The classification of infectious pathogens seems to follow, more or less, the evolutionary tree. A bacteriophage is any one of a number of viruses that infect bacteria A plasmid is a DNA molecule that is separate from, and can replicate independently of, the chromosomal DNA A transposon is a DNA sequencethat can change its relative position (self-transpose) within the genome of a single cell
Note that Pathogens can also be classified as to whether they stay mucosal, extracellular, intracellular, or are “obligate intracellular”. I think you should be able to give an example of one of these categories in each taxonomic division.
Interest in “infectious” diseases caused by prions, i.e., NON-nucleic acid infectious agents, seems to be growing rapidly. PrP, also called prion related protein, or protease resistant protein, is the infectious substance, and discovering it led to a Noble Prize in 1997. PRI-ON itself Stands for PRO-teinaceous IN-fectious particle. Prions arise due to CONFORMATIONAL CHANGES in NORMAL prion proteins. The then cause conformational changes in OTHER normal prion proteins. Kuru is an incurable degenerative neurological disorder (brain disease) that is a type of transmissible spongiform encephalopathy, caused by a prion found in humans. Taken from the Fore word "kuria/guria", 'to shake'. It is also known as the laughing sickness due to the pathologic bursts of laughter people would display when afflicted with the disease. Kuru was probably transmitted among members of the Fore tribe of Papua New Guinea via cannibalism.
BSE, or “Mad Cow” diease is the animal counterpart to human CJD or Creutsfeld-Jakob Disease, also commonly called Jakob-Creutsfeld Disease. Vacoulization (sponginess) of CNS tissue is the consistent diagnostic finding (identify the vacuoles). Where are they? Cells? Fibers?
Nucleic acid “core”, capsid, envelope are the three common features of all viruses. Humans~20,000, Viruses~20, Bacteria~200 genes.
Most viral classifications are totally illogical, but can be based on 1) system or organ they may infect, 2) common name, 3) proper “family” name, 4) strandedness (single or double), 5) DNA vs. RNA, and 6) common site of infection.
The hepatitis viruses were named in the order in which the virus was discovered and isolated, A E
These primitive organisms are not often implicated in human diseases DIRECTLY, but indirectly. Great fleas have little fleas upon their backs to bite 'em, And little fleas have lesser fleas, and so ad infinitum. And the great fleas themselves, in turn, have greater fleas to go on; While these again have greater still, and greater still, and so on. A bacteriophage is any one of a number of viruses that infect bacteria A plasmid is a DNA molecule that is separate from, and can replicate independently of, the chromosomal DNA A transposon is a DNA sequence that can change its relative position (self-transpose) within the genome of a single cell
* Most common contaminant of blood cultures, staph epidermidis
ZOONOSES are infectious diseases in which a third party “animal” (ZOO) vector, usually mammal, is involved. This classification is INDEPENDENT of their gram staining abilities. Anthraxherbivores Listeriameats, dairy products Yersiniarodents Tularemiarabbits Brucelladairy products Burkholderiaequines, etc. Leptospiramany animals, urine, soil Borreliaticks, lice Bartonellafleas, etc. Spirillumrat
Gram + bacilli (rods) and Gram – cocci Remember the exception rule: All common Cocci are Gram+ EXCEPT for neisseria. Bacilli are Gram- EXCEPT for Bacillus (anthracis), Cornyebacterium, Clostridium, Lactobacillus, Listeria, Propionibacterium (acne) (ABCCLLP)
The OBLIGATE intracellular organisms, because they are obliged to live IN human cells to survive. They have no cell walls, and no mitochondria, and therefore no ATP.
Fungi occur in tissues, and are generally classified into superficial (i.e., skin dermatophytes), and deep.
Fungi, like bacteria, are also classified into balls and rods, but NOW they are called yeasts and hyphae, rather than cocci and bacilli. The balls may have budding balls as well.
ONE celled parasites are (Proto-zoans), multi-celled parasites (META-zoan) are worms (i.e., helminths) and arthropods
Leishmaniasis is a disease caused by protozoans that belong to the genus Leishmania and is transmitted by the bite of certain species of sand flies. Often infects skin and soft tissues but may go deeper. Amoebiasis, or Amebiasis, refers to a diarrheal infection caused by the amoeba Entamoeba histolytica Trypanosomiasis or trypanosomosis is the name of several diseases caused by trypanosomes of the genus Trypanosoma. 36 countries of sub-Saharan Africa suffer from trypanosomiasis which is caused by either Trypanosoma brucei gambiense or Trypanosoma brucei rhodesiense. The other human form of trypanosomiasis, called Chagas Disease, causes 21,000 deaths per year mainly in Latin America Toxoplasmosis is a disease in cats and humans caused by the protozan Toxoplasma gondii. Giardiasis in humans is a diarrtheal infection of the small intestine by a single-celled organism Giardia lamblia.
You can also classify PROTOZOAN infections on the basis of HOW DEEP they go. LUMEN EPITHELIUM BLOOD INTRACELLULAR
Classical (top 4) human helminth diseases Key points of differentiation: Round or Flat, whole or segmented, nematodes or cestodes, Phylum Nematoda or Platyhelminthes. Does the phylum Annelida have many human parasites? NO
Ascaris (lumbricoides) life cycle, the most common and clinically important roundworm parasite in the world. Notice the difference between the friendly (non-government) diagram and the CDC confusing version!
Taenia solium (cysticercosis) life cycle: Scolex, Proglottids.
T solium, T saginata, D latum, H nana. Corresponding To Beef, Pork, Fish, and arthropod co-hosts, respectively. Do you get the feeling of columnar, cuboidal, and squamous geometries here, regarding the proglottids? Because quick ID of the parasite is usually based on proglottid identification: BIG COW = TALLEST MEDIUM PIG = CUBOIDAL DWARF (tapeworm) = most SQUAMOUS
What are “chiggers”? What is a phylum, what is a class?
Scabies is a MITE, causes a HUGE array of dermatoses, but the most likely place to ID them on a scrape is the dorsal M-P area.
Is it surprising that the most common anti-pathogen areas are also the same as the epithelia and mucosae protecting humans from EVERYTHING nasty? Is it also surprising that these areas are also rich in MALT? (Mucosal Associated Lymphoid Tissue)
Infectious agents spread geographically in the body exactly via the same routes which tumor cells do. Is this surprising? NO!
“WASH YOUR HANDS!” is the sign seen everywhere! Does an STD transmission overlap with several of the previous? It is surprising that the transmission routes are the same as the barrier locations? Ans: NO
A pathogen’s “I”nfectivity is DIRECTLY proportional to its intrinsic “V”irulence, and inversely proportional to its host’s “R”esistance. Does this look like Ohm’s law, I=V/R? Which of these three letters is the primary one in diseases of immunocompromised hosts?
An infectious “agent” can attack a host cell directly, damage a host cell by its toxins, or by creating a host inflammatory response which damages host tissues, so in this last case, an inflammatory reaction against a pathogen can actually cause further damage to the host. Can you think of any other possible ways a pathogen, any pathogen, can do damage? Not me.
Can you think of ANY other thing a virus can do? I can’t. Is infectivity the same as “virulence”? Sorta
Main concepts of an infectious agent’s immune evasion. Do these also look like mechanisms for tumor proliferation? You betcha?
By no surprise the common infections in immunosuppressed hosts theoretically, parallels the common opportunistic infections seen in AIDS patients. ANY usually non infective pathogen can do damage in immunocompromised (immunosuppressed) hosts, BUT here are the most likely ones!
Common diagnostic techniques for identifying infectious agents.
The spectrum pattern of host responses parallels the entire spectrum of ALL inflammatory morphologies. Notice these are all TYPICAL of ANY acute or chronic inflammatory process and NOT specific for infectious pathogens.
Does a specific organism cause this? NO Is it related to lack of blood flow and necrosis and secondary enteric invaders? YES Does the “acuteness” histologically relate to “acuteness” clinically as well? USUALLY
Is an abscess nothing more than a walled off or localized pocket of pus?
A CHRONIC inflammatory reaction is LESS likely to culture organisms than an ACUTE one. Why? Would I blame you if you called this “organizing” rather than “chronic”? Ans.: NO
Granulomatous reactions are commonly seen with mycobacteria, fungi, sarcoid, foreign bodies, and rarely with almost anything. Acid fast or fungal cultures are routinely done in granulomas and may possibly be positive in “fresh” granulomas, gram positive or gram negative bacteria are NOT common causes of granulomas. A granuloma which has a lot of fibrosis or calcification, is not “fresh” and much less likely to yield organisms.
Fibrosis often follows ANY kind of inflammatory process. Would this type of pattern imply ACUTE exposure to the pathogen? Ans.: NO
Hemosiderin (old hemorrhage) often accompanies fibrosis. Dystrophic or metastatic? Ans: Dystrophic
Calcification! Would a DENSELY calcified granuloma, seen radiologically, be likely to be active, or infectious, or yield positive cultures? NO! Why is this pic a great example of calcification, but a poor example of an infectious process?
Four types of common viral infections, classified clinically: 1) Transient acute, 2) Chronic latent, 3) Chronic, 4) Transforming. There is no consistent uniformity for viral taxonomy, so viral diseases can be classified according to their severity and/or acuteness or recurrence or sequelae of clinical expressions. Luckily, the classification is NOT based on viral taxonomy.
The common types of bacteria which infect humans. This is not at all a totally logical classification.
Morphologic types of fungi: yeasts and mold, independent of whether they are superficial, deep, or systemic. Coincidentally, just at bacteria are classified as balls (cocci) or rods (bacilli), fungi are morphologically classified into balls (yeasts) or rods (hyphae).
Protozoans are single celled organisms. Although metazoans technically are any multicellular organisms, they are often generally used synonymously with the word “worms”.
Classical viral infections which are TRANSIENT and ACUTE
Measles “giant” cell in measles pneumonia. The measles virus is a highly contagious airborne pathogen which spreads primarily via the respiratory system. The virus is transmitted in respiratory secretions, and can be passed from person to person via aerosol droplets containing virus particles, such as those produced by a coughing patient. Once transmission occurs, the virus infects the epithelial cells of its new host, and may also replicate in the urinary tract, lymphatic system, conjunctivae, blood vessels, and central nervous system. What are Koplik’s spots?
Parotitis, orchitis. Mumps (infectious or epidemic parotitis is a viral disease of the human species, caused by the mumps virus. Before the development of vaccination and the introduction of a vaccine, it was a common childhood disease worldwide. It is still a significant threat to health in the third world, and outbreaks still occur sporadically in developed countries. Spread via respiratory secretions also.
Poliovirus enters the body through the mouth (primarily fecal-oral), infecting the first cells it comes in contact with—the pharynx and intestinal mucosa. It gains entry by binding to a immunoglobulin-like receptor, known as the poliovirus receptor or CD-155, on the cell surface. The virus then hijacks the host cell’s own machinery, and begins to replicate. Poliovirus divides within gastrointestinal cells for about a week, from where it spreads to the tonsils (specifically the follicular dendritic cells residing within the tonsilar germinal centers), the intestinal lymph nodes including the M cells of Peyer’s patches, and the deep cervical and mesenteric lymph nodes, where it multiplies abundantly. The virus is subsequently absorbed into the bloodstream. The most feared consequence would be infections of the anterior horn cell neurons, and most deaths occurred due to diaphragm involvement.
Lymphocytic infiltrates in the “Virchow-Robbins” space IS classic for encephalitis. Notice that even though the clinical expression of “acute” encephalitis is acute, most of the inflammatory cells are “chronic”, i.e., “mono”-nucleated cells.
These viruses are all in the “Herpes” family and are CHRONIC and LATENT, often recurrent, and often travel along nerves and involve skin. What does ubiquitous mean?
Intranuclear INCLUSIONS and VESICLES are charactistic of herpes family viruses, herpes, varicella, zoster, CMV. Herpes doe NOT mean vesicle, it means SNAKE, because of the slithering pattern of the vesicles.
The intranuclear inclusions of herpesvirus CMV are characteristically describes as BASOPHILIC, as opposed to the inclusions of Herpes simplex and zoster which are EOSINOPHILIC. Are these inclusions the viruses themselves? NO Why? No virus is bigger than ½ micron! Could the BASOPHILIC intranuclear inclusions have viruses IN THEM however? YES!
VZ is so named because it causes both Chicken Pox (Varicella) in children, and Heepes Zoster (shingles) in adults. The neurotropic virus in adults travels along dermatome routes, and is famous for being latent often for many years, with occurrences related to immune impairment conditions. VZ loves to hang out in DRG’s! (Dorsal Root Ganglia)
The hepatitis viruses are classified as chronic! Are B and C the most likely to cause cirrhosis and hepatoma? YES
Which area do you think would bear the brunt of an early hepatitis infection, the are around the PORTAL vein, or the area around the CENTRAL vein? Ans: PORTAL
The arrowed “Councilman” bodies are thought by some to be rather diagnostic of viral (B) hepatitis. They are apoptotic hepatocytes. The inflammatory pattern is periportal at first but can soon become PAN-lobular. Chronic hepatitis is chiefly periportal.
Transforming viruses cause tumors.
“Mono” is severe pharyngitis, adenopathy, splenomegaly, and hepatitis. The classical “mono” cells are really lymphocytes, and “heterophile” antibodies are fairly diagnostic. “Hetero”-phile means crossing species, i.e., human antibodies causing horse RBC agglutination.
Bridging the gap between infection and neoplasms, HPV viruses cause squamous cell cancer of the cervix. Can you say then that squamous cell cancer is a STD or at least infectious disease? YES Could these cells be only CIN-III or HSIL or CIS only?
Gram + bacilli (rods) and Gram – cocci Remember the exception rule: Cocci are Gram+ EXCEPT for neisseria. Bacilli are Gram- EXCEPT for Bacillus (anthracis), Cornyebacterium, Clostridium, Lactobacillus, Listeria, Propionibacterium (acne) (ABCCLLP)
Common STAPH infections
A strep infection in immunocompromised hosts, often the very old and very young.
Diphtheria (Greek διφθέρα (diphthera) "pair of leather scrolls") is an upper respiratory tract illness caused by Corynebacterium diphtheriae, a facultative anaerobic, Gram-positive bacterium. It is characterized by sore throat, low fever, and an adherent membrane (a pseudomembrane) on the tonsils, pharynx, and/or nasal cavity. A milder form of diphtheria can be restricted to the skin. Less common consequences include myocarditis (about 20% of cases) and peripheral neuropathy (about 10% of cases). Listeriosis, a serious infection caused by eating food contaminated with the bacteria. The disease affects primarily pregnant women, newborns, adults with weakened immune systems, and the elderly. Bacillus anthracis can form dormant endospores (often referred to as "spores" for short, but not to be confused with fungal spores) that are able to survive in harsh conditions for decades or even centuries. Such spores can be found on all continents, even Antarctica. When spores are inhaled, ingested, or come into contact with a skin lesion on a host, they may become reactivated and multiply rapidly, usually lethal. Nocardia are found worldwide in soil that is rich with organic matter. In addition, Nocardia are oral microflora found in healthy gingiva as well as periodontal pockets. Most Nocardia infections are acquired by inhalation of the bacteria or through traumatic introduction. Clostridium: botulinum, dificile, perfringens, tetani
“MAC” is the most common and serious “atypical” mycobacterium, seen very often in AIDS patients.
Necrotizing (i.e., caseating) granulomas filled with acid fast bacilli. This is CLASSIC for TB.
The acid fast stain for acid fast bacteria is also called the Ziehl-Neilson stain, or simply AFB stain
Relapsing fever is an infection caused by certain bacteria in the genus Borrelia. It is a vector-borne disease transmitted through the bites of lice or soft bodied ticks.
A leading cause of worldwide blindness, this keratoconjunctivitis affects 100 million people world wide. It is spread by direct contact with infected individuals, such as towels. Trachoma is the Greek word for “rough eye”.
The agent of RMSF is an obligate intracellular Rickettsia rickettsii organism carried by the tick Dermacentor andersoni and Dermacentor variabilis, evoking microvasculitis and thrombosis of small vessels. Other rickettsia (prowazekii, typhi)cause typhus.
Yeasts are balls, hyphae are long cylindrically shaped structures, often arising from yeasts. Think of FOUR things when you hear FUNGUS: BALL (yeast) vs. ROD (hyphae) Superficial (i.e., dermatophyte, i.e., tinea) vs. Deep (Big 3: Histo-, Blasto-, Coccidio-) Probably granulomatous infection Immunocompromised host?
Without a doubt, by far, the most common and ubiquitous of all fungal agents.
Classical patterns of Candida, budding yeasts and PSEUDO-hyphae, staining very RED with the PAS stain and many others. The upper photo of budding yeasts could be from a culture because it has no tissue in it. Why are these termed, by the purists, as “pseudo”-hyphae? Ans: NO septae
India ink preps have been a standard part of CSF fluid taps for many years, especially in meningitis workups. These can be done within a minute of a LP with the simplest of reagents (i.e., India ink and microscope).
Both of these “mold” (hyphal) diseases can cause human diseases often in immunocompromised hosts.
Submit this to memory.
Tinea capitis, or Ringworm of scalp
Tinea corporis, or Ringworm of body
Tinea cruris, or jock itch
Tinea pedis, or Athlete’s foot. Is the 4-5 interspace by far the most common location? YES Is the 5th toe the most like to undergo frosbite or ischemic necrosis?
Onychomycosis What are the three most common specific organisms? ANS: the same as the one which cause ANY tinea!
These usually evoke granulomatous reactions in tissues. Histoplasmosis organisms are very small and often pack histiocytes, blastomycosis and coccidiomycosis are much larger round balls.
Histoplasmosis, best lab stain you will ever see, thanks to somebody on the Patho-L internet forum. I wish I could remember her name.
These should all be recognized as protozoal diseases.
Anopheles species mosquito of malaria
Do not make the mistake of confusing an overlying platelet with a malarial organism on a RBC. 250 million cases per year, world-wide, a health problem of immense importance! Gametes fusing starts a SEXUAL cycle. Sporozoites, merozoites multiplying is an ASEXUAL cycle.
The various types of malaria are differntiated by the appearance of the RBCs and the forms of the parasites in them. Plasmodium falciparum is potentially the most deadly, and is gives rise to “blackwater fever”, i.e., marked hemoglobinuria and renal failure. Gametocytes (upper) are commonly seen in falciparum, much more commonly than in any of the other 3 varieties.
“Comets” are rather diagnostic of P. ovale.
This is a very serious concern in Africa, in which the bite of the tsetse fly transmits the protozoan. This is a classical diagnostic appearance on a routine blood smear. South American trypanosomiasis is called “Chagas” disease.
Ascaris life cycle: Very simple: Larvae to MouthDuodenumBloodLiverHeartPulmonarySmall IntestineFertilizationSoil
• Less than ½ micron, usually MUCH
• DNA/RNA “CORE” (genome)
• Protein “CAPSID” (protein –NA “coat”)
• Sometimes a lipid “ENVELOPE”
• Limited number of genes coding for all
• NO consistent naming system
Upper and lower respiratory tract
infections, conjunctivitis, diarrhea
Upper respiratory tract infection
Pleurodynia, herpangina, handfoot-and-mouth disease
viruses A, B
Orthomyxoviridae SS RNA
Paramyxoviridae SS RNA
Paramyxoviridae SS RNA
Mumps, pancreatitis, orchitis
Hepatitis A virus
Acute viral hepatitis
Hepatitis B virus
Hepadnaviridae DS DNA
Acute or chronic hepatitis
Hepatitis D virus
Hepatitis C virus
With HBV, acute or chronic
Acute or chronic hepatitis
Hepatitis E virus
Systemic with Skin Eruptions
German measles (rubella)
Herpes simplex virus 1 Herpesviridae
Herpes simplex virus 2 Herpesviridae
Systemic with Hematopoietic Disorders
Herpesviridae DS DNA
Cytomegalic inclusion disease
Herpesviridae DS DNA
HIV-1 and HIV-2
Dengue virus 1–4
Yellow fever virus
Adult T-cell leukemia; tropical
Arboviral and Hemorrhagic Fevers
Togaviridae SS RNA
Dengue, hemorrhagic fever
Togaviridae SS RNA
Regional hemorrhagic Filoviridae
Hantavirus SS RNA
Papillomavirus Papovaviridae DS DNA Condyloma; cervical carcinoma,
squamous proliferations in
Central Nervous System
Venezuelan, St. Louis
• INFECT BACTERIA, but may
make a bacteria more difficult
to treat because it may
increase its “virulence”
or its susceptibility to
• GRAM staining with CRYSTAL VIOLET
– POSITIVE: THICK wall, ONE phospholipid layer
– NEGATIVE: THIN wall, TWO phospholipid
– COCCI (balls)
– BACILLI (rods)
• OXYGEN requirements
– AEROBIC (NEED O2)
– ANAEROBIC (do NOT NEED O2)
– “FACULTATIVE” AEROBIC, makes ATP if O2 is
Human treponemal Treponema pallidum
Venereal, endemic syphilis
Treponema carateum (T. Pinta (carate, mal pinto)
M. leprae (Hansen
M. kansasii, M. Avium
tuberculosis, M. bovis
• Like Bacteria, but…..
– NO cell wall (mycoplasma [MANY
– NO ATP (chlamydia [STD, worldwide
– NO life outside a cell (obligate
intracellular, rickettsiae [RMSF])
• YEASTS, HYPHAE
• CANDIDA, by far, the MOST
(“tinea”), i.e., epidermophyton,
• DEEP FUNGI (GRANULOMAS)
• TRANSIENT, ACUTE, e.g. Measles,
Mumps, Polio, West Nile
• CHRONIC LATENT (HERPES
FAMILY), HSV, CMV, VZ
• CHRONIC (HEPATITIS), Hep A, B, C
• “TRANSFORMING” (Epstein-Barr
EBV, Human Papilloma, HPV)
• MALARIA (Plasmodium sp., of which
falciparum is the most serius)
• Babesiosis, transmitted by deer tick,
• Trypanosomiasis (sleeping sickness)
• Chagas disease (also a trypanosome)
• Entamoeba histolytica