Download Microbiology

Pathobiology: Infectious Disease (Bosch)
PRIONS:

Creutzfeldt-Jakob Disease:
Overview: rare infectious spongiform encepthalopathy characterized by abnormal prion protein (PrP) and
resulting in rapidly progressive dementia
Pathogenesis: conformational change of PrP
o Converted from normal alpha helix form (PrPc) to beta pleated sheet form (PrPsc/PrPres)
o Results in resistance to proteolysis and ability to transform other normal PrPc molecules
Etiology of Initial Conformational Change:
o Usually occurs SPONTANEOUSLY*
o Other possibilities (less common):

Mutations in PRNP gene that encodes PrPc protein (familial cases)
 Polymorphisms in this gene may also influence disease expression

Direct infectious transmission of abnormal prior protein (ie. neurosurgery)
Pathology of the Brain:
o General: pathology appears to be secondary to accumulation of PrPc in the CNS (not well understood)
o Macroscopic Findings: usually no abnormalities
o Microscopic Findings: spongiform changes within the cerebral cortex and basal ganglia

Intracytoplasmic, clear vacuoles predominantly within neuronal processes

Eventual neuron loss and reactive gliosis (ie. reactive astrocytes)

PrPsc can be detected using immunohistochemistry
Clinical Manifestations:
o Disease of middle-aged to older adults
o Rapidly progressive dementia
o Frequently prominent startle myoclonus also present
o Life expectancy typically only several months
VIRUSES:

Characteristic Inflammatory Response: perivascular and interstitial lymphocytic infiltrates

Acute Transient Infection– Mumps Virus:
General Features:
o Paramyxovirus: enveloped, negative-sense, ssRNA
o Transmission: respiratory droplets
o Now have vaccination: previously seen in young children, but now outbreaks that do occur are
commonly in older children and young adults (due to lack of or incomplete vaccination)
Clinicopathologic Manifestations:
o General: usually relatively mild and self-limited systemic disease
o Incubation Period: 2-3 weeks
o Prodrome: 3-5 days (fever, malaise, myalgias, headache, loss of appetite, sore throat)
o Organ-Specific Features: lymphocytic infiltration*

Parotitis:
 Painful parotid gland swelling (sublingual and submandibular glands may also be
involved)
 Unilateral or bilateral
 Serum amylase often elevated

CNS Involvement: common (but usually no symptoms)

Orchitis: frequent in postpubertal males
 Often causes testicular atrophy
 Rarely leads to sterility

Pancreatitis: uncommon
 May produce transient hyperglycemia

Oophoritis: infrequent

Chronic Latent Infection- Herpesvirus:
General Structure of Herpesviruses: enveloped, dsDNA viruses
Varicella Zoster Virus (VZV):
o General Features: highly contagious organism

-

Transmission:
 Respiratory droplets
 Direct contact
 Aerosolization of fluid from skin lesions

Vaccination: currently available
o Microscopic Features of Active Infection:

General: identical to active HSV infections*

Intraepithelial vesicles: epidermal or mucosal
 Multinucleated epithelial cells with ground-glass chromatin
 Nuclear molding and large eosinophilic intranuclear inclusions
o Inclusions identified with Tzanck smear from base of vesicle
o Clinical Manifestations of Infection:

Chickenpox: primary infection after initial exposure to VZV
 Usually mild self-limited disease of children
 Fever, malaise, widespread pruritic rash
 Rash comprised of successive crops of small vesicles, pustules and crusted papules,
all in varying stages of evolution

Herpes Zoster (Shingles): reactivation of latent VZV in adults
 Painful, erythematous, vesicular rash in a dermatomal distribution (latency in
sensory nerve ganglia)
 Possible complications:
o Ocular involvement
o Postherpetic neuralgia
Cytomegalovirus (CMV):
o General Features:

Very common infectious agent: 50-80% of middle-aged adults seropositive

Transmission: via contact with infected bodily fluids (saliva, breast milk, urine, semen,
cervical secretions, blood)
o Microscopic Features of Active Infection:

Cytolomegaly: enlarged cells with a large, basophilic intranuclear inclusion
 Inclusion surrounded by a halo and multiple smaller basophilic inclusions
o Clinical Manifestations of Infection:

Healthy Adults: typically no symptoms
 May get mild, mononucleosis-like illness (fever, sore throat, lymphadenopathy,
fatigue)

Fetal Exposure in Utero:
 Most common TORCH pathogen: 1-2 newborns/1000 births have permanent CMVrelated problems
 Severe congenital disease: results from PRIMARY maternal infection during
pregnancy
o Multiple fetal CNS abnormalities (periventricular calcifications,
sensorineural hearing loss, microcephaly, chorioretinitis)
o Intrauterine growth retardation
o Hepatosplenomegaly
o Thrombocytopenia

Immunocompromised Individuals:
 Newly acquired/reactivated CMV: infection affects multiple organ systems
o Lungs, GI tract, liver, retina
o Often seen in transplant patients
Chronic Productive Infection- Hepatitis B Virus (HBV):
General Features:
o Structure: small, enveloped, circular genome with partially dsDNA

Various serotypes and genotypes that affect severity of disease and response to treatment
o Endemic Areas: China, Southeast Asia, Africa
o Transmission: sexual, parenteral and vertical
o Prevention: vaccination
-

Microscopic Features of Active Infection:
o Ground-glass hepatocytes: seen with high viral loads
Clinicopathologic Hepatic Manifestations of Infection:
o Acute Hepatitis:

General:
 May be fulminant: especially with HDV coinfection/superinfection
 Most infections clear in adults: using HBsAb (develop immunity)

Pathologic Findings:
 Hepatocyte injury and regeneration with associated mononuclear inflammatory
cell infiltrates (esp. cytotoxic T cells)
 May or may not have bile stasis
 Elevated ALT and AST (ALT more specific for liver injury)

Clinical Features:
 Variable in severity
 Common signs and symptoms:
o Malaise, anorexia, N/V, fever, right upper quadrant pain, jaundice/icterus
o Chronic Carrier State (+/- chronic hepatitis):

Characterized by: evidence of HBsAg with or without continuing liver disease for >6 months
 More common with HBV infection acquired early in life or in individuals with
impaired immunity

Range of symptoms:
 No symptoms with minimal evidence of hepatocyte injury (carrier state)
 Severe, progressive disease with gradual development of cirrhosis (diffuse hepatic
fibrosis and regenerative nodules)
o Hepatocellular Carcinoma: can occur with or without preceding cirrhosis
Potential Malignant Transformation- Human Papillomavirus (HPV):
General Features:
o Structure: nonenveloped, circular dsDNA virus
o Transmission: directly from person-to-person via infection of mucosal and cutaneous epithelial cells
o Viral Replication in Host:

In basal epithelial cells: replication of ONLY the viral genome

In superficial, more mature keratinocytes: production of virus particles
o Multiple Serotypes: over 1000

Low risk types (6,11): genome replicates as an extrachromosomal episome

High risk types (16, 18): genome integrated into the host cell DNA
Microscopic Features of Active Infection:
o Hallmark=formation of koilocytes:

Squamous epithelial cells containing hyperchromatic, wrinkled nuclei with perinuclear
clearing (esp. found in the superficial epithelium)
o Other features:

Epithelial thickening

Abnormal keratinization
Clinical Manifestations of Infection:
o General:

Frequently latent or subclinical

Treatment only required for symptomatic, potentially premalignant and malignant lesions
o Cutaneous Nongenital Warts:

Verruca Vulgaris (Common Wart): small, pale papules with roughened surface (often on the
dorsum of the hand and often self-limited)
o Mucocutaneous Anogenital Lesions:

General:
 Common sexually transmitted abnormalities affecting a wide variety of sites
 Can be detected by Pap smear, biopsy and HPV DNA typing

Condyloma Acuminatum (Venereal Wart): usually caused by types 6 and 11
 Slow-growing, fleshy, cauliflower like mass (often multiple lesions that become
confluent)

o
Dysplasia (Intraepithelial Invasion) and Invasive Carcinoma (Squamous Cell):
 Timeframe: develops a number of years after initial HPV infection
 Pathogenesis:
o Infection with high risk types leading to integration of viral DNA into host
cell genome and production of viral E6 and E7 proteins
o Inactivation of p53 and RB proteins, genomic instability and up-regulation
of telomerase
o Increased proliferation of genetically altered cells leading to
intraepithelial neoplasia and possible progression to invasive carcinoma

Progression also involves environmental influences (ie.
smoking) and host factors (ie. decreased immune status)
 Clinical Features:
o Dysplasia: flat patch or plaque
o Invasive Carcinoma: poorly demarcated ulcerating lesion
 Pathologic Findings:
o Dysplasia: atypical cells confined to the epithelium and often
accompanied by superficial koilocytosis
o Invasive Carcinoma: infiltrative nests of malignant cells with surrounding
desmoplasia
 Prevention: vaccination
Lesions seen with Epidermodysplasia Verruciformis:

Rare genetic disorder: associated with an increased susceptibility to HPV skin infections
BACTERIA:

Extracellular Bacteria:
Pyogenic Bacteria- Streptococcus pneumoniae
o General Features:

Shape: encapsulated, G(+) lancet shape diplococcic

Biochemical:
 Catalase negative
 Alpha hemolytic on blood agar (pneumolysin)
 Sensitive to optochin

Nasopharynx: common site of colonization (lack of normal clearance may result in infection)

Major virulence factors: polysaccharide capsule and pneumolysin
o Clinicopathologic Manifestations of Infection:

High Risk Group:
 Young children and older adults
 Immunocompromised
 Defective pulmonary/blood clearance (ie. decreased splenic function)

Vaccination: recommended for children and high risk populations

Inflammatory response: typical acute inflammation

Conditions Caused:
 Acute bacterial pneumonia (often lobar in adults; most common cause of CAP)
 Otitis media
 Bacteremia
 Meningitis
 Acute sinusitis
 Exacerbations of chronic bronchitis
-
Exotoxin Producing Bacteria- Clostridium perfringens
o General Features:

Shape: large, G(+) boxcar shaped, spore forming, anaerobic bacilli

Biochemical:
 Double zone of hemolysis on blood agar
 Anaerobic

Ubiquitous in environment: soil, decaying vegetation, normal intestinal flora

Major virulence factors: exotoxins (lecithinases, collagenases, hemolysins, hyaluronidases)
o
-

Clinicopathologic Manifestations of Infection:

Food Poisoning: due to ingestion of organisms (usually undercooked or improperly prepared
meat) leads to production of enterotoxin
 Self-limited episode of diarrhea and abdominal cramps
 6-24 hours after consumption

Gas Gangrene (Clostridial Myonecrosis): inoculation of organisms (ie. trauma) into poorly
oxygenated tissue
 Organism proliferates and produces exotoxins, which cause metabolic cause
production
 Necrosis of soft tissue and skeletal muscle (with minimal acute inflammatory
response)
 Can lead to life-threatening dissemination and sepsis
Spirochetes- Treponema pallidum
o General Features:

Structure: small, motile spirochete

Detection: special stains, dark field microscopy, serologic tests (VDRL, RR, FTA-ABS)

Transmission: sexual contact is primary method (parenteral and vertical transmission also)
o Clinicopathologic Manifestations of Infection:

Hallmark: dense, mononuclear inflammatory cell infiltrate with numerous PLASMA CELLS
causing obliterative end arteritis (ischemic injury)

Primary Syphilis: weeks after exposure (highly infectious)
 Lesions: deep painless genital papule that ulcerates (hard chancre)
 Associated Symptoms: regional lymphadenopathy
 Resolution: will resolve without treatment

Secondary Syphilis: 4-8 weeks after primary syphilis (infectious)
 Mucocutaneous eruption:
o Multiple, symmetric, reddish brown macules, papules and pustules often
affecting palms and soles
o Genital condylomata lata (plaques; esp. infectious)
 Associated Symptoms: constitutional symptoms, lymphadenopathy and patchy
alopecia

Tertiary Syphilis: years later, after a period of latency (not infectious)
 Aortitis: aneurysm formation
 Neurosyphilis: chronic meningitis, tabes dorsalis, general paresis
 Gumma formation: destructive granulomatous lesions at multiple sites (including
skin, liver, and bone)

Congenital Syphilis: results in a high rate of spontaneous abortion and stillbirth
 Rash: similar to secondary syphilis
 Periostitis: saber shins
 Hutchinson teeth
 Saddle nose: destruction of the nasal bridge
 Other Symptoms: rhinitis, hepatosplenomegaly, lymphadenopathy,
thrombocytopenia, neurlogic and ocular abnormalities
Obligate Intracellular Bacteria:
Chlyamydia trachomatis:
o Life Cycle:

Infectious elementary body: binds to target cell (usually COLUMNAR epithelial cell) and
induces its own endocytosis
 Intraphagosomal elementary body inhibits phagolysosomal fusion
 Transforms into reticulate body

Reticulate body: undergoes sequential divisions to produce a large intracytoplasmic inclusion

Transforms back into elementary body: to be released by exocytosis and infect other cells
o Transmission: person-to-person via infected secretions

Frequently via sexual contact

Primarily mucosal membrane infections (cervix, urethra, rectum, conjunctiva, pharynx)
o
Clinicopathologic Manifestations of Infection: depends on serotype and site of infection

Sexually Transmitted Infections:
 General:
o Highest infection rates in teens and young adults
o Often asymptomatic (esp. in women)
o Diagnosis made by:

Nucleic acid amplification

Isolation in cell culture

Antigen detection
 Cervicitis (with progression to PID):
o Symptoms:

Abnormal cervical discharge or bleeding

Dyspareunia (painful intercourse)

Pelvic pain

Fever
o Complications:

Infertility

Ectopic tubal pregnancy

Perinatal transmission during childbirth

Increased susceptibility to infection with HIV
 Urethritis: especially in men
o Symptoms:

Urethral irritation and discharge

Dysuria

Fever
o Complications:

Epididymitis

Infertility
 Proctisis:
o Symptoms: rectal pain, discharge or bleeding
 Pharyngitis
 Lymphogranuloma Venereum: caused by a different serovar (not often seen in US)
o Symptoms: small, painless genital ulcers that progress to painful,
supparative inguinal lymphadenopathy (buboes)

Constitutional symptoms also present
o Complications:

Fibrosis and resultant strictures

Lymphatic obstruction

Ocular Infections:
 Trachoma: primarily seen in developing countries
o Transmission: often carried by flies (poverty, overcrowding)
o Pathogenesis: inflammation and scarring of the conjunctiva and cornea
that can lead to blindness

Secondary bacterial infections can also occur
 Inclusion Body Conjunctivitis:
o Transmission: usually due to perinatal transmission, but can also be
found in adults
o Symptoms: mucopurulent discharge with corneal infiltrates

Reactive Arthritis (Reiter Syndrome): more common in men
 Pathogenesis: likely an immune mediated response to a chlamydial infection
 Symptoms: triad of polyarthritis, urethritis and conjunctivitis
o Often also associated with mucocutaneous lesions

Perinatal Infections:
 Conjunctivitis: opthalmia neonatorum
 Infant pneumonia
-

FUNGI:

Rickettsia rickettsii:
o General Features:

Structure: small, G(-), pleomorphic obligate intracellular coccobacilli

Transmission: via saliva of hard-bodied ticks (American dog tick Dermancentor variabilis)

Primary site of infection in humans: vascular endothelial cells (leads to vasculitis)
o Rocky Mountain Spotted Fever:

Overview:
 Potentially life-threatening
 Appropriate Abx treatment (doxycycline) should be started upon suspicion (do not
wait for confirmation with serological assay)

Clinicopathologic Manifestations:
 Initial Signs and Symptoms: non-specific (fever, severe headache, myalgias, N/V)
 Later Findings:
o Maculopapular rash: centripetal spread (extremities first); progress to
petechial lesions associated with thrombocytopenia
o Systemic organ involvement: GI, liver, CNS, joints, lungs, kidneys, heart
Facultative Intracellular Bacteria:
Mycobacterium leprae:
o General Features:

Structure: G(+), acid fast, rod-shaped, slow-growing bacillus

Infects: humans, armadillos, some non-human primates

Transmission: long-term person-to-person airborne transmission from patients with
mutibacillary leprosy thought to be the most common
 NOT highly contagious
 Most individuals are not even genetically susceptible
o Leprosy (Hansen Disease):

Overview:
 Prevalence: high in Southeast Asia, South America and Africa (esp. India)
 Primary effects: seen in the skin and peripheral nerves (as well as URT and eyes)
 Incubation period: long
 Treatment: curable with multidrug therapy taken for long period of time
o Dapsone, rifampin, clofazimine
 Continuum of clinical and pathologic manifestations: most individuals develop NO
DISEASE or subclinical findings*

Subtypes:
 Tuberculoid (Paucibacillary) Leprosy: seen in patients with effective cell-mediated
immunity
o Clinical Features: hypopigmented, anesthetic skin macules with
thickening of peripheral nerves
o Pathologic Findings: well-formed granulomas and few bacilli
 Borderline Forms of Leprosy:
o Clinical Features: multiple cutaneous papules, plaques and nodules
 Lepromatous (Multibacillary) Leprosy: patients with poor CMI
o Clinical Features: progressive formation of larger, deeper and more
destructive skin lesions

Involvement of the nose: saddle nose
o Pathologic Findings: sheets of foamy macrophages containing numerous
acid-fast organisms

Other Locations: also found in endothelial and Schwann cells

Trauma and Secondary Infections:
 Cause: due to lack of sensation in affected areas
 Result: leads to many of the deformities associated with the disease
General:
Diagnosis of Fungal Infections: morphologic identification, Ag/nucleic acid detection, culture
Special Mechanisms of Identification: GMS (silver stain), PAS stain, mucin stain


Fungi Causing Superficial Infections:
Candida albicans:
o General Features:

Ubiquitous: colonizes normal mucosal surfaces

Shape: budding yeast forms and pseudohyphae

Most common fungal pathogen: typically causes problems for immunocompromised
individuals (opportunistic infections)
o Clinicopathologic Manifestations of Infection:

Severity of disease ranges:
 Common superficial mucocutaneous candidiasis (ie. vulvovaginal infection, oral
thrush)
 Candidemia (often nosocomial and related to IV catheters) possibly leading to lifethreatening disseminated candidiasis (can affect multiple organs)
Endemic Fungi:
Blastomyces dermatitidis:
o General Features:

Endemic area: central and southeastern US

Dimorphic fungus: mycelial form in soil, yeast in the body

Infection: inhalation of aerosolized conidia and transformation to yeast phase at body
temperature (not contagious and therefore cannot be spread person-to-person)

Yeast appearance in tissue: large, broad-based budding, thick walled
o Clinicopathologic Manifestations of Infection:

Inflammation: initial PMN infiltration, followed by CHRONIC GRANULOMATOUS
inflammation

Pulmonary Disease: ranges from asymptomatic  subclinical flulike illness  acute or
chronic pneumonia (with fever, productive cough etc.)

Extrapulomary dissemination: may occur, especially to the skin and then the bones
 Skin Lesions: small papules and pustules that may enlarge to ulcerated plaques
with central scarring
Coccidiodes immitis:
o General Features:

Endemic areas: southwestern US, Central and South American (Valley Fever)

Dimorphic fungus: mycelial form in the soil, spherules in the body that reproduced by
endosporulation (spherules not contagious, therefore no person-to-person spread)

Infection: inhalation of airborne athroconidia and transformation to spherules

Spherule appearance in tissue: large, thick-walled with endospores
o Clinicopathologic Manifestations of Infection:

Inflammation: initial acute inflammation (with complement activation), and if not cleared,
eventual chronic granulomatous inflammation

Many cases subclinical: if it does produce symptoms, PULMONARY findings are most
common (with headache, arthralgias and skin manifestations)

Variants: similar to TB, these variants include cavitary, progressive pulmonary and
dissemination coccidiodomycosis
Histoplasma capsulatum:
o General Features:

Endemic areas: soil of Ohio, Missouri and Mississippi river valleys (esp. in areas inhabited by
bats and birds)

Dimorphic fungus: mycelial form in the soil and small intracellular yeast in the body

Infection: aerosolization and inhalation of mycelial fragments and conidia resulting in
pulmonary infection (no person-to-person spread)
o Clinicopathologic Manifestations of Infection:

Most are asymptomatic: organisms killed by macrophages and walled off in granulomas
(often calcify too present as coin lesion on X-ray)

Symptomatic cases: typically immunocompromised or inhaled a large inoculums
 Resembles TB (can be reactivation of latent infection of progressive disease with
dissemination)
 Progressive disease associated with loss of immune function

Opportunistic Fungi:
General: inflammatory response to these infections is often minimal
Cryptococcus neoformans:
o General Features:

Source: bird droppings and bat guano

Transmission: inhalation

Structure: narrow-based budding yeast with prominent polysaccharide capsule that inhibits
phagocytosis
o Clinicopathologic Manifestations of Infection:

Primary determinant: adequacy of host’s cell-mediated immune response

Pulmonary Disease: varies in severity, often producing only mild symptoms
 Fever, cough, dyspnea

CNS involvement: meningitis and meningoencephalitis; results in most common clinical
presentation of cryptococcal infection
 Headache, N/V, altered mental status, focal neurological deficits

Less frequently affected sites: skin, ones, eyes, prostate
Aspergillus fumigatus:
o General Features:

Ubiquitous: found everywhere in the environment

Transmission: inhalation of fungal spores

Characteristic appearance: uniform narrow septate hyphae (railroad track) that branch at 45
degree angles
o Clinicopathologic Manifestations of Infection:

Allergic Bronchopulmonary Aspergillosis: hypersensitivity reaction to colonization of the
airways (associated with asthma and CF)

Aspergilloma (Fungus Ball): localized collection of organism in PRE-EXISTING cavity
 Does not create a cavity for itself
 Hemoptysis common

Chronic Necrotizing Aspergillus Pneumonia: uncommon; associated with some degree of
immunosuppression

Invasive Aspergillosis: rapidly progressive life-threatening infection in severely
immunocompromised patients
 Angioinvasion: common, causing hemorrhagic and thrombotic complications
 Occasional dissemination: to extrapulmonary organs
Zygomycetes (Mucor and Rhizopus sp.)
o General Features:

Ubiquitous mold: found in soil and decaying matter

Low virulence: for immunocompetent individuals

Transmission: inhalation
o Clinicopathologic Manifestations of Infection:

Rare opportunistic disease: seen in immunocompromised individuals, most often with PMN
dysfunction or neutropenia
 Example: uncontrolled diabetes mellitus with ketoacidosis (PMN dysfunction)

Pathologic findings:
 Irregularly wide, ribbon-like, nonseptate hyphae branching at right angles
 Vascular invasion with associated hemorrhage, thrombosis and infarction

Rhinocerebellar disease: infection of sinuses that can lead to orbital involvement,
necrotizing cellulitis, facial paralysis or CNS extension (MOST COMMON)*

Other presentations: pulmonary, cutaneous, GI or dissemination forms

High morbidity and mortality rate: usually severe and life-threatening illness
PROTOZOA:

Extracellular Protozoa:
Giardia lamblia:
o General Features:

Source: most commonly identified intestinal parasite in the US (only need low inoculum)

Transmission: ingestion of cysts (contaminated water, person-to-person by fecal oral spread)

Infection: many produce no symptoms

o

Life Cycle: undergoes excystation to release flagellate trophozoites that multiply and colonize
upper SI; then undergo encystation during intestinal transit
Giardiasis:

Symptoms:
 Persistent watery diarrhea/steatorrhea after 1-2 week incubation period
 Abdominal cramping, bloating, constitutional sx (anorexia, malaise, weight loss)

Diagnosis:
 Examination of stool samples for cysts and trophozoites
 Detection of Ag in stool sample
 String test
 Duodenal aspirate
 Biopsy (trophozoites adhere to intestinal epithelium)

Treatment: metronidazole
Intracellular Protozoa:
Trypanosoma cruzi:
o General Features:

Transmission: by triatome (“kissing”) bug via infected feces
 Other: blood transfusions, perinatally, ingestion of contaminated food

Life Cycle (3 Stages):
 Replicated epimastigote form (inside insects)
 Infectious, non-dividing, flagellate trpomastigote form (enters host and circulates in
blood stream)
 Replicative amastigote form (inside mammalian host)
o Intracellular (esp. in cardiac and smooth muscle cells)
o Chagas Disease:

General:
 Major public health problem: in Central and South America (rural areas)
 Diagnosis:
o Identification of parasites in blood or tissue
o Xenodiagnosis
o Serologic methods
o PCR
 Management: focused on prevention (vector and transfusional control)

Acute Phase:
 Asymptomatic, OR
 Localized inflammatory swelling at entry site (chagoma) with mild constitutional
symptoms (most often subclinical and rarely severe)

Indeterminate Phase:
 Prolonged asymptomatic period with few circulating parasites

Chronic Phase: occurs decades later in 20-30% of infected individuals
 Myocarditis: focal collections of trypanosomes within cardiac myocytes associated
with myocardial damage and a mixed inflammatory cell infiltrate
o Conduction abnormalities with possible sudden cardiac death
o Dilated cardiomyopathy
o Congestive heart failure
 GI Involvement:
o Megaesophagus: difficulty swallowing
o Megacolon: severe constipation
 Nervous System Disease: meningoencephalitis
HELMINTHS:

Extracellular Helminths:
Wuchereria bancrofti:
o Overview:

Endemic areas: tropics and subtropics; major cause of long-term disability worldwide

Transmission: nematode filarial parasites via infected vector (ie. mosquito); sx only after
years of repeated exposure to infected vector

Prevention: mosquito control and mass treatment with anti-filariasis drugs
Filarial Life Cycle: five developmental stages between the vertebral and arthropod hosts

Adult female worms: present in the vertebrate (humans) and produce thousands of
microfilariae in the large lymphatics (first larvae stage)

Microfilariae: insect bites vertebrate and ingests microfilriae (highest concentration in the
blood correlates with peak insect feeding time)
 Undergo 2 thoracic changes in the insect thoracic muscles (2nd and 3rd larval stages)
 Inoculated back into human host

Nymph: once inoculated back into human host, this nymph develops into an adult worm
o Clinicopathologic Manifestations- Lymphatic Filariasis (Elephantiasis):

Signs/Symptoms:
 Fever, lymphadenopathy, chronic limb and genital swelling with associated skin
thickening
 Caused by adult worms in LNs and lymphatic vessels (produce inflammation and
damage)

Diagnosis: detection of microfiliariae or filarial Ag in the peripheral blood
Schistosoma sp.:
o General Features:

Endemic areas: tropics (Middle East, Southeast Asia, Africa- sub-Saharan esp.)

Large problem: 2nd only to malaria as a tropical health problem

Different forms:
 Hepatic/Intestinal schistosomiasis:
o S.mansoni
o S.japonicum
 Urinary schistosomiasis:
o S. haematobium
o Parasitic Life Cycle:

Intermediate host: SNAILS; release swimming cercariae into surrounding water

Cercariae: penetrate intact human skin, lose their tails, and disseminate hematogenously
 Mature into adult worms in portal cirulcation

Adult worms: paired adult worms migrate to the following areas to release eggs
 Mesenteric vein (mansoni and japonicum)
 Vesicular vein (haematobium)

Eggs: some are shed into urine or feces to deposit in fresh water and enter host snails
o Clinicopathologic Manifestations:

Early: days to weeks after exposure (often subclinical)
 Rash: pruritic popular rash (swimmer’s itch)
 Other Sx: fever, chills, cough, headache, myalgias, lymphadenopathy,
hepatosplenomegacy, eosinophilia

Late Complications: months to years after exposure
 General:
o Diagnosis: ova in stool or urine or biopsies of affected tissues
o Inflammation: chronic granulomatous inflammation and fibrosis
o Treatment: effective drug therapy available
 Hepatic/Intestinal Schistosomiasis:
o Colicky abdominal pain and bloody diarrhea
o Intestinal obstruction
o Hepatic periportal pipestem fibrosis, leading to signs and symptoms of
portal hypertension (ascites, hematemesis, splenomegaly)
 Urinary Schistosomiasis:
o Can also involved the genital tract (esp. in women)
o Dysuria, hematuria (possibly causing anemia) and urinary frequency
o Urinary obstruction, secondary chronic bacterial UTIs and kidney disease
o Carcinoma of the urinary bladder

Squamous cell: normally not located here, but undergoes
squamous metaplasia due to irriation

Additional Organ Involvement: lungs, CNS
o
-

Intracellular Helminths:
Trichinella spiralis (Intestinal Roundworm):
o Parasitic Life Cycle: all stages of development occur within a single host (rats, pigs, cats, dogs,
humans), but 2 different hosts are require to complete the life cycle*

Ingestion of infected meat (usually pork for human infections) containing encysted larvae

Cysts enter stomach and are digest out of animal muscle

Larvae penetrate villi of small intestine and develop into adult worms

Fertilization occurs and gravid female burrows into mucosa to produce new larvae

Newborn larvae disseminate via lymphatics and bloodstream

Formation of cysts in skeletal muscle (larvae remain viable for months to years)
o Clinicopathologic Manifestations:

Usually: asymptomatic and undiagnosed (occurs due to small number of larvae ingested)

Heavy Infestation:
 Enteral or Intestinal Phase: due to invasion of larvae and adult female worms in SI;
occurs in the FIRST WEEK after ingestion
o N/V/D, abdominal pain
o Mucosal hyperemia, edema, hemorrhage, inflammation and ulceration
 Parenteral or Migratory Phase: due to migrating larvae; beginning 1 week after
exposure
o Early Sx: fever, chills, facial edema (esp. periorbital), eosinophilia,
petechia (subungal- under nails, conjunctival)
o Later Sx: due to penetration of larvae into skeletal muscle

Muscle swelling, tenderness and weakness

Enlargement of muscle fibers with nuclear proliferation
(formation of nurse cells), surrounded by edema and interstitial
inflammation

Elevation of muscle enzymes (ie. CK)
 Encystation Phase with Tissue Repair:
o Encysted spiral-shaped larvae surrounded by fibrosis (capsule)
o Eventually, cyst wall calcifies
o Gradual resolution of symptoms