Thursday, February 22, 2018

Murder and Contagion

Alex for Michael - Thursday

I enjoy medical thrillers. Often the puzzle is as much in the medical aspects as in the whodunnit which adds to the interest. I 'met' Alex Lettau through a round table forum  for ITW a few months ago, and he had amazing things to say about malaria and other tropical diseases. Not really surprising since he's been practising in the area for thirty years, has several specialities including tropical medicine, has published multiple professional papers, and has been a medical missionary in Malawi, Nicaragua, and Papua New Guinea. Perhaps more surprising is that he  also writes fast-paced thrillers around Kris Jensen a medical detective with CDC. The first in the series is Yellow Death. I recommend you get a copy, not only because it's a really good, intriguing thriller, and not just because it won a National INDIE Excellence Award, but because, as you'll see below, Dr. Lettau is definitely not a person you want to cross!

It was just about the saddest day of my 37 year career in Infectious Diseases after I got the news that my patient, a 24 year-old woman who had contracted falciparum malaria on a mission trip to Liberia, had collapsed at home and died in the emergency room.  Two days earlier I had decided to treat her as an outpatient because she only had minimal symptomatology and had an extremely light parasitemia. Cause of death was spontaneous rupture of the spleen – rare in malaria and then almost always due to vivax rather than falciparum. 

The spleen, called “an organ of mystery” by the Greek physician Galen two centuries ago, is a fist-sized, highly vascular organ in the left upper abdomen tucked under and protected by the rib cage. Because of its rich blood supply, rupture of the normal spleen by severe blunt force abdominal trauma may cause fatal internal bleeding. However when the spleen enlarges, most commonly due to an infection such as mononucleosis or malaria, it emerges out from under the left rib cage and is susceptible to rupture from much milder direct trauma or even can rupture spontaneously. Chronic malaria may lead to a huge spleen as pictured, referred to as the tropical splenomegaly syndrome. Large spleens are also seen in visceral leishmaniasis and bilharzia.                                                              
Man with badly enlarged spleen
It has been known for centuries that an intentional targeted blow (mild enough to leave no mark) can easily cause a fatal rupture of a big spleen (thus it is also an organ of murder mystery!).  A specific weapon and method used in the Celebes was reported in the British Medical Journal November 24, 1951 (p 1281).                                                    

As mentioned by the author of the BMJ report, the Thugee cult of India also used this method to murder travelers, prior to stealing their possessions although their primary method of killing was by strangulation. The Thugees were an organized gang of professional assassins active in 13th-19th century India who acted in the name of Bali, the Hindu goddess of destruction. Their mission was to kill travelers by non-blood-letting methods prior to robbing them and it is estimated that they murdered a million or more before the British colonial government put an end to it!

So nowadays, leaving mass bioterrorism out of the discussion, how easy is it in real life to take advantage of an infectious disease or to utilize a micro-organism to murder a specific person (the “target”) and to get away with it? Short answer: It’s hard. The micro-organism needs to be a highly lethal, preferably untreatable infectious agent. The murderer also needs a source that supplies the agent and a means of delivery to infect the target, ideally without the target being aware of the exposure and even better if the infection is never specifically diagnosed. For the remainder of my guest blog, I will focus on rabies virus as a potential murder weapon.

Rabies is essentially 100% fatal once it reaches the brain to cause encephalitis. One problem is the long incubation period. After exposure say on the foot, rabies virus travels along nerve trunks and may take months to reach the brain. If the exposure is recognized, this delay allows for post-exposure rabies prevention using rabies immune globulin and vaccine. So the trick is to expose the target without their knowledge and then sit back and wait. I keep thinking I read once that the Mossad offed a target with a rabies-contaminated needle but I haven’t been able to find an internet reference.

Rabies virus is not a Tier 1 bioterrorism agent that is U.S government-controlled so it’s not illegal to possess a rabid animal carcass as a source of virus. Most countries outside of Western Europe and England have animal rabies. Worldwide, stray dogs are most commonly affected while in the US it’s the raccoon.                                                                 
Maybe not as cute as we thought...
Needlestick awareness of the target is an obstacle to overcome. If the target had significant neuropathy of the feet, an injection may not be sensed at all. The needlestick could also be set up to be “accidental”, perhaps purported to be a discarded needle from a drug abuser in which case the focus would be diverted to risk of hepatitis B and C and HIV.

There are non-needlestick options. Simple topical application of rabies-contaminated material onto an open wound such as a foot ulcer may transmit the virus. Intravenous injection would work if such an access were available. Presumed transmission of rabies by aerosol has been documented in two spelunkers after they visited a cave full of bats, but spritzing an extract of rabid raccoon saliva up the nose of the target is at best of unknown effectiveness because rabies virus does not attach to nasal mucosal lining cells. Oral exposure does not work either.

One advantage for the murderer is that rabies encephalitis is rare – I’ve yet to see a case in 37 years of practice. For that reason, it may not be looked for and therefore remain undiagnosed especially without an index of suspicion which would be low in the absence of a known animal exposure. The presumption would be that the target died of a more common type of encephalitis such as due to West Nile virus. Autopsies nowadays are rarely done. We recently cared for a woman in her 40’s without prior lung disease who became ill with cough, congestion, and fever just after a trip to Mexico. Four days later, she died of an overwhelming viral-type pneumonia. Multiple tests for influenza were negative. She did test positive for metapneumovirus which normally only causes common cold-type symptoms in patients without underlying lung disease or a weak immune system. She had neither but we had no real reason to refer her case to the Medical Examiner. A private autopsy would have cost the family 5000 U.S. dollars which they elected not to do.

In fiction, a targeted death by infection is much more doable. In one of my novels in progress (“Death by Full Moon”) a mad virologist serial killer is offing homeless people with a hybrid virus (rabies plus vesicular stomatitis virus – VSV). VSV is a logical (fictional) partner with rabies as it is a real virus in the same Rhabdovirus family as rabies and has receptors for nasal mucosal cells. The killer inoculates this hybrid virus into the nasal passages of the targeted victims on the pretense that he is administering a nasal spray influenza vaccine. The hybrid virus attaches and travels the short distance to the brain via the olfactory nerve leading to florid encephalitis in 2 days. The killer is rather obsessed with the full moon and times the exposures so that the victim goes mad on the night of a full moon. My series protagonist Dr. Kris Jensen, a specialist in Infectious diseases and former CDC epidemiologist investigates the deaths and tracks the killer down. Per the construct of thrillers, things go from bad to worse before the final battle between good and evil.  

There are certainly other infectious agents which could be used as a murder
weapon such as anthrax, cholera, Ebola virus, and H7N9 bird influenza. The feasibility will vary greatly around the world depending on factors such as the disease prevalence and the degree of sophistication of medical care, public health support and criminal investigation.

As to the future, a valid concern is that bioengineering will eventually be able to genetically tailor a lethal infectious agent to target a single individual. There is a fascinating lengthy story on that topic published in 2012 in The Atlantic (“Hacking thePresident’s DNA”). If someone could do that, they could easily add on genes for resistance to all antimicrobial drugs. That would be a truly frightening scenario.                                            


  1. Thanks, Alex. Truly chilling stuff. I remember reading several decades ago a science fiction story about murder via a DNA targeted virus, released into the wild half-way around the world, aimed at a single individual. Everyone else was just a carrier, but it was fatal for that one person. Shiver me timbers...

    1. Yikes, that is scary! Normally one would have to expose the target directly to transmit the infection. The virus in the story must have been highly infectious with a high basic reproduction number, meaning that one carrier would infect many others. That would allow rapid spread of the virus across the world.