Download Pathology of Infectious Diseases II

General Pathology
10/02/2008
Pathology of Infectious Diseases, Part II
Transcribers: Luke Powell, Marc Vance
66:33
21. He tells the story of finding a case of Neisseria meningitidis recently in the hospital. Is it dangerous
for the lab tech? No, because they have had the meningococcal vaccine, and were handling the
organism properly. However, those who were caring for the patient probably should take antibiotic
prophylaxis, probably ciprofloxacin.
22. Pyogenic bacteria. Here’s an abscess you can drain puss out of. We think of pyogenic bacteria as
puss producing organisms. Abscesses and puss are the typical pathological lesions you see with
these organisms. With strep throat, you get puss on the tonsils. The bacteria attach to the tissues
that they are going to cause infection in, and then they invade. This stimulates neutrophils to come
to phagocytize the bacteria. The neutrophils release enzymes to kill the bacteria that can also cause
damage to tissues. And also the bacteria can release exotoxins which can further damage the tissue.
That’s why you get the inflammatory reaction and necrosis associated with toxin mediated bacteria.
This is typical for many different organisms.
23. Tissue penetration can occur in a lot of different ways. This child has an orbital cellulitis due to
Haemophilus influenza. You see a big, swollen red eye. You can have the inflammation process
that’s not necessarily a collection of puss, but also could be a diffuse suppuration. You see the
redness, that’s a cellulitis.
24. Toxin production also aides in the penetration of tissue. This is necrotizing fasciitis, another disease
caused by Group A Strep (flesh eating bacteria). This patient developed the flesh eating bacteria in
the site of a skin biopsy and died two days later. The toxin producing Streptococci eat into the skin,
causing a cellulitis. They spread through the fascial planes, causing thrombosis, infarction, and
gangrene of the underlying tissues. If you get something like this on an extremity, you must
amputate to save the patient’s life.
This tissue from the thigh where the infection occurred shows inflammatory cells and bacteria in the
background. This strep spread throughout the person’s body and into every organ, killing the
patient at twenty-three years old.
25. Many times when bacteria produce disease, there are very specific relationships between structures
on the bacteria and cells in the host. Many bacteria are host specific, and even tissue specific in
terms of the things the bacteria have that help them to attach. Mycoplasma pneumonia is a good
example of this. The organism has a specialized attachment structure that allows it to attach to the
respiratory epithelium, causing local damage and coughing. You end up coughing and coughing with
this. It also stimulates the inflammatory response, and can cause pneumonia.
26. Many organisms don’t have to produce a lot of toxins to cause disease. The most common cause of
community acquired pneumonia is Streptococcus pneumoniae. This is what you would see in the
alveoli of someone with Pneumococcal pneumonia. You see the inflammatory reaction because of
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the neutrophil chemotaxis and increased vascular permeability which allows protein and fluid to
seep into the alveoli. This forms an excellent culture fluid for the bacteria, and it’s why they grow
and multiply, interfering with gaseous exchange. You can get significant disease that spills into the
bloodstream even without significant exotoxins. Exotoxins are not always needed for significant
disease.
27. Chronic infections such as Mycobacterium and Chlamydia trachomatis can occur when organisms
live inside of cells. Remember the Chlamydia and Rickettsiae are obligate intracellular bacteria that
always live inside host cells. This helps protect them from the immune system. It’s a virulence
mechanism they have adapted by living inside host cells including phagocytes.
28. Some diseases might be caused by our own immune reaction. It’s not something that the bacteria is
doing, it’s the reaction that our bodies have to the microorganism that can produce disease.
Perhaps the best example of this is acute rheumatic fever caused by Streptococcus pyogenes.
Following a sore throat with S. pyogenes, you get antibodies produced against the M protein of the
strep. These antibodies that are produced can cross-react with antigens in the heart, causing
damage to the heart. The mitral valve is shown damaged and calcified through dystrophic
calcification. Ultimately the valve can fail by mitral valve stenosis. You are also at risk of getting
subsequent bacterial endocarditis infections on the heart valves because they have been damaged.
The other example of autoimmune disease associated with Strep pyogenes is acute glomerular
nephritis. Here you have a type III immune complex development in the bloodstream which
precipitates in the kidneys. This follows a strep infection. That’s two examples of how strep can
produce an autoimmune reaction as a mechanism of disease.
29. It’s important to review again the differences between exotoxins and endotoxins. Remember the
endotoxins are thought to be only part of Gram (-) organisms because they are a part of the cell wall
(LPS). The exotoxins are proteins that are secreted by the bacteria, and they occur in the cytoplasm.
The LPS is associated with the outer membrane of the cell envelope of gram (-) organisms.
Endotoxin is released when dead organisms are lysed, while exotoxins are released by living
organisms.
30. There are a lot of different actions of exotoxins. A few you should be familiar with are in your book
and learning objectives. The diphtheria toxin interferes with protein synthesis. The cholera toxin
(from Vibrio cholera) is a diarrheal disease. The main symptom of cholera toxin is intense diarrhea.
There’s a bacteriophage encoded toxin that is released when the organism is in the bowel that
stimulates cyclic AMP through a complex reaction which ultimately causes the secretion of
bicarbonate and chloride into the bowel. Large amounts of fluid follow the chloride and
bicarbonate. Severe dehydration is a result, and it can be fatal in young children.
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Clostridium tetani produces lockjaw because the tetanus toxin interferes with the release of
inhibitory neurotransmitters which balance the neurons, causing them to always be in a hyperexcited state.
31. Remember endotoxins have a complex array of effects. Remember, exotoxins have specific
mechanisms and reactions at specific cells. Endotoxin is much more complex. It is composed of
lipopolysaccharide, and it does a lot of things. Endotoxin really accounts for what we call septic
shock.
One of the most common reasons that people die in the hospital is septic shock. This is because
they get a gram (-) bloodstream infection. This can occur in many people. Most acquire the
infection while in the hospital as a consequence of underlying disease. For example, cancer patients
often die from infection because they are weak from their malignant disease. The patient has poor
appetite and poor resistant to infection. In this immune-suppressed state, along with surgical
treatments for tumors, patients are at great risk for infection. The immediate cause of death for
most cancer patients is infection acquired because of their cancer.
32. This is an example here of what endotoxin can do and why it’s so severe when you have bacteria
that invade your bloodstream. You get damage to the endothelial cells of the bloodstream by the
endotoxin. This stimulates the coagulation cascade and disseminated intravascular coagulation.
The endotoxin also stimulates macrophage activity and IL-1. This in conjunction with the
hypothalamus is why you get fever. Of course you get all these other things such as complement
activation and increased vascular permeability and other things that can lead to hypotension and
shock. There’s a whole gamut of reactions that can occur because of these complex
interrelationships between the endotoxin and the entire body.
33. This is an example of a patient that had gangrene and DIC due to the endotoxic effects of
Meningococcal sepsis. Remember that the endotoxin is the most important virulence factor of
Neisseria meningitidis.
34. Another concept that you may have heard of in immunology is that of bacterial superantigens
(SAGs). Superantigens can be things like bacterial toxins that actually bypass the normal antigen
presentation because they bind Class II MHCs on antigen presenting cells and T cell antigen
receptors. They stimulate “cytokine storms.” They activate T-cells at many orders of magnitude
higher than normal. This is what causes the shock in toxic shock syndrome. Remember that toxic
shock syndrome is associated with a rash and multi-organ failure and can be caused by
Staphylococcus aureus as well as Streptococcus pyogenes. The toxic shock toxin that these
organisms produce is considered a superantigen and potent stimulator of T-cells. A vigorous
outpouring of cytokines is observed.
35. Let’s move on into viruses. You haven’t studied viruses so far, so this will be an introduction. We
have a number of case studies of viral diseases available in the IP labs that are available. There are
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four different IP labs that correspond to the lecture that we did on Tuesday and today. Virology will
be presented after the micro exam next week. Today is just an overview.
36. Viruses are much different from bacteria. The simplest viruses are simply nucleic acid surrounded
by a protein coat. Some of them are more complex and have various envelopes, but they will only
have one type of nucleic acid, either DNA or RNA. It could be either single or double stranded. The
RNA viruses must undergo a complex mechanism for replication. The main thing you have to
understand is that viruses, like Chlamydia and Rickettsiae, are obligate intracellular parasites. They
depend on the host cells metabolic machinery and amino acids and everything else in order to
assemble new virions. Viruses are the simplest form of life, and of course cannot be cultured in a
laboratory like bacteria. You have to grow them inside other cells for diagnosis.
Common among all viruses is the fact that they must find the cell they are going to invade. Many
viruses are tropic for specific types of cells. The HIV virus must infect T-cells. You can look at
different types of viruses, and they may go to only a certain cell, or other viruses can infect a
multitude of cells. But all viruses must get inside the cell to replicate.
They must have a form of attachment. They must have a form of penetration. And they must
“undress themselves” once they get inside the cells. They have to uncoat their nucleic acid, remove
their capsid, and then replicate their nucleic acid and then synthesize new virus proteins that will
make new capsids. Then all those things have to be put back together. They must then release
from the host cell. Here you see HIV budding off of the host cell. Some other viruses grow to large
numbers inside the host cell until the host cell simply bursts, releasing the viruses.
37. The influenza virus is one of the best studied viruses. It has two main surface antigens. It has the
hemagglutinin (the red spikes) and the neuraminidase (blue spikes). The hemagglutinin allows the
virus to bind to the respiratory epithelium. Then the neuraminidase actually facilitates the release
of the virus after it’s replicated from the infected cell. These two structures on the surface of the
influenza virus are very immunogenic. They are the basis for the influenza vaccine.
As health care people, we should get the flu vaccine. For our sake, and the sake of our patients, we
don’t need to get the flu.
The influenza virus exhibits antigenic drift, making vaccine production difficult. There are different
combinations of H and N antigens that are constantly mutating. Every year, the strains change, and
a new flu vaccine must be guessed and produced. Sometimes the vaccine is very good, other times
it is not as good. The vaccine is based on the H and N antigens.
A treatment for the flu is the new neuraminidase inhibitors. These drugs block the activity of
neuraminidase, treating the disease.
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Minor changes in the antigens are called “antigenic drifts.” Major changes are caused “antigenic
shifts.” The flu can be pandemic. In addition, the flu might not kill you, but it can leave you wide
open to a bacterial infection because of the damage done to the lower respiratory tract. So
pneumonia often ends up killing those with the flu.
38. Let’s talk about some ways that viruses kill host cells. Polio virus is a very simple RNA virus. It’s a
virus that has a particular tropic effect to the motor neurons in the nervous system. It attacks the
motor neurons in the spinal column, damages them, and that’s why you get paralysis. It actually
inhibits DNA and protein synthesis when it gets inside of neurons, and the cells die.
Some of the other ways that viruses produce damage is that they insert into the host cell
membrane. This can promote cell fusion, as seen in the measles. With measles, you can get giant
cells because of the influence of the virus causing the cells to fuse. The influenza virus simply
invades the epithelial cells, and kills them when the virus is released after replication.
Hepatitis B virus causes significant liver disease. When a hepatitis virus invades a liver cell, it will
express the viral proteins on the cell surface. What does that do? It tells the host immune system
that the virus is present. The collateral effect of this is that the host immune cells go and attack all
the infected cells in order to get to the virus. So the immune response is what actually kills the liver
cells, causing much of the liver damage in hepatitis. The greater the immune response, the greater
the damage.
39. HIV damages the host immune cells. The reason you get sick with HIV is that you get an
opportunistic infection with another virus or fungus because all of your T-cells are damaged by the
HIV. So you get Cryptococcus or Pneumocystis that are such a big problem for HIV patients. This is
not as much of a problem as it was in the past because we have better drugs that stimulate the
immune system. Early on in the history of HIV, patients died quickly because their T-cell counts
went so low.
Back to polio. It is an excellent disease in terms of understanding mechanisms because a lot is
known about it. When the polio virus invades the neurons of the spinal cord, the neurons die. If
you lose the innervations to the muscles of the legs, those muscles atrophy. The paralysis and the
atrophic limbs associated with polio are a result of the loss of muscle cells due to the loss of
innervations because of the polio virus.
You can also get slow viral infections. One of the most important reasons for the measles vaccine
was not because of the rash and fever of young kids, but the fact that about 1% of everyone that
gets the measles gets a reactivated virus months later. This reactivated virus is called subacute
sclerosing panencephalitis (SSPE). This is almost always fatal. So 1% of all people who get the
measles die, and a big reason that the measles vaccine was developed.
Human papilloma virus causes cell proliferation and cervical neoplasia. There’s a lot of publicity
about the Gardasil vaccine that prevents teenage girls from getting cervical cancer due to papilloma
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virus. There are a number of other viruses that cause neoplasia. The more we learn about viruses
and cancer, the more we find that infections are a cause of many cancers. There’s a table in the
textbook about various neoplastic viruses. We know hepatitis virus is often associated with liver
cancer. Burkett’s lymphoma is associated with Epstein Barr virus. Kaposi’s sarcoma is associated
with herpes virus.
40. This is what measles rash looks like and these are the giant cells that you get as a result of measles
virus.
41. The host response to viral infection is somewhat variable, but there are a few generalities that you
can make. The inflammation that you get in response to a viral infection is more typically
monocytes and lymphocytes as opposed to neutrophils, which you see with bacterial infection. Like
many bacterial infections, you get antibodies formed naturally as a consequence of the infection.
These antibodies help block attachment, penetration, and uncoating. Of course this is the basis for
many viral vaccines that we have. The vaccines will block one or more of the steps of the viral
replication process.
Something else that occurs in viral infections is interferon production. Interferons are naturally
occurring substances that inhibit the translation of viral proteins and prevent replication. They also
enhance T-cell and natural killer cell activity. Interestingly, interferons can now be made
synthetically to help bolster the immune system in viral infections (particularly in Hepatitis C).
Of course cellular immunity is also very important in protection against viruses. Someone with AIDS,
who has a depressed cellular immunity, is very susceptible to viral infections.
42. Viral latency is a phenomenon we see with some viruses. The best examples are Herpes viruses
such as Herpes zoster and Varicella zoster. Chickenpox occurs in young children. We now have the
varicella vaccine that we use to keep kids from getting chickenpox.
Shingles is the reactivation of the varicella virus that can remain in the body post-infection in the
dorsal spinal ganglia. When you get older, it can spread back out along the dermatome supplied by
the spinal nerve that is infected. Along the dermatome you get the typical chickenpox rash. In some
severe cases, you can see the varicella as is comes out along the trigeminal nerve.
Herpes viruses are particularly well known for remaining latent. If you get a cold sore early on in
your life, you may continue to get them on and off for the rest of your life.
43. You need to be familiar with prion disease. Prions are not really viruses. They are neuronal proteins
that undergo conformational changes. They are infections and transmissible. There are both
inheritable forms and sporadic mutations that occur. They produce a spongiform encephalopathy,
as seen here in the brain. What happens ultimately is you lose your mind, becoming demented.
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Then you can’t walk, and then you die. They don’t produce an inflammatory response. Think “mad
cow” disease, or Creutzfeldt-Jakob disease.
About four cases are reported in the state per year. The thing about this is that the prions are
resistant to most forms of disinfection, and they are transmissible. There have been cases of CJ
disease from cornea transplants. Brain autopsies are not done on these patients because brain
tissue can be infections. Spinal fluid is also risky. It’s hard to decontaminate instruments that come
in contact with CJ disease.
CJ is different from Mad Cow in that you get Mad Cow from eating meat from infected cow meat.
The cows transmit the disease because they eat the remains of other cows who could have been
infected. Hamburger can often have cerebral spinal fluid in it, so it could be dangerous. Patients
suspected with CJ disease are handled very carefully by the lab.
There’s often a question on board exams requiring us to know what a prion is, and the potential
infection control implications of it and the transmissibility (like corneas, brain tissue, and spinal
fluid).
44. Let’s move on to fungal disease. There’s a nice agar plate, but those are nasty molds.
45. We’ll say a few things about fungal diseases. Keep in mind that there are different types of fungal
disease in the sense that some of them are considered endemic (only occurring in parts of the
world), and other are worldwide. Candida is a worldwide mycosis (infection) problem. It is part of
the normal flora of our body, and everybody has it all over the world. Blastomyces is a disease that
occurs only in the eastern part of the US.
Most systemic fungal infections are transmitted by inhaling spores form the environment.
Histoplasma is an example of this; we see it fairly common in Alabama. Sporothrix is obtained by
pricking yourself on a thorn. In hospitalized patients, we are concerned about systemic invasion by
opportunistic fungi. With T-cell suppressed immunity, you can get all kinds of fungal infections that
spread throughout the body and can be fatal. Transplant patients are susceptible. Most fungal
infections are not person to person transferrable.
Dermatophytes are an exception to this. These are the ringworms, jock itch, and athlete’s foot
species. Of course you can spread these with person to person or animal to person contact.
46. We can also classify the fungi as true pathogens or opportunistic. The true pathogens mainly cause
respiratory, bone, and skin disease. The opportunistic diseases cause disease only in sick people.
This is an example of a fungus we see often in HIV patients called Cryptococcus neoformans. It’s a
fungus that has a predilection for the nervous system. It is acquired in the respiratory tract, but it
finds its way to the nervous system and shows up as an encapsulated yeast in the nervous system. It
has a capsule just like bacteria.
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47. Fungi exist in two different morphological types. They occur as yeast. You saw an example of
Candida in micro lab. Or they occur as molds, like this Aspergillus mold. They are identified
morphologically. Some fungi will go back and forth between the yeast form and mold form. The
ones we refer to as dimorphic can be a mold or yeast, depending on growth conditions. The
thermally dimorphic fungi appear in the environment as molds. After inhalation, at body
temperature they grow as yeasts.
48. There are a lot of different ways that fungi can cause disease. He will use aspergillus to show how
one fungus can produce four different types of disease. Aspergillus is a mold fungus. This is a silver
stain showing these septated hyphal aspergillus that branch at 45 degree angles in tissues here.
The first way that fungi produce disease in terms of aspergillus is by an allergic reaction. Many
people have allergies to the spores. You get an asthmatic like wheezing illness just by inhaling the
spores. Aspergillus is ubiquitous in the environment.
The second type of disease you can get is referred to as a fungus ball, or aspergilloma. Someone
with underlying lung disease like cavitary tuberculosis can inhale the spores, and they will grow
there in the cavitation in the lung. So even though they are not invading the lung tissue, they are
just growing there.
The third way the fungus could cause disease would be where the fungus actually invades the tissue.
In immune-compromised people, fungus can enter the bloodstream and go all over the body.
The fourth disease mechanism is the production of exotoxin. Fungi, just like bacteria can produce
toxins. Aflatoxin is a toxin produced by Aspergillus flavus that is a potent carcinogen. It can cause
liver cancer. You can get it from grains and corn, where the fungus grows. It’s especially important
in cows, because people will put corn or oats into a silo where is gets moldy. Then the cow eats it
and dies. These are also in the same family as “recreational fungi.”
49. Fungi can produce a lot of histological appearances in the tissues. You can’t always tell what you’ve
got just by looking at the tissues. When you look at the IP labs, you’ll see several different fungal
diseases and see what they look like. Fungi can masquerade and look like bacteria. Candida can
produce abscesses that look like staph or strep. Histoplasma produces granulomas that are
indistinguishable from tuberculosis. Many fungi produce granulomas. You’d have to do a stain to
see the Histoplasma in the granuloma to know for sure.
The dermatophytes produce a cellulitis appearance in the skin, but rarely invade deeper.
Blastomyces is particularly well known for abscesses and granulomas. Check out the IP labs.
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Mucor invades blood vessels and causes thrombosis and infarction. Check out the IP labs.
Particularly for the optometry students, Mucor and Rhizopus can be inhaled into the nose. If you
have type one diabetics, there is a condition called rhinocerebral mucormycosis that can develop.
The fungi come in through the nose, through the cribiform plate and then spread locally through the
tissues of the face. They get into the sinus and the orbit of the eye. In particular, they invade the
orbit of the eye and cause a severe infection of the eye, causing blindness and death. There’s a high
mortality in this. It could be that a patient that has the early stages of this infection might come to
the optometrist with visual problems. Be aware of this, especially with diabetics. Usually treatment
involves a surgical debridement by the eye surgeons. Again, there is very high mortality even when
treated aggressively.
Aspergillus leads to hypersensitivity.
50. We’ll spend the last few minutes talking about parasites. What’s this? Giardia. Get it from
streams, etc. while hiking. It’s the most common parasite we see in Alabama. Most parasites don’t
occur in Alabama, but Giardia does. They see it several times a year in the hospital, often from
people who have gotten diarrhea after drinking in the woods. It’s a little protozoan parasite.
51. One way that parasites produce disease is that they invade host cells and then multiply and kill them
in the process. Toxoplasma is a protozoan parasite that’s usually a problem only in immunecompromised persons. We see this in persons with HIV. This is the parasite that pregnant women
have to be concerned about because you can pass it on to the baby. Cats carry toxoplasma.
Pregnant women should not empty cat feces or take care of cat litter. You could transmit it to your
baby. Optometrists should be aware of toxoplasma for the reason that the disease can progress to
the eye, producing a retinitis. It gets to the eye through the bloodstream.
This is the brain of someone with HIV. The brain is cut coronally, and the lesions, or cysts, are seen
all over the brain. Brain cysts due to Toxoplasma gondii. If you have an HIV patient that complains
of headaches, this could be the culprit. Either toxoplasma or lymphoma. Toxoplasma grow in the
host cells, and then kill the cells by multiplying in them, much like viruses.
52. Hookworms eat host cells. They eat blood. They are caught by walking in dirt that contains the
infections form called Ancylostoma duodenale. Then go through the body, find their way to the
intestinal tract, attach to the epithelial cell with their hooks, and eat red blood cells. This causes
anemia because you can lose 100 mls of blood a day.
53. Tapeworms can actually take up space in the host, producing space occupying lesions. The
tapeworm can do two different things depending on how you get it. The human can be the
intermediate host, or the definitive host. If you eat infected pork, you can get the tapeworm in your
GI tract. Then, if you excrete the eggs of the tapeworm and then inhale them or swallow them, the
tapeworm can set up in you like it did the pig, in your muscles or brain. You can get cysticercal brain
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cysts (you are now the intermediate host). This is seen in Mexican immigrants because the pork in
Mexico isn’t inspected very well.
54. You can get parasites that invade the body and cause a systemic inflammatory response.
Schistosoma mansoni is the liver fluke. It has a complex life cycle. Essentially what happens is that
you pick up the infection from larvae that swim in water. They go through the body and then find
their way to the venules in the liver through a complex process of going through the skin, the
bloodstream, lungs, coughed up, swallowed, GI tract, liver venules. Then they reproduce there.
What they do, they lay their eggs in the venules of the liver. They then produce granulomas. A large
infestation leads to granulomas all over the liver, and then you get scarring because of the immune
response around the granulomas, causing cirrhosis of the liver. We don’t see that in this country
unless it’s a traveler that’s been to the far east.
Slide29: Review of laboratory techniques. The first step is generally a gram stain. Shown here is a CSF
gram stain with neisseria gonorrhea inside WBCs (gram negative intracellular cocci). The diagnosis of
probable meningococcal meningitis can be made from this slide.
Slide 30: Shown is an acid-fast stain showing mycobacterium. They do not stain with a gram stain – you
have to do an acid fast stain. This slide cannot tell you which mycobacterium it is, but in a patient with
suspected tuberculosis with acid fast bacteria present, you can treat for tuberculosis while waiting for
the conformational culture to grow out.
Slide 31: Shown here is a patient with white plaques all over the mouth. A 10% KOH solution can help
make these lesions more clear – but this is generally an easy diagnosis of oral thrush due to Candida
albicans that can be made visually.
Slide 32: Parasites are not grown in the lab; their larvae/eggs are looked for in stool. Shown is an egg of
Ascaris lumbricoides recovered from a stool sample, whose ovoid shape is indicative of this type of
parasite. Different types of parasites have very characteristic eggs.
Slide 33: Dark field examination is a good technique to quickly diagnose trepomena pallidum. For
example, a fluid from a chancre lesion found on genatalia can be collected and looked at under a
microscope under a dark field condenser. If you have modal spirochetes – you’ve made your diagnosis
(T. Pallidum)
Slide 34: In many cases special stains must be used to detect microorganisms. The PAS (periodic acid
Schiff) stains the glycoproteins in fungal cell walls. Shown here are the pseudohyphae of Candida
staining in deep magenta contrasting with the other light pink tissue.
Slide 35: Sliver stains are also useful for staining fungi as well as other bacteria. Shown here is
Histoplasma capsulatum in lung tissue stain black by the silver stain.
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Slide 36: Cultures are also widely done for diagnosis. If an unusual type of bacteria is suspected, you
need to communicate this to the microbiology lab that may need special techniques to detect the
microorganism.
Slide 37: Measuring antibody response is also important. For example, Rickettsiae (Rocky Mountain
spotted fever), mycoplasmas, HIV, and viral hepatitis are generally not grown in the lab – we measure
antibodies to them.
Slide 38: Antigen detection has advantages over culture because you can actually measure it quickly
without having to cultivate it. This is routinely used to detect histoplasmas, aspergillus, legionella, and
cryptococcus.
Slide 39: We used skin tests to detect delayed type hypersensitivity (prior exposure) to Mycobacterium
tuberculosis.
Slide 40: To diagnose viruses we have several options. In tissue culturing, you take the fluid/tissue that
is suspected to have the virus in it, inoculate it into a cell line, and stain them with a monoclonal
antibody looking for a viral inclusions. Serology tests are used to look for HIV and Hepatitis. PCR is
important for diagnosing many diseases, including Herpes encephalitis, which is diagnosed by PCR of the
spinal fluid. The lumbar puncture for a CSF PCR is much less invasive than the previous technique of a
brain biopsy. PCR is also used to measure viral load of Hep C and HIV – this can show the effectiveness of
treatment –> lower viral load = more effective drug. Histopathology is depicted in some of the lab cases
showing viral inclusions inside cells.
Slide 41: PCR is now the test of choice for Chlamydia and gonorrhea d. More PCR tests will be developed
in the future.6