tag:blogger.com,1999:blog-1812431336777691886.post971872348583507364..comments2024-02-29T03:57:00.088-05:00Comments on The Mermaid's Tale: ASTMH 2012Anne Buchananhttp://www.blogger.com/profile/09212151396672651221noreply@blogger.comBlogger15125tag:blogger.com,1999:blog-1812431336777691886.post-18190661321994193862012-11-18T19:17:29.825-05:002012-11-18T19:17:29.825-05:00These are very good points.
I have seen the same ...These are very good points.<br /><br />I have seen the same thing in rural Mexico, and did a bacterial (diarrheal) study in which we found that even the well water (much cleaner than the green-scum covered village pond) was contaminated. The greatest victims seemed to be infants threatened by diarrhea, but probably everyone was at some risk (my stay was only a couple of days, so not enough to make any judgements except that we did see affected infants)Ken Weisshttps://www.blogger.com/profile/02049713123559138421noreply@blogger.comtag:blogger.com,1999:blog-1812431336777691886.post-65534531818080497542012-11-18T19:05:20.369-05:002012-11-18T19:05:20.369-05:00Most Africans will tell you themselves that they k...Most Africans will tell you themselves that they know that disease risk would be mitigated with improved access to clean water. But even that isn't easy in an area where the climate alternates between drought and gushing rainy seasons.<br /><br />When we lived in Ghana, my mom at one point was thinking about no longer boiling our water. Once she had a look in the reservoir, she changed her mind. There was a dead lizard and a dead snake in it. I think that illustrates how difficult it can be to maintain a clean water supply in the tropics.<br /><br />As a child there, I actually got some kind of helminth infection. As all children invariably do, I fell and scraped my knee. It soon became strangely infected and started to migrate. I was lucky and was given a massive dose of antibiotics by injection. Most Ghanaians, especially at that time, would not have had access to such a treatment.<br /><br />Many who do not or have not lived in Africa often do not understand that living in the tropics presents very different challenges than living in a temperate climate. Marniehttps://www.blogger.com/profile/10850856778953207810noreply@blogger.comtag:blogger.com,1999:blog-1812431336777691886.post-48338915414642950102012-11-18T12:25:27.609-05:002012-11-18T12:25:27.609-05:00Marnie,
What you say about dracunculiasis, that i...Marnie,<br /><br />What you say about dracunculiasis, that it will likely be eliminated by the use of clean water and the wearing of shoes, echoes the greatest public health successes. Clean water arguably has done the most for health world wide than any medication ever will. Window screens are up there, too. The solution is often nothing fancy, though it does always involve money. And, of course, as Daniel has been pointing out, evolution can be counted on to make the fancy stuff obsolete before a new solution can be developed. Anne Buchananhttps://www.blogger.com/profile/09212151396672651221noreply@blogger.comtag:blogger.com,1999:blog-1812431336777691886.post-51562535106621203272012-11-17T16:08:37.608-05:002012-11-17T16:08:37.608-05:00The paper and its authors are very respectable and...The paper and its authors are very respectable and their generic conclusion seems plausible. I have only had a chance to look very superficially at it. However many things are correlated with pathogenic exposure so inferences are still rather speculative.<br /><br />On the other hand, many mapping studies are finding immune or inflammation related genes associated with chronic diseases that hadn't seemed related to infection, so the story again makes plausible sense.<br /><br />Of course, infection and inflammation are very generic kinds of reactions, and even finding 100 such gene regions needs to be seen in perspective.<br /><br />Traits that have possible human adaptive influences involve many things unrelated to inflammation (body size and shape and color and so on). Strong single-gene signals are few and far between. And since most traits of interest are complex, the effect of selection can be distributed across the contributing genes, to the extent that they might not be detectable at any one of them.<br /><br />These comments address your idea that pathogens are a 'dominant' cause, rather than just one of many possible causes.<br /><br />Infectious agents can impose very strong selection and rapid evolution, so the paper's findings are not surprising. How that works in the populations in which the data are found, which have traditionally been very small and widely dispersed, is a different question because of patterns of transmission require adequate host-demography. Perhaps the paper addresses this.<br /><br />As to your comments about children, I don't understand. Early mortality in children is extremely strong selection against their genotypes, and if helminths let you live long, that would _reduce_ their selective intensity, so that is something you should think about (or that I misunderstand from your comment).<br /><br />Hopefully measures such as you suggest will make any selective impact--and any disease impact--go away in the future.Ken Weisshttps://www.blogger.com/profile/02049713123559138421noreply@blogger.comtag:blogger.com,1999:blog-1812431336777691886.post-72991044384370676652012-11-17T13:19:41.076-05:002012-11-17T13:19:41.076-05:00Daniel and Anne,
The Matteo Fumagalli et al. pape...Daniel and Anne,<br /><br />The Matteo Fumagalli et al. paper finds that pathogens are a dominant cause of selection in humans. Moreover, among pathogens, it's helminths that impose the clearest selection signature. <br /><br />This really jibes with my observations of West Africa. Malaria is definitely a killer, but its victims are often children who don't live long enough to have children of their own.<br /><br />Not so for helminth infections such as dracunculiasis. People often live with these for many years.<br /><br />An interesting thing about dracunculiasis is that it will probably be more or less eliminated by communicating how it is transmitted, by providing access to clean water and by wearing shoes.<br /><br />Thank you for your very timely recent posts.<br /><br />Marniehttps://www.blogger.com/profile/10850856778953207810noreply@blogger.comtag:blogger.com,1999:blog-1812431336777691886.post-20811541905592958922012-11-16T16:43:45.469-05:002012-11-16T16:43:45.469-05:00And perhaps another interesting evolution / drug r...And perhaps another interesting evolution / drug resistance story has been the suggestion that we should consider not using aggressive therapy (high doses of antimalarials). I'm oversimplifying the argument, but basically the idea is that aggressive therapies more quickly lead to drug resistance. Anonymoushttps://www.blogger.com/profile/05068601494828074316noreply@blogger.comtag:blogger.com,1999:blog-1812431336777691886.post-61492519144269526502012-11-16T16:35:35.998-05:002012-11-16T16:35:35.998-05:00Hi Marnie, thank you very much for passing this on...Hi Marnie, thank you very much for passing this on. I had not seen it.Anonymoushttps://www.blogger.com/profile/05068601494828074316noreply@blogger.comtag:blogger.com,1999:blog-1812431336777691886.post-66907811659182865762012-11-16T16:34:29.632-05:002012-11-16T16:34:29.632-05:00Some nations have been pretty slow to make combina...Some nations have been pretty slow to make combination therapy the official approach to treating malaria. For that matter, in many places local distributors (with no medical training and sometimes fake or substandard drugs) are the main outlet for antimalarials. <br /><br />Also, in some places they are now treating vivax malaria with combination therapy (Cambodia is one place.) However, in Thailand they still treat vivax with chloroquine. Falciparum is widely resistant to chloroquine and it is thought that mixed infections (people infected with both vivax and falciparum) might lead to sustained resistance of falciparum to chloroquine. Anonymoushttps://www.blogger.com/profile/05068601494828074316noreply@blogger.comtag:blogger.com,1999:blog-1812431336777691886.post-41870828649514716132012-11-16T16:25:48.639-05:002012-11-16T16:25:48.639-05:00I'll say thanks very much from all of us, Marn...I'll say thanks very much from all of us, Marnie, as we've all been posting recently. I was trying just today to figure out how to move the author's name up under the post title, but couldn't. I know it's confusing as it is. If anyone knows the secret in Blogger, please let me know! <br /><br />I'll turn responding more fully to the paper you've linked to over to Ken, as he's the one with more to say on the subject of selection and the human genome. Except that I will say that this paper reports finding signatures of selection at immune genes; while GWAS have been pretty unsuccessful at finding genes for disease in general, over and over they _do_ report at least some association of whatever disease with immune genes as well. This starts to look like real evidence that disease might in fact have been a strong selective force. We know that's true for malaria. Which other diseases it might also be true for I think is still an open question. Anne Buchananhttps://www.blogger.com/profile/09212151396672651221noreply@blogger.comtag:blogger.com,1999:blog-1812431336777691886.post-47473390532089873242012-11-16T15:20:13.266-05:002012-11-16T15:20:13.266-05:00Yes, that's what I meant.Yes, that's what I meant.Ken Weisshttps://www.blogger.com/profile/02049713123559138421noreply@blogger.comtag:blogger.com,1999:blog-1812431336777691886.post-10678628582849313882012-11-16T15:16:49.742-05:002012-11-16T15:16:49.742-05:00By multi-component targeting, do you mean using mu...By multi-component targeting, do you mean using multiple drugs that are likely to target different aspects of the parasite or virus? If so, yes, that is the common recommendation for treatment of falciparum malaria. Artemisinin (which is the last drug without widespread resistance) is supposed to only be used in combination with other antimalarials that are thought to have different modes of action or targets and certainly have different half-lives. Artemisinin has a half life of hours whereas other drugs in the cocktail have half-lives of weeks or more. <br />There really aren't any drugs for treating dengue yet, but I imagine that after there are, and after drug resistance emerges with dengue, that drug cocktails will be the next move for dengue too. Anonymoushttps://www.blogger.com/profile/05068601494828074316noreply@blogger.comtag:blogger.com,1999:blog-1812431336777691886.post-34228554311821044092012-11-16T14:43:19.874-05:002012-11-16T14:43:19.874-05:00Sorry, my post should be addressed to Daniel, as I...Sorry, my post should be addressed to Daniel, as I see he is the author.Marniehttps://www.blogger.com/profile/10850856778953207810noreply@blogger.comtag:blogger.com,1999:blog-1812431336777691886.post-12713099034825424152012-11-16T14:41:47.405-05:002012-11-16T14:41:47.405-05:00Regarding the need to build houses that are less p...Regarding the need to build houses that are less prone to mosquitos, ones that are ventilated, liveable and also built off the ground, I stumbled on this article in Dwell Magazine a few years ago:<br /><br />An inno-native approach:<br /><br />http://www.dwell.com/articles/an-Inno-native-approach.htmlMarniehttps://www.blogger.com/profile/10850856778953207810noreply@blogger.comtag:blogger.com,1999:blog-1812431336777691886.post-66781829207060593832012-11-16T14:35:33.837-05:002012-11-16T14:35:33.837-05:00Hi Anne,
Thanks for all the amazing recent posts....Hi Anne,<br /><br />Thanks for all the amazing recent posts. At some point, I'd be interested on your thoughts on this paper:<br /><br />Signatures of Environmental Genetic Adaptation Pinpoint Pathogens as the Main Selective Pressure through Human Evolution<br /><br />Matteo Fumagalli et al.<br /><br />http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1002355<br />Marniehttps://www.blogger.com/profile/10850856778953207810noreply@blogger.comtag:blogger.com,1999:blog-1812431336777691886.post-20852866085584443542012-11-16T08:38:17.449-05:002012-11-16T08:38:17.449-05:00One way to combat the problem that intense applica...One way to combat the problem that intense application of an anti-parasite compound like a single drug is that as a result of the intensity of natural (actually, artificial) selection, the parasite population is forced to, and is able to, evolve genetic resistance. Resistant organisms find themselves without competition from their susceptible fellows, and can reproduce rapidly.<br /><br />From an evolutionary point of view, is it not correct that one idea in the case of diseases like dengue and malaria is to clobber the parasite out of existence if possible, rather than have to continue to combat it by continual symptomatic treatment?<br /><br />This is what rarely seems to work, because of parasite resistance evolution. The same is true with resistance to chemotherapy in cancer patients.<br /><br />So, one approach has been to apply major doses of more than one drug at the same time. This raises the likelihood, in theory at least, that no parasite individual (or individual tumor cell) will resistance to all of the agents hunting them down, before all of the parasites are gone.<br /><br />Is such multi-component targeting part of the strategy in relation to dengue or malaria?Ken Weisshttps://www.blogger.com/profile/02049713123559138421noreply@blogger.com