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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