Microbiology Exam 2 Flashcards

Diagnosing Infections

Phenotypic, Immunological, and Genotypic

Observation of microbe’s microscopic and macroscopic morphology, physiology, antimicrobial susceptibility, and biochemical properties

Analysis of microbe using antibodies or of patients’ antibodies using prepackaged antigens

Analysis of microbe’s DNA or RNA

Saliva, Sputum (thick stuff from a hacking cough), swab

- Blood

- Urine (through catheter or clean catch)

- Skin (swab)

- Spinal tap (CSF)

- Feces

- Vaginal swab or stick or Penis swab/stick

- Skin (scalpel)

A sterile transport swab with a carrier

It's promptly transported to a LAB, stored appropriately (usually in the fridge)

- Special swab and transport systems can be used to maintain it in a stable condition for hour

- May have nonnutritive maintenance media, buffering system, or anaerobic environment to prevent the destruction of O2 sensitive bacteria.

Expression of genes that is UNIQUE to that particular microbe

Phenotypic testing is based on the expression of a microbe’s genes, which lets us observe what the organism is actually doing — such as how it stains, how it grows or reacts on different media, and what its cell shape and structure (morphology) look like.

After a specimen (like blood, urine, or a throat swab) is collected, cultivation means growing and multiplying any microorganisms that might be present in that sample under controlled lab conditions.

This can mean using specialized media that reveals identifying characteristics such as colony appearance, motility, and gas requirements.

- Selective media: encourage growth of only one pathogen and used to enrich specimen.

- Differential: identify definitive characteristics and fermentation patters (bacteria itself is NOT changing, but the plate is changing)

In phenotypic testing, we’re not changing the bacteria itself (its genetics or inherent traits) — instead, we’re changing the environment, like the type of plate or media the bacteria is grown on.

For example:

• You might grow the same bacterial species on blood agar to see if it causes hemolysis, or on MacConkey agar to see if it ferments lactose.
• The bacteria stays the same, but its observable characteristics (phenotype) may look different because the plate conditions highlight different traits.

Enzymes that lyse RBCs to release iron-rich hemoglobin so bacteria is able to multiply. Beta, Alpha, and Gamma. Some microbes like to extract nutrients from RBCs.

Graphic method that essentially a flowchart leading to the identification of specimens. It allows you graph all the way down to a particular microbe.

Physiological reactions (physical change like color, bubbling, shape) of bacteria to nutrients and a special substrates provide indirect evidence of enzyme systems. This can be done manually or by machines.

- These tests are based on enzyme-mediated metabolic reactions, and usually visualized by a color change.

If you have a unknown microbe and a substrate, if there's product, the enzyme is there (and that microbe)

No product, then the enzyme is not there, and it lacks the enzyme that can utilize that substrate.

Biochemical testing is all about seeing what enzymes the bacteria have and how those enzymes react with specific substrates.

Think of it like giving the bacteria a little “quiz”:

• Each test gives it a different substrate (like sugar, amino acid, or chemical).
• If the bacteria has the right enzyme, it’ll “use” or break down that substrate — and you’ll see a reaction (color change, gas, acid, etc.).
• If it doesn’t have that enzyme, nothing happens.

All those reactions together form a kind of metabolic profile, which scientists use to identify the microbe.

This is used in determining drugs to be used in treatment. Most of the atuomated phenotypic systems incorporate a panel of commonly used antimicrobials for the particular infection site and stimultaneously test susceptibility while identifying the pathogen

• Patterns of sensitivity can be used in the presumptive identification of some species of Streptococcus, Clostridium, and Pseudomonas

• In the lab, if a bacterium stops growing when exposed to a certain antibiotic, it’s sensitive — meaning that antibiotic would likely work in a patient.
• If it keeps growing, it’s resistant, meaning that antibiotic wouldn’t help much.

And yes

Involves inoculating a lawn of cells onto agar in a Petri dish, mapping off blocks, and applying a different phage to each sectioned area of growth. Cleared areas corresponding to lysed cells indicate sensitivity to that phage.

- Involves viruses that attack bacteria in species-specific and strain specific ways.

- Used for tracing bacterial strains in epidemics.

Here’s how it works step-by-step:

1. You grow a lawn of bacteria (a uniform layer of bacterial growth) on an agar plate. - can be through a liquid culture spread on the agar plate.
2. The plate is divided into sections, and a different bacteriophage (virus) is added to each section. (doted onto the agar)
3. Each bacteriophage is specific — it only infects certain bacterial species or even certain strains within a species.
4. After incubation, you look for clear zones, called plaques, where the bacteria have been lysed (destroyed) by the phage.

Salmonella

If bacteria has specific receptors that phage is looking for THEN it can get inside. In other words, very particular phages will recognize bacteria and get inside bacteria via recognition of expression of proteins or receptors. If bacteria does not correct proteins for virus to adsorb too, then it will NOT bind to and cause cell death

All about the expression of proteins that allow the virus to get in, and kill bacteria cell

It is important to recognize if an isolated colony is clinically important (is there an infection?) or merely a contaminant or normal biota.

- Focus on the number of microbes (ex. few colonies of E. coli can be normal biota but a hundred colonies would mean an active infection). Sometimes, a single colony might mean an infection if it's not normal biota.

Ex. With mycobacterium tuberculosis, even finding just one colony of a known disease-causing organism (a true pathogen), or an opportunist in a place that should be completely sterile, is a strong indication that it’s causing an infection.

Culturing microbes takes a minimum of 18-24 hrs (often longer)

Many infectious conditions can be caused by non-culturable organisms, leaving a wide range of chance that the organism we do culture is a bystander.

MS DSB - Master's in DSB

- Miscellaneous (Phage typing, cell culture growth, and animal inoculation)

• Cell culture growth = growing microbes inside living cells to detect or study infections that can’t be seen on regular agar media.
• Animal Inoculation = If a sputum sample is suspected to contain Mycobacterium tuberculosis, but it’s hard to grow on media, scientists might inoculate a guinea pig. If the animal develops tuberculosis-like symptoms, that confirms the presence of M. tuberculosis.

- Susceptibility testing: a particular pattern of antimicrobial susceptibilities can lead to the identity of a microbe

- Direct examination (NO CULTIVATION):

Microscopy of patient specimens, usually after staining

- Selective/differential growth: Use of specialized media that reveal identifying characteristics such as colony appearance, motility, and gas requirements

- Biochemical testing: Growth of microbe in media that detects the presence of microbe’s enzymes, creating a metabolic fingerprint

Serology is the diagnostic testing of blood serum (the clear part of your blood) to detect antibodies or antigens related to infections

• Antibodies have extreme specificity for antigens
• Looking at the interaction between antibodies and antigens can help determine cause of disease.
• An unknown antibody can be detected using a known antigen or an unknown antigen can be detected using a known antibody.

Sera, Urine, CSF, whole tissues, saliva

First scenario: In patient's serum, the antibody is UNKNOWN. We added prepared microbial agent. If it binds, then it tells you that the person has the antibody (agglutination)

- tests if a person has antibodies (immunity/exposure).

Second scenario: You have an isolated colony of unknown microbes. But you have antibodies of a known identify. When you combine them, if they bind, you can tell (agglutinations), if they don't, you know it's not that microbe.

- identifies the specific bacterium or strain.

They had the infection, or they have a vaccine against it

PIA is a WIFE (acronym)

- Precipitation: Smaller complexes of antibody–antigen.

- Immunochromatography: Most common form is a lateral flow system, supplied in prepackaged cartridges that produce a colored stripe.

- Agglutination: Antibody-mediated clumping of whole cells.

- Western Blot: Electrophoresis separates proteins (either antigens or antibodies) and then labeled antibodies or antigens are used for detection.

- In vivo tests: Antigen introduced into a patient to elicit a reaction as in TB skin test.

- Fluorescent antibodies:

• Direct (DFA): Unknown specimen is exposed to known fluorescent Ab.
• Indirect (IFA): Patient’s antibody (its Fc portion) is probed with fluorescent Ab.

- ELISA: Sandwiching technique conducted in microwells using Ag, Ab, and a secondary Ab to produce a color change.

** note even if there's a color change, it is still this because it can happen due to binding between antibody and antigen.

FALSE

But,

• But if the antigens and antibody are suspended in a solution, under the right circumstances, the presence of binding can be seen as clumps in the solution

1. Size

2. Solubility

3. Location of antigen

In both reactions, antigen is interlinked by several antibodies to form insoluble clumps that settle out of solution.

Mostly, it's the parts of the antigen vs. whole antigen.

In agglutination, antigens are whole cells such as RBCs, bacteria, or viruses displaying surface antigens. This is seen MORE easily because of visible clumps.

• Red blood cells have surface antigens that determine your blood type (A, B, AB, or O).
• Bacteria and viruses have unique surface antigens that your immune system uses to recognize and attack them.

Precipitation: antigen is a soluble molecule.

Determining blood compatibility.

- Lateral flow test

- pregnancy, COVID-19 tests

- This is a plastic cartilage that directs fluid flow in one direction, where it will encounter antibodies.

- When the antigen encounters the antibodies, there is a color change.

• Sample applied: You put the fluid (blood, saliva, urine) onto the sample pad.
• Capillary action: The fluid naturally moves along the test strip by capillary action (like liquid wicking through paper).
• Conjugate pad release: As the sample passes the conjugate pad, it picks up the labeled antibodies stored there. These antibodies are usually attached to a visible marker (gold nanoparticles, colored beads, etc.).
• ________________________
• Migration to test line: The sample–antibody complex continues to move along the strip until it reaches the test line, where immobilized antibodies are waiting.
• These immobilized antibodies are also specific to the same antigen, but they bind to a different part (epitope) of the antigen than the conjugate antibody.
• When the antigen is sandwiched between the labeled antibody and the immobilized antibody, it forms a stable complex that stays at the test line.
• The visible marker on the conjugate antibody creates the line you can see, indicating a positive result.
• _________________________

• Binding and signal: If the target antigen is present, the labeled antibody–antigen complex binds to the immobilized antibodies at the test line, forming a visible line.

- The concentration of antibodies in a sample.

This tells us the minimum amount of antibody needed to react with the antigen.

- Antibody titer measures the concentration of antibodies in a patient’s serum by serially diluting it with a known antigen and identifying the highest dilution that still produces agglutination, helping diagnose past infections, immunity, or autoimmune disorders.

• Serotypes = subgroups of a bacterial species that differ in their surface antigens (like capsule, flagella, or cell wall molecules).
• Serotyping = a lab method that uses antigen–antibody reactions to identify and classify bacteria based on these surface antigens.
• Labs use antisera (solutions containing antibodies) that specifically bind to certain bacterial antigens. If binding occurs, it confirms the serotype of the bacteria.

• A sample of proteins from a bacterial cell or virus is separated via electrical charge within a gel
• The proteins distributed throughout the gel are transferred and immobilized on a filter
• The filter is incubated with patient fluid, such as serum, to see if antibodies are present that are compatible with the test antigen
• Sites of specific antigen–antibody binding will appear as a pattern of bands that can be compared with known positive and negative controls

• In a Western blot, the proteins separated from the pathogen (bacteria, virus, etc.) are the antigens.
• The patient’s antibodies in the serum are what recognize and bind to those antigens if the person has been exposed or infected.
• So when a band appears on the blot, it means the patient’s antibodies found a matching antigen.

In a Western blot, the lab knows the antigens — they are the proteins from the pathogen that are separated and immobilized on the membrane.

• What’s unknown is whether the patient has antibodies that recognize those antigens.
• By adding the patient’s serum, you can see which antibodies, if any, bind to the known antigens.
• The presence of binding (bands) tells you the patient has antibodies specific to that pathogen, indicating past or current exposure.

In this setup, there are usually two different antibodies involved, each with a specific role:

• Start with the antigen (protein):
  • You have a specific protein from a microbe that you want to detect antibodies against.
• Add patient antibodies:
  • You don’t know if the patient has antibodies to this protein yet.
  • If the patient’s antibodies bind to the protein, it means they have been exposed to the microbe or have immunity.
• Add secondary antibody:
  • A secondary antibody recognizes the patient’s antibody.
  • This secondary antibody is labeled with a marker, often a fluorescent tag.
• Detection:
  • When the secondary antibody binds, the fluorescent tag produces a visible signal or color change, showing where the binding occurred.

1. Indirect Testing

1. Start with the antigen:
   • You have a known antigen (like a protein from a microbe) on a slide.
2. Add patient serum:
   • The patient’s serum may contain antibodies that recognize that antigen, but you don’t know yet.
3. Add fluorescent secondary antibody:
   • This antibody is labeled with a fluorescent tag and specifically binds to the Fc region of the patient’s antibodies.
   • Fc region = the “tail” part of the antibody, not the part that binds the antigen.
4. Detection:
   • If the patient has antibodies against the antigen, the secondary antibody binds to them, forming antigen–antibody complexes.
   • Under a fluorescence microscope, these complexes light up, showing a positive reaction.

Main idea:

Indirect IFA detects unknown antibodies in patient serum by using a fluorescent-labeled secondary antibody to visualize them bound to a known antigen.

2. Direct Testing

• What’s being tested:
  • The unknown antigen (from a specimen) is fixed onto a slide. This could be a cell, tissue, or microbial sample.
• Adding antibodies:
  • You apply a fluorescently labeled antibody (FAb) that has a known specificity — it’s designed to bind to the antigen if it’s present.
• Detection:
  • If the antigen is present, the labeled antibody will bind directly to it.
  • You then use a fluorescence microscope to see the glowing signal where the antibody attached.
  • “Direct” = the fluorescent label is on the primary antibody itself.
  • Unknown antigen + known labeled antibody → binding → fluorescence signal.
  • Used for quick identification of pathogens or proteins in tissue samples.

Direct Immunofluorescence (DIF)

• Known: The antibody is known and already labeled with a fluorescent tag.
• Unknown: The antigen in the patient sample — you’re testing whether it’s present.
• Summary: Direct = known antibody looks for unknown antigen.

Indirect Immunofluorescence (IFA)

• Known: The antigen on the slide is known.
• Unknown: The patient’s antibodies — you’re testing whether the serum contains antibodies against the antigen.
• Summary: Indirect = known antigen looks for unknown antibody.

• IFA = “glowing cells” → tells you antibodies exist.
• Western blot = “band barcode” → tells you which proteins the antibodies bind to.

Enzyme-Linked Immunosorbent Assay (ELISA)

• Uses an enzyme-linked indicator antibody to visualize antigen – antibody reactions. Lab test used to detect the presence of either antigens or antibodies in a sample using enzyme-linked antibodies that produce a color change.

1. Direct ELISA

• Known: The antibody on the plate is known and enzyme-linked.
• Unknown: The antigen in the sample.
• Summary: Direct ELISA = detecting unknown antigen using a known labeled antibody.

2. Indirect ELISA

• Known: The antigen on the plate is known.
• Unknown: The antibody in the patient’s sample.
• Summary: Indirect ELISA = detecting unknown antibody using a known antigen and secondary labeled antibody.

3. Sandwich ELISA

• Known: Two antibodies — one immobilized on the plate and one enzyme-linked secondary antibody.
• Unknown: The antigen in the sample.
• Summary: Sandwich ELISA = captures unknown antigen between two known antibodies for high specificity.

• Start with a known antigen:
  • The antigen is stuck to the bottom of a well in a plate.
• Add patient serum:
  • If the patient has antibodies against that antigen, they will bind and stay in the well even after washing. The unbound antibodies will be washed out.
• Add enzyme-linked secondary antibody:
  • This indicator antibody binds to the patient’s antibody (specifically the Fc region of the bound antibody)
• Add substrate:
  • The enzyme reacts with a colorless substrate to produce a color change.
• Interpretation:
  • Color = patient has antibodies against that antigen → positive result.
  • No color = no antibodies detected → negative result.

___________________________________

• In an ELISA, the secondary antibody has an enzyme attached.
• You add a colorless substrate to the well.
• If the enzyme is present (meaning the patient antibody bound to the antigen), it reacts with the substrate and breaks it down (hydrolyzes it).
• This reaction produces a colored product, so the well turns color.
• If there’s no antibody binding, the enzyme isn’t there, the substrate stays colorless, and the well stays clear, which is a negative result.

Two antibodies.

• Start with a known antibody:
  • The antibody is stuck to the bottom of a well.
• Add the sample with unknown antigen:
  • If the antigen is present, it binds to the antibody, forming the first part of the “sandwich.”
• Add a secondary antibody:
  • This is another antibody that binds to the antigen and usually has an enzyme attached.
• Add substrate → color change:
  • The enzyme reacts with the substrate to produce color, showing a positive result.
  • No color means the antigen is absent → negative.
• Modern variation:
  • Some tests use computer chips that detect tiny electrical changes instead of color to sense if the antigen–antibody complex forms.

1. Direct ELISA

• Goal: Detect the presence of a specific antigen in a sample.
• Key: Uses a known enzyme-linked antibody to bind directly to the antigen.

2. Indirect ELISA

• Goal: Detect antibodies in a patient’s serum against a known antigen.
• Key: Uses a secondary enzyme-linked antibody to detect patient antibodies.

3. Sandwich ELISA

• Goal: Detect antigen with high specificity and sensitivity.
• Key: Antigen is “captured” between two antibodies (capture + detection).

Many viral and fungal diseases are diagnosed using the principle that complement can lyse red blood cells

KNOWN: antigen

unknown: patient's antibodies

1. Purpose: Detect antibodies in a patient’s serum against a known antigen.
2. How it works:
   • You mix the patient’s serum (unknown antibodies) with a known antigen and complement proteins.
   • If antibodies are present, they bind the antigen and “fix” the complement — meaning the complement is used up in forming the antibody–antigen complex.
   • If no antibodies are present, the complement stays free.
3. Detection using red blood cells (RBCs):
   • Add indicator RBCs + anti-RBC antibodies.
   • Positive result: No lysis of RBCs (complement was used up by patient antigen–antibody complexes).
   • Negative result: RBCs are lysed (complement is free to attack the RBCs because no antibody–antigen complex formed).

It is similar to serological testing, but an antigen or antibody is introduced into a patient to elicit some sort of visible reaction (welt or inflammation)

Ex.

• Tuberculin reaction:
• A small amount of purified protein derivative from Mycobacterium tuberculosis is injected into the skin
• The appearance of a red, raised, thickened lesion indicates previous exposure to tuberculosis

• The property of a test to focus on only a certain antibody or antigen. This means it can bind to ONE antigen.
• Does not react with unrelated or distantly related antigens
• Antibodies are specific to the antigen

Low false positives (no positive test unless the exact antigen-antibody complex is present).

• The detection of even minute (very small) quantities of antibodies or antigens in a specimen
• I can "feel the energy" even with a small amount.

low false-negative rate

• even if there is only one virus, the test can pick it up.
• Low false negative rate means the test is very unlikely to miss someone who actually has the infection.
• Because the test can detect even tiny amounts of antigen or antibody, if you test positive, you can be confident that you do have or had that disease/microbe.
• In other words, the test rarely says “negative” when you’re actually positive.

Anything dealing with nucleic acids!

WHY N?

1. Nucleic acid amplification tests: using primers to amplify specific DNA sequences. (PCR, TMA, other NAAT)

2. Hybridization: FISH (in situ)

3. Whole-genome sequencing: high-throughout methods have made whole-genome sequencing widely accessible.

- Results in the production of numerous copies of DNA or RNA molecules within hours

- Very sensitive, even amplify small amounts of nucleic acids in sample.

• Can amplify minute quantities of nucleic acids in a sample, greatly improving the sensitivity of diagnostic tests

• Can be performed on bacteria, viruses, protozoa, and fungi

- the purpose of amplification in PCR is to make millions of copies of a specific DNA segment so it can be easily detected, studied, or analyzed.

• Often, the amount of DNA in a sample is too tiny to test directly.
• By amplifying it, you increase the signal, making it possible to detect the microbe, study genes, or run further tests.

• Template DNA: The DNA you want to copy (from the microbe or sample).
• Primers: Short single-stranded DNA sequences that are complementary to the ends of the target region; they define what gets amplified.
• DNA polymerase: An enzyme (usually Taq polymerase) that synthesizes new DNA strands.
• Nucleotides (dNTPs): The building blocks (A, T, G, C) used to make new DNA.
• Buffer and ions: Maintain the optimal chemical environment for the polymerase to work.
• Thermal cycler: A machine that cycles through different temperatures to allow denaturation, primer annealing, and extension repeatedly

1. Real-Time PCR (qPCR)

• Measures DNA amplification as it happens using fluorescent labels.
• Tells you how much DNA is present, not just if it’s there.
• Key: quantitative + real-time tracking.
• Fluorescent probes (like TaqMan) → bind only to the target DNA sequence.
• During amplification:
  • As PCR copies DNA, more double-stranded DNA or target sequences are made.
  • The fluorescent dye/probe binds to the DNA, and the signal increases

2. Reverse-Transcriptase PCR (RT-PCR)

• Converts RNA → cDNA first, then amplifies it.
• Used for RNA viruses or gene expression studies.
• Key: lets PCR work on RNA templates.

3. Multiplex PCR

• Uses multiple primers in one reaction to detect several organisms at once.
• Great for differential diagnosis — you can check for multiple pathogens in the same sample.
• Key: one sample, many targets.

4. Panbacterial qPCR

• Uses a primer common to all bacteria to detect the total bacterial load in a sample.
• Good for studying microbiota or broad bacterial screening.
• Key: universal bacterial detection.

• Makes it possible to identify a microbe by analyzing segments of its genetic material
• Probes: Small fragments of DNA or RNA known to be complementary to specific sequences of nucleic acid isolated from a particular microbe
• Base-pairing of the probe to the nucleic acid can provide evidence of the microbe’s identity
• The probe often has a label (radioactive, fluorescent, or colorimetric), so binding produces a signal.

• Application of fluorescently labeled probes to intact cells within a patient specimen or environmental sample
• Used to locate “glowing cells” and determine the identity of a specific microbe
• Often used to confirm a diagnosis or identify the components of a biofilm
• FISH (Fluorescence In Situ Hybridization) is a technique that uses fluorescent probes to detect specific DNA or RNA sequences directly in cells or tissues. Here’s the breakdown in simple terms: How FISH works:
  1. Probe design:
     • A fluorescently labeled DNA or RNA probe is made to match a specific sequence of the microbe or gene of interest.
  2. Hybridization:
     • The probe is added to a fixed sample of cells or tissue.
     • It binds (hybridizes) to its complementary nucleic acid inside the cell.
  3. Detection:
     • Under a fluorescence microscope, the bound probe lights up, showing exactly where the target DNA or RNA is located.
  Key points:
  • “In situ” = in its natural location (inside cells or tissue).
  • Can be used for microbes, genes, or chromosomal abnormalities.
  • Highly specific because it relies on base-pairing of the probe.

Regular hybridization:

• Usually done in solution or on a membrane (like a blot).
• Detects whether a specific nucleic acid sequence is present in the sample.
• Doesn’t show where the target is in a cell or tissue — just that it exists.

FISH (Fluorescence In Situ Hybridization):

• Done “in situ”, meaning inside intact cells or tissues.
• Detects both the presence and the exact location of the target sequence.
• Uses fluorescent probes to visualize under a microscope.

• Southern Blot – detects specific DNA sequences in a sample using a labeled DNA probe.
• FISH (Fluorescence In Situ Hybridization) – detects DNA or RNA sequences inside intact cells or tissues using fluorescent probes.

1. Sample:
   • Cells, tissue sections, or microbial samples fixed on a slide.
2. Probe:
   • Fluorescently labeled DNA or RNA that is complementary to the target sequence.
3. Hybridization buffer/solution:
   • Maintains optimal conditions for probe binding.
4. Fixatives:
   • Chemicals like formaldehyde or paraformaldehyde to preserve cell/tissue structure.
5. Washing solutions:
   • Remove unbound probes after hybridization to reduce background signal.
6. Microscope:
   • A fluorescence microscope to visualize the fluorescent signal.

• Useful for rapid analysis of outbreaks and drug-resistant organisms
• Low cost
• Deep sequencing: A single genome can be scanned and analyzed multiple times with fewer errors

What they are:

• Microarrays are tiny “chips” or plates with thousands of known gene sequences from different microbes (bacteria, viruses, fungi).
• The sequences are selected based on the disease or syndrome you’re investigating.

How they work:

1. Prepare patient sample:
   • Extract DNA or RNA from the patient.
2. Hybridization:
   • The patient’s nucleic acids are added to the microarray.
   • If a patient’s sequence matches a sequence on the chip, it will bind (hybridize).
3. Detection:
   • The probe sequences on the chip are fluorescently labeled.
   • A computer reads the fluorescence pattern to identify which microbes are present in the sample.

Main use:

• Allows simultaneous detection of thousands of pathogens in one test.
• Helps diagnose infections based on syndrome rather than testing for one microbe at a time.

Antimicrobial Treatment

Administer a drug to an infected person that destroys the INFECTIOUS agent without harming the host cells!

• Toxic to the microbe
• Non-toxic to host (does not disrupt host healthy by allergies or making them likely to other infections)
• Microbicidal (kills) rather than Microbiostatic (stops or slows growth, but not kills)
• Soluble in body fluids
• Long-lasting half life (to act and is not excreted early)
• nonexistent or slow development of antimicrobial resistance
• Complements/helps host's defenses
• Active in tissues and body fluids
• Delivered to SITE OF ACTION

Use of a drug to prevent imminent infection of a person at high risk

Prophylaxis means preventing a disease before it happens

The use of drugs to control infection (specifically chemicals)

All-inclusive term for any antimicrobial drug, regardless of what type of microorganism it targets

by the natural metabolic processes (natural sources) of some microorganisms or created by scientists.

• Natural drugs come straight from living organisms (like penicillin from mold).
• Semisynthetic drugs are natural drugs that have been chemically modified to improve their properties — like making them more stable, broader in spectrum, or less likely to cause resistance.
• Synthetic drugs are completely made in the lab, designed to target specific microbial processes.

• Narrow-spectrum (limited spectrum): Antimicrobials effective against a limited array of microbial types—for example, a drug effective mainly on gram-positive bacteria
• Broad-spectrum (extended spectrum): Antimicrobials effective against a wide variety of microbial types—for example, a drug effective against both gram-positive and gram-negative bacteria

Antibiotics are common metabolic products of bacteria and fungi.

• Inhibiting the growth of other microorganisms in the same habitat reduces competition for nutrients and space
• Some bacteria and fungi naturally make antibiotics as part of their normal metabolism — basically, it’s how they compete and survive in their environment.
• These microbes produce antibiotic substances to kill or inhibit the growth of other microbes around them, so they can have more nutrients and space.

1. What is the identity of the microorganism? - many methods

2. What is the microorganism's susceptibility to various drugs? (can it be harmed or hindered)

3. How does the patient react to the drug?

The Kirby-Bauer test measures how well an antibiotic can stop bacterial growth. Small discs containing antibiotics (pre-measured amount) are placed on a plate with bacteria (special medium), and the drug spreads outward. If the antibiotic works, it creates a zone of inhibition (edge to edge of no growth) — a clear area where bacteria can’t grow. The size of this zone shows how sensitive or resistant the bacteria are to that antibiotic. It will then be compared with the standard for each drug, determining if its sensitive or resistant or in the middle.

It's an alternative to Kirby-Bauer. The E-test is used to determine the minimum inhibitory concentration (MIC) — the smallest amount of an antibiotic needed to stop bacterial growth. A plastic strip with a predefined gradient of antibiotic concentrations is placed on an agar plate that has been spread with bacteria. As the antibiotic diffuses from the strip, it creates zones where bacteria cannot grow. The point where bacterial growth stops along the strip shows the MIC value, indicating how sensitive the bacteria are to that antibiotic.

From bottom to top, the concentration of antibiotic increases as you go up the strip.

Instead of a perfect circle around a disc, the E-test creates an elliptical (oval-shaped) zone of inhibition that follows the antibiotic gradient on the strip. The point where the edge of bacterial growth meets the strip marks the minimum inhibitory concentration (MIC) — the lowest antibiotic concentration that prevents growth.

• Kirby-Bauer → circular zone → measures general susceptibility
• E-test → elliptical zone → measures exact MIC value

• Useful in determining the smallest effective dosage of a drug
• Provides a comparative index against other antimicrobials

The tube dilution test is used to determine the minimum inhibitory concentration (MIC) — the lowest concentration of an antibiotic that prevents bacterial growth.

Here’s how it works:

• A series of test tubes are prepared with the same amount of bacteria but increasing concentrations of the antibiotic (for example: 0, 20, 40, 60 µg/mL, etc.).
• The tubes are then incubated to allow bacterial growth.
• After incubation, you check for turbidity (cloudiness = bacterial growth).
• The first clear tube (no turbidity, sometimes shown as blue instead of pink) indicates that the bacteria stopped growing — that concentration is the MIC.

So basically:

• Cloudy = growth (bacteria resistant)
• Clear = no growth (bacteria inhibited)
• The lowest clear tube = the MIC value

- It didn't get to the site of the infection

- Resistant microbes

- An infection may be caused by one or more pathogen, some which may be resistant

The ratio of the dose of the drug that is toxic to humans to its effective dose. The therapeutic index (TI) measures a drug’s safety margin — it’s the ratio between the toxic dose and the effective dose. A high TI means the drug is safer (there’s a big gap between helpful and harmful doses), while a low TI means it’s riskier because the effective and toxic doses are close together. TI of 1.1 is riskier than TI of 10.

• The range of blood level of the drug in which it is producing the desired effect without toxicity

FALSE, it should be higher...

So, the higher the therapeutic index, the greater the margin of safety for that drug.

- Antimicrobial treatment drugs should kill or inhibit ONLY microbial cells without also damaging host tissues. Best drugs block actions or synthesis of microbes but not vertebrae cells.

Ex. peniciliin - excellent selective toxicity, only blocks synthesis of cell wall in bacteria.

1. Inhibition of cell wall synthesis

2. Inhibition of nucleic acid structure and function

3. Inhibition of protein synthesis, involving mainly ribosomes

4. Interfering with cell membrane structure or function

5. Inhibition of folic acid synthesis

Folic acid (vitamin B₉) is super important to microbes because it’s essential for making DNA, RNA, and amino acids

• Folic acid helps make nucleotides, the building blocks of DNA and RNA.
• Microbes can’t get folic acid from their environment (unlike humans who get it from food), so they have to synthesize it themselves.
• Because of that, antibiotics like sulfonamides (sulfa drugs) target the enzymes microbes use to make folic acid — stopping their growth without harming human cells.

1. Toxicity to human organs

2. Human Allergic response to drugs (drugs can act as antigens) - Penicillin, then Sulfonamides

3. Altercation or Supression of Human Microbiota

After an antimicrobial destroys beneficial resident species, other microbes that were once in small numbers can begin to overgrow and cause disease

Ex.

• Vaginal yeast infection (by Candida albicans) after antibiotic treatment
• Antibiotic-associated colitis due to the overgrowth of Clostridioides difficile after antibiotic treatment

a superinfection happens when antibiotics kill off the normal, helpful microbes in your body — like the ones in your gut or on your skin — and this gives opportunistic pathogens (like Candida or C. difficile) a chance to overgrow.

Basically, the antibiotic wipes out the good guys, and the bad ones take over, causing a new infection on top of the original one you were treating. oth Candida albicans (a yeast) and Clostridioides difficile (a bacterium) normally live in small amounts in your body — Candida in places like your mouth, gut, and vagina, and C. difficile in your intestines.

They usually don’t cause problems because your normal microbiota keep them in check. But when antibiotics kill off that good bacteria balance, these guys can overgrow — leading to infections

• Effective against more than one group of bacteria
• Example: tetracyclines

• Only target a specific group
• Examples: polymyxin and penicillin

1. Penicillin

• B-Lactams are large/diverse group of antibiotics
• The β-lactam ring binds to enzymes (called penicillin-binding proteins, or PBPs) that bacteria use to build their cell wall. When the ring binds to those enzymes, it blocks them from forming cross-links in the peptidoglycan layer (the strong mesh that gives bacterial cells structure). Without those cross-links, the bacterial cell wall becomes weak and leaky, so the cell eventually bursts (lyses) — especially when it takes in water through osmosis
• Naturally or synthesized in lab
• Three parts: B-lactam ring, thiazolidine ring, variable side chain

2. Cephalosporin (used when penicillin is not effective)

• Isolated from Cephalosporium acremonium
• B-lactam ring that can be synthetically altered
• Similar mode of action to penicillins

3. Carbapenem

• Reserved for use in hospitals when other drugs do not work (due to major antibiotic resistance)

4. Other miscellaneous drugs

• Bacitracin, Isoniazid (mycobacterium tuberculosis), vancomyocin

Inhibits β-lactamase enzymes and is added to other penicillins to increase their effectiveness in the presence of penicillinase-producing bacteria

Some bacteria make an enzyme called β-lactamase (or penicillinase), which basically destroys the β-lactam ring in penicillin and makes the antibiotic useless.

To stop that, scientists created β-lactamase inhibitors (like clavulanic acid). These inhibitors are added to penicillins — for example, in Augmentin (amoxicillin + clavulanic acid).

The inhibitor’s job is to bind to and block the β-lactamase enzyme, so the enzyme can’t destroy the penicillin. That way, the antibiotic can still attack the bacterial cell wall effectively

Targets the Cell Wall

• Narrow spectrum of action
• Used to treat staphylococcal infections in cases of penicillin and methicillin resistance or in patients with an allergy to penicillin
• Vancomycin binds directly to the amino acid chain (D-Ala-D-Ala) on the peptidoglycan subunits themselves.
• This physically blocks the enzymes from linking those subunits together — imagine it grabbing the building blocks and saying, “nope, you’re not getting glued today.”
• Without proper cross-linking, the cell wall stays weak, and the bacteria eventually bursts (lyses) due to osmotic pressure.

1. Aminoglycosides = "awful translation)

• 6-carbon ring attached to one or more sugar
• Product of actinomycetes: streptomyces and micromonospora
• BROAD spectrum
• Cause misreading of mRNA, affect the 30S, resulting protein is non-functional in bacteria.
• They bind irreversibly to the 30S ribosomal subunit, which is the part that helps read mRNA and match tRNAs correctly. This binding causes misreading of the mRNA code, so the ribosome adds the wrong amino acids to the growing protein chain. The result? Defective, nonfunctional, or toxic proteins that can kill the bacterial cell.

2. Oxazolidinoes

• Synthetic Drugs
• Prevent initiation and block ribosome assembly (binds to 50S and keeps both subunits from coming together)
• MSRA and VRE (antibiotic resistant organisms)

3. Pleuromutilins

• Block peptidyl transferase
• Formation of peptide bonds is blocked, and it prevents elongation, so you have a truncated protein.
• External skin application only

4. Tetracyclines/Glycacyclines

• Blocks the A site for tRNA, so it cannot come in and bring more amino acids for elongation. No protein is synthesized.
• Derived from streptomyces
• Natural compound or synthetic
• Broad-spectrum
• They bind to the 30S ribosomal subunit, right where the A site (aminoacyl site) is located. The A site is where new tRNA molecules normally come in carrying amino acids. By blocking the A site, tetracyclines prevent tRNA from binding—so no new amino acids can be added to the growing protein chain. Translation basically stalls, and the bacteria can’t make proteins needed to survive.

5. Macrolides

• Broad-spectrum and low toxicity
• Lactone ring with sugars attached
• Mostly semisynthetic
• Middle ear, respiratory, and skin infections
• Bind to the 50S ribosomal subunit of bacteria. This blocks the exit tunnel through which the growing protein chain normally leaves the ribosome. As a result, protein elongation stops, and the bacteria can’t make essential proteins. Because protein synthesis is halted, the bacteria stop growing (bacteriostatic) or sometimes die (bactericidal, depending on the drug and concentration).

Inhibits proper protein synthesis

• Aminoglycoside
• Insert on sites on the 30S subunit and cause the misreading of the mRNA, leading to abnormal proteins
• Broad-spectrum; used to treat infections caused by gram-negative rods, certain gram-positive bacteria
• used to treat bubonic plague, tularemia, and tuberculosis
  

Macrolide Antibiotic - inhibits protein synthesis as it inhibits translocation of subunit during translation

- Can be used to treat mycobacterium infections in AIDS patients

• During translation, the ribosome moves along the mRNA in a process called translocation.
• After a new amino acid is added, the tRNA in the A site moves to the P site, and the ribosome shifts along the mRNA so the next codon can be read.
• Some antibiotics (like macrolides and lincosamides) bind to the 50S subunit and block this movement.
• If the ribosome can’t translocate, no new amino acids are added, and protein synthesis stops.

They prevent proper metabolism, preventing microbes from replicating, then not allowing them to make proteins, and this class can be used with other drugs.

- Sulfa drugs or sulfonaminds

• Sulfisoxazole: treat acute UTI and certain protozoan infections
• Silver sulfadiazine: prescribed for treatment of burns
• Trimethoprim: may be given in combination with sulfamethoxazole
• Sulfamethoxazole and Trimethoprim: Interfere with folate metabolism by blocking enzymes required for the synthesis of tetrahydrofolate, which is needed by the cells for folic acid synthesis and eventual production of DNA, RNA, and amino acids. Treatment of UTI and protozoan infections

1. Fluoroquinones (Ciprofloxacin, Levofloxacin, Nalidxic Acid, Trovafloxacin)

• Broad spectrum
• High potency
• Absorbed from intestine
• Inhibits helicase, so prevents unwinding of DNA (blocks replication and transcription)

2. Ansamycin

• Ex. Rifampin
• Limited spectrum
• Mainly treats gram + and few gram - (as it cannot pass through cell envelope well)
• Leprosy and Tuberculosis
• Inhibits the initiation of transcription of DNA (@DNA level, block DNA/RNA polymerase from binding)

1. Polymyxins

• Bacillus polymyxa
• Narrow-spectrum
• fatty-acid component allows for detergent activity, pokes holes in membrane causing leaking outside of bacteria cell, leading to lysis and death
• TOXIC to kidneys (last-resort)
• Interact with membrane phospholipids; distort the cell surface and cause leakage of protein and nitrogen bases, particularly in gram-negative bacteria
• Treat drug-resistant pseudomonas and severe UTIs caused by gram-
• Polymyxin B and E

- Daptomycin (subgroup)

- Type of polymxin (disrupts cell membrane)

• Lipopeptide made by Streptomyces
• Most ACTIVE against gram+ bacteria
• Can treat biofilms

• Bacteria in biofilms (like on catheters, teeth, or medical implants) are much harder to kill—up to 1,000× more resistant—than the same bacteria floating freely in liquid (planktonic form).
• This happens because biofilm bacteria express different phenotypes:
  • They produce a protective matrix (slime layer) that blocks antibiotics.
  • They slow their metabolism, making antibiotics that target growing cells less effective.
  • They can communicate and cooperate, sharing resistance genes.

1. Interrupt quorum-sensing pathways

2. Daptomycin

3. Pretreatment

• Pyrantel (inhibits round worms by paralyzing their muscles not allowing them to grab onto intestines of host)
• Everything but metronidazole, which is for protozoa

STOP penetration (virus into host cell), multiplication (replication, transcription, translation of viral molecules), and maturation of viral particles

Receptor/Fusion/Uncoating Inhibitors

• Enfuvirtide (Fuzeon) - BLOCKS HIV infection by preventing binding of viral receptors to cell receptors and preventing fusion
• Amatadine and its relatives such as zanamivir, oseltamivir - interfering with fusion of virus with cell membrane and release and stop action of virus into cell for assembling

- Analogs are used, such as fake nucleotides, that mess with the DNA structure and inhibit proper binding of key molecules (prevent synthesis, etc.)

1. Remdesivir - purine analogs that terminate RNA replication in COVID

2. Ribavirin - purine analongs, used for hep C.

Non-nucleotide analogs are drugs that look similar to the natural building blocks (nucleotides) of DNA, but they aren’t real nucleotides.

• For HIV, these drugs target reverse transcriptase (RT) — the enzyme that turns viral RNA into DNA.
• The fake nucleotide gets in the way: the enzyme can’t properly bind or use it, so DNA synthesis stops.
• Example: AZT (zidovudine) — it mimics a nucleotide, but once incorporated, it prevents the viral DNA chain from growing, blocking HIV replication.

This prevents a mature virion from forming or being released.

Ex. Indinavir and Saquinavir

Protease inhibitors; insert into HIV protease, stopping its action and resulting in inactive noninfectious viruses -

• HIV protease is an enzyme the virus needs to cut long viral protein chains into functional pieces that form new, infectious virus particles.
• Protease inhibitors are drugs that fit into the protease enzyme’s active site, like a key in a lock, but block its action.
• Without protease activity, the virus can’t properly assemble its proteins, so the new virus particles are malformed and noninfectious.
• Result: the virus can’t spread effectively to infect new cells.

• Adaptive response in which microorganisms begin to tolerate an amount of drug that would ordinarily be inhibitory (adapt to the drug so the drug cannot inhibit and the microbe can grow)

• Intrinsic: bacteria must be resistant to any antibiotic that they themselves produce
• Some bacteria naturally make antibiotics to kill other microbes. To avoid killing themselves, these bacteria have built-in (intrinsic) resistance to their own antibiotic.
• Example: Streptomyces species produce streptomycin, but they have mechanisms to protect themselves from being affected by it.
• Avoid poisoning yourself.

_______________________________

• Acquired: bacterial resistance to a drug to which they were previously sensitive

1. Mutation

• Permeability or uptake of drug into bacteria is decreased, could be due to new shaped receptor from mutation

2. Horizontal Transfer - GAIN new genes

• Plasmids can be transferred through C, T, and T
• Transposons: duplicated and inserted sequences from one plasmid to another
• Rapid proliferation of drug-resistant species

3. New enzymes synthesized to inactivate the drug (occurs when new genes are acquired)

4. Drug is eliminated (through new genes which add pumps or transporters)

5. Binding sites can be decreased in number or affinity (due to new genes)

6. A new or alternative pathway the drug can act (due to mutations of original enzymes)

True

• If the drug is not present in the population, the number of these resistant forms will remain low
• If the population is exposed to the drug, sensitive individuals will be killed, and the resistant forms will remain

Preparations of live microorganisms fed to animals and humans to improve intestinal biota

GIVES actual bacteria

• Replace lost microbes
• Supplement biota

Safe and effective

• Gives bacteria food
• Nutrients that encourage the growth of beneficial microbes in the intestine
• Feeds nutrients to the resident microbiota to encourage growth

• Probiotics = live beneficial bacteria you consume to help balance your gut microbiota (e.g., yogurt with Lactobacillus).
• Prebiotics = non-digestible food components (usually fibers) that feed the good bacteria already in your gut, helping them grow and thrive (e.g., inulin in onions or garlic).

Infectious Diseases Manifesting in the Nervous System

The brain and spinal cord is made up of neurons and surrounded by neurons. Brain is inside skull and spinal cord is inside the spinal column.

Brain is surrounded by the meninges: (outside to inside) - Dura mater, arachnoid mater, and pia mater

Subarachnoid space

clear, serum-like

Provides liquid cushion for brain and spinal cord and provides nutrients to CNS

- Bony casings of brain and spinal cord

- CSF serves as cushion against impact

- BBB (filter medications and microbes)

Cells that make up the walls of the blood vessels around the brain allow FEW molecules to pass (freer passage of ions, sugars, other metabolites)

- PROHIBITS most microbes

- HARD to introduce drugs and antibiotics to CNS

- SELECTIVE

False

- CNS has a different or partial immune response when exposed to immunologic challenge

- Functions in the CNS are vital for life, and the normal CNS can cause temporary damage

- Cells in the CNS have lower levels of MHC antigens and complement proteins

Microglial cells show phagocytic activity

- Brain macrophages

- Phagocytic activity is still LESS than other phagocytic cells in the body.

FALSE

True

Recent microbiome studies reveal a relationship or potiental link between the gut microbiome and nervous system as gut microbiota may induce CNS autoimmunity and can cause changes in brain chemistry and behavior.

Inflammation of the meninges

• Different microbes cause meningitis and produce a similar constellation of syndromes (bacteria, virus, or fungi)
• Noninfectious causes of meningitis exist as well but are less common (trauma, cancer, autoimmune disorder)
• Serious forms of acute meningitis are caused by bacteria
• Entrance into CNS is facilitated by co-infection or previous infection with respiratory viruses
• Acute or Chronic disease

7 Different Types

Obtain CSF through a lumbar puncture

Gram stain and/or culture of CSF

• A Gram stain is done to see bacteria under the microscope and get a quick idea of the type (Gram-positive or Gram-negative).
• A culture grows any bacteria present so they can be identified and tested for antibiotic sensitivity.

Begin treatment with broad-spectrum antibiotics immediately (then shift treatment after confirmation of diagnosis)

• Photophobia
• Headache
• Painful or stiff neck
• Fever
• Increased WBC in CSF
• Certain microorganisms may cause additional characteristic symptoms

True

• Successful microorganisms have specific virulence factors

Weak antigen (like a bacterial capsule made of sugar) is attached—or “conjugated”—to a strong protein antigen to make it more visible to the immune system.)

• Some bacteria (like Neisseria meningitidis or Haemophilus influenzae type b) have sugar capsules that don’t trigger a strong immune response, especially in young kids.
• By linking that sugar to a protein, the immune system recognizes it better and makes strong, long-lasting antibodies.

Neiserria meningitdis, Streptococcus Pneumoniae, Haeomphilus Influenzae.

• Gram Negative Diplococci
• Also known as meningococcus
• Associated with epidemic forms
• Meningococcemia: also gets in the blood stream on top of the brain and spinal cord (RARE, high mortality rate)
• Endotoxin acts as a potent WBC stimulator
• Damage to blood vessels caused by cytokines released by WBC leads to vascular collapse, hemorrhage, and crops of red or purple lesions called petechiae on the trunk and appendages

Mode of Transmission: DROPLET

Virulence Factors:

• Endotoxin: (lipooligosaccharide) that triggers a strong inflammatory response in the body, which can lead to fever, shock, and damage to blood vessels.
• Capsule: The bacterium has a polysaccharide capsule that protects it from being engulfed and destroyed by phagocytic immune cells, allowing it to survive and spread within the bloodstream.
• IgA protease: Neisseria meningitidis produces an IgA protease enzyme that breaks down immunoglobulin A (IgA) antibodies on mucosal surfaces, helping the pathogen evade the immune system and colonize the nasopharynx.

Culture/Diagnosis: gram stain/culture of CSF, blood/rapid antigenic test, oxidase test, PCR

Prevention: Conjugated vaccine, ciprofloxacin, rifampin, or ceftriaxone to protect contacts (CRC)

Treatment: Ceftriaxone and Penicillin

Distinctive features: petechiae, meningococcemia, rapid decline

Epidemiological Features: 14% of bacterial meningitis; increasing in men having sex with men; meningitis belt: 1,000 cases per 100,000 annually

Neisseria meningitidis is oxidase-positive, and the oxidase test helps confirm that.

Here’s how it works:

• The oxidase test detects if the bacterium produces the enzyme cytochrome c oxidase, part of its electron transport chain.
• When a reagent (like tetramethyl-p-phenylenediamine) is added, it turns dark purple if the enzyme is present.
• Since Neisseria meningitidis has this enzyme, the color change appears, showing it’s oxidase-positive ✅

Neisseria Meningitdis

*14% of all cases

Streptococcus pneumoniae.

• Also known as Pneumococcus
• Small Gram Positive
• Flattened coccus, end-to-end pairs
• No petechiae
• Most likely to occur in patients with underlying susceptibility.

Mode of Transmission: DROPLET

Virulence Factors:

• Capsule: polysaccharide capsule which protects against phagocytosis
• Induction of apoptosis: S. pneumoniae can trigger programmed cell death (apoptosis) in host cells, including immune cells, which weakens the body’s defense response and helps the infection progress.
• Hemolysin: produces an alpha-hemolysin which induces damage to CNS. This toxin damages host tissues, including the cells of the central nervous system (CNS). It contributes to inflammation and tissue injury during infections like meningitis.
• Hydrogen Peroxide Production - The bacteria produce hydrogen peroxide as a byproduct, which can damage host cells and contribute to tissue injury in the CNS, worsening symptoms during infection.

Culture/Diagnosis: Gram stain/culture of CSF (distinct appearance on gram stain of CSF)

Prevention: TWO vaccines

Treatment: Vancomyocin + ceftriaxone or cefotaxime (resistant S. pneumoniae is serious threat)

Distinctive features: Serious, acute, most common meningitis in adults

Epidemiological Features: Most common cause of bacterial meningitis in the United States (58% of cases)

Alpha hemolysis

Hydrogen Peroxide

• Gram Negative Coccobacillus
• One of the most severe forms of meningitis in humans
• Often called "Hib" because serotype is most common cause of infection
• Vaccine - reduced asymptomatic carriage rates

Mode of Transmission: DROPLET

Virulence Factors: Capsule

Culture/Diagnosis: culture on chocolate agar

Prevention: HiB vaccine, ciprofloxacin, rifampin, ceftriaxone (CPC)

Treatment: Ceftriaxone

Distinctive features: Serious, acute, less common since vaccine was made

Epidemiological Features: HIA now becoming common in North America; before Hib vaccine, 300,000–400,000 deaths worldwide per year from b serotype

Listeria monocytogenes

• Gram-Positive (ranges in shape from coccobacilli to long filaments in palisade formation)
• NO capsule or endospores
• 1-4 flagella
• Not fastidious, resistant to cold, heat, salt, pH extremes, and bile
• Grows inside host cells, moves from an infected cell to an adjacent healthy cell
• Listerosis (infected caused by agent). Mild or subclinical in healthy adults. Fever, diarrhea, sore thraot
• Affects brain and meninges, resulting in septicemia in elderly, immuno, fetuses, and neonates
• Death rate - 20%
• Associated with contaminated dairy products, poultry, meat

Mode of Transmission: Vehicle (Food)

Virulence Factors: Intracellular growth

Culture/Diagnosis: Cold enrichment, rapid methods

Prevention: Cooking food, avoiding unpasteurized dairy products

Treatment: Ampicillin + gentamicin

Distinctive Features: asymptomatic in healthy people, meningitis in neonates, elderly, and immunocompromised

Epidemiological Features: Mortality as high as 33% in symptomatic cases

Fastidious means that a microorganism has very specific and complex nutritional or environmental requirements in order to grow.

In other words, fastidious bacteria are “picky eaters” — they need special nutrients, conditions, or growth media that ordinary bacteria don’t.

• FUNGUS - transmitted in bird droppings
• Spherical to ovoid shape with large capsule (tumor-like mass in brain)
• causes chronic meningitis with gradual onset of symptoms
• Those who are immunocompromised, fast onset and acute disease
• Widespread in human habitats

Mode of Transmission: vehicle (air, dust)

Virulence Factors:

• Capsule: This thick polysaccharide capsule protects the fungus from being eaten (phagocytosed) by immune cells like macrophages. It also helps the pathogen avoid detection by the immune system and resist oxidative stress.
• Melanin Production: produces melanin in its cell wall, which protects it from damage caused by the host’s immune defenses (like oxidative bursts) and from environmental stress. Melanin also makes the fungus more resistant to antifungal drugs.

Culture/Diagnosis: Negative staining, biochemical tests, DNA probes, cryptococcal antigen test

Prevention: None

Treatment: Amphotericin B, flucytosine followed by fluconazole

Distinctive Features: Acute or chronic, most common in AIDS patients

Epidemiological Features: In the United States, mainly a concern for HIV+ patients; 90% drop in incidence in the 1990s due to better management of AIDS; worldwide: 1 million new cases per year

• "Valley Fever"
• Endemically in natural reservoirs
• Fungus with distinct morphology, and two different strains
• 25C - moist white to brown colony with abundant, branching, septae hyphae
• 37-40C - parasitic phase, small spherule
• True systemic fungal infection, high virulence
• More serious due to genetic susceptibility
• Might form maculopapular rash, starts in lungs (inhale spores), travel to meninges

Mode of Transmission: Vehicle (air, dust, and soil)

Virulence Factors: Granuloma (spherule) formation

• When the fungus enters the body, it forms spherules—large, round structures that contain hundreds of tiny endospores. These spherules are too big for immune cells like macrophages to engulf and destroy. As a result, the immune system walls them off by forming granulomas (clusters of immune cells surrounding the pathogen).

Culture/Diagnosis: Identification of spherules, cultivation on Sabouraud’s agar

Prevention: Avoiding airborne endospores

Treatment: Fluconazole and Amphotericin B

Distinctive Features: exclusively in endemic regions

Epidemiological Features: Incidence in endemic areas: 200–300 annually

• wide variety of viruses can cause 4 out of 5 meningitis
• Aseptic meningitis - viral, shows symptoms, but no bacteria/protozoa/fungi in CSF
• Majority of cases in CHILDREN (90% caused by enteroviruses)
• HSV-2, other HHV, and HIV can manifest this
• Milder than bacterial or fungal
• resolved in 2 weeks (self-resolved, can be treated with antivirals)
• Mortality rate is less than 1%

Mode of Transmission: DROPLET

Virulence Factors: lytic infection of host cells

Culture/Diagnosis: Initially, no microbe, followed by viral culture or antigen test

Prevention: N/A

Treatment: None (unless specific virus found and antiviral exists)

Distinctive Features: milder than bacterial or fungal

Epidemiological Features:

In the United States, four of the five meningitis cases caused by viruses; 26,000–42,000 hospitalizations per year

• Usually, a result of infection transmitted by mother in utero or during passes through vertical transfer
• As more premature babies survive, rates of neonatal meningitis increase
• Morbidity have increased, but mortality has decreased
• Most common causes: Streptococcus agalactiae and Escherichia coli
• Listeria monocytogenes is also frequent in neonates (can be found females and adults)

Escherichia coli

(K1 strain)

Mostly in premature babies

Streptococcus agalactiae

• Group B streptococci (gram +), even though part of normal microbiota
• colonizes 10%-30% of female genital tracts
• MOST frequent cause of neonatal meningitis
• Treated with IV penicillin G, sometimes supplemented with an aminoglycoside

Mode of Transmission: Vertical (during birth)

Virulence Factor: Capsule

Culture/Diagnosis: Culture mother’s genital tract on blood agar; CSF culture of neonate

Prevention: Culture and treatment of mother

Treatment: Penicillin G plus aminoglycosides

Distinctive Features: Most common, positive culture of mother confirms diagnosis

Epidemiological Features: before intrapartum antibiotics in 1996: 1.8 cases per 1,000 live births; after intrapartum antibiotics: 0.32 case per 1,000 live births

• Gram Negative Bacteria
• prognosis in premies is poor (20% mortality rate, brain damage for those who survive)
• Transmitted via birth canal

Mode of Transmission: Vertical (during birth)

Virulence Factor: N/A

Culture/Diagnosis: CSF Gram stain/culture

Prevention: N/A

Treatment: Ceftazidime or cefepime and/or gentamicin

Distinctive Features: Suspected if infant is premature

Epidemiological Features: Estimated at 0.2–5 per 1,000 live births; 20% of pregnant women colonized

• Listeria can de BOTH adults and neonates

Mode of Transmission: Vertical

Virulence Factor: Intracellular growth

Culture/Diagnosis: Cold enrichment, rapid methods

Prevention: Cooking food, avoiding unpasteurized dairy products

Treatment: Ampicillin, trimethoprim-sulfamethoxazole

Distinctive Features: N/A

Epidemiological Features: Mortality as high as 33% in symptomatic cases

• Found mainly in environments that survive dry conditions
• Implicated in outbreaks of neonatal and infant meningitis through CONTAMINATED formula
• rare cases
• Mortality rate can be 40%

Mode of Transmission: Vehicle (baby formula)

Virulence Factor: ability to survive dry conditions

• Highly resistant outer membrane and protective cellular mechanisms. This ability allows it to persist in formula production and storage areas, increasing the risk of infection when contaminated formula is prepared and consumed.

Culture/Diagnosis: chromogenic differential agar or rapid detection kits

Prevention: Self preparation, use of, or avoidance of powdered formula

Treatment: broad-spectrum antibioitcs until main cause determined

Distinctive Features: N/A

Epidemiological Features: Rare (only handful of cases) but deadly

Inflammation of the brain (encephalitis) and meningitis - due to close association of the brain and spinal cord, infection of one can cause the other)

Two causative agents are amoebas (protozoa):

1. Naegleria fowleri

2. Acanthamoeba

Naegleria fowleri; primary amoebic meningoencephalitis

- causes rapid, destruction of brain and spinal tissue

- Cases are rare, but the disease advances so rapidly that treatment is futile.

• Small, flask-shaped ameoba that moves by a single, broad pseudopod
• Round, thick-walled cyst is resistant to temperature extremes and chlorination (natural bodies of waters)
• Typically impacts subarachnoid space
• Infections reported in peole who have been swimming in warm bodies of freshwater
• When a person swims in contaminated lake water, Naegleria fowleri can enter the body through the nose, travel along the olfactory nerve, and reach the brain, where it establishes infection.

Mode of Transmission: Vehicle (exposure while swimming in water)

Virulence Factors: Invasiveness

• The virulence factor “invasiveness” refers to a microbe’s ability to enter, spread, and multiply within host tissues. For an agent like Naegleria fowleri, invasiveness means it can penetrate the nasal mucosa, move along nerve pathways, and invade the brain tissue, causing severe damage as it spreads.

Culture/Diagnosis: Examination of CSF, brain imaging, biopsy

Prevention: limit warm freshwater or untreated tap water from entering nasal passages.

Treatment: Pentamidine, Sulfadiazine

Epidemiological Features: United States: zero to seven cases a year; 97% case fatality rate; spreading to northern states as climate warms

Acanthamoeba; granulomatous amoebic meningoencephalitis

• can cause keratitis and cutaneous ulcers

• Large, amoeboid trophozite with spiny pseudopods and a double-walled cyst
• Invades broken skin, conjuctiva, lungs, and urogenital epithelia
• Course of infection is lengthier than PAM (with 2-3% survival rate)

Mode of Transmission: Direct Contact

Virulence Factors: Invasiveness

Culture/Diagnosis: Examination of CSF, brain imaging, biopsy

Prevention: N/A

Treatment: Surgical excision of granulomas; pentamidine

Epidemiological Features: Predominantly occurs in immunocompromised patients

• Almost caused by VIRAL infection, most of the time
• Signs and symptoms: behavior changes or confusion due to inflammation, decreasing consciousness and seizures
• Symptoms of meningitis
• Treated with acyclovir (for HSV caused)

1. Arboviruses

2. HSV 1 or 2

3. JC virus

4. Post-infection encephalitis

• Viruses transmitted by arthropod vectors (mosquitos). Most vectors feed on BLOOD of hosts. Sometimes birds and mammals
• Humans are DEAD-END hosts (we do not allow the life cycle to occur, once we are infected, we cannot pass it down)
• Worldwide distribution
• Clustered in tropics and subtropics; periodic epidemics in temperate zones
• Peak incidence is usually from late spring through early fall
• Warm-blooded hosts maintain the infection during cold and dry seasons (millions of yearly infections and thousands die)
• NO satisfactory treatment

Mode of Transmission: Vector (anthropod bites)

Virulence Factors: (AFI)

• Attachment: The virus has surface proteins that allow it to specifically bind to receptors on host cells, such as neurons or endothelial cells. This is the first step that lets the virus enter and infect the body.
• Fusion: After attaching, the virus can fuse its envelope with the host cell membrane, allowing its genetic material to enter the cell and start infection.
• Invasion Capabilities: Once inside, the virus can spread to different tissues, including crossing the blood-brain barrier to infect the central nervous system—causing inflammation of the brain (encephalitis)

Culture/Diagnosis: history, rapid serological tests, nucleic acids amplication

Prevention: Insect Control

Treatment: NONE

Distinctive Features: history of exposure to insect is important

• HSV 1 and HSV2 can cause encephalitis in newborns of HSV+ mothers
• Virus is disseminated and progress is poor. Virus is disseminated and progress is poor” means that the virus has spread widely throughout the body or brain tissues instead of staying localized. When HSV-1 becomes disseminated, it can cause widespread inflammation and damage in the brain, leading to severe symptoms, complications, and a poorer prognosis (meaning recovery is more difficult and the condition can be life-threatening).
• Older children and young adults (5 to 30) are also susceptible
• Treated with acylovir

Mode of Transmission: Vertical or reactivation of latent infection

Virulence Factors: N/A

Culture/Diagnosis: Clinical presentation, PCR, Ab test, growth of virus in cell culture.

Prevention: Maternal screening for HSV

Treatment: Acyclovir

Distinctive Features: In infants, disseminated disease present (rare between 30-50 years old)

Epidemiological Features: HSV-1 is the most common cause of encephalitis (two cases per million per year)

Acute encephalitis;

newborns of HSV+ mothers

Older children and young adults (5-30)

Older Adults (+50)

HSV-1, represents a reactivation of dormant HSV from the trigeminal ganglion.

HSV-1

• Acute Encephalitis

Mode of Transmission:

• Ubiquitous (widespread virus)
• Ubiquitous means the JC virus is found almost everywhere—most people are exposed to it during childhood and carry it in a latent (inactive) state in their kidneys or lymphoid tissues.

Virulence Factors: N/A

Culture/Diagnosis: PCR of cerebrospinal fluid

Prevention: None

Treatment: No effective proven drug, but mefloquine has been used

Distinctive Features: In SEVERELY immuncompromised (AIDS). Most people have this virus as normal microbiota, but when they become immunocompromised, they see the manifestation of this virus.

Epidemiological Features:

Postinfection encephalitis

- could also be due to overactivation of immune system

• Acute Encephalitis

Mode of Transmission: sequelae of measles, other viral infections, occasionally vaccinations

Virulence Factors: N/A

Culture/Diagnosis: History of viral infection or vaccination

Prevention: N/A

Treatment: Steroids, anti-inflammatories

Distinctive Features: Hist of virus/vaccine exposure critical

Epidemiological Features: Rare in the United States due to vaccination; more common in developing countries, more common in boys than girls

1. Toxoplasma gondii

2. Subacute sclerosing panencephalitis

3. Prions

Subacute Sclerosing Panencephalitis (Measles Virus)

- Symptoms take longer to show up, and they can be confused with other diagnosis

• Less striking symptoms

- Most common cause is Toxoplasma, and most common (postinfection viral) cause is measles.

Tachyzoites and Pseduocysts

• Protozoan parasite
• Flagellated, can attach at least 200 species of birds and mammals
• Extensive worldwide distribution
• Majority of the world's population is infected at some point
• When in fetus and immunodeficient people, it's MOST severe and fatal
• People w/ history of Toxoplasma are more likely to display thrill-seeking behaviors (especially with dormant cysts) - and it messes with fear and reward pathways
• Brain inflammation + behavioral change
• Usually asymptomatic, but can have sore throat, lymph node enlargement, and low-grade fever
• chronic or subacute encephalitis in patients with immune suppresion

Mode of Transmission: Vehicle (meat) or fecal-oral

Virulence Factors: intracellular growth

Culture/Diagnosis: serological detection of IgM, culture, and histology

Prevention: personal and food hygiene

Treatment: pyrimethamine and/or leucovorin and/or sulfadiazine

Distinctive Features: subacute, slower development of disease

Epidemiological Features: considered a neglected parasitic infection (NPI)

• 15% to 29% of U.S. population is seropositive; internationally, seroprevalence is up to 90%; disease occurs in 3% to 15% of AIDS patients

Here’s why:

• IgM antibodies are the first type of antibody produced by the immune system when the body is first exposed to a pathogen.
• So, if someone’s serum contains anti–Toxoplasma IgM, it shows their immune system is currently responding to the infection or was infected very recently.
• In contrast, if only IgG antibodies are present, it usually indicates a past infection or long-term immunity.

Cats (the definitive hosts) release oocysts in their feces, which sporulate in the environment and can contaminate food or water. When intermediate hosts (like rats, mice, or humans) ingest these oocysts, the parasite travels through the bloodstream and can form cysts in tissues such as the brain and muscles.

Infected rodents show altered behavior (less fear of predators), making them more likely to be eaten by cats — which continues the parasite’s life cycle.

In humans, transplacental transmission can occur if a pregnant person becomes infected, potentially leading to congenital toxoplasmosis, which causes enlarged liver/spleen, hydrocephalus, or stillbirth.

- Pregnant People

- 33% chance of mother transmitting infection to fetus via placenta

Congential infection is in 1st or 2nd trimester

- can lead to stillbirth, liver/spleen enlargement, liver failure, hydrocephalus, convulsions, damage to retina/blindness

Felines, both wild and domestic

Cats serve as the reservoir and definitive host for Toxoplasma gondii because they’re the only animals in which the parasite can complete its sexual life cycle and shed infectious oocysts in their feces.

The modes of transmission to humans are:

• Fecal–oral route: Ingesting oocysts from cat feces, contaminated soil, water, or unwashed produce.
• Foodborne route: Eating undercooked or raw meat containing tissue cysts (especially pork, lamb, or venison).

• "SLOW VIRUS infection"
• Symptoms appear years after initial episodes of measles
• Caused by DIRECT viral invasion of neural tissue
• Unclear what factors lead to persistence of virus in some people
• In subacute encephalitis caused by measles, even after the initial infection and rash resolve, mutated measles virus or lingering viral RNA can persist in the brain. Over time, it evades the immune system and causes progressive tissue damage, leading to neurological decline.

Mode of Transmission: persistence of measles infection

Virulence Factors: cell fusion, evasion of immune system

Culture/Diagnosis: EEGs, MRI, serology (Ab versus measles virus)

Prevention: None

Treatment: None

Distinctive Features: History of measles

Epidemiological Features: Occurs in one in six people who have recovered from measles

EEG

• What it shows: Characteristic periodic, generalized, high-voltage spike-and-slow-wave complexes (often occurring every 4–10 seconds).
• Why that matters: This stereotyped periodic pattern is strongly associated with SSPE and supports the diagnosis when seen in the right clinical setting.

MRI

• What it shows: Asymmetric white-matter changes (T2/FLAIR hyperintensities), cortical atrophy, and later widespread demyelination; lesions often start in the occipital/parietal regions and progress.
• Why that matters: MRI demonstrates the structural brain damage and demyelination expected from a chronic viral process, correlating with the encephalitic and degenerative features of SSPE.

Serology / CSF antibody testing

• What to test: Anti-measles antibodies in serum and especially in CSF.
• Key finding: High measles IgG titers in CSF (and an elevated CSF:serum antibody ratio or evidence of intrathecal antibody synthesis).
• Why that matters: Persistent/intrathecal production of measles antibodies indicates chronic measles virus infection of the CNS rather than just prior exposure — essentially the immunologic proof that measles virus is present in the brain.

False

They are infectious cause they can cause disease but they have no genetic material

In prion diseases, the normal brain protein (PrPᶜ) is misfolded into an abnormal, infectious form (PrPˢᶜ). This altered protein then induces other normal PrPᶜ proteins to also spontaneously misfold, creating a chain reaction. Over time, the accumulation of PrPˢᶜ proteins forms plaques and causes spongiform (hole-like) damage in the brain tissue, leading to severe neurological symptoms.

• It can also cause disease when transferred to a new host such as contaminated instruments or infected meat.

• Subacute Encephalitis
• proteinaceous infected particles with NO nucleic acids
• misfolded proteins, they are NOT alive
• Generally, you inherit a mutated form of the prion protein which gets further transformed (for fatal familial insomnia)
• Cause transmissible spongiform encephalopathies in humans
• CJD, Kuru, Fatal familial insomnia (inherited), Gerstmann-Straussler-Schneiker disease

Mode of Transmission:

• CJD = direct/parental contacted with infected tissue or inherited
• vCJD= vehicle (meat or parenteral)

Virulence Factors: avoidance of host immune response

• No immune recognition: Since prions (PrP^Sc) come from the normal cellular prion protein (PrP^C), the body doesn’t recognize them as “non-self.” The immune system is tolerant to these proteins and doesn’t mount an antibody or T-cell response.
• Lack of nucleic acids: Prions don’t have DNA or RNA, so the immune system’s usual viral and bacterial detection mechanisms (which recognize foreign genetic material) don’t detect them.
• Resistance to degradation: Prions are highly resistant to proteases and other enzymes that would normally break down abnormal proteins, so they persist in the body.

Culture/Diagnosis: Biopsy, image of brain

Prevention: Avoiding infected meat or instruments; no prevention from inherited form

Treatment: None

Distinctive Features: Long incubation period; fast progression once it begins

Epidemiological Features: CJD (one case per million worldwide, seen in older adults) and vCJD: 98% of cases in UK

False; RNA virus

Pregnant People

• Causes congenital Zika virus syndrome, with microencephaly
• Additional symptoms of the syndrome include vision problems, involuntary movements, seizures, and irritability

• Zika virus
• Transmitted by aedes mosquito bite (via sexual intercourse) and in utero
• When adults are infected, they have a range of symptoms, from none to all: skin rash (maculopapular), conjuctivits, muscle, joint pain, can also trigger Guillain-Barre syndrome in some

Mode of Transmission: Vertical (mother to placenta), vector-borne, sexual contact, possibly blood transfusions

Virulence: proteins that reduces innate immune system response

Culture/Diagnosis: PCR testing

Prevention: avoiding mosquitos, NO VACCINE

Treatment: supportive

Epidemiological: Originated in Africa but spreading throughout world in 2016; small outbreaks in other parts of the world since

Slow, progressive zoonotic disease characterized by fatal encephalitis

Virus enters the NS and causes involuntary control of muscles

• Furious rabies: agitation, discomfort, seizures, and twitching AND hydrophobia
• Dumb rabies: paralyzed, dis-oriented, and suporous
• Both forms lead to death from cardiac or respiratory arrest as both forms progress to a coma phase.

Treatment begins after EXPOSURE and BEFORE symptoms develop

• Passive and active postexposure immunization
• Vaccination of domestic animals, vets, animal handlers, lab, and travelors
• Vaccine incorporated as BAIT to treat wild animals

• Structure of virus: glycoprotein spikes, matrix protein, then nucleocapsid
• Reservoir: wild mammals such as skunks, raccoons, badgers, cats, bats, and canines
• Spread to domestic animals and humans through bite, scratches, and inhalation of droplets
• Rabies Preventio

Mode of Transmission: Parenteral (bite trauma) and DROPLET

Virulence: envelope glycoprotein

• The envelope glycoprotein helps rabies cultivate by mediating host cell binding, entry, and spread through the nervous system — making it essential for infection and neuroinvasion.

Culture/Diagnosis: DFA (direct fluorescent antibody test)

Prevention: Inactivated vaccine

Treatment: Postexposure passive and active immunization; induced coma and ventilator if symptoms start

Epidemiological: United States: 1–5 cases per year; Worldwide: 35,000–55,000 cases annually

• Acute enteroviral infection of spinal cord which can cause neuromuscular paralysis
• Fever, headache, nausea, sore throat, myalgia
• Attacks spinal ganglia, cranial nerves, and motor nuclei

• Paralytic disease: Various degrees of flaccid paralysis of the muscles of the legs, abdomen, back, intercostals, diaphragm, pectoral girdle, and bladder. Temporary but can have long-lasting effects
• Bulbar poliomyelitis: brain stem, medulla, cranial nerves. Loss of control of cardiorespiratory regulatory centers
• Post-polio syndrome: progressive muscle deterioration in 25% to 50% of patients decades after the initial infection

motor

anterior horn of the spinal cord

• RNA single-stranded virus
• Humans are the only reservoir
• Vaccination as early in life w/ four doses, starting at 2 months of age
• poliovirus (part of picornavirus family)

Mode of Transmission: fecal-oral, vehicle

Virulence: attachment mechanisms

Culture/Diagnosis: viral culture, serology

Prevention: live attenuated vaccine (developing world) and inactivated oral vaccine (developed)

Treatment: none, palliative, supportive

Epidemiological: Polio has been 99% eradicated, except in Afghanistan and Pakistan, as of 2021

Gram+

Endospore Forming (under anaerobic conditions only)

Rod

35,000

unhygienic practices during childbirth

• Tetanospasmin
• It's a neurotoxin which binds to target sites on peripheral motor neurons on the spinal cord, brain, and sympathetic nervous system
• Blocks inhibition of muscle contraction, causing muscles to contract uncontrollably (allowing for excitatory to continue) resulting in spastic paralysis
• Death results from paralysis of respiratory muscles and respiratory arrest

• Tetanus
• common resident of soil and GI tracts of animals

Mode of Transmission: Parenteral, direct contact

Virulence: tetanospasmin exotoxin

Culture/Diagnosis: sympotamtic

Prevention: Vaccination with tetanus toxoid (modified) in combination with diptheria and pertussis toxoid

• booster - every 10 years
• never be given to injured, non-immunized people, not completed the series, last booster was more than 10 years ago
• can also be given with passive TIG

Treatment: Combination of passive antitoxin and tetanus, toxoid active immunization, metronidazole and muscle relaxants, sedation

Epidemiological: Worldwide, +/-25,000 newborn deaths annually in developing countries

• Associated with eating poorly preserved foods
• Three types: foodborne, infant, and wound (anerobic microbe

• Botulinum exotoxin
• Toxin travels from the bloodstream to the neuromuscular junctions of skeletal muscles
• Prevents the release of acetylcholine, resulting in flaccid paralysis
• Botox is utilized by doctors to treat uncontrolled muscle spasms, migraine headaches, and other conditions (cosmetically as well)

• Botulism - gram + endospore forming
• Normally, acetylcholine (ACh) is released at the synapse to trigger muscle contraction and continue the action potential. However, in the presence of botulinum toxin, the release of ACh is blocked, preventing muscle contraction and leading to paralysis.

Mode of Transmission: Vehicle (foodborne toxin, airborne organism), direct contact (wound), and parenteral (injection)

Virulence: botulinum exotoxin

Culture/Diagnosis: culture of organism; demonstration of toxin

Prevention: Food hygiene; toxoid immunization available for laboratory professional

Treatment: Antitoxin, penicillin G for wound botulism, and supportive care

Epidemiological: United States: 75% of botulism is infant botulism; over 150 cases annually

Category A Bioterrorism Agent

Epidemiological Features

United States: 75% of botulism is infant botulism; over 150 cases annually

Category A Bioterrorism Agent

• African Sleeping Sickness
• Hemoflagellate: lives in the blood and tissues of the human host
• Millions in African affected
• Transmitted by tseste fly
• Intermittent fever, enlarged spleen and swollen lymph nodes, joint pain, personality/behavioral changes, extreme fatigue and sleep disturbances (due to circadian rhythm disruptions) , uncontrollable sleepiness during the day (sleeplessness at night)
• Muscle tremors, shuffling gait, slurred speech, seizures, local paralysis
• Death results from coma, secondary infections, and heart damage

Mode of Transmission: Vector, vertical

Virulence: Immune evasion by antigen shifting

• In African sleeping sickness (caused by Trypanosoma brucei), the parasite uses antigenic variation (or antigen shifting) to evade the immune system. Here’s how it works: the parasite’s surface is covered with proteins called variant surface glycoproteins (VSGs). The immune system recognizes these proteins and makes antibodies against them. But before the immune system can eliminate all of the parasites, some of them switch to a different VSG, changing their “appearance.” This constant switching confuses the immune system and allows the parasite to stay in the host for long periods, causing a chronic infection.

Culture/Diagnosis: microscopic examination of blood, CSF

Prevention: vector control

Treatment: Suramin or pentamidine (early), eflornithine or melarsoprol (late)

Epidemiological: brucei gambiense: 7,000 to 10,000 cases reported annually; actual occurrence estimated at 600,000; T. brucei rhodesiense: estimated 30,000 cases occur annually

Clostridium tetani

Clostridium botulinum

Streptococcus pneumonia (meningitis)

Listeria monocytogenes (meningitis, neonatal meningitis)

Streptococcus agalactiae (neonatal meningitis)

1. Neiserria meningitdis (meningococcal meningitis)
2. Haemophilus influenzae (meningitis)
3. Escherichia coli (KI strain) - neonatal meningitis
4. Cronobacter sakazakii (neonatal and infant meningitis)

HSV 1/2 (encephalitis)

JC virus (progressive multifocal leukoencephalopathy)

Arboviruses (encephalitis)

Zika virus

Poliovirus

Measles virus (SSPE)

Rabies virus

Cryptococcus neoformans

Coccidoides

(Meningitis)

Creutzfeldt-Jacob prion (CJD)

Naegleria fowleri (meningoencephalitis)

Acanthamoeba (meningoencephalitis)

Toxoplasma gondii (subacute encephalitis)

Trypanosoma brucei (ASS)

Infectious Diseases Manifesting in the Respiratory System

Trachea, then into the bronchi, bronchioles, and alveoli

• Nasal hairs
• Ciliated epithelium (trachea and bronchi in the ciliary escalatory)
• Mucus
• Coughing, Sneezing, Swallowing

• Complement action in lungs
• Increased cytokines and antimicrobial peptides
• • In the alveoli of the lungs, macrophages (called alveolar macrophages) patrol the air sacs and remove any dust, debris, or microorganisms that enter when you breathe.
  • In the tonsils, which are clusters of lymphoid tissue at the back of the throat, macrophages help detect and destroy pathogens that enter through the mouth or nose.Macrophages INHIBIT alveoli of lungs and clusters of lymphoid tissue in tonsils. This means that macrophages, which are immune cells that “eat” and destroy pathogens, are found in specific parts of the body where infections are likely to start.
• Secretory igA (inside mucus)

- large number of commensal organisms (one species gains benefits) due to constant contact with environment

• Upper and lower respiratory tract
• Nine major bacterial genera and yeasts (especially in URT)
• Microbial antagonism
• Normal biota bacteria which can causes disease:
• Streptococcus pyogenes
• Haemophilus influenzae
• Streptococcus pneumoniae
• Neisseria meningitidis
• Staphylococcus aureus

• Identify which disease is often caused by a mixture of microorganisms.
• Identify two bacteria that can cause dangerous pharyngitis cases.

• Common Cold (rhinoviruses, coronaviruses, adenoviruses, RSV)

Mode of Transmission: droplets and indirect

Virulence: attachment proteins, most symptoms induced by host response

• uses attachment proteins on its surface to bind tightly to receptors on the cells lining your nose and throat — this is how it successfully enters and infects those cells. Most of the symptoms you feel (like congestion, sore throat, and runny nose) aren’t directly caused by the virus destroying cells, but rather by your immune system’s response to the infection — the inflammation and release of immune molecules cause the familiar cold symptoms.

Culture Diagnosis: Not needed

Prevention: No vaccine (HYGIENE)

Treatment: ONLY supportive care no chemotherapeutic agents

Epidemiology: highest incidence among preschool and elementary schoolchildren, with average of three to eight colds per year; adults and adolescents: two to four colds per year

• inflammatory condition of any of the four sinuses in skull
• allergy OR infection
• Patients suffering from cold can also get this (sequela because you get fluid and mucus trapped inside sinuses, allowing bacteria and fungi to incubate)
• Sinus pain, nasal congestion, pressure, headache, toothache
• discharge is OPAQUE and can yellow and green
• Multiple causative agents: viruses (most common - same ones as cold), bacteria (from normal biota, 2% of cases), fungi (rare but occurs when antibacterial drugs can't solve)

• Sinusitis

Mode of Transmission: direct and indirect contact

Culture Diagnosis: culture not performed, diagnoses based on clinical presentation

Prevention: hygiene

Treatment: none

Distinctive features: viral and bacteria more common

Epidemiology: follows common cold

• Sinusitis

Mode of Transmission: Endogenous (opportunism)

Culture Diagnosis: culture not performed, diagnoses based on clinical presentation; occasionally X-rays or imaging used

Prevention: N/A

Treatment: no antibiotic unless unresolved for some weeks

Distinctive Features: viral and bacterial more common than fungal

Epidemiology: United States: affects 1 of 7 adults; between 12 and 30 million diagnoses per year

• Sinusitis

Mode of Transmission: introduction by trauma or opportunistic growth

Culture Diagnosis: culture not performed, diagnoses based on clinical presentation; occasionally X-rays or imaging used

Prevention: N/A

Treatment: Physical removal of fungus, or anti-fungals in severe cases

Epidemiology: fungal sinusitis varies with geography; in the United States: more common in SE and SW; internationally: more common in India, North Africa, Middle East

• sequela to common cold
• NOT communicable disease
• many different causative agents: bacteria, viruses, yeast
• inflammation of eustachian tubes and buildup of fluid in the middle ear
• Bacteria can migrate along the eustachian tubes, increasing the inflammatory response
• Fullness/pain in ear, loss of hearing
• Young children: irritability, trouble sleeping/eating/hearing
• Infection can cause eardrum to burst

Fluids builds up in eustachian tubes

• caused by a mixed biofilm of bacteria attached to the membrane of the inner ear

Effusion

• Otitis media
• most common cause
• Gram + diplococci joined end to end

Mode of Transmission: endogenous *may follow upper respiratory tract infection by S. pneumoniae)

Virulence: Capsule OR hemolysin

• Capsule – Some bacteria like Streptococcus pneumoniae have a polysaccharide capsule that helps them avoid phagocytosis by immune cells, allowing them to survive and multiply in the middle ear.
• Hemolysin – Certain bacteria (like S. pneumoniae or S. pyogenes) produce hemolysins, which are toxins that damage host cells, including those in the ear tissues. This triggers inflammation and fluid buildup, leading to ear pain and pressure.

Culture/Diagnosis: clinical symptoms and failure to resolve in 72 hours

Prevention: Pneumococcal conjugate vaccine (PCV13)

Treatment:

• Most often, “watchful waiting” for 72 hr
• Tubes can help alleviate symptoms in recurrent infections
• Amoxicillin (high rates of resistance) or amoxicillin + clauvanate + cefuroxime; antibiotic usage recommend for babies < 6 months old.

Epidemiological: 30% of cases in the U.S

• Yeast (Fungal)
• Otitis Media

Mode of Transmission: not KNOWN

Virulence: biofilm formation

Culture/Diagnosis: MALDI-TOF or PCR; CDC will identify if requested

Prevention: None

Treatment: Consult w/ CDC (antibiotic resistance)

Epidemiological: First appeared in 2009; increasing in U.S.

• Inflammation of throat, causing swelling and pain
• Inflammatory white packets (exudates) on walls of throats, difficulty swallowing, foul breath
• Viral - mild and sometimes lead to horseness
• Bacteria - more painful, often has fever, headache, and nausea
• Caused by the same viruses causing the common cold, but most serious cases are caused by Streptococcus pyogenes and Fusobacterium necrophorum

1. Streptococcus pyogenes
2. Fusobacterium necrophorum
3. Viruses (same ones that cause common cold)

Streptococcus pyogenes

• Gram +
• Grows in chains
• Facultative anaerobe
• Produces capsule and slime layer
• Untreated streptococcal infections can lead to Rheumatic fever, scarlet fever, and glomerulonephritis

Virulence

• Surface antigens of S. pyogenes mimic host proteins and protect microbe from being affected by lysozyme
• M protein aid - resisting phagocytosis and adhesion
• Streptolysin O and streptolysin S: injure cells and tissues
• Erythrogenic toxin: produced by lysogenic strains of S. pyogenes, key for scarlet fever
• Some streptococcal toxins act as superantigens

• Pharyngitis

Mode of Transmission: Droplet or Direct

Virulence:

• LTA, M protein, hyaluronic acid capsule, SLS and SLO, superantigens, induction of autoimmunity

Culture/Diagnosis: beta-hemolytic on blood agar, sensitive to bacitracin

Prevention: hygiene

Treatment: penicillin, cephalexin (allergic to penicillin)

Distinctive Features: more severe than viral

Epidemological: United States: 10% to 20% of all cases of pharyngitis

• Pharyngitis
• Gram - bacteria
• potientally dangerous bacteria that causes 15% of acute pharyngitis (>15 y/o)
• Causes peritonsillar abscess called Lemierre's syndrome (life threatening, mostly in males and sepsis via drainage which can be sent to jugular vein and the heart)

Mode of Transmission: endogenous

Virulence: Invasiveness, endotoxin

Culture/Diagnosis: Culture anerobically, CT for abscess

Treatment: Penicillin

Distinctive: can lead to Lemierre's syndrome

Epidemiological:

Causes up to 15% of acute pharyngitis in teens/young adults

• Pharyngitis

Mode of Transmission: all forms of contact

Culture/Diagnosis: Goal is to rule out S. pyogenes (and F. necrophorum); further diagnosis usually not performed

Prevention: Hygiene

Treatment: Symptom relief

Distinctive: hoarseness

Epidemological: ubiquitous; responsible for 40% to 60% of all pharyngitis

ONLY 3 - Whooping Cough, RSV, and Influenza

• Pertussis
• Catarrhal Phase: bacteria in respiratory tract cause cold symptoms
• Paroxysmal Phase: most contagious, almost last 6 wees, coughing sheds microbes into the air: UNCONTROLLABLE coughing with whooping sound, can result in broken vessels in eye, vomiting, hemorrhages in brain
• Convalescent Phase: bacteria are decreasing, but ciliated epithelia have been damaged, requiring weeks to months of recovery

False;

small, gram -

STRICTLY aerobic

• Pertussis (Whooping Cough)
• Small, Gram -, strictly aerobic, fastidious

Mode of Transmission: DROPLET contact

Virulence:

• Filamentous hemagglutinin: essential for attachment/adhesion
• Pertussis toxin: causes massive mucus production
• Tracheal cytotoxin: causes direct destruction of ciliated cells
• Endotoxin: leads to the production of a host of cytokines (When a pathogen infects the body, it can cause an overproduction of cytokines (a “cytokine storm”). This intense immune response can lead to tissue damage, inflammation, and worsening symptoms.)

Culture/Diagnosis: PCR or growth on blood agar, charcoal, or potato-glycerol agar, diagnosis can be made on symptoms

Prevention: high vaccination coverage has kept incidence low in the U.S. Current vaccines are acellular formation of antigens. Booster needed after 11 y/o

Treatment: Azithryomycin; drug resistant B. pertussis is concerning threat

Epidemiological: United States: 19,000 cases in 2017, 14,000 in 2018; internationally: hundreds of millions of cases annually

• Respiratory Syncytial Virus
• Infects the respiratory tract and produces giant multinucleated cells (syncytia)
• peak incidence in winter and early spring
• Premature babies as well as children 6 months of age or younger are especially susceptible
• Signs/Symptoms: fever (3 days), rhinitis, pharyngitis, otitis
• More serious infection - progress to bronchial tree, parenchyma, croup and difficulty breathing, w/ stridor
• Highly contagious through droplet and fomites
• Passive antibody therapy and ribavirin is available through inhaled aersol

• RSV

Mode of Transmission: droplet and indirect

Virulence: syncytia formation

Culture/Diagnosis: RT-PCR

Prevention: Passive-antibody (humanized monoclonal) in high-risk children

Treatment: ribavirin plus passive antibody for severe cases

Epidemiological: United States: general population, less than 1% mortality rates, 3% to 5% mortality in premature infants or those with congenital heart defects; internationally: seven times higher fatality rate in children in developing countries

• All cases of influenza are caused by one of three influenza viruses: A, B, or C, belonging to the Orthomyxoviridae family
• Headache, chills, dry cough, body aches, fever, stuffy nose, and sore throat, extreme fatigue (few days to weeks)
• Leave patients to secondary infections, leading to pneumonia
• Patients with emphysema or cardiopulmonary disease, along with very young, elderly, or pregnant patients, are more susceptible to serious complications

Hemagglutinin (H):

• Has agglutinating action on red blood cells
• Binds to host cell receptors of respiratory mucosa

Neuraminidase (N):

• Breaks down protective mucus coating of the respiratory tract
• Assists in viral budding and release
• Participates in host cell fusion

We get flu shots every year because the glycoproteins (hemagglutinin and neuraminidase) on the influenza virus mutate frequently — a process called antigenic drift.

• Antigenic drift: gradual changing of amino acid composition of influenza antigens which results in decreased ability of host memory cells to recognize them
• Antigenic shift: swapping out of one of the strands of viral RNA with a gene or a strand from a different influenza virus (infected host has both subtypes), and there is NO recognition by host memory cells

drier

winter

• Cold air makes respiratory tract mucous membranes more brittle, facilitating invasion by viruses
• Mucous membranes are less viscous, which enables the flu-virus to penetrate the cells and the epithelium very easily

• Influenza

Mode of Transmission: Droplet, direct, and indirect

Virulence: Glycoprotein spikes, antigenic shift and drift

Culture/Diagnosis: RT-PCR

Prevention: vaccines

• Three major types of influenza vaccines in the United States:
• Inactivated, Recombinant, and Live Attenuated influenza vaccines
• The vaccine does not cause the flu

Treatment: Oseltamivir (Tamiflu), baloxavir (Xofluza)

Epidemiological: For seasonal flu, deaths vary from year to year; United States: range from 17,000 to 52,000; internationally: range from 250,000 to 500,000

1. Tuberculosis

2. Community-acquired pneumonia (3 causes)

3. Hospital-acquired pneumonia

4. Hantavirus pulmonary syndrome

• Ancient disease, now remerging due to HIV epidemic, drug-resistant strains, and 1/3 of the world is infected
• Main cause is bacteria Mycobacterium tuberculosis

1. Primary

• Infectious dose: 10 bacteria
• Bacteria continue to multiply inside alveolar macrophages
• Tubercles: Granulomas containing a core of TB bacteria in enlarged macrophages and an outer wall made of fibroblasts, lymphocytes, and macrophages
• Can become necrotic caseous lesions which can be calcified
• Breakdown of these calcified lesions can lead to secondary or reactivation of TB

2. Extrapulmonary TB

• Organs involved: regional lymph nodes, intestines, kidneys, long bones, genital tract, brain, meninges

3. Secondary (reactivation) TB

• Dormant bacteria in the lungs can be reactivated when immunity wanes
• Able to remain dormant for weeks, months, or years later
• Severe symptoms: violent coughing, greenish or bloody sputum, low-grade fever, anorexia, weight loss, fatigue, night sweats, and chest pain
• Actually get the disease - the untreated disease has a 60% mortality rate

1. The TB skin test (Mantoux test)

• causes a welt (raised bump) if you’ve been exposed to Mycobacterium tuberculosis because of a delayed-type hypersensitivity reaction — an immune system response mediated by T cells, not antibodies.
• Tuberculin reaction

Here’s what happens:

• The test injects a small amount of tuberculin (purified protein derivative, PPD) just under the skin.
• If you’ve been exposed to TB before, your memory T cells recognize the TB proteins in the PPD.
• Those T cells release cytokines, which recruit macrophages and other immune cells to the site.
• This causes localized inflammation, resulting in a firm, raised welt within 48–72 hours.

So the welt doesn’t mean you currently have active TB — it just means your immune system has seen TB antigens before (from infection or vaccination).

2. IGRA: blood test to determine T-cell reactivity to M. tuberculosis

IGRA stands for Interferon-Gamma Release Assay — it’s a blood test used to detect Mycobacterium tuberculosis infection (like the TB skin test, but more specific).

Here’s how it works

• Long, thin, acid-fast rod, strict aerobe
• Lipid component in mycobacterial cell wall associated with viral strains (mycolic acid and waxes makes organisms resistant to drying and disinfectants)
• MAC (mycobacterium avium Complex, causes disseminated tuberculosis infection in AIDs patients)

Mode of Transmission: Vehicle (airborne)

Virulence: Lipids in wall, ability to stimulate strong cell-mediated immunity (CMI)

Culture/Diagnosis:

Culture, PCR test (Xpert®), IGRA, complemented by skin test and chest X-ray

Prevention: Avoiding airborne M. tuberculosis AND BCG vaccine in other countries

Treatment:

• Active tuberculosis: First 2 months: Rifampin, isoniazid, ethambutol, pyrazinamide
• Four to seven months: uses only two drugs that susceptibility testing have shown to be effective
• Patient noncompliance leads to drug-resistant strains: Multidrug-Resistant Tuberculosis (MDR-TB)
• Extensively Drug-Resistant Tuberculosis (XDR-TB)

Distinctive Features: Remains airborne for long periods; extremely slow-growing, which has implications for diagnosis and treatment

Epidemiological: remains airborne for long periods; extremely slow-growing, which has implications for diagnosis and treatment

• TB

Mode of Transmission: Vehicle (airborne)

Virulence: lipids in wall, ability to stimulate strong cell-mediated immunity (CMI)

Culture/Diagnosis: culture, PCR test (Xpert®), IGRA, complemented by skin test and chest X-ray

Prevention: avoiding airborne M. tuberculosis; BCG vaccine in other countries

Treatment: multiple-drug regimen, which may include pretomanid, bedaquiline; and linezolid; in Serious Threat category in CDC Antibiotic Resistance Report

Distinctive Features: much higher fatality rate over shorter duration

Epidemiological: United States: a fewer cases per year; worldwide: 500,000 new infections with MDR-TB in 2020

• Inflammatory condition of the lung in which fluid fills the alveoli
• Caused by many microbes which must be able to AVOID phagocytosis or AVOID being killed once inside alveolar macrophages
• Viral is generally milder than bacterial
• Begins with runny nose, congestion, headache, fever
• Lung: chest pain, fever, cough, discolored sputum
• Pale and sickly due to pain and difficulty breathing

1. Droplet

• Rhinoviruses (or endogenous transfer)
• Streptococcus pneumoniae (or endogenous transfer)
• Mycoplasma pneumoniae

2. Vehicle (Inhalation of Spores)

• Histoplasma capsulatum (in soil)
• Pneumocystis jirovecii

3. Vehicle (Water Droplets)

• Legionella species

Mode of Transmission: Droplet contact (or endogenous transfer)

Virulence: N/A

Culture/Diagnosis: Failure to find bacteria or fungi

Prevention: Hygiene

Treatment: None

Distinctive Features: Mild

Epidemiological: 9% of CAP cases

• CAP
• Small, gram + flattened coccus in pairs
• Alpha-hemolytic
• For 50% of healthy people, it's in normal microbiota
• Infection occurs when bacteria is inhaled into deep areas of lungs or shared respiratory droplets between people

Mode of Transmission: Droplet contact (or endogenous transfer)

Virulence: CAPSULE

• Polysachharide component prevents effective phagocytosis, blocks complement, causes inflammatory buildup in lung

Culture/Diagnosis: Gram-stain, alpha-hemolytic on blood agar

Prevention: Vaccine (children and older adults) - PCV13 or PPSV23

Treatment: doxycycline, ceftriaxone, with or without vancomycin; much resistance

Distinctive Features: SEVERLY ILL

• Organism is resistant to penicillin and its derivatives, macrolides, tetracyclines, and fluoroquinolones

Epidemiological: 5% of cases, serious threat

• (CAP) Walking pneumonia/atypical pneumonia (symptoms do not resemble those of pneumococcal or other ones)
• LACKS a cell wall, irregulary shaped
• Transmitted by aersol droplets among individuals
• Diagnosis through ruling out other causes, PCR, or serological analysis

Mode of Transmission: Droplet

Virulence: Adhesins

Culture/Diagnosis: Rule out other etiologic agents; serology; PCR

Prevention: No vaccine, no permanent immunity

Treatment: erythryomycin

Distinctive Features: mild, walking pneumonia

• Darling disease
• Ohio Valley Fever, Spelunker's Disease
• Benign/Severe, Acute/Chronic
• Healthy people can fight out, but immunocompromised can lead to lesions in lungs
• Most serious forms in those with AIDS
• Chronic pulmonary histoplasmosis: signs and symptoms similar to TB
• Endemic to all continents except Australia

Mode of Transmission: Vehicle (inhalation of spores in contamined soil)

Virulence: Survival in phagocytes

Culture/Diagnosis: Rapid antigen tests, microscopy

Prevention: Avoid soil with bird and bat droppings

Treatment: Itraconazole

Distinctive Features: many asymptomatic infections

Epidemiological: the United States, 250,000 infected per year; 5% to 10% have symptoms

• CAP
• Agent of pneumocystits pneumonia (PCP pneumonia)
• Primarily in those w/ AIDS
• normal biota in healthy people
• Fungus multiplies intracellularly and extracellularly
• Antifungals are ineffective, can have lesions all over heart, lungs, skin, liver, if you don't have a properly functioning immune system

Mode of Transmission: Vehicle (inhalation of spores)

Virulence: N/A

Culture/Diagnosis: Microscopy

Prevention: Antibiotics given to AIDS patients

Treatment: Trimethoprim/sulfamethoxazole

Distinctive Features: mostly occurs in AIDS patients

Epidemiological: exclusively in severely immunocompromised patients

• CAP Pneumonia
• Weakly gram negative (various shapes)
• Legion convention outbreak
• Widely distributed in aqeous environments (tap water, cooling towers, spas, ponds, and freshvirus)
• Opportunistic disease (mostly in elderly, rarely in healthy children and adults)

Mode of Transmission: Vehicle (water droplets)

Virulence: N/A

Culture/Diagnosis: Urine antigen test, culture requres selective charcoal yeast extract agar

Prevention: N/A

Treatment: Fluoroquinolone, azithromycin, clarithromycin

Distinctive Features: Mild pneumonias in healthy people; can be severe in elderly or immunocompromised

Epidemiological: United States: on the rise; 6,000 to 8,000 cases annually

• Healthcare-Associated Pneumonia
• Most causes are due to ASPIRATION from UPT
• Elevation of patients’ heads to 30 to 45° angle helps reduce aspiration of secretions as well as proper care of ventilation and respiratory equipment
• Deep breathing; frequent coughing
• Empiric antibiotic therapy started asap
• 1% of hospitalized people develop, often associated with mechanical ventilation via endotracheal or tracheostomy tube
• 30-50% mortality rate
• Staphylococcus aureus (usually MRSA)
• Klebsiella pneumoniae
• Enterobacter
• Escherichia coli
• Pseudomonas aeruginosa
• Acinetobacter
• Most cases are polymicrobial in origin

Mode of Transmission: Endogenous (aspiration)

Virulence: N/A

Culture/Diagnosis: culture of lung fluids

Prevention: Elevating patient’s head, preoperative education, care of respiratory equipment

Treatment: Varies by etiology

Epidemiological: United States: 300,000 cases per year; occurs in 0.5% to 1.0% of admitted patients; mortality rate in the United States and internationally is 20% to 50%

• Symptoms during prodromal phase: fever, chills, myalgias, hedache, n, v, d
• Cough is common, but not early symptom
• Soon, severe pulmonary edema and acute respiratory distress occur
• Severe breathing difficulties after hantavirus antigen spreads through blood

** virulence factor here is not the virus itself, but it causes overactivation of the immune system leading to respiratory distress and inflammatory response

Transmission and epidemiology:

• Airborne via dust contaminated with urine, feces, or saliva of infected rodents
• Incidence is increasing in areas of the United States, west of the Mississippi River

Treatment and prevention:

• Diagnosis through detection of IgM antibody to hantavirus or PCR techniques
• Supportive Care