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Preventing meningitis caused by parasites
#61
What the recent cases seem to have in common is they grow their own vegetables. However, that doesn't prove that is how they got infected nor does it mean that other local sources are any less likely to have the slugs or their larvae.
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#62
Anyone who has had symptoms in the last year should get a test for this. If you've had a virus, flu, anxiety attack, food poisoning, gastro disturbances, headaches, woke up feeling weird etc...
you probably got it.
I'd suspect the buggars are crawling up the county water spigots or in the storage tanks. I know lots of people who have it that do NOT grow there own food, nor eat farmer market greens, and are not unsanitary, it could be from restaurants/food stands.
Its a shame just when the buy local and raw food movements were gaining ground. Now its back to the overpriced poisonous plastic water bottles.
We need more info. about the symptoms, progression and treatments.
Thank you for all your diligent work in bringing this to the public shekepal and alaskasteven.
Deadly slugs, biting ants, stinging caterpillars, noisy frogs,
Its our punishment for electing a republican. Guess we'll have to dump em in Maui if we want to have anything done about it.
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#63
Here is Dr. Prociv’s (and Dr. Carlisle's -they are married) reply to the questions. He is now retired, recently moved (his files are all in boxes where they are not ready to hand), so he is fielding some of these questions from memory without being able to refer to his papers. Ironically, I also have about a two-foot high stack of photocopies & reprints of journal articles on Angiostrongylus cantonensis boxed and stored in a barn in the Sierra Nevada Mountains where they are completely inaccessible at the moment. Fortunately, however, there does appear to be quite a wealth of newer information available online regarding research on rat lungworm.

Following below Dr. Prociv’s replies are in plain text, questions for him are in italics, with parenthetical remarks and information from me inserted in brackets. He writes:

Thanks for your further communiques. They remind me of something I’d overlooked – the role of paratenic hosts. I recall in Tahiti and the Cook Islands there have been reported outbreaks after people ate raw shrimp [called freshwater "prawn" in Puna] salads, and also in parts of the Pacific, coconut crabs and land crabs have been recognized as sources of Angio for humans. Obviously, the infective L3 can survive passage into certain other host without undergoing further development and from them pass to rats or people. Crustaceans and land planarians have been confirmed, while other species may yet be discovered for this role. These are recognized scavengers that probably eat slugs and snails. I’d imagine that in such cases you’d probably be eating only small numbers of L3s from such paratenic hosts, but that’s all you need for symptoms.

The point about water filtration: from memory, the L3s are about 400 microns long by possibly 20 wide. Sorry, but this could be incorrect; I need my references for specific dimensions, but can’t access them yet -you could try searching online; I’d say a 20 water filter should remove most L3, but a smaller mesh would be even safer.

[Searching online I have located several notes saying A. cantonensis L3-stage larvae measure 425 to 524 microns in length and from 23 to 34 microns in diameter. If anyone else finds figures different than these, then please do post them. If these figures hold up then they are good news as regards using 20 micron filters on catchment tank water. Research is needed to determine the effect of home in-line UV light sterilization units on L3 as well. My experience during several years in South America was that a combination of physical micropore filter and UV sterilizer worked much better than either method by itself.]

Q: Here is another question together with some interesting comments in a post to the Punaweb discussion on angio. This is the first time I've heard of using anything prophylactically against angio; any comment on ivermectin as a prophylactic agent for angio in dogs? I've asked for a citation to track down how that 77.5% slug L3 infection number was determined (sounds very specific, perhaps more so than is certain to be the case, so I wonder about the method used).

A: Yep, the problem with killing the worms migrating thru the CNS is that this would simply exacerbate the clinical problem; a dead worm stops moving, starts disintegrating and so stimulates a much more aggressive inflammatory reaction, possibly even serving as a nidus for bacterial infection. If you have worms moving thru your brain, you want them to get out of there ASAP, which is what they’ll do, eventually, left to their own devices. In the young child who died here in 1998 there were hundreds/thousands of maturing worms in the pulmonary arterial system, just as you’d expect in a rat, so these had all obviously passed successfully out of his CNS and were about to complete their life-cycle, i.e. start sexual reproduction. Sadly, this child was simply overwhelmed by a massive infection. Now, the only drug I know that kills nematode larvae in tissues is ivermectin (and its relatives), but it has never been shown to work against migrating L3s in the CNS (and you wouldn’t want that there, anyway, as just explained). However, were you to take the drug just as the L3s were entering your system (from an ingested snail, say), and before they reached the CNS (the window of opportunity is only 1-2 days), then maybe ivermectin would work – as it does for heartworm in dogs (and probably Toxocara, and even hookworms, and therefore maybe Angio.). So, if people suspect heavy exposure, it wouldn’t hurt to take ivermectin – but when do you stop taking it?!

[Searching online I have located records of animal studies on rat lungworm L3 therapies using albendazole, cucumin, interleukin-12, mebendazole, and a combination of interleukin-12 and mebendazole. The lattermost is intriguing enough to share these summary snippets and source info-

“Treatment with mebendazole in combination with IL-12, however, resulted in low levels of worm recovery and dramatic lessening of the eosinophilic meningitis....This study could be used in developing strategies for the treatment of human angiostrongylosis.”

and

“To address previous doubts that chemotherapy can lead to exacerbation of neurologic damage due to simultaneous death of a large number of A. cantonensis organisms in the brain, chronological changes in the brains of mice treated with mebendazole at 4 dpi were monitored between 5 to 14 dpi (data not shown). Chemotherapy did not shorten the period before the onset of eosinophilic meningoencephalitis. Eosinophilic meningoencephalitis still first appeared around 11 dpi, as was the case for the nontreated mice. But the severity of meningitis was lessened to a moderate degree due to the lower number of worms.”

Combined Treatment with Interleukin-12 and Mebendazole Lessens the Severity of Experimental Eosinophilic Meningitis Caused by Angiostrongylus cantonensis in ICR Mice
Wen-Yuan Du,1 Jiunn-Wang Liao,2 Chia-Kwung Fan,1 and Kua-Eyre Su1*
Infect Immun. 2003 July; 71(7): 3947–3953.
doi: 10.1128/IAI.71.7.3947-3953.2003.
PMCID: PMC161979
Copyright © 2003, American Society for Microbiology ]

*Edit: Here is the link to the full text of this article; I forgot to insert it with the original posting. The numbers located by the authors' names tie to their contact info at this site.
http://www.pubmedcentral.nih.gov/article...tid=161979

Q: What I keep not being able to understand is that scientists, including ones with the CDC, say that they find nematodes in the slime of the semi slug, just not that many, and that either no one knows how many nematodes have to be ingested or that you may only need a few to cause symptoms, but that it is doubtful that you can get the illness from the slime. Now, if you have ever gotten freshly slimed by a semi slug, you know it takes much scrubbing and something like clorox to get the slime off. It is incredibly viscous and I can imagine, particularly in this climate, the slime not drying for a little while, allowing the nematodes to stay alive. If you pick lettuce, or green pepper or anything else and just eat it right from the garden, which is what I used to do here years ago, and it happens to have slime on it, this means that you could be eating live nematodes, does it not?

A: Unless more recent work has been done on this, my impression from past studies was that the slime story was inconclusive. In slugs/snails, the L3s settle within muscle tissues, so it’s unclear how/why they’d be leaving for the outside world (although definitely possible). I’m not saying it’s wrong, but that I’d like to see more/better evidence. However, if there really were Angio L3s in slime, then you’d be wasting your time washing the lettuce, as the slime is so tenacious and, when dry, almost imperceptible. I’ve also found tiny snails right in the heart of a lettuce bought from a supermarket!

[This is why I, for myself and my family, will be using a 5 gallon bucket and doing a salt brine soak of veggies which may have infected little slugs hidden in them, then agitating the veggies and rinsing well. The salt brine should cause any little slugs and snails to immediately detach from the leaf surface; soaking veggies for awhile may dissolve any slime with live L3 (if any L3 are indeed present and alive in the slime of those particular veggies after all the rat control measures), and may disrupt the tissues of any L3 which are present. After agitating the veggies again in a second bucket of clean water, a final rinse with distilled water could further disrupt any L3 present in dried slime (which by that point would hopefully have dissolved).]

A, cont.: From my own backyard studies, I discovered that there were lots of different species of nematode larvae (which all look almost identical with each other) in these molluscs; unless you were a specialist in this area, you would confuse the free-living or other parasitic species with L3 of Angio (the differences are subtle, so you’d need to know what to look for, and to examine them very carefully). This might explain the high prevalence of larvae (77.5%) in the local semi-slugs - they might not all have been Angio. Also, finding nematode larvae in slime proves nothing, unless they were confirmed [as via clinical experiments feeding bits of slimed-with-L3-present veggie to certified parasite-free rats and then later, after the appropriate grow-out period for rat lungworm, sacrificing the rats and checking for presence of the worms] to be the culprit – and you’d also want to confirm they [the L3] were alive/infective.

[Indeed, searching online in following up on this comment I found several general surveys of parasites in tropical rats which identified multiple parasites of all different sorts in them. Illustrative and typical is the note that rats examined were “...found to be a host for 9 species of nematodes in Kuala Lumpur and Singapore by Schacher and Cheong (I960). On Tioman R. sp. tiomanicus is a host for "at least 7 species of nematodes. Three of these 7 (Sypiacia maris, Angiostrongylus cantonensis and Ntpposlrongylus brasilieiisis) have been recorded from R. r. diardi elsewhere in Malaya. In addition. R. sp. tiomanicus harbours at least four species of cestodes (tapeworms), one trematode (liver fluke) and a pentastomid (tongueworm). Thus, in numbers of species of parasitic helminths there is certainly no major difference between the commensal R. rattus of the mainland and the principal commensal (and forest) rat of Tioman.” From: Notes on the Endoparasites, by Frederics; L. Dunn.

So, yes, there are all sorts of nematodes and other helminth larvae present in rats. It is tough to differentiate between some species of helminth larvae so this may affect species-accurate counts in some studies. The main actionable point I take from this, though, is "Kill the rats!"]

Q: When the semi slug is tiny, and black in color it is does not carry the nematode, according to some studies. Only as it matures and turns grey which is when it is about 1/2 inch and gets up to its adult size of about 3 inches, is it infected with nematodes. Not that you would intentionally eat one of these things, but they could be overlooked and sliced up or put into a blender for a smoothie.

A: I’ve never heard of this study, but it shouldn’t be a difficult one to do. I’d like to see the original paper. It stands to reason that the larger a snail is, the higher worm load it’s going to carry, as these beasts keep on accumulating Angio larvae for life (the L3s stay in its tissues until it dies). However, if you’re going to ingest one of these accidentally, I suppose you won’t have an opportunity to examine it, for size or color! Given that it takes the larva at least 2 weeks to develop in the snail (from the first stage: L1, thru to the infective L3), then perhaps this is sufficient time for the snail to grow significantly in size. I have no idea how fast your slugs/snails grow, but ones I observed here [Queensland, Australia] years ago did it pretty fast, from egg to maturity in a few weeks. The larvae found in a very young one might simply not yet have attained the infective L3 stage.

That’s about all I can say in response to the postings so far, but please don’t hesitate to ask if you have more questions, or need clarification of some points. I reckon there’s a strong case for someone to be doing a little more basic research over there, as this problem sure does have local flavours and variations, and it wouldn’t cost too much to find some answers. (Isn’t your new President a Hawaiian? Maybe he’d be sympathetic . . . )

Dr. Prociv’s comments conclude there.

As Dr. Prociv has noted above, more research is needed. Quite frankly it does not seem to me like the questions which need answering would be too difficult or expensive to resolve at even a modest lab set up for conducting rodent research, as long as someone on the team has a bit of experience in tropical parasitology to oversee the process and confirm valid methods and results. If there are local researchers at the university or in the public health system who would like to lean into this issue with some simple basic experiments, but who lack funding and support, then if they identify themselves I am sure there would be a strong groundswell of enthusiasm from residents of Puna, Friends of Puna’s Future, and others for the Council and other entities to appropriate funds toward such research. This really is an issue for the state of Hawaii to take on (the business of government being business, all too often in practical effect) as it will be a disaster for tourism if more people come to grief and the tourists not only stop ordering salads at restaurants and resort hotels but stop coming altogether. Several Puna locals can sicken and die, apparently, without a big noise arising and heaven and Earth being moved on the issue but if just one tourist child dies then I'd predict all Hades would break loose in the national media. What a black eye for tourism PR that would be.

One last note, in our online discussion the question was asked “Is there any research what those infected people had in common? Poor hygiene,weakened immune system,etc.?” I am sure the intention was constructive and the comment innocent of any intention to cast aspersion, nor has anyone seemed to take it that way so far, yet in my experience it is important to not unnecessarily associate a stigma of any sort (e.g., poor hygiene, weakened immune system) with an epidemiological issue. Stigma generates shame ...and shame leads to people hiding in embarrassment and fear rather than stepping forward and seeking assistance. When people hide then the accuracy of the picture painted by statistical reporting suffers and it becomes manyfold more difficult to identify and intervene in eliminating pockets of infestation.

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A pleasant slideshow: http://www.thejoymovie.com

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Astonishing skill! This archer is a real-life Legolas and then some!
http://geekologie.com/2013/11/real-life-...rs-anc.php

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#64
"I'd suspect the buggars are crawling up the county water spigots..."

That's a tad alarmist. Not that I want to get this or would wish this on anyone but people accept a much higher risk of death or crippling from motor vehicle accidents.
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#65
Here is the article written by scientists on island that show 77.5 percent of P.martensis collected in their sampling carry A. cantonensis
http://www.bioone.org/perlserv/?request=get-document&doi=10.2984%2F1534-6188%282007%2961%5B457%3ADOPCMP%5D2.0.CO%3B2

And, I think alaskasteven mentioned something about it being a good idea to do studies to see if the rat can be infected by the slime. Here is one that was done in Malaysia.
http://www.sciencemag.org/cgi/content/ab.../3804/1057
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#66

Thanks, Shekelpal; the refs are much appreciated.

In a way the indication L3 in slime are infective may be bad news, since this broadens the pool of potential routes via which L3 can infect humans well beyond the bodies of terrestrial and freshwater mollusks and freshwater crustaceans. In another way, though, the second part of what the abstract says may offer some huge good news even given that L3 are alive and infective in slime:

"Experimental evidence from rats suggests that the local human population, exposed to repeated low-level infections, may become immunized against the rare massive exposure and against clinical disease that might otherwise result after ingestion of heavily infected raw mollusks."

http://www.sciencemag.org/cgi/content/ab.../3804/1057

This aspect would be good to know much more about!

Even just a couple of L3 can be very dangerous depending on where in the brain they are burrowing (some important brain structures are only the size of a grain of salt to the size of a grain of rice, so a 2cm larvae burrowing through the center of a critical tiny structure can wreak havoc). So, it would be exciting if killed-L3 proteins, injected into the body, could be demonstrated to generate an immune response against subsequent live L3 invasion.

If so, then --via routine immunization of Puna tots, children, adults, and perhaps immunization of pets & farm animals as well-- there would be yet another angle for preventing catastrophic harm if rat control, slug control, and veggie inspection/cleaning all fail. Far safer to generate an immune response with dead L3 introduced to the body, I would think, than acquiring such at random via the natural experiment wherein immunity may be generated through accidental ingestion of one, two, or several L3 but at grave risk of discomfort and even severe permanent neurological damage.

In the meanwhile, if this report is accurate then it suggests lifelong residents of Puna and those who have been eating Hawaiian veggies for many years both in Puna and on the other islands may have developed some degree of protection through prior low-level exposures, but tourists --and tourist children in particular-- are wide open to devestating attack.

Tourist immune systems would not have had opportunity to do battle with an L3 before, so would have no acquired immunity whatsoever protecting them against being hit hard. Again, if the well-being of Puna's population is not sufficient in itself for the powers which be to bestir themselves, then perhaps a clear, present, and growing danger to tourism will prove an adequate motivation for action. The sort of straightforward basic research being discussed here is not pocket change but is nothing compared to government expenditures in other areas (and it is our tax money being spent, after all, so we have legitimate cause to feel an investment in how it is being spent).


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A pleasant slideshow: http://www.thejoymovie.com

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)'( )'( )'( )'( )'( )'( )'( )'( )'( )'( )'( )'( )'( )'( )'( )'( )'( )'( )'( )'( )'(

Astonishing skill! This archer is a real-life Legolas and then some!
http://geekologie.com/2013/11/real-life-...rs-anc.php

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#67
quote:
Originally posted by robguz

What the recent cases seem to have in common is they grow their own vegetables. However, that doesn't prove that is how they got infected nor does it mean that other local sources are any less likely to have the slugs or their larvae.

Yes,but a lot of other people are growing their vegetables too and didn't get thick.
A long time I knew a lady who was sometimes eating left overs from her adult daughter infected with hepatitis (don't remember which type) and never got the disease.She was a kind of fatalist in this matter..
___________________________
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just ask a question first.
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#68

Seems like I am always the last person to hear news about something, so everyone else probably already knows all about this upcoming meeting, but I'm posting this here just in case. Over on Damon's weblog this news of an upcoming meeting on rat lungworm disease control was shared-

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Informational Meeting on Rat Lungworm This Saturday… Zsolt Halda Released From Hospital
Posted on January 27, 2009 by Damon Tucker

Hat tip to Richard Ha:

Rat Lungworm Meeting this Saturday, Jan. 31, at noon at SPACE in Kalapana Seaview Estates. We hope to have many well-informed people attending as the purpose of this meeting is informational. Zsolt Halda, who has just been released from the hospital, will be there.

*update*

Jane Whitefield gives us these directions to SPACE, which is hosting the Rat Lungworm meeting mentioned here this Saturday, 1/31/09:

You drive down Hwy. 130 toward Kalapana. When you dead end at the lava, turn left. This is Hwy. 137. Drive toward Kehena and Kalapana Seaview Estates (it’s probably a 10-minute drive and very hilly, but overlooks the ocean - Spectacular!). Turn left into Seaview. Travel up the entrance road until you see the sign on the right that says “SPACE,” with a hand pointing to the left. Follow that to the entrance and parking lot.

She tells us, too, that there is a Yahoo group called Parasites out of Paradise if anyone is interested in learning more.

There is some other good information that is coming out now.

I previously blogged about this here, here and here.

-----------------------------

Being off-island at the moment I will not be able to attend, so sure would appreciate the favor if folks could please post a summary of news and updates shared at this meeting.


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A pleasant slideshow: http://www.thejoymovie.com

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)'( )'( )'( )'( )'( )'( )'( )'( )'( )'( )'( )'( )'( )'( )'( )'( )'( )'( )'( )'( )'(

Astonishing skill! This archer is a real-life Legolas and then some!
http://geekologie.com/2013/11/real-life-...rs-anc.php

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#69

Dr. Prociv writes again from Australia:

Any study of mebendazole makes me worry, as it's been around for decades, and does not reach anywhere near the effective tissue levels of albendazole and its metabolites; i.e. if meb's going to work, albendazole will do it 100 times better. Anyway, as outlined before, I wouldn't want to take something that killed the worms in my CNS, regardless of studies in mice. There are huge differences between mice and humans, including relative sizes of organ systems. Further, giving an interleukin is simply out of the question in the real world. And there are always apparently inexplicable variations in larval numbers recovered from tissues; without reading the original paper, I'd be dubious about the significance of L3 recoveries.

Thanks for the Pacific Science paper on the distribution of Parmarion martensie; it's fascinating to see that it's also in the family Helicarionidae, same as ours here [in Queensland, Australia]; probably very similar. Given that our Helicarion sp. seems to be the best Angio host here, and is closely related to those acting as intermediate hosts elswhere, I'd say this is probably the group that evolved with Angio and rats (unlike Achatina, the Giant African snails).

And many thanks for the 1967 paper by Heyneman & Boo Liat, also about a helicarioniid intermediate host. Years ago, I worked on Angio in oil palm plantations in Malaysia, and in fact met Lim Boo Lait (in Kuala Lumpur, 1985 and 1987) and talked about it with him. He never mentioned his paper! (but he was an old man by then), although he did have a reputation as outstanding scientist and fieldworker, so I wouldn't question the validity of his findings. Anyway, this clears my doubts about larvae in snail mucus - the few other papers I have seen have not been convincing, but I wouldn't argue with Lim!

Infective larvae of the rat lungworm Angiostrongylus cantonensis, presumed cause of human eosinophilic meningoencephalitis, are shed in mucus exuded by naturally infected Malayan slugs (Microparmarion malayanus). Larvae passed by slug hosts were recovered from lettuce and produced normal infection in white rats. Lettuce sold in the local public market also yielded small numbers of infective larvae. Experimental evidence from rats suggests that the local human population, exposed to repeated low-level infections, may become immunized against the rare massive exposure and against clinical disease that might otherwise result after ingestion of heavily infected raw mollusks.
-Without seeing the whole paper, relying solely on the above abstract, I can make several pertinent comments. First, L3 in snail mucus are almost certainly going to be protected to a degree against desiccation (which is a major threat to the survival of most helminthic parasite larvae), and hence viable when ingested. Second, as I've stressed before, you don't need to ingest many L3 to get sick; from my own experimental work and casual observations, I'd say at times just one or two would be enough to cause at least focal signs (e.g. cranial nerve weakness, headache) - but to get seriously affected, as in a case of coma, you'd need a big dose, and hence ingestion of an entire slug/snail would seem in order.

Finally, that end bit there about stimulating protective immunity, with due respect, is a load of bollocks. That was all the rage back then (and still seems to be, in some circles), but the more you look at it, the more it seems that host immune responses have very little effect against relatively big metazoan parasites (in contrast to small things, like viruses, bacteria, or even fungi). Sure, your protective mechanisms will immobilize or wipe out a few, but in heavy exposure they won't protect you against severe disease - in fact, an overly aggressive response could speed up your demise, by trapping those worms where you don't want them.

BTW, there is a diagnostic test: we've been using it for years (now done only at Westmead Hospital, in Sydney), based on finding antibodies to Angio L3s. Trouble is, it can take a long time to become positive, sometimes even weeks after the first symptoms, so you could have a very sick patient still testing negative. And it takes time to do, and costs (labor-intensive). The most sensitive and specific diagnostic test is finding eosinophils in the CSF - they appear early, and in the right clinical/epidemiological setting can indicate only angiostrongyliasis (of course, there are other parasitic infections that can cause CSF eosinophilia, but you'd find a different exposure history). Regardless, while having a diagnosis is nice, it won't help you with specific treatment; trying to alleviate the symptoms is about the best we can do at this point (despite the numerous case reports of steroids making a difference: they're all anecdotal, based on odd cases where the patient improved after being given steroids, but what you're not hearing about is the many more who didn't, or got worse, with steroids; their cases don't get published).

I hope I've covered all the points you've raised, but please don't hesitate to follow this thru!

All the best

PP

---

Alaskasteven comments:

It sure is disappointing to read Dr. Prociv's frank comments on the dubious worth and even potential liability of stimulating protective immunity via injections of killed-L3 proteins, but my guess is he is probably correct about this, alas.



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A pleasant slideshow: http://www.thejoymovie.com

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)'( )'( )'( )'( )'( )'( )'( )'( )'( )'( )'( )'( )'( )'( )'( )'( )'( )'( )'( )'( )'(

Astonishing skill! This archer is a real-life Legolas and then some!
http://geekologie.com/2013/11/real-life-...rs-anc.php

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#70
I've got bad news to possibly report.

A new case in Hilo possibly linked to Rat Lungworm... not confirmed yet:

1. Tweet #1:

I just talked to a client whose sister-in-law passed away in Hilo. Brain being autopsied. Sent her your link to 1/31 meeting...

Me: Was this one of the cases that has already been documented? There are 2 people that I know of in Coma's in Honolulu cause ratlungworm?


2. Tweet #2:

I don't think it's been confirmed. Encephalitis for now. Not sure if she even made it to Hnl. 44 years old.

Me: Let me know if you hear if it was related to the ratlung problem. I've been keeping tabs on it and know a lot of people close to situation...



I'll keep tabs with this latest possible case out of Hilo just a few days ago.




Damon Tucker's Weblog
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