Comin' to America: Marburg Hemorrhagic Fever

I like this understated headline from the RockyMountainNews: "Rare Marburg hemorrhagic fever shows up in Denver". Well, golly gee! Of all the fevers you don't want to just show up on your doorstep, Marburg hemorrhagic is one of the rarest. In fact, this is the first reported case in the United States. The CDC's Dr. Pierre Rollin (seen here and here doing field work in Africa... and by the way, you don't expect the first search hit for an infectious disease doctor to be IMDB...) says the patient recovered fully. Apparently, the case was unconfirmed until just days ago (my guess is that since the incubation period isn't longer than two weeks, the CDC was waiting to make sure the infection was contained before making an announcement).

Maramagambo Python Cave

The AP article says the unidentified patient had been visiting #CDC photo removed# the "python cave" of Maramagambo Forest in Uganda and had come in contact with fruits bats. If you have any interest in hemorrhagic fevers, you will recognize that fruit bats are also the reservoir for Ebola, Marburg's cousin in the Filoviridae family, and the cave connection has been a feature of pop virology since at least The Hot Zone, which featured Kitum Cave. So why is it called the python cave, anyway?

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18-Oct-2009
EDITED PER BLOGGER DMCA POLICY:

I received a DMCA takedown notice from Blogger. Blogger set this post to "Draft" status so that it was no longer published on the web. Blogger's takedown notice didn't say what the offending material in this post was (!!), and, of this date, the notice has not been posted on ChillingEffects.org as Google's DMCA policy says it will be.

However, based on the comments section below, I'm guessing the complainant is a certain Flickr user who posted photos of a cave in Maramagambo Forest, so I'm removing his photo of the cave. That's a shame as it was a nicely illustrative photo. Complainants like this are sort of a pain. While within the letter of the law, the question of the ethics of reproducing a freely found photo is quite different. I was not obscuring authorship, I linked back to the photo's source, I don't get any financial gain of any sort from this blog, and the photo was originally published on the web for everyone to see for free.

The act of publishing in and of itself implies the intention for intellectual works to be disseminated to the public. (That's not just my idea but a component of American copyright law--it's why there is a public domain for things to eventually end up in.) So, to publish your work for free and then restrict its dissemination is sort of, um... well, how would you put it?

As an aside:
Some commenters on this post were upset by the offhand way I say it was "stupid" to visit the cave (see below). I didn't mean so much to call the photographer, per se, stupid (as I don't know the circumstances of the photo and the photographer--for example, perhaps the photographer had never even heard of these sorts of viruses before visiting Uganda) as to call the whole business of visiting these caves a general stupidity. Commenters said, essentially, "hey, we're not stupid 'cause the photos were taken before the government said the fruit bats were a possible reservoir for the virus." I would like to point out, however, as The Hot Zone was published in the early 1990s and identified caves like this as a likely source of the virus, I find it impossible to believe there wasn't long-standing scientific speculation about these caves. This doesn't make specific tourists stupid, but it does make a case for the general stupidity of these cave visits.

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... stupid people! Actually, it's hard to imagine, but the [now removed] photos... were potentially taken within a few feet of a virus that could kill thousands or millions of people throughout America or Europe. In fact, the international community recognized this, and Uganda closed down tourism to the python cave after another tourist from The Netherlands brought Marburg back to Europe and died last summer.


Lutheran Medical Center

The patient was cared for at Lutheran Medical Center in Wheat Ridge, CO, # photo removed # a 400-bed hospital employing about 500 Registered Nurses and 5 Nurse Practitioners. As part of a protocol for an unknown infection, they followed standard contact precautions, including gowns and gloves. I was just thinking that at my hospital "standard precautions" really just means gloves and actually gloves only when making certain types of patient contact. Maybe this patient's symptoms were such that they took more precautions with him. The CDC has posted guidelines for US health care workers dealing with viral hemorrhagic fevers and linked to it from their Marburg page.

A 2003 study in Emerging Infectious Diseases could identify only two risk factors for contracting Marburg. One was working as a miner and the other was receiving an injection. So, as long as a nurse doesn't have a needle-stick incident, contraction probably isn't too big a worry. In fact, of the all health care workers who were enrolled in the study, none had antibodies for Marburg: "Types of patient contact included administering injections (38%); cleaning up blood, vomitus, urine, or feces (28%); washing bed clothes (7%); washing corpses (6%); and receiving a needlestick injury (2%)."

VSV-G vaccines and tetherin

But what if you were a nurse who had a needle-stick incident? Well, right now you'd be screwed, I think. But maybe in the near future, there will be a prophylactic. Feldmann et al. (2007), working with the related Ebola virus, were able to protect monkeys from lethal doses of virus by using a post-exposure dose of vaccine created by integrating an Ebola glycoprotein into a vesicular stomatitis virus: "treatment is particularly suited for use in accidentally exposed individuals and in the control of secondary transmission during naturally occurring outbreaks or deliberate releases." And although Feldmann et al. were working with Ebola, Daddario-DiCaprio et al. (2006) produced a similar experiment using the Marburg glycoprotein. This 2006 study looked at the efficacy of this antigenic delivery method as a preventive vaccine, but since the 2007 study uses the same essential methodology in a post-exposure context, it seems highly likely that a post-exposure treatment for Marburg could be created as well.

An emerging treatment option that has just been published in February and March issues of Journal of Virology involves the use of tetherin (formerly CD317), a cellular component that keeps new virions from detaching from infected cells. (See some great photos of budding Ebola virus at PLoS Pathogens.) Two teams (Sakuma et al & Jouvenet et al) found that tetherin has specific action on a spectrum of viruses including Marburg. However, Vincent Racaniello over at virology blog recently blogged a PNAS article showing that Ebola glycoprotein inhibits tetherin activity on the cell surface.

The announcement of this whole Marburg episode occurs just shortly after a Filipino man contracted Ebola from pigs...

1. Bausch DG, Borchert M, Grein T, Roth C, Swanepoel R, Libande ML, et al. (2003). Risk Factors for Marburg Hemorrhagic Fever, Democratic Republic of the Congo Emerging Infectious Diseases, 9 (12)


2. K. M. Daddario-DiCaprio (2006). Cross-Protection against Marburg Virus Strains by Using a Live, Attenuated Recombinant Vaccine Journal of Virology, 80 (19), 9659-9666 DOI: 10.1128/JVI.00959-06


3. Heinz Feldmann, Steven M. Jones, Kathleen M. Daddario-DiCaprio, Joan B. Geisbert, Ute Ströher, Allen Grolla, Mike Bray, Elizabeth A. Fritz, Lisa Fernando, Friederike Feldmann, Lisa E. Hensley, Thomas W. Geisbert (2007). Effective Post-Exposure Treatment of Ebola Infection PLoS Pathogens, 3 (1) DOI: 10.1371/journal.ppat.0030002


4. N. Jouvenet, S. J. D. Neil, M. Zhadina, T. Zang, Z. Kratovac, Y. Lee, M. McNatt, T. Hatziioannou, P. D. Bieniasz (2008). Broad-Spectrum Inhibition of Retroviral and Filoviral Particle Release by Tetherin Journal of Virology, 83 (4), 1837-1844 DOI: 10.1128/JVI.02211-08


5. T. Sakuma, T. Noda, S. Urata, Y. Kawaoka, J. Yasuda (2008). Inhibition of Lassa and Marburg Virus Production by Tetherin Journal of Virology, 83 (5), 2382-2385 DOI: 10.1128/JVI.01607-08