Preventing meningitis caused by parasites

[AlohaSteven]

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

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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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