistance get a hold and where?</P> <P>The&nbsp; malariologist Verdrager (<A title="The Journal of tropical medicine and hygiene." href="http://www.ncbi.nlm.nih.gov/pubmed/3543384"><U>J Trop Med Hyg.</U></A> 1986 Dec;89(6):277-89) concluded that&nbsp;one important factor might be&nbsp; importation of "non-immune migrants to a hyperendemic malaria area"&nbsp;and he noted that in Pailin, Western Cambodia on the border with Burma, &nbsp;another factor might be a particularly efficient mosquito, then called Anopheles balabacensis, and&nbsp;the third&nbsp;factor a rather indiscriminate chemoprophylactic approach&nbsp;using chloroquine in table salt supplies. &nbsp;In Irian Jaya, Indonesian New Guinea, where there had also been a chloroquinized salt project, the level of chloroquine resistance in Plasmodium falciparum was much lower than in Païlin; this&nbsp;he said was associated with the absence of a non-immune population and the lower dose of chloroquine base used in the salt.</P> <P>In the 60s when&nbsp; selecting for&nbsp;chloroquine-resistance in mice using drug in the food we found we had to use use immunosuppression and a high drug level which would reduce parasitaemias by 95%.</P> <P>It is also worth noting that in Africa there was no confirmed chloroquine-resistance until it was imported in the late 70s. This was a region where chloroquine was used on a very large scale but where, because of high endemicity, &nbsp;the adult and&nbsp;teenage populations were largely clinically immune, while continuing to be an important&nbsp;reservoir for transmission.</P> <P>The contrast with early (late 50s-early 60s) development of chloroquine-resistance in SE Asia and S.America,&nbsp; suggests that&nbsp;while the African use of&nbsp;chloroquine was high, the drug&nbsp; selection pressure on the parasite population there was quite low, and the fitter wild type parasites found a drug-free haven in adult hosts, which would ensure they would survive as an important part of the parasite population.</P> <P>It is not often recognised that this could mean that&nbsp; wild types&nbsp;might then very &nbsp;likely out-compete&nbsp;any mutants in the vector mosquito, as they would almost certainly be more fit, as&nbsp;vector stages are&nbsp;unaffected by chloroquine.</P>
William Jobin
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Drug dependency is the problem
<p>Thank you David Warhurst for your very penetrating analysis of the reasons for drug resistance in Burma and Africa.</p><p>But I think the more important point is that drug resistance occurs when health authorities adopt drug dependent strategies, instead of employing integrated strategies. &nbsp; In a rational and integrated strategy one balances drug use with several other components for malaria suppression, such as environmental management of water and mosquito habitats, health education, larviciding, screening of houses and sleeping areas, land reclamation, improved irrigation and drainage works, and crop selection. &nbsp;Automatically this reduces drug use and the pressure toward drug resistance.</p><p>Do you see my point? &nbsp;The attempts to suppress malaria transmission in Burma have been too narrowly conceived, as have the attempts by WHO in Africa. &nbsp;A strategy is used which is in truth, drug dependent. &nbsp;That is why drug resistance is coming again.</p>

William Jobin Director of Blue Nile Associates