Tekmira's Failed Ebola Trial: The Value of Real-time Research

It is significant that the trial of TKM-Ebola, Tekmira's anti-Ebola antiviral was halted for futility (as it did not appear to improve clinical outcome). Such a result is disappointing but underscores the importance of clinical trials of compounds that, albeit promising results in non-human primates, have not been used in human infections. 

During the height of the Ebola media blitz I was often asked about how these antivirals should be used and whether trials should even be pursued because blanket administration is the "right thing" to do. I strongly pointed out that such a blind approach is fraught with problems such as obtaining informed consent and controlling for extraneous variables that may muddle the treatment effect, often invoking comparisons to the Tuskegee syphilis study (which lacked informed consent) and the events depicted in the movie The Constant Gardner.

Clinical trials of medications and interventions against Ebola are ongoing and just because one product did not work doesn't mean others won't. Determining the benefit of ZMapp, brincidofivir, favipiravir, vaccination, as well as aggressive intravenous fluid resuscitation and electrolyte management (where I think the real benefit will be found) remain important tasks ahead. 

The unfortunate results of this trial are just as important for clinical management as they are for research standards, which are crucial to adhere to even in infectious disease emergencies.

Vibrio Vulnificus in Florida: Will it Ever Be Safe to Go Back in the Water?

I think it's interesting to follow what infectious disease stories are picked up by the press and (no pun intended) go viral and which ones are ignored. There doesn't seem to be much of a pattern except that post-Ebola the media is definitely covering infectious diseases stories much more regularly,

A case in point is the interest in the Vibrio vulnificus infections in Florida. What triggered the media coverage were 2 fatal cases and the, shark attack connoting phrase, "flesh-eating". While this is an important infection for myriad reasons, it is unclear to me what is new.

Some facts about this microbe: 

• This infection was known to Hippocrates!
• The US experiences about 100 cases annually -- a little more than the number of shark attacks in the US in 2010 
• Most oysters harbor the bacterium
• There are clear risk factors for severe disease, chiefly liver disease, which can include necrotic skin lesions as well as bloodstream infections 

The formula here is one either ingests the bacteria while eating raw shellfish (always a risk) or gets exposed in the ocean where V.vulnificus naturally lives and thrives in summer. As I mentioned above, there are clear risk factors for severe disease and nowhere near all exposures result in severe disease. So, if you have liver disease raw shellfish and Gulf Coast ocean swimming will always be a risk and astute physicians have been warning their patients of that risk for decades.

When this infection is put into its proper context, it will be safe to go back in the water again.

Flu Vaccine: Boldly Going Where No Vaccine Has Gone Before

I just read about a fascinating infectious disease experiment that is ongoing on the International Space Station. The experiment is focused on determining what effect being in space for a prolonged period will have on influenza vaccine response.

In this study, astronaut Scott Kelly and his Earth-bound twin Mark Kelly both will receive influenza vaccines at regular intervals and have the resulting immune response measured. As all immune systems in every species that possesses one on Earth involved in a gravity-laden setting, it is not surprising  that the absence of gravity can alter function. For example, space is known to be a T-cell suppressing activity. Also, the environmental microbiological environment on the space station is one very different than that on Earth and that difference likely impacts immune function as well. 

The nuanced changes in immune response to the flu vaccine will be fascinating to see unraveled. Such experiments will play a role in understanding T-cell function more fully, a crucial need in the quest to improve vaccines and understand the intricacies of the immune system.

Entourage: Concretizing the Disease Dynamics in Concurrent Sexual Networks

A diagram showing how  concurrent sexual relationships foster the spread of HIV

Last night I watched the movie Entourage, which is based upon the HBO television program of the same name in which the exploits of a rising Hollywood star and his hometown "entourage" are detailed.

I didn't expect to find an important infectious disease topic in the movie but I am always on the look-out and--sort of fitting for a Hollywood star-focused movie--concurrent sexual networks came up when one character is put in a dilemma when his two concurrent sexual partners find out about each other and one of whom reveals she has a sexually transmitted infection which is assumed to be genital herpes.

Concurrent sexual networks are a pattern of sexual contacts that involve having more than one sexual partner at a time, as opposed to the serial monogamous relationships. While the number of total sexual partners over a specific period of time may be equivalent between an individual in serially monogamous relationships and one who is concurrent sexual relationships, the infectious disease implications are very different. 

Concurrent sexual relationships dramatically increase the ability of a sexually transmitted infection to find new hosts, especially if the other partner also is involved in another concurrent sexual relationship. Amplification of spread is much more easily achieved in such a scenario.

It was study of the explosive nature of the HIV epidemic in Africa that really concretized the importance of concurrent sexual relationships and informed the "zero grazing" campaigns.

While a zero grazing policy may be anathema to the Hollywood elite depicted in the movie, it is fuel for the sexually transmitted infection fire. 

MERS Storms the Korean Peninsula

As the outbreak of MERS cases in South Korea continues it appears that what is responsible for the 30--2 of which have been fatal and one of which was imported to China--is a combination of lax infection control coupled with a possible super-spreader event. This camel and bat-linked coronavirus, which has killed about 36% of the 1200 people it has infected thus far, has now been reported in 16 nations (including the US for those of you who have forgotten). 

To recap the events: mid-May a man who traveled to the MERS epicenter, the Middle East, returned to South Korea and was subsequently diagnosed with MERS. Being the 1st MERS case in South Korea and with a consequent delay in diagnosis patient's who were co-located were exposed and infected (primary transmission) then went on to infect others (secondary tranmission) who then went on to infect others (tertiary transmission, which has been confirmed in 2 cases).

This cluster, which is exclusively hospital-based thus far, has vaulted South Korea to the #3 MERS country, behind Saudi Arabia and the UAE.  Such a cluster reinforces the need for meticulous infectious control when dealing with a respiratory virus like MERS that has proven adept at exploiting lapses in infection control. South Korean authorities have since apologized for their handling of the initial stages of this outbreak which have led to over 1300 people being monitored after contact with case patients. 

Also, the index patient is responsible for infected at least 11 (maybe 22) other individuals (Ro = 11 - 22) clearly putting this man in the category of a super-spreader as his disproportionate contagiousness has clearly fueled this outbreak (similar to what occurred with the related SARS in 2003).

These events have, understandably, provoked fear in the South Korean populace and have prompted school closures as well as a travel alert in Taiwan. 

It is important to remember, at this stage, that no community transmission has occurred in South Korea and, though it is a possibility, swift action on the part of public health authorities can extinguish the outbreak. What also must be emphasized to clinicians world-wide is that MERS (and other infectious diseases) can appear anywhere and, to paraphrase Louis Pasteur, prepared minds are the ones that are lucky enough to discover them before too much damage is done.