Micro: SG Ch.4

The 1925 Serum Run to Nome has been called

"The Great Race of Mercy". The 674 mile serum run included 20 drivers, 150 sled dogs and lasted 5 1/2 days. It is memorialized in the Iditarod Trail Sled Dog Race. In modern times the fastest time for the Iditarod was by Martin Buser in 2002, with a time of 8 days, 22 hours, 46 min and 2 sec.

Diphtheria symptoms have been described as

"a slight fever and red ulcers in the back of the throat and in the mouth. As the bacteria multiplied and more toxin was released, the ulcers thickened and expanded, forming a tough, crusty, almost leathery membrane made up of dead cells, blood clots and dead skin. The membrane colonied ever larger portions of the mouth and the throat, until it had nowhere left to go and advanced down the windpipe, slowly suffocating the victim."

How does your text characterize life?

- Ability to move or grow. If taken individually, does not represent life signs. - Heredity: transmission of organism's genome (complete set of chromosomes and genes of an organism) to the next generation by chromosomes, which carry DNA (molecular blue print of life) - Reproduction: generation of offspring necessary to continue a specie's line of evolution. All organisms manifest asexual reproduction (dividing into two cells by fission/mitosis). Many organisms display sexual reproduction - Growth: 2 meaning - increase in size of pop through reproduction and enlargement of a single organism during maturation - Development: all changes over the life span of an organism that complete the full expression of its genome - Metabolism: encompasses thousands of chemical rxns that all cells need to func. Either synthesize new cell components/release energy that drives cellular activities. Both types are supported and regulated by unique molecules of life called enzymes - Responsiveness: capacity of cells to interact with external facts through irritability, communication, or movement. Irritability - receiving and reacting to stimuli. Communicate with other cells by sending and receiving signals. Self-propulsion or motility using specialized locomotor sturctures - Transport: system for controlling the flow of materials. Includes carry nutrients and water from the external environment into cell's interior. Without these, metabolism would cease. Cells secrete substance, expel waste, in reverse direction, movement of this type functions as the gatekeeper for cellular activities. All provide microorganisms with the capacity to adapt and evolve

Lyme disease?

- Borrelia burgdorferi and rarely, Borrelia mayonii Spirochete

Diphtheria

- Corynebacterium diphtheriae - Club-shaped Bacillus - Palisades Pleomorphic - multiple shapes. Supposed to a rod but can be club like

Define pleomorphic

- Pleon = more and morph form or shape. Due to individual variations in cell wall structure caused by nutritional or slightly heredity differences. Reaches an extreme in the mycoplasmas, which entirely lack cell walls and display extreme variations in shape

Strep throat?

- Streptococcus pyogenes - Cocci Chains - Strepto

Cholera?

- Vibrio cholerae Vibrio shape

3 exotoxins associated with Bacillus anthracis

1) protective antigen (PA), Edema factor(EF) and Lethal factor (LF). Note; one virulence factor not shown is the capsule. The capsule inhibits phagocytosis. Protective antigen functions as the binding site for Edema factor and Lethal factor. Once inside the cell, Edema factor leads to the edema through the Calmodulin pathway, while Lethal factor leads to necrosis by inhibiting MAP Kinases.

Identify the primary properties that define life and livings things

Ability to move or grow. If taken individually, does not represent life signs. Heredity: transmission of organism's genome (complete set of chromosomes and genes of an organism) to the next generation by chromosomes, which carry DNA (molecular blue print of life) Reproduction: generation of offspring necessary to continue a specie's line of evolution. All organisms manifest asexual reproduction (dividing into two cells by fission/mitosis). Many organisms display sexual reproduction Growth: 2 meaning - increase in size of pop through reproduction and enlargement of a single organism during maturation Development: all changes over the life span of an organism that complete the full expression of its genome Metabolism: encompasses thousands of chemical rxns that all cells need to func. Either synthesize new cell components/release energy that drives cellular activities. Both types are supported and regulated by unique molecules of life called enzymes Responsiveness: capacity of cells to interact with external facts through irritability, communication, or movement. Irritability - receiving and reacting to stimuli. Communicate with other cells by sending and receiving signals. Self-propulsion or motility using specialized locomotor sturctures Transport: system for controlling the flow of materials. Includes carry nutrients and water from the external environment into cell's interior. Without these, metabolism would cease. Cells secrete substance, expel waste, in reverse direction, movement of this type functions as the gatekeeper for cellular activities. All provide microorganisms with the capacity to adapt and evolve

Describe the fundamental characteristics of cells.

Assume cubical/spherical/cylindrical shapes Have a cell membrane that encases an internal matrix called the cytoplasm All cells have 1+ chromosomes containing DNA All possess ribosomes for protein synthesis and exhibit highly complex chemical rxns Divided into two groups: prokaryotic cells and eukaryotic cells

Anthrax Cases in the US Prior to 2001.

Between 1955 and 2000, there were 203 human cases of Anthrax in the United States. Below relates a few of these cases. In July 1987, a North Carolina textile worker developed a swollen red sore on his right forearm. This sore eventually filled with fluid and turned to a black scab. He also developed chills and fever. The textile milled produced yarn and Bacillus anthracis was isolated from 5 samples of Asian cashmere, 1 sample of Australian wool and 2 samples of debris. Further investigation found B. anthracis in 8 of 12 samples from a Texas plant that washed the wool before it was shipped to North Carolina. In August 2000, a North Dakota farmer found 5 cows dead in his field of Anthrax. Four days later he developed a bump on his cheek the size of a quarter covered which eventually became covered with a black scab. He developed no fever or other symptoms. One hundred fifty seven animals died on 31 North Dakota farms. In July of that same year, a Minnesota farmer found a cow unable to stand. It was slaughtered and butchered. Five of his family members ate hamburger from the cow. One individual developed abdominal pain, diarrhea and fever while another developed diarrhea. Both family members recovered. In August 2000, the same farmer found 5 cattle dead. Each tested positive for Anthrax. Tests of the meat from the earlier cow were also positive for Anthrax. Family members exposed to the beef were treated with antibiotics.

Anthrax - 2001

Between Oct 2 and Nov. 20, 2011, 22 cases of anthrax were confirmed, 11 cases of inhalational anthrax (5 fatalities), and 11 cases were cutaneous anthrax (none were fatal).

Clinical Connections: The Glycocalyx and Infections

Capsules are formed by many pathogenic bacteria, such as Streptococcus pneumoniae (a cause of pneumonia, an infection of the lungs), Haemophilus influenzae (one cause of meningitis), and Bacillus anthracis (the cause of anthrax). Encapsulated bacterial cells generally have greater pathogenicity because capsules protect the bacteria against white blood cells called phagocytes. Phagocytes are a natural body defense that can engulf and destroy foreign cells, which helps to prevent infection. A capsular coating blocks the phagocytes from attaching to, engulfing, and killing bacteria. By escaping phagocytosis, the bacteria are free to multiply and infect body tissues. Encapsulated bacteria that mutate to non-encapsulated forms usually lose their pathogenicity. Other types of glycocalyces can be important in formation of biofilm infections (see 4.1 Making Connections, The Glue of Life, p. ) The thick white plaque that forms on teeth comes in part from the surface slimes produced by certain streptococci in the oral cavity. This slime protects them from being dislodged from the teeth and provides a niche for persistent colonization that can lead to dental disease. The glycocalyx of some bacteria is so highly adherent that it is responsible for harmful biofilms developed on nonliving materials implanted in the body, such as plastic catheters, intrauterine devices, metal implants and pacemakers.

Anthrax

Clinical Disease: There are three forms of Anthrax: Cutaneous Anthrax, Digestive Anthrax, Inhalational Anthrax

Describe the shapes of bacteria and possible variants:

Coccus - spherical or ball-shaped. Can be perfect spheres, ovals, bean-shaped, or point variants. Staphylococcus aureus (10,000X) Bacillus: cylindrical (longer than wide) is termed a rod; Legionella pneumophilia (6,500X). Rod shape. Blocky, spindle-shaped, round-ended, long and threadlike (filamentous), or even clubbed or drumstick shaped. Rod is short and plump = coccobacillus Yersinia pestis. Gently curved = vibrio. Vibrio cholerae (13,000X) Spirillum: curviform or spiral=shaped cylinder. Rigid helix, twisted twice or more along its axis like a corkscrew. Aquaspirillum (7500X) Spirochete: periplasmic flagella, more flexible form that resemebles a spring. Borrelia burgodorferi (10000X)

Identify a pleomorphic organism.

Corynebacterium diphtheriae: generally rod-shaped, but in culture they can display club-like shaped, swollen, curved, filamentous, and coccid variations

Diphtheria and Dogsleds

Diphtheria is an upper respiratory tract infection. Symptoms include: sore throat, low fever and formation of a thick pseudomembrane in the back of the throat, which can lead to suffocation. In Spain the disease was known as El garatillo or the strangler. It was first described in 1492 by Hartmann Schedel in Nuremberg, Germany and again in 1576 by Guillaume deBaillon in Paris, France. It was named in 1821 by Pierre Bretonneau in Tours France to describe the pseudo-membrane that forms.

Serum Therapy

Emil von Behring and Shibasaburo Kitasato inactivated toxin of C. diphtheriae and injected it into guinea pigs and rabbits. Serum harvested from these toxin-treated animals was then injected into susceptible animals and found to protect them from a virulent form of C. diphtheriae. Because the immune serum neutralized the toxin, it was called anti-toxin. On Christmas day in 1891, this anti-toxin was used to treat an ill girl in a Berlin Hospital who survived[1]. Von Behring received the first Nobel Prize in 1901 for this work. At the time of von Behring's work, diphtheria was killing more than 50,000 annually in Germany. Large-scale production of anti-toxin was achieved in horses in 1894 and this anti-toxin became the standard for treatment of diphtheria. This serum therapy provides passive immunity. [1] Some researchers dispute this Christmas miracle as a fabricated story, but nonetheless, vonBehring was credited with the development of serum therapy.

Biofilms

Fimbriae and Glycocalyces play a role in the formation of biofilms. Biofilms were initially identified as bacterial slime layers but are communities of many different organisms, a biological system.

The bacterium was eventually cultured by

Friederich Loeffler in 1884 and became known as the Klebs-Loeffler bacillus until 1896 when it was renamed Corynebacterium diphtheriae. The organism requires special medium to grow in culture.

Based on the Gram stain procedure described by Hans Christian Gram, there are two types of cell walls

Gram positive and Gram negative.

Identify several arrangements of bacteria and how they are formed:

Greatest variety in arrangement occurs in cocci. Exist as singles, pairs (diplococci), tetrads (groups of 4), irregular clusters (staphylococci and micrococci), or chains of a few 100s of cells (streptococci). More complex grouping is cubical packet of 8, 16, or more cells = sarcina. Differences results from a division of a coccus in a single plane, two perpendicular places, or sev intersecting plates, after division, resulting daughter cells stay attached Bacilli are less varied because only divide in the transverse place. Single cells, pair of cells with their ends attached (diplobacilli), or as a chain of sev cells (streptobacilli). Palisades, typical for corynebacteria, formed when the cells of a chain remain partially attached by a small hinge region at the ends. Cells fold/snap back upon each other orienting cells side by side Spirlla are occasionally found in short chains. Spirochetes rarely remain attached for division.

Vaccination

In 1913, vonBehring developed a Toxin-Anti-toxin vaccine, which contained a carefully balanced mixture of toxin and anti-toxin. The toxin provided the antigenicity while the anti-toxin neutralized its toxic effects. In 1929, A.T. Glenny, Barbara Hopkins and Gaston Ramon inactivated diphtheria toxin with formaldehyde and demonstrated that while the diphtheria toxin lost its toxicity, it was still capable of inducing immunity. In the 1920s, the number of diphtheria cases in the U.S. was 150,000 with 13,000 deaths. After the vaccine is introduced in 1941, the number of cases dropped to 19,000 by 1945. Currently in the U.S., between the years of 1980 and 1995, only 41 diphtheria cases were reported. Four of these individuals died and all the fatalities occurred in unvaccinated children.

Accident at Sverdlovsk

In April, 1979, an outbreak of Anthrax in Sverdlovsk, USSR (now Yekaterinburg, Russia) occurred. Affected individuals ranged from age 26 to 68 years. In the end, 94 people were infected and 64 individuals died. Autopsies showed the lungs of the individuals had filled with fluid. The death certificates indicated that these individuals died of influenza, sepsis and pneumonia, however, Bacillus anthracis was recovered from 20 individuals who died. Officials blamed the outbreak on gastrointestinal anthrax from eating infected meat. Records were confiscated by the KGB.

Cell Wall

Just inside the glycocalyx (if a cell has one) is the cell wall. The basic structure of a cell wall is the peptidoglycan

Cell membrane

Just interior to the cell wall is the cell membrane.

In 1884

Loeffler concluded that C. diphtheriae produced a soluble exotoxin. In 1888, Emile Roux and Alexandre Yersin in Louis Pasteur's lab injected liquid medium from a culture of C. diphtheriae and reproduced the illness in guinea pigs.

Making connections: Biofilms - The Glue of Life

Microbes rarely live in isolation. More often they cling together in complex masses called biofilms. The formation of these living layers is a universal phenomenon that all of us have observed. Consider the scum that builds up in toilet bowls and shower stalls in a short time if the are not cleaned; or the algae that collect on the walls of swimming pools and, more intimately, the constant deposition of plaque on teeth. Fossil from ancient deposits tell us that microbes have been making biofilms for billions of years. It is through this process that they have colonized most habitats on earth and created stable communities that provide access to nutrients and other essential factors. Biofilms are often cooperative associations among several microbial groups (bacteria, fungi, algae, and protozoa) as well as plants and animals. Substrates favorable to biofilm development have a moist, thin layer of organic material such as polysaccharide or glycoproteins deposited on their exposed surface. This has a sticky texture that attracts primary colonists, usually bacteria. These early cells attach and begin to multiply on the surface. Here, they lay down a glycocalyx consisting of fimbriae, pili, slime layers or capsules. These substances bind the cells to the substrate and begin the development of the biofilm matrix. As the biofilm evolves, it undergoes specific adaptations to the habitat in which it forms. In many cases, the earliest colonists contribute nutrients and create microhabitats for other microbes to attach and grow into the film, forming complete communities. The biofilm varies in thickness and complexity, depending upon where it occurs and how long it keeps developing. Complexity ranges from single cell layers to thick microbial mats with dozens of dynamic interactive layers. Biofilms are a profoundly important force in the development of terrestrial and aquatic environments. They dwell permanently in bedrock and the earth's sediments, where they play essential roles in recycling elements, leaching minerals, and forming soil. Biofilms associated with plant roots promote the mutual exchange of nutrients between the microbes and roots. AS we will earn in Chapter 7, the microbes in these communities have "conversations" using a special chemical vocabulary, which greatly influences the actions of the biofilm. Researchers are currently analyzing the effects of biofilms created by our own microbiota - microbes that live naturally on the body. These associations are common on the skin and in the oral cavity and large intestine. In these locations, microbes signal each other as well as human cells in ways that shape the conditions there. Biofilms accumulate on damaged tissues (such as heart valves), hard tissues (teeth), and foreign materials (catheters, intrauterine devices [IUDs], artificial joints).Microbial biofilms play a key role in the majority of infections and diseases -for example, cholera, urinary tract infections, sexually transmitted infections, endocarditis, middle ear infections and pneumonia. New evidence indicates that bacteria turn on different genes when they are in a biofilm than when they are "free-floating" or planktonic. This altered gene expression gives bacteria a different set of characteristics, often making them impervious to antibiotics and disinfectants.

Diphtheria Resurgent

Outbreaks may still occur world-wide. One noted outbreak occurred after the break-up of the Soviet Union. Vaccination rates had fallen in the Commonwealth of Independent States. As a result, in 1998, the International Red Cross estimates there were 200,000 cases in these former Soviet republics with 5000 deaths. The Guinness Book of World Records identified diphtheria as "the most resurgent disease One lesson from this story: while much progress has been made in the area of infectious disease, there is a danger in complacency towards vaccination. If a disease is not a problem anymore, does not necessarily follow that the disease is eradicated.[1] As vaccination levels decline, the number of susceptible individuals increases and the more individuals the microbe can infect and cause disease. Vigilance in vaccination is important. As you will see in the case of smallpox, we have eradicated some diseases but this is not always the case.

In 1888

P. Ernest and Victor Babes described metachromatic granules in C. diphtheriae bacteria when stained with Methylene blue.

Outline the size ranges among bacteria and in comparison to other organisms:

Range from barely visible with light microscope (0.2 micrometers) to 1000x that size. Cocci = 0.5-3.0 micrometers in diameter; bacilli = 0.2-2.0 micrometers in diameter and 0.5-20 micrometers in length. Human hair visible on 200X Lymphocyte, yeast cell, ragweed pollen visible on 2,000X E coli = 2 micrometers Ebola virus = 1.2 micrometers in diameter Rhinovirus = 0.03 micrometers and 30 nm Staphylococcus = 1 micrometer RBC = 12 micrometers - Visible at 20,000X

The following represents a timeline of events in the anthrax mailings

Sept. 11, 2001: Terrorists hijack four airline jets and crash them into the World Trade Center towers in New York City, the Pentagon in Virginia and a field in rural Somerset County, Pa. Sept. 18, 2001: The first letters containing anthrax are mailed. Oct. 4, 2001: Bob Stevens of American Media in Florida is hospitalized with inhalation anthrax. Oct. 5, 2001: Stevens, 63, dies. It's the first anthrax death in the U.S. in 25 years. Oct. 8, 2001: Anthrax is found in the Boca Raton, Fla., offices of American Media, publisher of the National Enquirer. The building is closed. Oct. 9, 2001: More letters laced with anthrax are posted, and the FBI begins investigating the incidents. Oct. 12, 2001: An NBC employee in New York City tests positive for anthrax poisoning. Oct. 15, 2001: Senate Majority Leader Tom Daschle (D-SD) tells reporters anthrax was found in his office. Oct. 16, 2001: The 7-month-old son of an ABC News freelance producer tests positive for anthrax poisoning. The baby developed a rash soon after visiting the network's Manhattan offices on Sept. 28. Oct. 18, 2001: A CBS employee and a New Jersey postal worker test positive for anthrax poisoning. Oct. 23, 2001: Two postal workers from the Brentwood facility in Washington, D.C., are confirmed to have died from inhalation anthrax. Oct. 26, 2001: A U.S. State Department mailroom staffer is hospitalized with anthrax poisoning. Oct. 28, 2001: Another New Jersey postal employee tests positive for anthrax poisoning. Oct. 30, 2001: A New Jersey patient becomes the 15th reported case of anthrax poisoning. Oct. 31, 2001: Kathy Nguyen, an employee of the Manhattan Eye, Ear and Throat Hospital, dies from inhalation anthrax. Nov. 21, 2001: Ottilie Lundgren, 94, of Connecticut, becomes the fifth person to die from inhalation anthrax. June 25, 2002: FBI agents search the residence of Steven Hatfill, a scientist who worked in the government's biodefense labs at Fort Detrick, Md. August 2002: Hatfill is named a "person of interest" by law enforcement officials. December 2003: The Brentwood postal facility reopens in Washington, D.C., after more than $130 million worth of renovation and cleanup. July 13, 2004: The New York Times is sued by Hatfill for defamation. He also sues the Justice Department. Jan. 12, 2007: A federal judge dismisses Hatfill's libel suit against The New York Times. June 27, 2008: Hatfill receives a $5.8 million settlement in his suit against the government. July 29, 2008: Bruce E. Ivins, another government scientist suspected in the 2001 anthrax attacks, commits suicide.

Epidemic In Nome: Iditarod

Serum therapy was the treatment option used during one of the more famous outbreaks of diphtheria in U.S. history. In Dec 1924, two cases of tonsillitis had been diagnosed in Nome Alaska. These cases were actually mis-diagnosed diphtheria cases. On Jan. 20, 1925, 3 year old Bill Barnett was correctly diagnosed with diphtheria. The Nome physician, Dr. Curtis Welch realized the anti-toxin stocked at the Nome hospital for diphtheria was hopelessly out-dated. The hospital had requested of shipment of anti-toxin but it had not arrived before the port of Nome was closed for the winter. Bill Barnett dies the following day. Dr. Welch tried some old-fashioned remedies to help alleviate some of the symptoms. These included stimulants to strengthen the heart and swabbing the throat with chloride of iron. But these remedies did not work. The day Barnett dies, 7 year-old Bessie Stanley is diagnosed with diphtheria. Dr. Welch used the expired anti-toxin but she dies anyway. As a result, the town council initiated quarantine procedures for Nome and on Jan. 22, the governor of the state of Alaska was notified of the public health situation. A request for more anti-toxin was made to the U.S. Public Health Service, however, the harbor at Nome was hopelessly frozen shut for the winter so the anti-toxin could not be shipped in by boat. Bush planes could bring the anti-toxin in but an open cockpit and water-cooled engines, made this a risky situation in the extreme cold. Additionally, the amount of daylight hours at that time of year in Alaska made flying nearly impossible. The only other means available then of bringing the anti-toxin in to Nome was by dogsled, a 700 mile trek from Nenana to Nome, Alaska. The governor of the Alaska was unwilling to risk the precious anti-toxin. Governor Scott Bone, began assembling the best dogsled teams for the run to bring the anti-serum from Nenana to Nome. Leonhard Seppala, a renowned Norwegian dogsled driver was dispatched from Nome with his celebrated dog, Togo, to participate in the relay. He would rendezvous at Shaktoolik to run the final leg of the journey over the treacherous Norton Sound. The governor was vociferously criticized for this decision by the editor, William "Wrong Font" Thompson, of the Daily Fairbanks News-Miner. On Jan 24, there were two more fatalities reported in Nome and 20 more confirmed cases. Estimates were that there could be 50 more potential cases. On Jan. 26, three hundred thousand units of anti-toxin were located at the Anchorage Railroad Hospital and were rushed to Nenana by rail. The shipment arrived on Jan.27 at Nenana and the dogsled relay began. The temperatures in the interior of Alaska were -50 degrees F. Other remedies attempted by other physicians included infection of mercury, swabbing or injecting carbolic acid into the membrane or forcibly remove the membrane with forceps or to suck the membrane from the throat. In the 1880s, some physicians attempted a tracheotomy to help the patients breathe which reduced the mortality from 100 to 75 %.

Diarrhea Doozies

Sixty young men and women came to the clinical research center at Stanford University to determine whether hair-like structures called fimbria have a significant place in disease. The students would drink a fruit-flavored cocktail containing a special diarrhea-causing strain of Escherichia coli. Thirty cocktails had E. coli with normal fimbria, while 30 had E. coli with fimbria mutated beyond repair. Students drank the cocktail. The experiment was a double-blind experiment, neither the students nor the health professionals knew who was drinking the diarrhea cocktail and who wasn't. Results: It was found that the great majority of volunteers who drank the mutated bacterial cells experienced no diarrhea, while those who drank the normal bacteria cells had attacks of diarrhea.

Surface Coating/Glycocalyx

The next interior structure is the surface coating or glycocalyx There are 2 types of glycocalyces

Wrap Up

The outbreak of pneumonococcal pneumonia described above points out that certain bacterial structures, such as a capsule, enhance virulence. Studies have shown that the capsule allows the bacterium to avoid being engulfed by white blood cells called phagocytes. It is an accepted fact that strains of Streptococcus pneumoniae with capsules are virulent while those lacking a capsule are not. This knowledge has been used to make a vaccine using 23 types of polysaccharide capsular antigens. When this vaccine is administered, it will elicit specific antibodies that provide protection from the most common strains causing pneumonoccal pneumonia. The serum antibodies that arise after vaccination specifically coat the bacterial capsule and allow for uptake of the bacteria by the host phagocytes. This disease is significant, as the Centers for Disease Control and prevention (CDC) estimate that about half million cases occur each year, resulting in about 40,000 deaths in the United States. As was the case with this outbreak, the highest mortality rate (30-40%) occurs in the elderly or in those with underlying medical conditions.The CDC estimates that about half of these deaths could be prevented through use of pneumococcal vaccine.

Atypical Cell Walls

There are some bacteria that have atypical cell walls. For each of the following cells, distinguish how the cell wall is different.

Syphilis?

Treponema pallidum Spirochetes

Cell Wall and Infections

Variation in cell wall anatomy contribute to several differences between the two cell types besides staining reactions. The outer membrane contributes to an extra barrier in gram-negative bacteria that makes them more impervious to some antimicrobic chemicals such as dyes and disinfectants, so they are generally more difficult to inhibit or kill than are gram-positive bacteria. One exception for alcohol-based compounds, which can dissolve the lipids in the outer membrane and disturb its integrity. Treating infections caused by gram-negative bacteria often involves different drugs than gram-positive infections, because of the special requirement that the drugs must cross the outer membrane. The cell wall or its parts can interact with human tissues and contribute to disease. The lipopolysaccharides have been referred to as endotoxins because they stimulate fever and shock reactions in gram-negative infections such as meningitis and typhoid fever. Proteins attached to the outer portion of the cell wall of several gram-positive species, including Corynebacterium diphtheriae (the agent that causes diphtheria) and Streptococcus pyogenes (the cause of strep throat) also have toxic properties.The lipids in the cell walls of certain Mycobacterium species are harmful to human cells as well.Because most macromolecules in the cell walls are foreign to humans, they stimulate antibody production by the immune system

The first driver

William "Wild Bill" Shannon begins his part of the relay with 9 dogs. He arrives at Minto with severe frost bite. The trail he followed had been rutted by horses, which damaged the dogs paws and ankles. He moved the dogsled team to the smoother ice of the Tanana River and he runs alongside the team. At Minto, he has to leave 3 of his dogs behind. Two will eventually die from the cold. He continues on to Tolovana where he relays with Edgar Kallands on Jan 28. Kallands continues the relay and arrives at Manley Hot Springs Roadhouse. The innkeeper at the roadhouse reported that Kallands hands were frozen to the handle of the sled and he had to pour hot water to thaw them. Dan Green then takes the anti-toxin to Fish Lake and Johnny Folger to Tanana. On Jan 29, the relay continues the next 170 miles from Tanana to Galena with drivers, Sam Joseph, Titus Nikolai, Dave Corning, Harry Pitka, Bill McCarty and Edgar Nollner. On Jan. 30, Nollner hands the anti-toxin to his brother George who continues on 18 miles to Bishop Mountain. At Bishop Mountain, Charlie Evans continues with the anti-toxin but forgot to cover the exposed areas of his mixed breed leaders, who collapse along the way. He then has to lead the team on to Nulatto himself. The dogs later died of frostbite. Tommy Patsy continues the relay 36 miles to Kaltag where the relay continues with a driver named "Jackscrew". At this time, the number of diphtheria cases in Nome is 27 with another fatality. The out-dated anti-toxin, however useful it might have been is now gone. In order to speed the dogsled relay, the Alaska governor has added more relay drivers to help Leonhard Seppala with the last leg of the relay. "Jackscrew" continues on Jan. 31 from Kaltag portage to "Old Woman Shelter". Victor Anagick then takes it 34 miles to Unalakleet and Myles Gonanagnan continues 40 miles to Shaktoolik. As a winter storm begins to move into Alaska, the wind chill is -70oF with driving snow and gale force winds making the relay even more difficult. Leonhard Seppala had not yet arrived at Shaktoolik so Henry Ivanoff heads out to meet Seppala along the trail. Ivanoff and his team run into a reindeer and he and the dogs became hopelessly entangled. As Ivanoff attempts to reorder the team, Seppala is passing on the nearby trail. Fortunately, Ivanoff spots Seppala in time and is able to hand the serum to Seppala who turns around and heads back toward Nome. Seppala arrives at Isaac's Point and rests a few hours. As Seppala is traveling across the ice pack of Norton Sound, the wind has increased to 65 mph and wind chill is still -70oF. Dr. Welch in Nome orders a stop to the relay due to the winter weather but the messages never reach to drivers. Seppala makes it to the next roadhouse at Golovin and hands the anti-toxin to another driver, Charlie Olson. Olson had been added to the relay by the governor. At this time, the number of diphtheria cases in Nome is 28. The anti-toxin being sent would only treat 30 individuals. Olson continues on to Bluff and hands the serum off to Gunnar Kaasen, a friend of Seppala's who tried to wait out the storm. After 3 hours, the storm is continuing to worsen so at 10 PM, Kaasen sets off with his lead dog, Balto. Visibility is so poor at times that Kaasen cannot see the dogs leading the sled. He is blown off course and has passed the next relay point Solomon before realizing it. He continues on. The winds at one point flip the sled over and Kaasen must remove his gloves to find the precious anti-toxin package in the snow drift. He suffers severe frostbite. When he arrives at Point Safety on Feb. 2, he is ahead of schedule and the next driver is asleep. Kaasen rests for a time but fears the delay in assembling the next team so he does not wake Ed Rohn and continues the last 25 miles to Nome. He arrives at Nome at 5:30 AM on Feb. 2, severely frostbitten. While Gunnar Kaasen and his dog, Balto, receive much of the credit for the serum run, it should be noted that Leonhard Seppala and Togo played a significant role. Since Seppala was dispatched from Nome to meet up with the dogsled teams and run the most dangerous leg of the race, he and his team, traveled more than 261 miles. While the official death toll from the Nome epidemic is 5-7, Dr. Clark estimates at least 100 additional cases occurred in the Eskimo camps outside of Nome, but since many natives bury their dead without reporting so the true number of cases may never be known.

Diphtheria is a

contagious disease, which is transmitted by direct contact with aerosolized droplets. The first clinical observation of the disease was by Hippocrates in the 4th Century BCE. Diphtheria resulted in many epidemics in 17th century Europe and was first reported in North America in 1735. The bacterium which causes diphtheria was first recognized by Edwin Klebs in 1883.

In 1992

following the break-up of the Soviet Union, a team of Russian and American scientists examined remaining autopsy records and performed PCR on some of tissue samples. Bacillus anthracis was identified and the scientists concluded that the source of the Anthrax was an accidental release of Antrhax spores from a bioweapons plant near Sverdlovsk. Victims were downwind of the plant. For more information about this release, I would suggest Anthrax: The Investigation of a Deadly Outbreak by Jeanne Guillemin.

determination of gram + and gram -

is based on whether or not a cell reatins the primary dye-iodine complex after decolorization and based on the cell wall

For three weeks in Spring 2001

nine cases of pneumonia occurred in elderly residents (median age of 86 years) living in a long-term care facility in New Jersey. Seven of the nine patients had Streptococcus pneumoniae isolated from blood cultures, with capsular serotyping revealing that all isolates were the same strain—type 14. Seven of the nine patients also lived in the same wing of the nursing home. Even the two patients with negative blood cultures had Gram-positive diplococcus in their sputum and chest X rays consistent with pneumonia. Epidemiological studies of the patients and uninfected controls revealed that all who developed pneumonia had no documented record of vaccination with the pneumococcal polysaccharide vaccine (PPV). In contrast, about 50% of infection-free patients had been vaccinated with PPV. Even though other risk factors were assessed, the lack of vaccination with PPV was the only one strongly associated with illness. Despite treatment, four of the nine patients with pneumonia died. Once the outbreak was recognized PPV was offered to those 55 residents who had not yet been vaccinated. Thirty-seven of these were vaccinated, whereas the other 18 were either ineligible or refused the vaccine. As a control measure, the facility decided to admit in the future only those patients with a history of PPV vaccination.

If a patient recovered

patients generally coughed up "incredible quantities of a tough whitish slough from their Lungs for a considerable Time together. And on the other Hand, have seen large Pieces of crust, several inches Long and near an Inch broad, torn from the Lungs by the vehemence of the cough."

During the 1918 influenza pandemic

scientists were Gram staining sputum samples to try and identify a bacterium causing the outbreak. Unfortunately, soldiers had drained the alcohol from the bottles in the lab and replaced it with water