How Are Infectious Agents Classified?
Where can they grow and what inflammatory response do they produce?
Extracellular organisms: propagate outside of human cells; elicit
primarily an acute inflammatory reaction with PMN's with formation of an exudate
most bacteria many fungi multicellular parasites
Obligate intracellular organisms: require host cell machinery to
propagate; elicit a chronic inflammatory reaction with mostly mononuclear cell
infiltrates in tissues
viruses chlamydia rickettsia
Facultative intracellular organisms: can propagate outside of host cells
if necessary; produce a granulomatous response
mycobacteria pathogenic fungi unicellular parasites
How and where do they get into tissues? The signs and symptoms may point
to a particular site or organ system:
Ingested into the gastrointestinal tract, with abdominal pain, nausea, vomiting, diarrhea, melena - micro-organisms contaminating food or water (Shigella, Salmonella, Vibrio cholerae) Inhaled into the respiratory tract, with cough, chest pain, dyspnea, hemoptysis - micro-organisms in the air that is breathed Ascend into the urinary tract, with dysuria, hematuria, pelvic pain, flank pain - micro-organisms that get into the bladder via the urethra (or via a catheter) and can ascend as far as the kidneys Ascend into the biliary tree, with vague abdominal pain, jaundice - micro-organisms that gain access to the common bile duct from the gastrointestinal tract and can ascend as far as the intrahepatic ducts of the liver Cross mucosal surfaces, with local irritation, ulceration, pain, or late sequalae only - micro-organisms penetrate oral, anal, genital, or conjunctival mucosae (human papillomavirus, human immunodeficiency virus, herpes simplex virus, Neisseria gonorrheae)
Trauma - direct spread - micro-organisms are directly inoculated into
wound sites
How do they spread within the body?
Travel via the bloodstream - septicemia
Travel via the lymphatics - enlarged, tender lymph nodes suggest possible
infection at the site from which the lymphatics drain
Travel via a body cavity - can spread in the CSF, peritoneal fluid, joint
space, etc.
Cross the placenta to the fetus - basis for congenital infection
When does infection occur?
Colonization: the presence of organisms on a body surface or in a lumen,
but not producing disease
all persons have bacteria (and some fungi) on skin surfaces or in the oral
cavity. this complicates interpretation of culture results, because you must be
aware of the possibility of contamination of a specimen in the collection
process (e.g., did you have aseptic technique when the blood culture was drawn? Is the sputum specimen mostly oral flora?)
Invasion: organisms have moved into tissues to cause disease Virulence: the ability of an organism to cause infectious disease
some organisms, such as Staphylococcus epidermidis, diptheroids, or
Entameba nana, are unlikely to cause disease some organisms, such as Vibrio cholerae, Salmonella typhi, Mycobacterium
tuberculosis, or Yersinia pestis (plague) are highly infectious and potentially fatal
Resistance: the ability of the host to prevent infection from occurring
and infectious disease from developing. Resistance is normally aided by:
barriers to infection: intact, functional epithelial surfaces (mucociliary apparatus of respiratory tract, gastric mucosal acid production, antibacterial action of bladder mucosal secretions and saliva of oral cavity) immune system (inflammatory cells such as neutrophils and lymphocytes, as
well as immune globulins) normal anatomical structure (e.g., intact epithelium is a good barrier)
Resistance is diminished by:
debilitation from malnutrition (poor diet, alcoholism) neoplasia poorly functioning immune system (congenital or acquired) drug therapy - corticosteroids, antibiotics previously damaged or abnormal anatomical structure from congenital,
circulatory, infectious, autoimmune disease, etc., particularly with obstruction
of any lumen or orifice
How is infection diagnosed?
Gram stain and Culture: obtain a sample of exudate or body fluid, answer
in minutes (gram stain) to hours to days (culture) for bacteria, weeks for
mycobacteria
requires collection of the specimen with the appropriate devices requires filling out the proper laboratory request forms (the lab is not able to "do everything" on every submitted sample) requires setting up the cultures on the appropriate media
View Gram stain diagrams
Serology: used for organisms that are difficult (viruses) to culture;
answer in hours to days
can be "paired sera" with an initial "acute" titer followed by a "convalescent" titer in about 2 weeks to determine if there is a rise in antibody to a specific organism can differentiate the titer according to either IgG or IgM antibody. IgG
antibodies can persist for months to years, so they only give an indication of
some past infection. IgM antibodies tend to appear only with acute infection.
Thus, hepatitis A virus serologies are generally ordered as IgG and IgM to
determine if there has been recent infection.
Microscopy: cytology or tissue biopsy used when morphologic appearance is
diagnostic (fungi, Pneumocystis); answer in minutes (frozen section) to a day
the pattern of inflammation can be helpful in searching for infectious
agents; a variety of special stains can be done (PAS, GMS, acid fast, tissue
gram stain, etc) staining of the organisms with an antibody tagged with a fluorescent dye (direct fluorescence antigen detection) is a quick means for diagnosis though organisms can be identified, speciation and antibiotic sensitivities cannot be determined
Molecular probes: using markers for the genetic material in micro-organisms
Epidemiology in infectious diseases
Statistical review of infectious disease cases
prospectively: each state has a list of diseases that MUST be reported to
the health department by YOU the health care worker. Statistics can be compiled
in regard to incidence and distribution (age, geography, season, etc) retrospectively: medical records can be reviewed, laboratory reports
analyzed, patients followed up, or anatomic pathology material (surgical
pathology, autopsy records) reviewed
Patterns of infectious disease can be determined over time
some infections (such as rotavirus) are more common in the spring and
summer, while others (such as influenza) are more common in winter; this alerts
you to the need to be aware of such seasonal changes and what the more likely
diagnoses will be in your patients. geographic localization of infections help to determine where prevention
strategies or treatment programs should be employed, or help to localize a
source of infection (such as a contaminated well or a restaurant) a sharp increase in cases can alert the health department to the need to
identify a potential epidemic in the making
Epidemiologists and public health department workers can collect additional data:
interview infected persons to determine how, when, and where they became
infected follow up contacts of infected persons (such as sexual partners of persons with sexually transmitted diseases (STD's) such as gonorrhea, syphilis, and HIV test food and water, or test animal vectors, for presence of infectious agents
A course of action is taken (quarantine, immunization program, closure of a business or facility, specific treatment of contacts or a subset of the population, etc.)
Review of Pathologic Findings with Infectious Agents
BACTERIAL INFECTIONS
How do bacteria cause disease? Here are some examples:
Growth in tissues destroys the tissues from release of proteolytic enzymes Release of exotoxins
Vibrio cholerae - severe watery diarrhea Corynebacterium diptheria - growth promotes elaboration of a myocardial
toxin Staphylococcus aureus - acute self-limited diarrhea
Release of endotoxins
gram negative bacteria such as E. coli and Klebsiella are most prone to do this attract neutrophils, cause fever, can produce shock
Antigens are similar to host antigens, generating immune reaction:
Group A Streptococcus producing post-streptococcal glomerulonephritis and
rheumatic heart disease
Appearances
Microscopic: primary cellular response is neutrophils (chemotactic
factors include C5a, leukotrienes, HPETE) which is non-specific and destructive
Gross: redness, swelling, purulent exudate (pustule, abscess), necrosis
Clinical: fever (interleukin), pain (bradykinin, prostaglandin),
increased WBC count
Sites of infection and organisms involved
Skin infection
Staphylococcus aureus - impetigo Streptococcus - often due to hemolysins, toxins, and streptolysins
elaborated by the bacteria Vibrio vulnificans - necrotizing skin infection with sepsis
Respiratory tract Gastrointestinal tract
Salmonella typhi - typhoid fever with longitudinal ulcers of small
intestine (mononuclear inflammation), neutropenia, and splenomegaly Vibrio enteropathogenic E. coli - "traveler's diarrhea" - enterotoxin
produces diarrhea similar to, but not as severe as, cholera; can be life-threatening in infants and children Shigella - bacillary dysentery from superficially invasive bacteria with
ulceration of colon Helicobacter (Campylobacter) pylori - gastritis Clostridium difficile - pseudomembranous colitis from enterotoxin when
normal gut flora diminished by antibiotic therapy food poisoning
Staphylococcus aureus - enterotoxin - diarrhea hours after ingestion Salmonella - diarrhea and cramps 1 to 2 days after ingestion of bacteria Clostridium botulinum - botulism with paralysis from neurotoxin in poorly
prepared food
Urinary tract Genital/congenital
Neisseria gonorrheae - gonorrheal infection Streptococcus - group B strep with stillbirth and neonatal infection Listeria monocytogenes - chorioamnionitis with abortion, stillbirth, or
neonatal sepsis with meningitis
Heart (endocardium): infection arrives from bloodstream and settles on
valve, producing a vegetation; aided by presence of an anatomically abnormal
valve or a large inoculum (intravenous drug use)
Staphylococcus aureus Streptococcus Pseudomonas
Meninges: infection arrives from bloodstream, from sinuses, or via direct
trauma
E. coli - neonatal Streptococcus group B - neonatal Hemophilus influenzae - in children Neisseria meningitidis - starts inocuously in nasopharynx, can lead to
disseminated intravascular coagulopathy (DIC) and adrenal hemorrhage and
necrosis (Waterhouse-Friedrichson syndrome) Streptococcus pneumoniae - in older persons
VIRAL INFECTIONS
Viruses must attach to, enter into, and replicate within host cells; once
established in the target organ, a viremia can result wtih dissemination. Forms
of infection can include:
Abortive infection: the infection does not take hold Acute infection: self-limited, such as a cold or flu Latent infection: the virus is present but not actively producing demonstratable disease (typical for varicella-zoster virus or human immunodeficiency virus) Persistent infection: the virus continues to proliferate without
extensive cellular destruction (typical of chronic active hepatitis)
Morphologic appearances
No characteristic gross or clinical appearance of viral infection
Microscopic appearance characterized by interstitial lymphocytic
infiltration (as a result of cell-mediated immune response) and characteristic
viral cytopathic effects:
Herpesviruses
Herpes simplex genitalis: genital vesicles Herpes simplex labialis: cold sores Varicella-zoster virus
Herpes zoster: "shingles" seen peripheral nerves from long
latent infection activated in debilitated adults Varicella zoster: chicken pox in kids is a mucocutaneous, asynchronous
vesicular disease
Cytomegalovirus: either a congenital infection or an opportunistic
infection (as in AIDS) Human herpesviruses 6, 7, and 8: HHV-6 and HHV-7 have been associated with the skin lesion known as exanthem subitum, while HHV-8 is associated with the development of Kaposi's sarcoma
Epstein-Barr virus
Infectious mononucleosis: lymphadenopathy and hepatosplenomegaly in young
adults; rarely hepatitis Neoplasia: African Burkitt's lymphoma, nasopharyngeal carcinoma
Human papillomavirus (HPV) - associated with epithelial dysplasia and
neoplasia (such as cervical dysplasias and cervical cancer) in genital and oral
regions of infection
Poliovirus: affects anterior horn cells of spinal cord and brainstem to
produce paralysis
Rotavirus: produces mild diarrhea (half of childhood cases in U.S.)
Viral pneumonias: a whole host of viruses can produce pneumonitis and can
be difficult to diagnose; bacterial pneumonias often follow. Culture is
expensive and often of low yield. Serology may be helpful. Patient is usually
given supportive therapy until infection subsides. Knowing the actual cause may
not help clinically, but may be of value epidemiologically (to track and prevent
influenza epidemics). The most common viral pneumonias are:
Influenza Adenovirus Respiratory syncytial virus (in children)
Human retroviruses: human immunodeficiency virus (HIV) and human T
lymphocytotrophic viruses (HTLV); attack immune system
FUNGAL INFECTIONS
Candida: found commonly on skin, in oral cavity, in vagina, and sometimes
in GI tract but usually justs sits on the epithelial surface. Produces disease
when it becomes invasive (in debilitated or immunosuppressed individuals).
Inflammatory response is more neutrophilic than granulomatous.
Pathogenic fungi: have an environmental form and a tissue form at 37o C; many are inhaled and produce pulmonary disease; can disseminate in
immunocompromised persons; produce tissue granulomas
Histoplasma capsulatum: histoplasmosis, small fungi like to grow in
macrophages; endemic to Mississippi and Ohio river valleys Cryptococcus neoformans: cryptococcosis, narrow-based budding fungi have
big mucoid capsules that show up with India ink prep; produces pneumonia and/or
meningitis; no specific geographic distribution Coccidioides immitis: coccidioidomycosis produced by big fungal
spherules; endemic to desert southwest (mainly Arizona, California) Blastomyces dermatitidis: blastomycosis is rare and produced by
broad-based budding organisms (seen in North America) Paracoccidioides brasiliensis: paracoccidioidomycosis with mucocutaneous
granulomas produced by organisms with multiple budding (seen in South America)
Mucormycosis: these are the "true" fungi in three genera (Mucor, Rhizopus, Absidia) that all look and act similarly in tissue with broad, short, non-septate hyphae. Acquired in hospital by diabetics and immunosuppressed
patients.
Aspergillosis: several species of Aspergillus cause human disease
characterized by pulmonary involvment and rare dissemination; produces narrow
branching septate hyphae in clusters or balls; likes to colonize debilitated and
immunocompromised patients, particularly with pre-existing lung disease
Allergic form: non-invasive Aspergillus produce bronchial asthma Colonizing form: Aspergillus grows in old lung cavities Invasive form: Aspergillus loves to invade blood vessels
MYCOBACTERIAL INFECTIONS
Granulomatous disease - formation of granulomas with epithelioid cells, giant cells, lymphocytes, fibroblasts as a result of cell-mediated immune response
M. tuberculosis (MTB)
Pulmonary disease
primary - children - Ghon complex (peripheral mid-lung granuloma with large hilar nodes); only a few persons develop severe disease, the majority heal and calcifiy, but a few organisms remain secondary - reactivation tuberculosis - adults - cavitation
Disseminated tuberculosis - miliary tuberculosis, either in lung or in
distant organs Debilitation and malnutrition favor development of disease; clinically
active tuberculosis characterized by fever, night sweats, weight loss
"Atypical" mycobacteria
M. kansasii - acts like MTB M. avium-intracellulare (MAI) - seen in AIDS M. bovis - GI tract granulomas
M. leprae: Leprosy (Hansen's disease) characterized by poor transmissibility (takes years of contact) and slow course. Diagnosed by skin biopsy. There are two forms:
Lepromatous leprosy - poor immune response, dissemination, marked skin and nerve involvement Tuberculoid leprosy - better immune response with localized skin and nerve involvement
SPIROCHETAL INFECTIONS
Syphilis - produces characteristic chancre in primary stage, skin rash in
secondary stage, and several possible complications years later in tertiary
stage:
Primary: chancre (a sharply demarcated ulcer) appears in a couple of
weeks in 1/3 to 1/2 of patients Secondary: mucocutaneous rash appears in a couple of months in a few
patients; plasma cell infitrates are characteristic Tertiary: systemic complications develop years to decades later in a
small minority
cardiovascular syphilis - thoracic aortic aneurysms from endaortitis neurosyphilis - tabes dorsalis of spinal cord; dementia gummatous necrosis - scarring leads to syphilitic hepatitis, orchitis,
osteomyelitis Congenital syphilis: spirochetes can cross the placenta in the third
trimester; can cause hydrops fetalis and stillbirht; neonates may have pneumonia
alba, osteochondritis, meningovascular infection, extramedullary hematopoiesis
Lyme disease - Borrelia burgdorferi produces erythema chronicum migrans of
skin in primary stage, systemic dissemination in secondary stage, and arthritis
in late tertiary stage
PROTOZOAL INFECTIONS
Gastrointestinal
Amebiasis: produced by Entameba histolytica and causes diarrhea in some
people, even weeks later (travelers) and rarely invades to produce abscesses in
distant organs (liver) after colonic lesions are gone Giardiasis: produced in traveler's by Giardia lamblia causes
malabsorption and diarrhea from inflammation of small intestine Cryptosporidiosis: produced in AIDS patients by Cryptosporidium to cause
(usually) mild inflammation of small intestine with diarrhea
Pulmonary: Pneumocystis carinii (jirovecii) causes a florid pneumonia in
immunocompromised patients
Bloodstream
Malaria
African trypanosomiasis
Parenchymal organs and tissues
Chagas disease: heart failure in 10% Leishmaniasis: kala-azar from L. donovoni produces hepatosplenomegaly and
lymphadenopathy; cutaneous leishmaniasis can be localized (oriental sore) or
mucocutaneous Toxoplasmosis: from Toxoplasma gondii, can be a congenital infection or a
CNS infection in AIDS
HELMINTHIC INFECTIONS
GI tract worms
Ascaris lumbricoides: a big worm but little serious disease (rarely
causes intestinal obstruction, appendicitis) Trichuris trichiuria: whipworm in colon can cause diarrhea Enterobius vermicularis: pinworm infection is relatively common and
causes anal pruritis Tapeworms:
Taenia solium (pork) and Taenia saginata (beef): cysticersosis results
when the eggs of T. solium are ingested and cysts can develop in soft tissues
(brain is worst) Echinococcus: ingestion of eggs causes hydatid disease in liver, lungs,
bone Necator, Ancylostoma: hookworm in small intestine causes blood loss and
anemia Strongyloides stercoralis: causes small intestinal inflammation with
malabsorption Flukes: many produce liver and biliary tract disease that can mimic
lithiasis and hepatitis; Paragonimus involves the lung
Bloodstream worms
Schistomomiasis: produces eggs that cause cirrhosis of the liver (S.
mansoni and S. japonicum) and cystitis, bladder cancer (S. hematobium) Filariasis: lymphatics often involved in chronic infection Trichinosis: skeletal muscle involved
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