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December 29, 2004

Hunting The Elusive Marburg

The search for the biological host of the Ebola-related Marburg virus has gotten more confusing, as a new study of pygmies with high risk factors for the disease in the Democratic Republic of the Congo found that the pygmies, for whatever reason, are less likely to have been exposed to Marburg than surrounding populations.

This is more or less a shocking development, as authors of the study expected the exact opposite result. Given the high risk factors of the pygmy population a higher incidence of exposure to the virus among the diminutive study participants was almost de rigeur.

Most study participants reported activities (hunting 60%, entering caves 98%) and contacts with wild animals (rodents 79%, bats 78%, monkeys or apes 99%) thought to be risk factors for the primary transmission of filoviruses.
...
Pygmies were significantly more exposed to wild animals than the nonmining general population; the difference was particularly large concerning contact with bats. From one fourth to one third of study participants reported a direct or potential contact with someone with a febrile hemorrhagic syndrome.
...
Almost all study participants had been exposed at least once in their life to invasive modern or traditional medical treatment, including injections and scarification, by which an iatrogenic secondary transmission could have occurred.

Mine work and caving are considered the greatest risk factors for Marburg. Two of the three previous outbreaks of Marburg in Africa have been traced to caves or mines. The origin of the third is unknown, as the index case, an Australian hitch-hiker in Zimbabwe, died before a complete epidemiological survey could be compiled.

The most widely accepted hypothesis for the transmission of Marburg has been that it springs from human interaction with wildlife or insects within caves and mines, but that hypothetical vector will now have to be re-examined in light of the Marburg seronegativity of the pygmies in the study, which as a group have a higher incidence of caving and wildlife interaction than the surrounding population, yet display lower rate of exposure to the virus.

One possible revision to the hypothesis may be that transmission of the Marburg virus is not necessarily related to caves per se, but rather to mining activity within caves. Other studies and epidemiological information from previous Marburg outbreaks have shown that one of the groups at highest risk for Marburg are gold-miners.

A datum that would initially seem to argue against the modified hypothesis is that there is no human mining activity in one of the most famous of all caves associated with the Marburg virus, Kitum Cave on Mount Elgon near the Uganda/Kenya border. Though it was already known as a home for Marburg, Kitum Cave became famous after the publication of Richard Preston's book, The Hot Zone. There's a photo of Preston entering the cave in full bio-hazard gear here.

But, just because there is no human mining activity in Kitum Cave does not mean that there is no mining activity at all.

What makes the savannah elephants of Kenya's Mount Elgon unlike any others is that they go deep into caves in the side of the mountain, to mine the walls for salt.
...
Elephants, like all animals, need salt in their diet - up to 100g a day. Salt is found in the soil and in plants, but on Elgon, with its steep slopes and heavy rainfall, much of the salts have been leached away and levels are very low. This leaves the cave walls as the most concentrated salt source available. The elephants' behavior has developed over thousands of years, and by leading their young into the caves, their knowledge is passed on through the generations.

Elephants aren't the only animals entering Kitum in search of salt. As the cave is the only natural source for salt in the area, almost every mammal species in the park has been spotted in the cave at one time or another, including primates, the meat of which has been implicated in many hemorrhagic fever outbreaks.

If the results of the Durba pygmy study do point out a differential risk factor when it comes to mining as opposed to simply entering a cave, then another facet of accepted hemorrhagic fever transmission theory is called into question.

At present, the exact vector by which Ebola and Marburg filoviruses are transmitted to humans is unknown. It is thought that an animal or insect is the primary carrier of the host, and it is via human/primate interaction with the unknown host that the virus spreads. In the past, I've theorized that one of the two Rockfowl species in Africa might serve as the Ebola virus reservoir, but the seeming association of Marburg and mining calls that into question.

Indeed, such an association calls the entire theory of an unknown animal/insect host into question, as the number of animal or insect species found in a gold mine is going to be necessarily limited, and none of those tested so far, including a number found near the Gorumbwa mine in Durba, have proven to be the theoretical host. So many of the animal species living commensally with humans have been tested in fact that, for Ebola at least, the idea that the host is one commonly encountered by humans has been discarded.

Human filovirus infection index patients, when detailed information is available, have most frequently been men who work in the field, particularly in forests, excavations, caves, or mines. Commensal species (e.g., Mus musculus, Rattus spp.), on the other hand, might be expected to come into contact with persons working around the home. For this reason, we omit from consideration species known to be commensals with human.

What if, instead of residing in an animal or insect, the filoviruses that cause Marburg and Ebola live instead inside soil dwelling bacteria, specifically cave-dwelling bacteria, and only come into contact with humans, primates or other animals when the soil their host bacteria lives in is disturbed, either by human activity in the Durba gold mines, or by animals seeking salt in Kitum Cave? Evidence in support of this hypothesis appears in another study, this one conducted by University of Kansas Professor Townsend Peterson. In a search for a potential mammalian filovirus host, he located 11 mammal families whose range overlapped that of the four known filoviruses. All were either bats, rodents, or insectivores, species that could be expected to regularly come into contact with soil and cave dwelling bacteria, either through hunting or roosting behaviors.

Arguing against this hypothesis is that, of the known viral bacteriophages in existence, none are closely related to the filoviruses, at least none that I have been able to find are. However, given our relative paucity of knowledge when it comes to bacteria/viral interactions, it would not be a great surprise to learn that members of the Filoviridae could infect bacteria. Certainly the various transmission vectors will need to be re-examined based on the results of the Durba pygmy study.

Posted by Bigwig at December 29, 2004 02:02 PM | TrackBack
Postscript:
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Comments

Why would anyone deduce that pygmies would have higher rates of infection. Wouldn't it be more likely that an isolated community with increased exposure would more likely become more resistant over the generations?

Posted by: Sully at December 29, 2004 02:46 PM

The study didn't measure infection rates, but rather exposure rates. People become immune to Marburg by developing antibodies for Marburg after being exposed to the virus but afterwards those antibodies are present.

What the study found was that those antibodies are found at a lower rate among pygmies than among the general population--arguing that, for some reason, pygmies are less likely to be exposed to Marburg in the first place.

Given that they were engaging in most of what were thought to be the high risk behaviors, their lack of exposure to the virus was surprising.

Unless I totally misread the study, which is always a possibility.

Posted by: Bigwig at December 29, 2004 02:56 PM

Or unless Pygmies are more susceptible to Marburg, which would mean less individuals survive the initial infection, and would thus lower the percentage of seropositive persons in the population.

Then again, filoviruses could be from outer space, transmitted by aliens who come to earth to harvest species for their zoos.

It's a possibility. ;-)

Posted by: Captain Holly at December 29, 2004 03:03 PM

OK, that makes decidedly more sense Big. My money is on the bats as the culprit (carrier). I think the aliens are a long-shot Cap. ;>

Posted by: Sully at December 29, 2004 03:55 PM

Well, the only variable left then, is height.

Very interesting post, thanks. I just knew you'd get back to this eventually.

Posted by: Stephen at December 29, 2004 06:23 PM

I'm with you, Stephen. I think height is the variable. Marburg thrives in the relativly high altitude ot 6 feet off the ground.

Posted by: Kehaar at December 29, 2004 10:03 PM

Tongue was only partly in cheek there, Kehaar, but there none-the-less.

Sid has found a real conundrum in search of a theory.

Maybe it's coming from cookies--in a jar on a shelf they can't reach!

Posted by: Stephen at December 30, 2004 05:45 PM

A missionary from the Durba area told me that the mines were using redundant warheads for gunpowder at the time of the Marburg outbreak. The warhead in use at the time of the Marburg outbreak was thought to be inferior in explosive power. Only the men in the mine at that time were infected. The theory of a germ warfare warhead was offered to the UN but was rejected as an avenue for medical research. Why?

Posted by: a. mac donald at May 13, 2005 04:14 PM
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