Thursday, May 12, 2011

Black Market Penicillin During World War II: “The Third Man”

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Penicillin was used by US and British military during WWII and saved a lot of soldier’s lives from infected wounds and contagious illness [i.e., pneumonia and venereal disease]. People outside of the military relied on black market penicillin.  Since it was not regulated, the use varied and many uses were questionable [i.e., taken prophylactively to prevent disease in sex workers and their customers]. In addition, as Graham Greene portrays in his novella “The Third Man”, the medication was either diluted down with colored water or the powder penicillin was diluted with sand. Many people died due to ether ineffectiveness of therapy or side effects of dirty diluents


In the novella, Rollo Martins learns his friend Harry Lime [thought to be dead] was trafficking black market penicillin:
POLICE INVESTIGATOR:  “…Stage three was when the organizers decided that the profits were not large enough.  Penicillin would not always be impossible to obtain legitimately; they wanted more money and quicker money while the going was good. They began to dilute…You can be immunized from the effects of penicillin…A number of children simply died, and a number went off their heads. You can see them now in the mental ward…”

This quote brings up a number of contemporary issues:  be wary of non-regulated medications, overuse or inappropriate use of an antibiotic can lead to resistance, antibiotics don’t immunize—vaccines do, and children with meningitis—whether they receive proper medication or not--can suffer severe sequelae. Later posts will take these issues further, but adaptation of organisms and their resistance to antimicrobials is alluded to by the police investigator when he mentions “You can be immunized from the effects of penicillin.” When organisms are exposed to repeated amounts of an antibiotic, if not killed, they adapt and become less susceptible; they can appear immune.

Around the time when Alexander Fleming discovered penicillin in 1928 he knew that resistance in Staphylococcus existed, and warned that resistant organisms may become a problem. They did, and a lot of organisms, pneumococcus included, developed resistance. Resistance didn’t take long to develop in many organisms, and is the reason why penicillin has very few legitimate uses today.  Newer antibiotics are becoming less useful with time—due to unnecessary and unregulated use, but also because these organisms adapt.  Much like the black marketeers, they are survivors—they profit in gaps or niches they see for themselves. 

Friday, May 6, 2011

Genesis: Bubble-swirl of primeval sea

Genesis, by Bruce Taylor; mixed media, matted
with texturized white mat, framed under glass;
photo by Doran 2011
There is a danger in taking a photograph of a framed print, yet Bruce Taylor's work "Genesis" was so intriguing that I had to ask to display it, and he agreed.  If you wish to learn more about his original, feel free to contact him.

I've asked J. S. Lee from The Tenth Muse for one of her new-beginning-type poems.  In another way, her poem displays the same awe for existence....better than I could write here.

diary


I can smell the rain on the wind
the warmth in the air it lofts skyward,
soft and soughing.
Untame spring unfolds her wings,
sings in words I cannot yet hear.
There is existence and then there is existence.
Today I tremble because I am
afraid of both.

--J. S. Lee
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Tuesday, May 3, 2011

She Could Have Been a Laundress: Carriers of Typhoid

The Nurse's Residence on North Brother Island, NY
Photograph by Richard Nickel, Jr.
Kingston Lounge, with permission



















We all cart things around with us:  kids, electronics, or perhaps bags of goodies.  Even when our hands are free we carry tiny, if not microscopic, particles and organisms. Our own bodies have a distinct mixture of organisms on and within us.  Mostly, these organisms protect us from disease [commensals], but sometimes we succumb to one of them [either opportunists or pathogens] and get sick.  Sometimes these organisms cause disease in others.

Knowledge of the carrier state became known in the late 1880’s, mainly with three pathogens:  Cholera, Diphtheria, and Typhoid.  But, Robert Koch, the bacteriologist largely accredited with developing germ and contagion theory, also felt that malaria was carried by humans, and that sterilization of their blood with quinine would stop their carrier status.  During the Spanish-American War in 1898, it was thought that over 90% of soldiers carried typhoid.

Typhoid is caused by Salmonella enterica, serotype [or serovar] typhi,  although serotype paratyphi causes a similar syndrome.  This is not the same type of Salmonella of recent foodborne [cilantro and peanut butter] outbreaks. Ingestion of typhoid is the main route of infection, even if only small amounts are ingested. 

Carriers either have been sick and recovered--they carry typhoid within their gastrointestinal tract; or have been exposed and carry it even though they have never themselves been ill.  Mary Mallon maintained she’d never been sick.  It was impossible, to her, that she alone had infected 54 or more people; she, to herself, was undeserving of the dirty title "Typhoid Mary."  Mary likely had typhoid as a child or was exposed to it in Ireland.  When she immigrated, along with her few possessions, she carried typhoid with her.  In  1906 she became a cook for the Warren family.  Cooking was one job that paid fairly well, and she was good at.  She never considered being a laundress—it didn’t pay as well.  In Mary's case, she carried typhoid into the kitchen of the Warren family.  

Soon after Mary arrived, people within the Warren family became ill.  She took care of them.  George Soper, the sanitary engineer of the New York Department of Health official pinpointed Mary as the source.  She was given 3 choices—be quarantined, quit cooking and be a laundress [or something else], or have her gallbladder removed.  She ended up being quarantined for three years.  It didn’t have to be that way.  Yet, she refused to believe that she caused the spread, since she herself wasn’t sick.  She was a poor, too proud, cook that felt that she was being targeted unnecessarily.  She stayed in Riverside Hospital on North Brother Island, NY for three years until she finally promised to quit cooking.  She left the hospital, promptly changed her name to Mary Brown, and started cooking again—at a Maternity hospital.  As a cook, she earned more than she would have as a laundress.  After more infections started to crop up, Mr. Soper hunted her down and yelled "Gallbladder removal or quarantine for the rest of your life!" [well, these probably weren't his exact words].  This was 1915, and the authorities had no choice but to quarantine her for the rest of her life.  She again stayed at Riverside Hospital on North Brother Island, until she died in 1938.


Richard Nickel, Jr at the Kingston Lounge is a very gifted photographer [of "guerrilla preservation and urban archaeology"] that has captured images of the now abandoned hospital and associated buildings on North Brother Island. Much of his work can be viewed here.  The pictures I have used, with his permission, are of the Nursing residence where Mary often visited, and examples of patient and examination rooms at the Riverside hospital.  I liken the disrepair and abandonment in these photos to how Mary likely felt.  It didn’t have to be that way.  She had choices, at least initially.

Examination Room on North Brother Island, NY
Photograph by Richard Nickel, Jr.;Kingston Lounge, with permission
A private room at Riverside hospital on North Brother Island
Photograph by Richard Nickel, Jr.; Kingston Lounge, with permission
In other areas of the world, another known carrier, Mr. N the milker [Folkstone, UK] gave up his profession after realizing the harm done [over 200 people infected by him].  Unfortunately other carriers were institutionalized for years, driven insane by isolation, quarantined well into the antibiotic era, as in the Long Grove Hospital in Surrey that closed in 1992. 

Mary was offered gallbladder removal as an option.  Was this a good option?  There were exceptional risks to surgery then, like infection and blood loss.  Why would removing the gall bladder help?  Even early in the 20th century, there were suspicions that people that continually shed typhoid in their feces had a reservoir.  When typhoid was found in some resected gall bladders, removal became an option to decrease carriage. It appeared to work too.
File:Mary Mallon in hospital.jpg
Mary Mallon [foreground] at Riverside
Hospital; Wikipedia, Creative Commons Attribution License






















To back up a bit, how does the carrier state for typhoid exist?  Salmonella enterica serovar typhi is able to evade the immune system in some people.  It enters the gastrointestinal tract, hides within immune cells, and gets carried to the regional lymph nodes.  In many cases, it enters the bile duct in the gastrointestinal tract and hides within the gall bladder—releasing occasional organisms into the gastrointestinal tract and leaving via feces.  This is where good hand-washing practices comes into play—Mary likely didn’t follow this hygienic practice.  The organism in food gets eaten by others, and the whole process continues.  Many people fall ill, and some die.


Within the bile duct, Crawford et al, found that cholesterol on gallstones attract typhoid.  It attaches to the stone and forms a biofilm—a protective layer—that is impermeable to the effect of bile salts and antimicrobials.  This is likely why the carrier state persists.  Biofilms are known to also form on other surfaces like blood and urinary catheters, implanted joints, and heart valves--leading to recalcitrant infections.  Additionally, people with gallstones may shed more typhoid than people without, and mice with infected gallstones were found to shed three times more typhoid than infected mice without gallstones. If anyone within Mary's time knew this, perhaps they could have been more persuasive.



This biofilm formation makes it nearly impossible to eradicate the carrier state.  Cholecystectomy [gallbladder removal] is the only way at this point to decrease typhoid carriage.  However, Crawford and others are looking at ways to either decrease biofilm formation or penetrate its barrier.



A biofilm with "slime" protecting organisms [not typhoid in this picture]; taken from
Monroe D (2007) Looking for Chinks in the Armor of Bacterial Biofilms.
PLoS Biol 5(11): e307. doi:10.1371/journal.pbio.0050307
 

















Many people have died from typhoid, some famous like William Wallace Lincoln, Abraham’s son, and Virginia Woolf’s brother, whose death is portrayed in a couple of her novels.  But as many as 17 million regular people are infected and thousands die annually.  Typhoid vaccines, both oral and injectable, exist, but need to be more available to developing countries where typhoid is endemic.  Having clean water would also help stop its spread.  Decreasing the incidence of typhoid would surely decrease carriage state as well.


So Mary could have been a laundress.  This would have decreased the number of infections she caused, but she still would have been a carrier.  Perhaps having her gallbladder removed wasn’t such a bad idea after all—even with the risks involved.  It surely would have been better than being locked away for the rest of her life.



Sources:

  • Kingston Lounge; photographer Richard Nickel, Jr; North Brother Island Photoessay
  • Winslow; The Conquest of Epidemic Disease:  A Chapter in the History of Ideas; The University of Wisconsin Press; 1980 [republished from Princeton University Press 1943]
  • Littman et al; The Chronic Typhoid Carrier:  I. The Natural Course of the Carrier State; AJPH 1948;38;1675-9.
  • Brooks J. The Sad and Tragic Life of Typhoid Mary; Can Med Assoc J 1996; 154[6];915-6.
  • Dougan G, John V, Palmer S, Mastroeni P. Imunity to Salmonellosis; Immunological Reviews 2011; 240: 196-210.
  • Crawford RW, Rosales-Reyes R, Ramirez-Aguilar M, et al; Proc Natl Acad Sci U S A. 2010 March 2; 107(9): 4353–4358.Published online 2010 February 22. doi: 10.1073/pnas.1000862107.
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