Showing posts with label science blog. Show all posts
Showing posts with label science blog. Show all posts

Friday, October 16, 2020

Disease Post: Plague

OK, I am going to try for this post. I hope you are ready for a long one.

The plague is my very favorite infectious disease. It is so interesting and the history of it is devastating and fascinating. And what better way to celebrate the month of Halloween than talking about the Black Death? I mean, have you seen plague doctor outfits? They are terrifying (and I LOVE them). And yes, I do have a plague doctor costume, thanks for asking. 

It also helps me be a crazy rat lady since rat fleas (and/or other rodent fleas) are the primary carriers of plague. My rats do not have plague or fleas though, don't worry.

Plague of Marseilles- costumes for plague doctors. Credit- Wellcome Collection and Attribution 4.0 International

Background:
Plague is caused by a bacterium called Yersinia pestis. Y. pestis is a gram-negative (does not have peptidoglycan in its cell walls) rod or coccobacillus (round rod). It is a facultative anaerobe, which means that it "prefers" to have oxygen, but can survive without it by switching to fermentation for energy. This makes them fairly resilient little bugs.
Plague plush from Giant Microbes.
Historically, the plague has caused massive amounts of devastation worldwide and is still present all over the world. I will include a brief history later. 
 
Yersinia pestis is a zoonotic disease, meaning humans get it from animals and/or insects. In this case, the carriers are fleas.
Plague infographic from the WHO

How is it spread?
The infectious dose (or how many bacteria are needed to establish an infection) is not known, but is suspected to be quite low.
 
There are three different forms of plague: pneumonic (respiratory), septicemic, and (the famous) bubonic.
 
Let's start with bubonic plague and septicemic plague because they are similar. People get these by being bitten by an infected flea or by contact with contaminated animal tissue and/or fluid (like skinning or handling a plague-infected animal). Bubonic plague can turn into septicemic plague as the bacteria infiltrates the body and, therefore, the blood stream. And it can become pneumonic plague, too, if the bacteria spread to the lungs. Bubonic and septicemic forms do not spread from person to person.

Pneumonic plague can develop as mentioned above, or can be caught directly through respiratory droplets in the air. If a sick person or animal is coughing (or even just breathing), they release infectious bacteria into the air in tiny respiratory droplets. These can be inhaled by another person or animal, establishing an infection in the lungs. This form can be transmitted person-to-person, but usually requires close contact. You can find more detailed information about transmission from the CDC.

Image from the CDC

Symptoms:
As I mentioned above, there are three forms which will present with different symptoms, though all three will present with a fever, chills, weakness, and (often) headaches. Vomiting, diarrhea, and abdominal pain are seen in some cases, too.

Bubonic plague has an incubation time of seven days or less from infection until the time a person shows symptoms. This form is characterized by the presence of one or more bubos. A bubo is a lymph node that  becomes inflamed, swelling enough to be visible. These are usually located in the neck, armpit, and/or groin. The bubos are tender and painful. From here, the infection can start to infect the bloodstream to develop into septicemic and/or pneumonic plague. Without treatment, estimated death rates are between 50%-70%.

Septicemic plague is the infection of the blood. It is not generally the initial infection that is established, but there are many records of people getting the plague this way. Once the bacteria is in the blood stream it can get just about anywhere. The CDC also notes that people may bleed into the skin or other organs and tissues will start to die and possibly develop gangrene (and turn black=the Black Death). One of my text books (Medical Microbiology by Murray et al.) estimates that 75% of people who have or develop septicemic plague die without treatment.

Pneumonic plague is generally the most worrisome. The incubation is shorter, generally 2-3 days. After the initial symptoms, patients will develop respiratory symptoms within a day or so. According to the CDC, the respiratory symptoms include: shortness of breath, cough, chest pain, and possibly bloody mucous. This is the only form of plague that can spread person-to-person and it is highly infectious. Most sources estimate that the death rate of pneumonic plague is 90% or more if not treated quickly (within 18-24 hours, according to the WHO).
 
Prevention and Treatment:
The good news is that plague is easily treated with a few common antibiotics! However, it needs to be caught as early as possible, especially for pneumonic plague. People do die even with treatment, especially if treatment is too late.

But plague, if there are no bubos, looks like lots of other illnesses. Diagnosis is helped if your doctor knows you have been exposed to fleas or wild rodents, especially in endemic areas (meaning it is "native" to those areas, like much of Asia, Africa--especially Madagascar, and the Southwest United States). 
 
Your pets can also become infected by the same means people can and your pets can spread it to you. Flea control is important and it is best to avoid wild rodents, especially ones that appear ill or have died. Wear gloves while handling dead animals that may be infected.

There is not great prevention besides that. There was a vaccine available in the United States, but not anymore. It did not protect against pneumonic plague. I'm sure there are groups working toward a vaccine, but no one knows if/when one will be available.
The plague of Florence, 1348; a scene from Boccaccio's Decameron. Etching by L. Sabatelli the elder after G. Boccaccio. Credit: the Wellcome Collection and Attribution 4.0 International

Extras 
History:  
The plague has been around for centuries. It was also used in early biological warfare (bodies of plague victims catapulted into cities or enemy camps). Italian Gabriele de'Mussi gave an account of the Black Death origin in 1346: the Mongol army hurled plague-infected cadavers into the city of Caffa. This transmitted plague to the inhabitants, and those who fled took the plague with them towards Europe. This is explained by Mark Wheelis in his paper Biological warfare at the 1346 Siege of Caffa. Ultimately, it is suspected that the Black Death originated somewhere in Asia, though theories of exactly where differ.

There are three main plague pandemics (Perry et al). The first was in the early middle ages (the Plague of Justinian from 541 CE until the mid-700s) and is one of the earliest records we have of the plague. It is suspected to have originated in China and spread to Egypt and then to Constantinople. At the peak of the first pandemic, it is suspected to have killed 10,000 people per day and killed about 40% of citizens. A bit later, in 588 CE, there was another wave that spread it through the Mediterranean and about 100 million people died.

The second pandemic was the one most people are familiar with, from the 14th century to the 19th century. What is known as the Black Death started in this time period. The plague spread from China or somewhere in Asia along the Silk Road, infecting Asia, Europe, and Africa. China lost about half of its population, Europe lost a third to a half of its population, and Africa lost about an eighth of its population. For the record, people at the time did not call the plague the "Black Death," that is a more modern term. They called it the "great pestilence" or the "great mortality" mostly.

The third pandemic was in the 19th and 20th centuries. A wave began in China in 1855 which spread through China, to India, killing more than 12 million people in the two countries. From there, the plague traveled to Russia, causing a large outbreak in Siberia in 1910. It was during this pandemic, in the late 1800s, that the plague bacterium was identified and isolated. Alexandre Yersin is credited with the discovery and the bacteria was eventually named after him.
 
Bioterrorism:
Part of the fear of plague has to do with its potential as a bioterrorism agent. This is part of what keeps this on the select agent list in the United States.

As mentioned above, cadavers of plague victims were intentionally thrown into the city of Caffa, causing an outbreak and causing the disease to spread. This is not the only time that this was done in the history of warfare.

I remember learning about this in history and in my biodefense class. This sentence sums it up fairly well, though it does not go into all the cruel experiments that the Japanese performed on the Chinese. "In World War II, the Japanese military experimented with plague in human subjects at their clandestine biological research facilities in Manchuria, and on several occasions dropped Y. pestis-infested fleas from low-flying planes on Chinese civilian populations, causing limited outbreaks of bubonic plague and initiating cycles of infection in rats" (Dennis, David T. Plague as a Biological Weapon).

The end-goal with Y. pestis as a biological weapon was to successfully aerosolize it, to cause pneumonic plague. I have in my old class notes that "aerosol release of Y. pestis would be odorless, colorless, and likely to be unnoticed until the first victims fell ill," but I have not been able to locate a source yet, so take it with a grain of salt. 
 
It was estimated by a committee of experts that "intentional release of 50 kg of aerosolized Y. pestis over a city of 5 million would... cause 150,000 cases of pneumonic plague and 36,000 deaths...[and] without adequate precautions, an initial outbreak of pneumonic plague involving 50% of a population could result in infection of 90% of the rest of the population in 20–30 days and could cause a case fatality ratio of 60–70%" (Dennis, David T. Plague as a Biological Weapon).

About the bacteria:
I was always interested in the bacteria itself and its interactions with flea and animal hosts. That isn't talked about much because people are concerned with the diseases of people. The flea is initially infected by taking blood from an infected host. I won't get into technical details, but so you know, it does affect the flea by blocking digestion until the flea regurgitates the bacteria when they bite another host. The blocked gut of the flea will eventually kill it. Animal carriers are often symptomatic and can also die of the plague.

There are some genes that the bacteria has that they can switch between based on which host it is in to help it adapt to either the temperature and environment (like pH) of the flea versus animal hosts

The bacteria switches between gene expressions based on the host and the host temperatures. Generally, the bacteria grows best at lower temperatures but can switch gene expression to help them survive and grow at normal human temperatures.

Fun Facts:
The plague doctor mask had the beak which was to be stuffed with flowers, spices, and/or herbs--anything that smelled nice because the belief was that disease traveled through bad smells or miasma.

The plague doctor outfit did actually afford them protection, but not because of the potpourri in the mask. The mask protected their faces from respiratory droplets. They also covered themselves from head to toe in mostly leather, which fleas could not bite through.

Books and Media:
There are several books and such concerning the plague that are great.

For educational purposes, The Black Death: The World's Most Devastating Plague by Dorsey Armstrong from Great Courses is amazing. It goes into details of spread and impacts of the plague (during and after) on society, art, economics, and more. You can get it through Great Courses or through Audible. 
 
This Podcast Will Kill You did a two-part episode on the plague that is very good.

The Great Mortality: An Intimate History of the Black Death, the Most Devastating Plague of All Time by John Kelly is said to be good. I have not read it yet, but I would like to.

The Black Death by Philip Ziegler sounds great, but is another one that I have not read.

Journal of the Plague Year by Daniel Defoe. Arguably, this account is not entirely credible as the author wrote it 57 years after the fact. But he did experience the plague and it is considered to be an accurate account of the time. It was good either way.

Year of Wonders by Geraldine Brooks. This is a historical fiction novel, but it is based on a real town in England that isolated themselves when they found that the plague had reached them. A friend gifted this book to me years ago and it was enjoyable.

The Plague by Albert Camus. I am embarrassed to admit that I have not read this book yet, though I want to, obviously.
 
Crow Boy by Philip Caveney is a fictional story about a modern boy in Edinburgh who travels back in time to 1645, during a plague outbreak. I enjoyed this one, even though the plague doctor was fake and kind of evil.

This is a silly video that will get the original song stuck in your head forever, but it's funny. We watched it at some point during my Masters program: Black Death (Hollaback Girl) aka Fleas on Rats.

There are so many more books that I have not yet read. If anyone has a particularly good suggestion, please drop it in the comments. And if you know of anything about plague doctors, I definitely need to know!

I hope you enjoyed my plague post. If you made it this far, thanks for reading!
 
Sources: 
Perry, Robert D and Fetherston, Jaqueline D. Yersinia pestis--etiologic agent of plague. 1997.
Medical Microbiology sixth edition by Patrick R. Murray, Ken S. Rosenthal, and Michael A. Pfaller
Armstrong, Dorsey. The Black Death: The World's Most Devastating Plague. 2016. Great Courses.
Dennis, David T. Plague as a Biological Weapon. 2009.

Sunday, September 20, 2020

Disease Post: Diphtheria

This is a disease that I have always found interesting and horrifying.

Image credit: CDC/Sarah Bailey Cutchin

Background:
The disease diphtheria is caused by a bacteria called Corynebacterium diphtheriae. The part that causes the most problems is the toxin that the bacteria produces (diphtheria toxin). However, not all C. diphtheriae actually have the toxin gene (but this is still infectious and dangerous without the toxin). There are also other Corynebacterium species that can carry the diphtheria toxin, but they cause infections in animals (CDC).

The bacteria is a gram positive (it has a peptidoglycan cell wall) bacillus (rod-shaped bacteria). It is an aerobic bacteria, meaning that it requires oxygen to live.

How is it spread?
There are two different types of diphtheria infection: cutaneous and respiratory.

The cutaneous infection can occur when the bacteria gets in the skin. This can happen if a person comes into physical contact with someone else who has a cutaneous infection, which causes infectious ulcers on the skin. It is also possible to catch it from a surface that has been touched by someone who is infected.

The respiratory infection is the most worrisome type of diphtheria infection. People catch this from inhaling the bacteria via respiratory droplets in the air.

C. diphtheriae is present worldwide. Humans are the only known reservoir, but vaccine non-compliance and the presence of asymptomatic carriers keeps the bacteria around.

Symptoms:
The cutaneous infection is less deadly. The bacteria colonizes the skin and gets deeper into the skin through breaks or cuts. A papule develops and then becomes an ulcer that is usually chronic and slow or non-healing. There can be redness, pain, and swelling according to the Mayo Clinic. The ulcer may be covered with a grayish membrane and is infectious. According to the CDC, this form rarely results in more serious disease.
Diphtheria ulcer on a patient's leg. Image credit: CDC
 
The respiratory infection is the one most people talk and worry about. Symptoms usually start within two to five days of exposure and generally begins with a sore throat, malaise, and low-grade fever (WHO, CDC). The toxin (more on that shortly) causes dead tissue to build up in the throat, eventually forming a "pseudomembrane." According to the CDC, "[The pseudomemebrane] can cover tissues in the nose, tonsils, voice box, and throat, making it very hard to breathe and swallow." As you can imagine, difficulty breathing can lead to many other issues. According to the CDC, without treatment up to half of patients will die of the disease. Even with treatment, the CDC states that one in ten will still die of the disease. And just for the gross out factor: the pseudomembrane can start to slough off and further block your airway. Yuck!
Child with a swollen neck due to diphtheria. Image credit: CDC.
 
The toxin, diphtheria toxin, causes the most problems. The toxin inhibits protein synthesis (keeps cells from making proteins, which are needed for just about everything that happens in your body). "If the toxin gets into the blood stream, it can cause heart, nerve, and kidney damage," according to the CDC. Some of this damage can be long-lasting, even after the infection is cleared.

Prevention and Treatment:
The best prevention for this disease is the vaccine. Keeping up immunization and getting booster shots are the most important ways to keep diphtheria infections to a minimum. The vaccine is a toxoid vaccine, meaning it is actually a vaccine for the toxin, not to the bacteria itself. It is often included with the vaccine for tetanus and/or pertussis: Tdap, DTaP,  DT, and Td vaccines.

For treatment, antibiotics like penicillin or erythromycin can help get rid of the bacteria. But it is important to neutralize the toxin. There is a diphtheria antitoxin available for this and sometimes people will get injections made from the blood of people who have cleared the infection in order to stimulate antibody production to the toxin and bacteria.

So that's C. diphtheriae! I always liked to use diphtheria as a supporting argument for vaccination. Along the lines of: "Do you know what happens to you when you get diphtheria? The skin in your throat sloughs off and then you die."

Sources:
Medical Microbiology sixth edition by Patrick R. Murray, Ken S. Rosenthal, and Michael A. Pfaller

Sunday, February 23, 2020

Disease Post: Brucellosis

This is one of my favorite "bugs!"

Background:
Bucellosis is caused by a bacteria from the genus Brucella. There are a few different species that cause disease in animals and humans. For humans, the three species that usually cause disease are suis, abortus, and melitensis.
Brucella colonies on blood agar. Image from Pixnio.

Brucella species are small, anaerobic, gram negative coccobacilli, meaning that they do not require oxygen and do not have peptidoglycan in their cell walls and stain red/pink on a gram stain (bacteria that stain purple are gram positive). Coccobacilli describes the shape--they are between cocci (round) and baccili (rod-shaped).

They are facultative intracellular organisms, which means that they have to be inside another cell for part of their life cycle, but can also live outside of another cell. In the case of Brucella species, the cell they tend to invade is the macrophage. Macrophages are important cells in your immune system. Briefly, they usually "eat" things that are dangerous, like bacteria, and break it up into pieces. Then they take those pieces and display them on the surface of their cells using special cell receptors that will signal other immune cells to look for them. That way, the rest of your immune system can respond to the invaders. Brucella bacteria hiding in these cells, it makes it much more difficult for your body to find and fight off.

How is it spread?
Humans usually get this disease either by being in close contact with an infected animal or by eating contaminated animal products. Namely unpasteurized milk, which is contaminated with the bacteria when an animal is infected (this is why drinking unpasteurized milk is so dangerous). The bacteria can cause infection if inhaled, ingested, or through the skin. Most commonly, it infects via mucous membranes (for example: the eyes, throat, or respiratory tract).

According to the CDC, person-to-person spread is rare, but is most common if a mother is infected, she can infect her breastfeeding infant.

This disease is most worrisome in animals, both wild and agricultural. It is also found world-wide.

The bacteria are not especially hardy, they don't form spores and they can be killed with heat. However, they manage to survive in the environment for several years, if the conditions are right.

The incubation period for this bacteria is about two to four weeks, so there can be quite a delay between getting infected and showing symptoms.

Symptoms:
Many of the symptoms are flu-like: fatigue, fever, sweating, headache, body aches, anorexia, nausea, and malaise (generally not feeling well). According to the CDC, some symptoms can be recurring or persist for a longer period of time. Most commonly these symptoms are: recurrent fever, arthritis, swelling of the heart, neurological problems, chronic fatigue, swelling of the male reproductive system (namely the testes and scrotum), and swelling of the spleen and/or liver.

The good news is that brucellosis is rarely fatal in humans, but it is still considered a potential bioweapon because it can be easily spread and incapacitate people.

The chronic symptoms that are so common with this microbe are due to a couple things: incomplete antibiotic treatment, which causes relapses, and persistent infection by the bacteria in tissues (like bone, spleen, liver, et cetera). It can be difficult to get rid of.

Brucella colonies on serum dextrose. Credit: Royal Veterinary College and Wellcome Collection

Prevention and Treatment:
One way to prevent human infection is by pasteurizing milk and other dairy products. Eating under-cooked meat is not recommended as it could be contaminated with Brucella. There is also a vaccine for herd animals to B. abortus.

People who work with animals like cattle, pigs, goats, and sheep should wear protective clothing, like gloves and goggles.

Because the bacteria hides inside cells, antibiotic treatments can last a long time (often 6 weeks) and often more than one antibiotic is needed. Doxycycline with with rifampicin can be used, or doxycycline with gentamicin. Trimethoprim-sulfamethoxazole can be used for women who are pregnant or for young children.

Miscellaneous Information:
What I find super interesting about this bacteria is that it causes abortion (and infertility), which can lead to further infections in animals. It almost plays off of the maternal instinct. For example, if a cow is infected and it causes the cow to have an abortion, the cow may survive. However, the aborted fetus is infectious. Other cows may come into contact with the aborted fetus as they inspect it and then the bacteria can infect the new animal. A bit evil and fascinating.

Brucellosis is known by many other names, including: Malta fever, Mediterranean fever, Cyprus fever, goat fever, Gibralter fever, to name a few.

Sources:
The Centers for Disease Control: Brucellosis
Microorganisms and Bioterrorism edited by Burt Anderson, Herman Friedman, and Mauro Bendinelli
Emerging Infectious Diseases by Lisa A. Beltz
Medical Microbiology 6th edition by Patrick R. Murray, Ken S. Rosenthal, and Michael A Pfaller