INFECTIOUSINFECTIOUS

DISEASESDISEASES

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Categories of INFECTIOUS AGENTS• Prions

• *Viruses• Bacteriophages, Plasmids, Transposons

• *Bacteria

• Chlamidiae, Rickettsiae, Mycoplasmas

• *Fungi: Yeasts, Hyphae• Parasites: Protozoa, Worms, Arthropods

Classes of Human Pathogens and Their Habitats

Taxonomic SizeSite of

Propagation Sample Species DiseaseViruses 20–300 nm Obligate intracellular Poliovirus Poliomyelitis

Chlamydiae 200–1000 nm Obligate intracellular Chlamydia trachomatis Trachoma, urethritis

Rickettsiae 300–1200 nm Obligate intracellular Rickettsia prowazekii Typhus fever

Mycoplasmas 125–350 nm Extracellular Mycoplasma pneumoniae Atypical pneumonia

Bacteria 0.8–15 µm Cutaneous Staphylococcus aureus Wound

Mucosal Vibrio cholerae Cholera

Extracellular Streptococcus pneumoniae Pneumonia

Facultative intracellular Mycobacterium tuberculosis Tuberculosis

Fungi 2–200 µm Cutaneous Trichophyton sp. Tinea pedis (athlete's foot)

Mucosal Candida albicans Thrush

Extracellular Sporothrix schenckii Sporotrichosis

Facultative intracellular Histoplasma capsulatum Histoplasmosis

Protozoa 1–50 µm Mucosal Giardia lamblia Giardiasis

Extracellular Trypanosoma gambiense Sleeping sickness

Facultative intracellular Trypanosoma cruzi Chagas disease

Obligate intracellular Leishmania donovani Kala-azar

Helminths 3 mm–10 m Mucosal Enterobius vermicularis Enterobiasis

Extracellular Wuchereria bancrofti Filariasis

Intracellular Trichinella spiralis Trichinosis

PRIONS, “BSE” (Cows), “CJD”, Kuru (Humans)

NON-Nucleic Acid

PrP = Prion Protein

Diagnostic Test : NL-COW MAD-COW

http://www.youtube.com/watch?v=w5aAPEYIL9A

Bovine Spongiform Encephalitis, Creutsfeldt-Jakob Disease

VIRUSES• Less than ½ micron, usually MUCH

less

• DNA/RNA “CORE” (genome)

• Protein “CAPSID” (protein –NA “coat”)

• Sometimes a lipid “ENVELOPE”

• Limited number of genes coding for all other structures

• NO consistent naming system

RespiratoryAdenovirus Adenoviridae DS DNA Upper and lower respiratory tract

infections, conjunctivitis, diarrhea

Rhinovirus Picornaviridae SS RNA Upper respiratory tract infection

Coxsackievirus Picornaviridae SS RNA Pleurodynia, herpangina, hand-foot-and-mouth disease

Coronavirus Coronaviridae SS RNA SARS, URIs

Influenza viruses A, B

Orthomyxoviridae SS RNA Influenza

Respiratory syncytial virus

Paramyxoviridae SS RNA Bronchiolitis, pneumonia

DigestiveMumps virus Paramyxoviridae SS RNA Mumps, pancreatitis, orchitis

Rotavirus Reoviridae DS RNA Childhood diarrhea

Norwalk agent Caliciviridae SS RNA Gastroenteritis

Hepatitis A virus Picornaviridae SS RNA Acute viral hepatitis

Hepatitis B virus Hepadnaviridae DS DNA Acute or chronic hepatitis

Hepatitis D virus Viroid-like SS RNA With HBV, acute or chronic hepatitis

Hepatitis C virus Flaviviridae SS RNA Acute or chronic hepatitis

Hepatitis E virus Norwalk-like SS RNA Enterically transmitted hepatitis

Systemic with Skin EruptionsMeasles virus ParamyxoviridaeSS

RNA Measles (rubeola)Rubella virus Togaviridae SS

RNA German measles (rubella)Parvovirus Parvoviridae SS

DNA Erythema infectiosum, aplastic anemia

Vaccinia virus Poxviridae DS DNA Smallpox vaccine

Varicella-zoster virus Herpesviridae DS DNA Chickenpox, shingles

Herpes simplex virus 1 Herpesviridae DS DNA "Cold sore"

Herpes simplex virus 2 Herpesviridae DS DNA Genital herpes

Systemic with Hematopoietic DisordersCytomegalovirus Herpesviridae DS DNA Cytomegalic inclusion disease

Epstein-Barr virus Herpesviridae DS DNA Infectious mononucleosis

HTLV-I Retroviridae SS RNA Adult T-cell leukemia; tropical spastic paraparesis

HIV-1 and HIV-2 Retroviridae SS RNA AIDS

Arboviral and Hemorrhagic FeversDengue virus 1–4 Togaviridae SS RNA Dengue, hemorrhagic fever

Yellow fever virus Togaviridae SS RNA Yellow fever

Regional hemorrhagic fever viruses

Filoviridae SS RNA Ebola disease

Hantavirus SS RNA Korean pneumonia

Warty GrowthsPapillomavirus Papovaviridae DS DNA Condyloma; cervical carcinoma,

squamous proliferations in general

Central Nervous SystemPoliovirus Picornaviridae SS

RNAPoliomyelitis

JC virus Papovaviridae DS DNA

Progressive Multifocal Leukoencephalopathy (opportunistic)

Arboviral encephalitis viruses

Togaviridae SS RNA

Eastern, Western, Venezuelan, St. Louis

BACTERIOPHAGESPLASMIDS

TRANSPOSONS• INFECT BACTERIA, but may

make a bacteria more difficult to treat because it may

increase its “virulence” or its susceptibility to antibiotics

BACTERIA• GRAM staining with CRYSTAL VIOLET

– POSITIVE: THICK wall, ONE phospholipid layer

– NEGATIVE: THIN wall, TWO phospholipid layers

• SHAPE– COCCI (balls)– BACILLI (rods)

• OXYGEN requirements– AEROBIC (NEED O2)– ANAEROBIC (do NOT NEED O2)– “FACULTATIVE” AEROBIC, makes ATP if O2 is

present.

Species Frequent Disease Presentations

Infections by pyogenic cocci

Staphylococcus aureus, S.

epidermidis*Abscess, cellulitis, pneumonia, septicemia

Streptococcus pyogenes, β-hemolytic

Upper respiratory tract infection, erysipelas, scarlet fever, septicemia

Streptococcus pneumoniae (pneumoccoccus)

Lobar pneumonia, meningitis

Neisseria meningitidis (meningococcus)

Cerebrospinal meningitis

Neisseria gonorrhoeae (gonococcus)

Gonorrhea

Gram-negative infections, common

Escherichia coli Urinary tract infection, wound infection, abscess, pneumonia, septicemia, endotoxemia, endocarditis

Klebsiella pneumoniae “ Enterobacter (Aerobacter) aerogenes

“

Proteus spp. (P. mirabilis, P. morgagni)

“

Serratia marcescens “ Pseudomonas spp. (P. aeruginosa)

“

Bacteroides spp. (B. fragilis) Anaerobic infection

Legionella spp. (L. pneumophila) Legionnaires disease

Contagious childhood bacterial diseases

Haemophilus influenzae Meningitis, upper and lower respiratory tract infections

Bordetella pertussis Whooping cough

Corynebacterium diphtheriae Diphtheria

Enteropathic infections

Enteropathogenic E. coli Invasive or noninvasive gastroenterocolitis, some with septicemia

Shigella spp.

Vibrio cholerae

Campylobacter fetus, C. jejuni

Yersinia enterocolitica

Salmonella spp. (1000 strains)

Salmonella typhi Typhoid fever

Clostridial infections Clostridium tetani Tetanus (lockjaw)

Clostridium botulinum Botulism (paralytic food poisoning)

Clostridium perfringens, C. septicum

Gas gangrene, necrotizing cellulitis

Clostridium difficile Pseudomembranous colitis

Zoonotic bacterial infections

Bacillus anthracis Anthrax (malignant pustule)

Listeria monocytogenes Listeria meningitis, listeriosis

Yersinia pestis Bubonic plagueFrancisella tularensis Tularemia

Brucella melitensis, B. suis, B. abortus

Brucellosis (undulant fever)

Burkholderia mallei, B. pseudomallei

Glanders, melioidosis

Leptospira spp. (many groups)

Leptospirosis, Weil disease

Borrelia recurrentis Relapsing feverBorrelia burgdorferi Lyme borreliosisBartonella henselae Cat-scratch disease; bacillary

angiomatosisSpirillum minus, Streptobacillus moniliformis

Rat-bite fever

Human treponemal infections

Treponema pallidum Venereal, endemic syphilis (bejel)

Treponema pertenue Yaws (frambesia)

Treponema carateum (T. herrejoni)

Pinta (carate, mal pinto)

Mycobacterial infections

Mycobacterium tuberculosis, M. bovis (Koch bacillus)

Tuberculosis

M. leprae (Hansen bacillus)

Leprosy

M. kansasii, M. Avium (Complex), M. intracellulare

Atypical mycobacterial infections

M. ulcerans Buruli ulcerActinomycetaceae Nocardia asteroides Nocardiosis

Actinomyces israelii Actinomycosis

ChlamydiaeRickettsiae

Mycoplasmas• Like Bacteria, but…..

–NO cell wall (mycoplasma [MANY pneumonias])

–NO ATP (chlamydia [STD, worldwide blindness])

–NO life outside a cell (obligate intracellular, rickettsiae [RMSF])

FUNGI• YEASTS, HYPHAE

• CANDIDA, by far, the MOST PREVALENT ONE

• DERMATOPHYTES(superficial), (“tinea”), i.e., epidermophyton, trichophyton, microsporum

• DEEP FUNGI (GRANULOMAS)– HISTOPLASMOSIS

– BLASTOMYCOSIS

– COCCIDIOMYCOSIS

YEASTS, HYPHAE

PARASITES• PROTOZOA

• “META”-ZOA (HELMINTHS)

• “ECTO”-PARASITES, i.e., ARTHROPODS

PROTOZOA

• PLASMODIUM (MALARIA)

• LEISHMANIA• ENTAMOEBA • TRYPANOSOMA• TOXOPLASMA• GIARDIA

SINGLE CELL

INTESTINAL or BLOOD

Species Order Form, Size DiseaseLuminal or Epithelial

Entamoeba histolytica Amebae Trophozoite 15–20 µm Amebic dysentery; liver abscess

Balantidium coli Ciliates Trophozoite 50–100 µm Colitis

Naegleria fowleri Ameboflagellates Trophozoite 10–20 µm Meningoencephalitis

Acanthamoeba sp. Ameboflagellates Trophozoite 15–30 µm Meningoencephalitis or ophthalmitis

Giardia lamblia Mastigophora Trophozoite 11–18 µm Diarrheal disease, malabsorption

Isospora belli Coccidia Oocyst 10–20 µm Chronic enterocolitis or malabsorption or both

Cryptosporidium sp. Coccidia Oocyst 5–6 µm

Trichomonas vaginalis Mastigophora Trophozoite 10–30 µm Urethritis, vaginitis

BloodstreamPlasmodium species Hemosporidia Trophozoites, schizonts,

gametes (all small and inside red cells)

Malaria

Babesia microti, B. bovis Hemosporidia Trophozoites inside red cells Babesiosis

Trypanosoma species Hemoflagellates Trypomastigote 14–33 µm African sleeping sickness

IntracellularTrypanosoma cruzi Hemoflagellates Trypomastigote 20 µm Chagas disease

Leishmania donovani Hemoflagellates Amastigote 2 µm Kala-azar

Leishmania species Hemoflagellates Amastigote 2 µm Cutaneous and mucocutaneous leishmaniasis

Toxoplasma gondii Coccidia Tachyzoite 4–6 µm (cyst larger) Toxoplasmosis

HELMINTHS (ROUND[nematode]), FLAT[cestode])

• Roundworms, Tapeworms• Complex Life Cycles: sexual, asexual

• ROUNDWORMS (nematodes): ASCARIS, TOXOCARA (VLM), STRONGYLOIDES, ENTEROBIUS

• TAPE(FLAT)WORMS (cestodes): TAENIA (solium vs. saginata), DIPHYLLOBOTHRIUM, HYMENOLEPSIS

Ascaris life cycle

In small intestine TWICE

ARTHROPODS:INSECTS: = 6 legs

• LICE

• BEDBUGS

• FLEAS

ARACHNIDS: = 8 legs• MITES (chiggers)

• TICKS

• SPIDERS

CLASS INSECTA, 6 legs

C

R

A

B

L

O

U

S

E

L

O

U

S

E

BEDBUG

FLEA

CLASS ARACHNIDA, 8 legs

TICK ADULT MITE LARVAL MITE

BLACK

WIDOW BROWN

<--RECLUSE

SCABIES

BARRIERS• ALL ANATOMIC MUCOSAL

POSSIBILITIES–SKIN

–GI

–RESPIRATORY

–UROGENITAL

SPREAD• DIRECT EXTENSION

• LYMPHATICS

• BLOOD

• NERVE

SAME AS TUMOR?

RELEASE(TRANSMISSION)

• SKIN SHEDDING

• COUGHING/SNEEZING

• URINE

• FECES

• BLOOD

• VECTORS, e.g., insects, “zoonosis”

• “STDs” (Sexually Transmitted Diseases)

I=V/R

INFECTIVITY, GENERAL• AGENT HOST CELL

• AGENT TOXINS NECROSIS

• AGENTHOST CELLULAR REACTIONDAMAGE/DEATH

INFECTIVITY, VIRAL• ATTACHMENT• ENTRY• TRANSCRIPTION (forw./rev.)• TRANSLATION

– INCLUSIONS– REDUCED HOST CELL FUNCTION– CELL INJURY, LYSIS, DEATH– LATENCY– NEOPLASM?, aka, “transforming”

INFECTIVITY, BACTERIAL• ADHERENCE• ENTRY• TOXINS

–ENDO, Gram - , bacterial components (LPS)

–EXO, Gram -/+, secreted proteins

IMMUNE EVASION• INACCESSIBILITY to host defense (Mr.

Myagi, “no be there”)

• VARYING (mutating) antigens

• SHEDDING antigens, like jet or sub tactics

• RESISTING INNATE (NATURAL) immunity

• IMPAIRING T-CELLS

INFECTIONSof IMMUNOSUPPRESSED HOSTS• Protozoal/Helminthic:

Cryptosporidium, PCP (Pneumocystis Carinii [Jirovecii] Pneumonia), Toxoplasmosis

• Fungal: Candida, and the usual 3• Bacterial: TB, Nocardia, Salmonella• Viral: CMV, HSV, VZ

DIAGNOSTIC TECHNIQUES• DIRECT PATHOGEN IMAGING, gross/micro

• GRAM STAIN• “SPECIAL” (NOT H&E) STAINS, e.g., PAS• AGAR, e.g., CULTURES• TISSUE CULTURE, CPE (CytoPathological

Effect)• ANTIBODIES (SEROLOGY)• PCR, POLYMERASE CHAIN REACTION, e.g.,

viral “LOAD” amazingly specific and sensitive. WHY?

CELLULAR HOST RESPONSES

• SUPPURATIVE (NEUTROPHILS, PMNs) (cultures may be positive)

• MONO-NUCLEAR, i.e., Lymphocytes, Macrophages (i.e., Monocytes), GRANULOMAS

• FIBROSIS

• HEMOSIDERIN

• CALCIFICATION

ACUTE APPENDICITIS

ABSCESSABSCESS

CHRONIC “MONONUCLEAR” CHRONIC “MONONUCLEAR” INFLAMMATIONINFLAMMATION

GRANULOMA

FIBROSIS

H & E PRUSSIAN BLUE

H

E

M

O

S

I

D

E

R

I

N

CalcificationCalcification

The 4 Biggies•VIRAL•BACTERIAL•FUNGAL•PARASITIC

VIRAL• 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)

BACTERIAL•Gram+•Gram-• MYCO-bacteria• SPIROCHETES• ANAEROBIC• “OBLIGATE” INTRACELLULAR

FUNGAL• YEASTS

–CANDIDA

–CRYPTOCOCCOSIS

• MOLDS (HYPHAL)–ASPERGILLIS

–MUCORMYCOSIS (ZYGOMYCOSIS)

PARASITES•PROTOZOA (GI, BLOOD)

•METAZOA (WORMS)

VIRAL• TRANSIENT, ACUTE

–Measles: Skin, URI, Lung, GI, Cornea, Brain

–Mumps: Parotitis, Orchitis, Pancreas, CNS

–Polio: Myelitis (Anterior horn motor neurons)

–West Nile (arbo-): Meningoencephalitis

VIRAL• CHRONIC LATENT (HERPES FAMILY), HSV, CMV, VZ

–Herpes Simplex Virus

–CytoMegalo Virus

–Varicella-Zoster Virus (DRG)

HSV

CMV (HHV-5) pneumonia

BASOPHILIC

CONGENITAL

IMMUNOSUPPRESSED

VZ Virus

VIRAL• CHRONIC (HEPATITIS), Hep. A, B, C

–A, Mildest, most universal

–B, Most dangerous in the acute phase, but most are SUB-clinical

–C, Most common cause of persistent transaminitis

–D, E…

NORMALNORMAL LIVER

ACUTE VIRAL HEPATITIS

VIRAL“TRANSFORMING”

Epstein-Barr, EBV, lymphoma (Burkitts), nasopharyngeal

Human Papilloma, HPV, cervical cancer (squamous cell), types 16 and 18 are always at the top of the list!

MONONUCLEOSIS, caused by EBV

PHARYNX

NODES

SPLEEN

LIVER

HETEROPHILE

“MALIGNANT” cells on PAP smear, caused by HPV

BACTERIAL•Gram+ (Staph, Strep)•Gram- (rods)• MYCO-bacteria (TB)• SPIROCHETES (SYPHILIS)• ANAEROBIC (ABSCESSES)• “OBLIGATE” INTRACELLULAR

BACTERIAL• Gram+ cocci (Staph, Strep)

SKIN

RESPIRATORY TRACT

S

T

A

P

H

STREP:

SKIN

RESPIRATORY

ERISIPELAS

GRAM POSITIVE RODS

• DIPTHERIA

• LISTERIA

• ANTHRAX------• NOCARDIA

• CLOSTRIDIUM

GRAM NEGATIVE COCCI

•Neisseria–GONORRHEA

–MENINGITIS

GRAM NEGATIVE RODS

• Bordetella pertussis

• Pseudomonas aeruginosa

• Klebsiela/Aerobacter

• Yersinia pestis (plague)

• Hemophilus ducreyi (chancroid)

•E. COLI

MYCOBACTERIA(acid fast)

•Tuberculosis• “Atypical” mycobacteria, the

most important of which is MAC (Mycobacterium Avium Complex, in HIV patients)

• Leprosy

MORE ACID-FAST BACILLI, AFB (MAC)

SPIROCHETES•SYPHILIS (

Treponema pallidum)

• RELAPSING FEVER (Borrelia sp., via lice and ticks)

• LYME DISEASE (Borrelia burgdorferi, via deer ticks)

SYPHILIS• PRIMARY (CHANCRE)

• SECONDARY (MANY skin manifestations)

• TERTIARY (GUMMAS, CNS, BONE)

• CONGENITAL

ANAEROBES• Clostridium (Gram + bacillus)

–Cause of many/most cases of “gas” gangrene

“OBLIGATE”intracellular bacteria

• Chlamydia trachomatis– Conjunctivitis– LGV (LymphoGranuloma Venerium)– Urethritis

• Rickettsia (Rocky Mountain Spotted Fever, Typhus)

• Mycoplasma (very common cause of community acquired pneumonias)

RMSF

FUNGAL• YEASTS

–CANDIDA

–CRYPTOCOCCOSIS

• MOLDS (HYPHAL)–ASPERGILLIS

–MUCORMYCOSIS (ZYGOMYCOSIS)

Candida albicans• Oral

• Vaginal

• Esophageal

• All of the above are “moist” non-keratinized squamous mucosa, aren’t they?

• Immunocompromised, e.g., HIV, Diabetes

Budding Yeasts and “PSEUDO” hyphae

Budding cryptococcal yeasts, India ink prep, CSF

CRYPTOCOCCUSNEOFORMANS

MOLDS• Aspergillus

• Zygomycosis (Mucormycosis)

DERMATOPHYTES(“TINEAS”)

(superficial fungi)

•EPIDERMOPHYTON

•MICROSPORUM

•TRICHOPHYTON

SIGNIFICANT FUNGI(deep)

• HISTOPLASMOSIS, tiny granules within macrophages, ~3μ

• BLASTOMYCOSIS, ~20μ

• COCCIDIOMYCOSIS, ~50μ

PROTOZOA• MALARIA (Plasmodium sp., of which

falciparum is the most serius)

• Babesiosis, transmitted by deer tick,

• Leishmaniasis

• Trypanosomiasis (sleeping sickness)

• Chagas disease (also a trypanosome)

• Entamoeba histolytica

GAMETOCYTESAre COMMONAnd SAUSAGEshaped

SCHUFFNER‘S

DOTS

Affected RBC’s are NOT enlargedNO SCHUFFNER’s DOTS

SCHUFFNER‘S

DOTS

“comets”

TRYPANOSOMIASIS

METAZOA(ROUNDworms/FLATworms)

• Strongyloides (microscopic roundworm)

• Tapeworms (Beef, Pork, flatworm)• Trichinosis (larva in skeletal muscle)• Schistosomiasis (bladder cancer)• Filariasis (elephantiasis)

• VERY OFTEN, COMPLEX LIFE CYCLES

Ascaris life cycle