Infectious disease study notes General - known immunodeficiency often provides the portal - Epstein-Barr virus causes inectious mono in helathy people, but causes cancer in AIDS victims and boys with X-linked immunodeficiency - patients given glucocorticoids often have major problems with superficial fungi - therapy iteslf can provide the gateway - candida and C. difficile thrive when antibiotics kill off their microbiological competitors - e. coli can infect bladders with indwelling catheters - a few organisms when found always indicate disease - superinfection - an infection which results because tissues are made vulnerable by another infection - hyperinfection - orders of magnitude more infectious agents than you should have, because of a fundamental chane in your relationship with your parasite - fomites - inanimate objects that carry infectious organisms - nosocomial infection - hospital aquired infection - endemic - a never ending epidemic - pandemic - an epidemic involving the whole world - epizootic - an epidemic among animals Introducing the viruses - most frequent cause of human illness - largest virus is the smallpox virus - .2-.3 microns; smallest is the polio virus (.028 microns) - infectious agent in the virion; coat is the caspid, which surrounds the nucleic acid - each virus must: 1) attach to the cell; 2) penetrate; 3) un-coat; 4) replicate - these stages are the virus cycle - an eclipse phase almsot always occurrs between un-coating and replication; a virus integrated into the host genome, able to replicate with the dividing cell, is a provirus - viremia means viruses in the bloodstream - double-stranded DNA viruses - adenovirus, hepadnavirus family (hep B), herpes virus, papovirus family, poxvirus family (molluscum contagiosum, smallpox) - RNA viruses - reovirus family, coronavirus family, orthomyxovirus family, picornavirus family, enterovirus subfamily, hepatitis A, rhinovirus family, paramyxovirus family, measels, mumps, parainfluenze, respiratory syncytial virus, retrovirus family, togavirus family, rubella, arboviruses - DNA viruses replicate in the nucleus, and RNA viruses replicate in the cytoplasm - viruses do harm by : 1) destroying our cells as their progeny are released 2) rendering infected cells non-functional 3) exciting cell-mediated immunity, which destroys otherwise-healthy cells which happen to be infected by the virus 4) causing cell overgrowth, which may be unsightly, a fertile ground of carcinogenesis, or full-blown malignancy - neutralizing antibodies prevent or eliminate viral infection by binding to the viruses themselves - cell-mediated immunity and interferon are also important - viral inclusions are aggregates of virus proteins, visible by light microscopy -intranuclear - adenovirus - CMV - herpes simple I&II - herpes zoster - measles - intracytoplasmic - CMV - rabies - molluscum contagiosum - chlamydia Virus respiratory disorders - URI involve the nose, sinuses, throat, tonsils, and/or middle ear - LRI involve the larynx, trachea, bronchi, alveoli, and/or pleura - in a typical viral interstitial pneumonitis, inflammatory cells fill the alveolar spaces - in fatal chest colds, there is more florid cell damage; death results when the airways are sufficiently damaged to allow fibrin to escape and block air flow and exchange - rhinovirus - the common cold; URI directly, do not cause LRI - coronaviruses - the second most common cause of the cold; do not cause LRI - adenovirus - common colds, chest colds, red eyes, and/or GI upsets; necrosis is typical of the most severe adenovirus preumonitis, which can be fatal; pathologists notice enlarged, basophilic nuclei without any texture; these denote smudge cells - influenza - primarily an infection of any and all parts of the respiratory tree - 1 to 2 days after exposure - fever, headache, myalgias, and fatigue - in severe cases, necrotizing lesions of the airway appear - A - pandemic influenza - B - epidemics - children badly affected - C - sporadic, URI - para influenza infections - causes symptoms similar to influenza; cause laryngotracheobronchitis - echovirus - an oral-fecal route pathogen which reaches the other tissues via the bloodstream, produces sore throat and perhaps a rash; also linked to myocarditis - coxsackie virus A - produces an annoying, blistering infection of the throat; also produces mild hand, foot, and mouth disease - coxsackie virus B - can involve the pleura; it is also implicated in both acute myocarditis and in chronic immune-mediated myocarditis - respiratory syncytial virus - causes epidemics of potentially-lethal bronchiolitis and pneumonia in children and debilitated adults; in fatal cases, we see epithelial syncytia in the terminal bronchiolar mucosa - mycoplasma pneumoniae is another very notable cause of chest cold, probably more common than these viruses GI tract viruses - mumps - a childhood illness featuring inflammation of hte major salivary glands - encephalitis and/or meningitis are usually mild; researchers notice that lab findings of viral meningitis are present in about half these kids - even with immunization, about a few thousand cases each year - viral enteritis/diarrhea - rotavirus - an important cause of mild winter vomiting and diarrhea in children; most adults are immune; rotavirus kills about a million kids each year - Norwalk agent - causes outbreaks of vomitting and/or diarrhea at any time, in children or adults - both are transmitted by fecal-oral route; damage to epithelial cells allows fluid into the gut, resulting in diarrhea - remaining cases are probably caused by adenoviruses; despite the frequent diagnosis of GI virus, food poisoning is probably more common Rash viruses - human papillomavirus type 2 - most common cause of warts - HPV 16 & 18 - most common cause of cancer of the cervix - measles - affects only humans - transmission is by droplets; incubation period is two weeks - complications include significant pneumoitis, hemorrhagic rash, and an severe autoimmune post-measles encephalitis which often causes permanent brain damage - look for multinucleate "Warthin- Finkeldey" giant cells, each nucles bearing an intranuclear inclusion - we believe that measles does not damage the fetus - German measles (rubella, threee day measles) - this mild illness, with a rash and arthritis, causes fetal damage - serious rubella ought to be a thing of the past, but its still with us - smallpox (variola) - first disease to be conqured by science - transmitted by droplet infection, multiplies in the throat, enters the bloodstream, and multiplies further in the lymphoid tissue; the spots become vesicles and then pustules; systemic involvement caused death - erythema infectiosum and roseola infantum - trivial childhood diseases - these viruses hang aroung for life and can cause troubles later; papovirus is infamous as the cause of aplastic crises in hereditary hemolytic diseases; herpes 6 is newly-recognized as an opportunist in AIDS and others Herpes viruses - 6 viruses; eachproduces a mild illness upon entering the body; the virus then lies latent within the host genome, awaiting reactivation, for the rest of the person's life - herpes simplex 1 - usually contracted by getting kissed, as a baby - a majority of adults have the virus, though most never become sick or suffer only fever blisters - the virus climbs sensory nerves and hides in nervous tissue - cold sore, fever blister, sun blister - the virus can also cause generalized severe vesicular eruptions of the skin; also herpes ulcers of the cornea, or even necrosis of the temporal lobes of the brain - pathologists recognize typical herpes cells in sections or touch preparations ; the nucleus loses its texture and becomes pale and swollen - herpes simplex 2 - this virus is usually contracted through sexual contact, and produces painful, recurrent blisters on the genitals; pathology is identical to HSV-I; - if present in the birth canal, then the newborn will contract the virus during delivery - this is deadly, ceasarean section is indicated - herpes necrotizing encephalitis is almost always due to type I herpes, but many patients experience viral meningitis during the first episode of herpes 2 - human herpes 6 - can cause disease by itself, and blamed for accellerating the course of HIV - invades B lymphocytes - chickenpox / herpes zoster - rash consists of vesicles which arise in successive crops over the body - after recovery the virus hides out in the dorsal root, and/or sensory trigeminal ganglia - herpes zoster is recurrence of the chickenpox rash, typicall along the distribution of a sensory nerve root - the lesion is uncomfortable, and eye involvement is very serious; it is preceeded by parathesia and pain after herpes zoster is notorious - a varicella virus vaccine is available, and implementing its use would save money - cytomegalic inclusion disease - very common viral infection - the person meeting the virus sheds it only for a few days; adults may note an infectious mono-like infection which lasts up to a few weeks; if aquired through pregnancy, the virus is shed through pregnancy and lactation - has ability to damage the unborn child - a child with congenital CMV syndrome is small for gestational age, jaundiced, afflicted with hemolytic anemia, afflicted with thrombocytopenia and purpura, blind, deaf, retarded, and/or epileptic - hallmark is very large nuclei with large intranuclear inclusions; the inclusion is huge and is surrounded by a clear halo; there are also small basophilic inclusions in the cytoplasm - CMV in the immunosupressed involves the lungs or GI tract, AIDS patients are prone to develop CMV chorioretinitis, which results in blindness - infectious mononucleosis / Epstein-Barr virus (human herpes virus 4) - EBV is the most notable cause of mononucleosis - most people meet the virus in childhood and never become symptomatic - transmitted by saliva; incubation is about 6 weeks - virus has a special trophism for B-cells, in which it multiplies - the EBV receptor is the C3d receptor - eventually B cells that bear viral antigens are eliminated by cell-mediated and humoral immunity - proliferation of B-cells bearing EBV antigens on their sufaces is upsetting to T-supressor cells and T-killer cells - the patient with infectious monnucleosis has fever, malaise, fatigue, and generalized lymphadenopathy - the spleen is packed with activated cells and may rupture - about half of patients get cold agglutins and autoimmune hemolytic anemia - mild thrombocytopenia - rash - ampicillin sore throat - if you have X-linked recessive lymphoproliferative immunodeficiency, you'll probably die of infectious mono - heterophile antibodies are IgM antibodies which agglutinate sheep red cells - Forsmann antibodies are heterophile antibodies that are absorbed by guinea pig kidney but not by beef RBC's - mono test Abs are induced by EB virus infectious mono - serum IgG anti-EBV capsid indicates past or present EBV infection - serum IgM anti-EBV capsid indicates current infection - EBV early antigens indicate early or chronic EBV disease - EBV immortalizes the lymphocytes that it infects Arboviruses - yellow fever - prototype of viral hemorrhagic fevers - primarily affects monkeys, humans become infected with the Aedes mosquito - patient develops a flu-like symptom; liver failure becomes apparent - most patients recover; some death results from brain or heart damage - dengue - aedes mosquito borne - sever arthralgias and myalgias - most common arthropod-borne viral infection; upto 10,000 cases each year - regional hemorrhagic fevers - mostly tick borne; produce flu-like symptoms with bleeding tendencies - range from mild to severe - most virulent is Lassa fever; it is East African - contracted from animal droppings - can be contagious from person to person - there is a Lassa fever serum factor which strongly interferes with platelet function - Colorado tick fever resembles Rocky Mountain spotted fever Chronic Fatigue Syndrome - 6 or more months of disabling fatigue requiring >50% reduction in dialy activities - patients will self-diagnose - many patients are depressed - viral epidemiology - herpes 6 may be one player Chlamydial Disease - chalmydia are degenerate bacteria that are obligate intracellular parasites; they must get their ATP from the host - host response in neutrophilic - ornithosis - psittacosis, parakeet fever - by chalmydia psittaci; from inhaled bird droppings - get interstitial pneumonia - giesma shows inclusion bodies in the cytoplasm - trachoma - causes preventable blindness - reaches fingers by means of fingers, fomites, or flies - results in inflammation of conjunctiva (pannus) - many are vitamin A deficient as well - by chlamydia trachomatis - inclusion conjunctivitis - caught from people with genital chlamydia; famous swimming pool conjuncitvitis - lymphogranulum venereum (LGV) - infection of the anogenital region with aggressive chlamydia trachomatis - primarily in tropics - small ulcer at site of innoculation - lymph nodse then supparate - end result is rectal strictures and/or elephantiasis - chlamydial urethritis / cervicitis - usually caused by less virulent strains of chlamydia trachomatis than LGV - NGU - important cause of fallopian tube infections - can be transmitted to the baby during birth - chlamydia pneumoniae - important cause of wheezy adult lung infections Rickettsial diseases - rickettsia are degenerate bacteria that cannot grow except within cells - never part of the normal flora - prefer endothelial cells of host - typical finding is vasculitis, with damaged vessels surrounded by lymphocytes and macrophages - Ab response is good, and can be treated with tetracycline - typhus fever - a dread disease caused by rickettsia prowazekii; transmitted by louse feces - rash, headache, fever, mental changes, and even gangrene - swelling and necrosis of endothelial cells - death results from brain, heart, and lung involvement - there is a milder Brill-Zinsser disease; a single case can cause an epidemic among refugees - murine typhus is caught from rat fleas - endemic whenever there is poverty - Rocky Mountain spotted fever - can kill a person - riskettsia rickettsi is a tick-borne rickettsia which invades both endothelial and vascular smooth muscle cells - spots may be hemorrhages from necrosis of the skin arterioles - vasculitis can be fatal if untreated - scrub typhus - caused by R. tsutsugamushi, carried by a mite, endemic throughout the Orient - Q-fever - a pneumonia caused by coxiella burnetti - common among sheep; can be transmitted by ticks or droplets - bacillary angiomatosis - an opportunistic infection caused by a rickettsia closely related to bartonella quintana - dilated vessels in the liver, spleen, and elsewhere are typical - also infects inner-city drunkards Mycoplasmal diseases - little bacteria without cell walls (can't kill them with penicillin or cephalosporin) - mycoplasma hominis and ureaplasma urealyticum are causes of NGU - mycoplasma pneumoniae - most common chest cold - generally URI - incubation 2 weeks - AB speed recovery - excites cold agglutins in half of the patients Intro to bacteria - fast growers deprive the host tissues of nutrients, and lower tissue pH - exotoxins - soluble molecules produced by living organisms which do harm - endotoxins - LPS protein complexes; cause high fever, capillary permeability, shock, DIC - disrupt neutrophils and cause macrophages to release preposterous amounts of IL-1 and alpha-TNF - bacteremia is bacteria in the bloodstream - septicemia - diseases associated with bacteria travelling around the body via the blood - sepsis - bacterial infection in the bloodstream making the patient hypotensive or tachypneic or otherwise causeing cardiovascular insufficienc Pyogenic cocci - striking neutrophilic response to invaders; spreading infections are called cellulitis or phlegmon Staphylococcal infections - normal flora of nose and skin - virulence factors - coagulase, hemolysin, protein A (ties up Abs) - Abs against staph are of limited effectiveness - coagulase positive staph (pyogenes and aureus) is a potent pathogen - catalase positive - most common cuase of bacterial skin abscess - furuncels are single pimples, carbuncles are pimple clusters linked together by tracks of tissue necrosis which involve the fascia - staph sepsis is rare but serious - impetigo is a pediatric infection limited to the stratum corneum of the skin - look for honey-colored crusts - staph infections of the nail bed (paronychia) and palmar fingertips (felons) are especially painful and destructive - propionibacterium causes acne - staph endocarditis is common and can involve either side of heart - while S. aureus can invade the gut, it is much more common to encounter food poisoning due to strains which have produced enterotoxin B, from unrefrigerated meat or milk products - toxic shock syndrome produces shock syndrome toxin 1 - scalded skin syndrome is caused by strains of epidermolytoc toxin - methicillin resistant staph aureus - causes much alarm; most hospital strains are sensitive - coagulase negative staph (epidermidis) are skin commensals and opportunists which infect the prosthetic heart Strep infections - live in throats and cause sporadic and epidemic human disease - group A - pyogenes - strepo throat - group B - newborns - group D - enterococcus causes UTI, as well as endocarditis - can't type - viridians - virulence factors are capsular polysaccharides, M-proteins, streptokinase, streptodornase, and streptolysin A - streptococcal pharyngitis - "sore throat", retropharyngeal abscess, cellulitis of deep neck is Ludwig's angina - scarlet fever - caused by strain that makes erythrogenic toxins; has rash with many PMNs - skin infections with strep are more likely to cause cellulitis with obvious lymphangitis - erysipelas is a severe skin infection cuased by group A strep; usually no tissue necrosis; indurated, thick, red areas of skin are characteristic - flesh-eater bacterium - produces rapidly spreading necrotizing erysipelas and myositis and fascititis - virulence factors pyrogenic exotoxin A (causes activation of 15% of T-cells) and pyogenic exotoxin B (destroys flesh) - pueperal sepsis - childbed fever- group A sterep on hands of med students - phlegmasia alba dolens - milk leg - group A deep venous thrombi - strep pneumoniae - superinfects viral pneumonia - pneumococcal infections - causes lobar pneumoniae, stopped at interlobar fissures - thrives in large airways of smokers - spontaneous pneumococcal peritonitis complicates ascites in cirrhotics and nephrotic syndrome patients; pneumococcal sepsis is deadly - encases itself in a polysaccharide capsule Nisserial infections - meningococcal infections - neisserai meningitidis is gram negative diplococci which is carried in nose and throat - has virulence factor that cleaves alpha heavy chains - classic cause of Waterhouse-Friederichsen syndrome - deadly necrosis of adrenal glands - any febrile illness with petechiae is meningococcal sepsis until proven otherwise - gonococcal infections - neisseria gonorrhoeae is classic cause of gonococcal urethritis - prone to spread to eye, especially in newborn - women prone to gonococcular salpingitis - people with hereditary deficiencies of any of the complement factors 5-9 are especially prone to neisserial sepsis - branhamella - once thought to be a harmless commensal, now an important cause of pneumonia in the elderly Gram negative rods - lethal gram-negative sepsis - kills by endotoxin release, DIC, or spread of organisms - endotoxin relaxes cappillaries and results in massive production of alpha-TNF - E. coli infections - most UTI - intra-abdominal supparation, think E. coli, enterobacter, or proteus - perirectal infections - think mixed, including E. coli - great cause of gram-negative sepsis - klebsiella and enterobacter - klebsiella pneumoniae (Friedlander's bacillus)- necrotizing lobar pneumonia or necrotizing bronchopheumonia; both produce red mucus; hard to treat with antibiotics - enterobacter - gram-negative rod with similar behavior to klebsiella, though less slimy; neither bug infects the intestines - proteus and serratia - proteus - chronic UTI; can produce characteristic odor and kidney stones; produces suppartive, intractable infections - serratia - "red bug" -once considered a non-pathogen; another important cause of various infection - pseudomonas - graphe bug, water bug - aeruginosa- famous opportunist - especially common on burn unit, in lungs of CF, and ears of diabetis, and those with severe neutropenia; pus may be flourescent - ecthyma gangrenosum is a severe pseudomonas soft tissue infection - virulence factor exotoxin A - prevents assembly on ribosomes - legionella - pontaic fever is a mild febrile illness - Legionaires' disease is a vicious bronchopneumonia which is likely to be fatal unless an appropriate antibiotic is administered - most at risk are smoker-drinkers - anaerobic gram-negative infections - supparative and spreading infections - bad smells are famous - bacteroides, fusobacterium, peptococcus, peptostreptococcus - hemophilus influenzae infections - coccobacillus causes infections in children who are not fully immune-protected - lung infections are common in smokers - most virulent is strain is type B - H. parainfluenzae and H. aphrophilus cause disease in humans - hemophilus ducreyi - causes chancroid, a rare sexually-transmitted disease of those with poor personal hygiene - Whooping cough - bordetella pertussis flourishes among cilia of respiratory epithelium - has exotoxin that causes fever, malaise, increase lymphocytes - key recovery is IgA antibodies - pertussis in adults that have a cough - diptheria - corynebacterium diptheriae is a clssic respiratory pathogen that causes much disease - almost exclusively in immigrants - forms fibrinous pseudomembrane - if membrane slips off, the child may choke to death - toxin ties up carnitine and blocks protein synthesis, damaging heart and muscle Enteric pathogens - cause diarrhea by three known mechanisms 1) invade gut wall directly; diarrhea results from inflammatory exudate, stools contain polys 2) release enterotoxins into gut or into food; no polys in stool 3) can attach to mucosal cells and cause them to secrete too much water; no polys - E. coli - toxigenic E. coli produce heat-labile enterotoxin which makes enterocytes pump water into the lumen - salmonella - salmonella typhi produces typhoid fever, very rare nowadays - by fecal-oral route - organisms silently damage and penetrate the bowel epithelium, and enter lymphoid tissue - incubation 1-2 weeks - rose spots are characteristic - hepatosplenomegaly and spiking fevers are typical - other salmonella causes enteric fever, plain food poisoning, or sepsis - these organisms invade gut mucosa (S. cholerasuis, S. typhimurium, S. paratyphi) - raw eggs and poultry teem with slamonella - gastric acid is an omportant barrier - sickel cell patients are prone - shigella (bacillary dysentery) - can cause disease in a few hours - do not spread beyond the gut - shigella and yersinia enterocolitis are notorius for producing a seronegative spondyloarthritis if the patient is HLA-B27 positive - vibrio family - cholera is important in the Ganges - produce diarrhea by interotoxin which activates adenyl cyclase in enterocytes; this causes secretion of interstitial fluid - non-cholera vibrios cause skin infections and sepsis - helicobacter - causes diarrhea- C. jejuni; H. pylori in ulcers - y. enterocolitica - new cause of dysentery - may account for zoonotic appendicitis - bacillus cereus - fried rice bug - common cause of food poisoning - C. perfringens - can produce food poisoning, with nausea and vomiting Clostridia - gram negative anaerobes - grow optimally without other bacteria - tetanus - spam of voluntary muscles - caused by C. tetani - if introduced into necrotic tissue, they will germinate and elaborate their own toxins; death results from respiratory failure; the lesion is molecular - botulism - is a paralyzing food poisoning resulting from the ingestion of pre-formed toxin of C. botulinum; death results from respiratory paralysis - septic clostridial infections - usually by C. perfringens; may take form of necrotizing cellulitis, or gas gangrene - the gas is produced by fermentation - no inflammatory infiltrate with gas gangrene - pseudomembranous colitis is caused by C. difficile - which overgrows the gut when antibiotics are administered; focal necrosis followed by inflammation and fibrin exudation The bacterial zoonoses - anthrax is by bacillus anthracus - gram positive rod - first lesion is filled with purple, broken down blood - the pustule ruptures and becomes necrotic - involvement of blood may carry the disease to other organs - listeriosis - by listeria monocytogenes - Chinese pictogram bug - produces amniotitis and fetal inflammation following asymptomatic infections of the maternal bloodstream - opportunist among the immunosupressed - erysipelothrix rhusiopathae - causes erysipeloid, a spreading skin infection from handling meat or seafood - plague - from rat via the flea - etiologic agent is yersinia pestis - bubonic plague invovles the lymph nodes draining the site of the flea bite - patient dies of sepsis - pneumonic plague begins in the lungs, death resulting from necrotizing pneumonia - septicemic plague - kills in short order - tularemia - by francisella tularensis - handling sick rabbits - can enter through skin, lungs, eye, mouth - mix of supparation and granuloma formation; recovery with scarring - pasteurella multocida - usually follow dog or cat bites - brucellosis - from infected goats, dogs, cats - patients have bacteremia and fever - produces a mix of abscesses and granulomas - glanders - by pseudomonas mallei - affects donkeys and horses - meliodosis (pseudomallei) common in SE Asia - look for abscesses and granulomas - both diseases are hard to treat - leptospirosis - by spirochete leptospira interrogans - look like viral meningitis - caught by dogs and cats, fresh-water sports - bad cases with lymphadenopathy, hepatits, DIC, and renal tubular disease are called Weil's disease - relapsing fever - by spirochete borrelia recurrentis - carried by ticks or lice by animal reservoirs - produces systemic mixed inflammatory response - stain with Wright's stain - rat bite fever - two diseases both with pain at infection and later fever - spirillium minus - may last for a month or two - streptobacillus moniliformis - Haverhill fever - over quick, but arthritis may be troublesome - cat scratch disease - fever and localized lmphadenopathy; may persist for several months - by rochalimea henslae - cause bacillary angiomatosis in AIDS - Whipple bacillus - hasn't grown yet, but seems to be most closely related to actinomycetes Other bacteria Syphilis - great pox, VD - STD by treponema pallidum - chronic, non-fatal infections - cannot be grown in vitro - use darkfield or immunoflourescence - extremely vulnerable to the environment - primary syphilis - one week to three months - hard chancre - indurated ulcer - this heals in a few weeks - the lesion is obliterative endarteritis - dense infiltrate composed of plasma cells - secondary syphilis - weeks to a few months after the chancre has gone away - fleeting, variable rash over the skin and mucosal surfaces - affects palms and soles - condylomata lata are localized forms of the rash seen on the lips, genitals, and anal region -lesions teem with spirochetes - virtually all patients will be seropositive - tertiary syphilis - involvement of the proximal aorta causes aortic insufficiency and weakness of aortic wall, which will dialte and eventually rupture; look for tree-barking - neurosyphilis takes three major forms 1) general paresis - dementing disease with hypomantic psychosis 2) meningovascular syphilis - fibrosis of meninges 3) tabes dorsalis - sensory syndrome involving dorsal columns - gummas - granulomas with gummatous necrosis, with plenty of plasma cells - common in liver and testis - saddle nose is common - congenital syphilis - infection of the fetus - saber shins - dental deformities - gummas destroying bridge of nose - pulmonary consolidation - hepar lobatum - liver damage due to gummas - rash resembling secondary syphilis - mental retardation - necrotizing inflammation of the umbilical cord - spirochete does not cross the placenta until the fifth month - syphilicitics make antibodies to beef heart - easily treated with penicillin - other treponematosis - caused by organisms that look identical to syphilis spirochete, but are not STD - yaws - skin ulcers; gummas usual in late stages; treatable with penicillin, caused by treponema pertenue - trech mouth and chronic gingivitis Lyme disease - aquired from ixodes ticks that have feasted on deer mice - resembles syphilis in both its etiology and pathology - primary lime disease - spreading, ring-like erythematous rash - lesion is called erythema chronicum migrans - in secondary and tertiary stages - arthritis, cranial nerve palsies, non-suppartive meningitis, encephalitis, myocarditis, stillbirth - antibodies against its flagellum cross-react with an axonal protein - lots of plasma cells Exotic bacterial infections - granuloma inguinale - chronic STD caused by the intracellular pathogen calymmatobacterium donovani - sores on penis and wherever it rubs - mixture of abscesses and granulomas - easiest to see on silver or Giesma (Donovan bobies) - chanchroid - uncommon, STD caused by hemophilus ducreyi; ulcer similar to syphilis, but no induration - poor personal hygeine allows infecdtion to develop Tuberculosis - white plague - presently resurgent in the U.S. - etiologic agents are mycobacterium tuberculosis and mycobacterium bovis - grow slowly - both bacilli are red snappers because of their characteristic staining on Ziehl-Neelsen acid-fast technique - most people never get sick from the bug - bacterium can live indefinitely in caseous necrosis - predisposers - immunosuppression, alcoholism, Hodgkin's, glucocorticoids - 3 million die every year of TB - TB bacilli love oxygen - produces no exotoxins, endotoxin, or histolytic enzyme - TB granulomas are called tubercles, if they are caseating in the center then soft tubercles - primary tuberculosis - single lesion (Ghon focus) occurs just under the pleura in the midportion of one lung - granulomas have walled off bacilli in lymph nodes and lung - Ghon complex is lung and node - viable bacilli remain in the Ghon complex for life - asymptomatic - progressive primary TB - overwhelming infection that affect children - secondary TB - active TB - occurs when bacilli escape the Ghon complex or more bacilli enter from outside - usually at apex of lungs - the better the patient's cell-mediated immunity, the more granulomas - TB tends to calcify - polys are most abundant when the caseum has eroded into the large airways - arrested TB - secondary TB that has calcified or been replaced by collagen - cavity - coughing up debris after the caseation has entered a large airway - milliary TB - results when many TB bacilli enter the bloodstream but the granulomatous response is good - when TB ruptures into pulmonary artery, there is miliary involvement of lungs - progressive isolated organ TB - most often involves adrenals, cervical lymph nodes, fallopian tubes, epididymis, kidney, meninges, and Pott's disease (collapse of the spine) - death results from pulmonary TB from exsanguinating hemoptysis or asphyxiation - BCG is given in third world countries to produce the same immunity as does a primary infection - both classic TB and TB of the lymph nodes is treated with short chemotherapy Atypical mycobacterial infections - mycobacterium kansasii, M. intracellulare, and M. avium - vicious lung infections; some are immunocompromised - M. scrofulae - casuses cervical adenitis - scrofula, the king's evil Leprosy - Hansen's disease - a dread, chronic poorly-transmissible disease caused by mycobacterium leprae - acid fast rod that grows only within host cells - cell-mediated immunity keeps the organism at bay in most people who meet it - in tuberculoid leprosy, there is a brisk cell-mediated immune response to the organism, have a positive 48 hour lepromin skin test, and end up with many granulomas and only a few leprosy bacilli - in lepromatous leprosy, cell-mediated immunity is inadequate, and lepromin test is negative - a patient with tuberculoid leprosy who eventually becomes anergic because of the infection will transform to lepromatous leprosy - the bacilli only grows in the cooler parts of the body - the skin and cutaneous nerves, upper airways, testes, hands, and feet - the granulomas do more damage to the peripheral nerves than is seen in lepromatous leprosy, and this causes most of the problems - lepromatous leprosy patients have masses of histiocytes which do not form good granulomas; pathologists describe lepra cells nad globi - leprosy is weakly transmittable - leprosy is a major underlying cause of amyloidosis A (30%) Nocardiosis - infection with nocardia, a low-virulence, filamentous, gram-positive, weakly acid fast bacterium - immunosuppressed patients develop lung infections with nocardia steroids - multiple lung abscesses without granulomas - normal people develop nocardia brailiensis skin infecions Actinomycosis - chronic fibrosing, pus-producing infections due to anaerobic actinomyces bacterium, usually actinomyces israelii - normal commensal organisms in the tonsils and tooth crud - they overgrow after surgery or a pre-existing abscess - classic form is lumpy jaw with running sores in the mouth and on the face and neck - actinomycoses at other sites follows bite or punch injuries - smears of actinomycosis pus show naked-eye sulfur granules Candidiasis - monilliasis, yeast infection - candida albicans is the usual agent - a normal commensal, which overgrows when normal flora are killed - or when lots of glucose around; cuases nali fungus - cuases infection of wet skin; also thrush Mucormycosis - mucor, zygomycosis, phycomycosis - infection by such bread molds as Rhizopus - spores germinate best at low pH, and then hyphae invade the vessels - typical patients are ketoacidotic patients - nose, head, and face are most often involved - candida is the only fungus that enters the body via a primary infection in the lungs Aspergillosis - usually by fumigatus or nigger - more pathogenic than mucor, also invades the blood vessels - a wad of harmless fungus growing in an old TB cavity - invasive aspergillosis - common, life-threating disease hard to diagnose among the immunosuppressed - people are also allergic, which causes type I (asthma), type III (organic pneumoconiosis), and type IV (more organic) Cryptococcus - opportunistic fungal infection by a yeast that abounds in pigeon droppings - reproduces by narrow yeast budding - most common site of infection is the meninges - usually no inflammatory response Blastomycosis - blasto, North American blasto, Chicago disease - infection by blastomycosis dermatitidis, a yeast found primarily in the Mississippi River valley - large size, thick walls, single, broad based buds - response is a mix of supparation and loose granuloma formation - blasto is not much seen in immunocompromised patients; it is a primary infection - responds poorly to anti-fungal agents Paracoccidiomycosis - South American blastomycosis - fungal infection caused by a huge yeast, paracoccidiodes brasiliensis - most in Amazon basin - mouth and lungs are usual site of involvement Coccidiomycosis - infection by coccidioides imitis, in U.S. southwest - fungus appears in tissue of a large spherule - takes form of a severe chest cold with joint pains; can be lethal - blacks and Philipinos; immunosuppressed patients are at an extra risk Histoplasmosis - infection by histoplasma capsulatum, a tiny, non-encapsulated yeast - in U.S., Mississippi vally, and Kansas City - inhaled from bird or bat guano - only the spores produced by the mycelium are contagious - first time is primary pulmonary histoplasmosis - mild fever and chest cold - latent histoplasmosis is resiue of old, healed infection - tiny calcified granulomas are found in lungs, spleen and liver - chronic pulmonary histoplasmosis - cavitating, granulomatous disease of the lungs - disseminated histoplasmosis - kills people who cannot muster an immune response - single organ histoplasmosis - esp. adrenal glands Other deep fungi - mycetomas - Madura foot, maduromycosis - deep infection of skin and subcutaneous tissue - usually in the foot; casued by nocardia brasiliensis - sporotrichosis - produces a superficial or deep spreading infections following a prick from a rose or bayberry thorn Eukaryotic infectious agents Amebiasis - infection with entamoeba histolytica - usually is commensal, and symptoms are unusual - typically aquired in the third world - ingestd cysts are activated from in the stomach, releasing active trophozoites, many years may elaspse between inoculation and symptomatic disease - colon is affected - ulcers are full of fibrin and debris as well as amoebas - most serious is extra-intestinal - amoebas to liver - E. histolytica strains are probably non-pathogenic, and even the presence of virulent strains in stool does not indicate that this is the cause of the symptoms Balantidium Coli - very large coliated intestinal parasite is a minor pest; caught from pig feces - pathology similar to amebic colitis Amebic meningoencephalitis - naegleria fowleri live in stagnant ponds, esp. in the warmer states - enter CNS through nasal mucosa, crib plate, and CN I - produce a purulent, necrotizing, hemorrhagic infection of the brain and its coverings - acanthoma - related and causes chronic meningoencephalitis in immunosuppressed Giardiasis - most ubiquitous gut protozoan - giardia lamblia, an intestianl flagellate, aquired from drinking stream water - concentrates in duodenum and sends cysts out in the stool - most never become symptomatic - low IgA, immunosuppression, and general hypogammaglobulinopathy make it more severe Cryptosporidiosis - newly discovered but common disease; produces self-limited diarrhea - can be fatal in a malnourished child; AIDS and AIDS-related complex get long-standing diarrhea that can be fatal - tiny acid-fast organism is a common veterinary pathogen and veterinary commensal - sit in brush border of the gut - isosporidia belli is a related organism seen in AIDS patients - it causes diarrhea and malabsorption - sarcocystosis is an uncommon, mild infection acquired from eating undercooked beef or pork; causes intestinal problems which last a few weeks Trichomoniasis - trichomonas vaginalis - very annoying, non-lethal STD pathogen - most are asymptomatic; best known for producing vaginitis in women during reproductive years - many get urethritis and prostatitis - itching, burning, and discharge - strawberry vagina Pneumocystis pneumonia - by pneumocystis carinii - lungs - trophozoites grow on the pneumocytes and damage them - alveoli fill with organisms and cell debris - first known as the cause of plasma cell interstitial pneumonitis in malnourished kids - the macrophage receptor necessary to fight pneumocystis has been identified - can cause mild respiratory illness Malaria - infestation by any of four plasmodium species - tremendous morbidity - plasmodia are intracellular parasites carried by the female anopheles mosquitos - humans are the immediate host - sporozoites from the mosquito travel to the liver, where they multiply - merozoites from the liver enter erythrocytes, where they multiply to produce trophozoites and then schizonts - these disrupt red cells - plasmodium malariae - produces fever spikes at 72 hour intervals - plasmodium ovale and plasmodium vivax produce fever spikes at 48 hour intervals - plasmodium falciparum produces fever spikes at 48 hours and is bad; can affect red cells of any age; can plug vessels - massive hemolysis correlates with the paroxysms of fever, chilling, and so forth - hepatomegaly - can be plugging of brain vessels by parasitized red cells - blackwater fever results from vigorous hemolysis, and renal failure resulting from hemoglobinuria Toxoplasmosis - by toxoplasmosis gondii - in cats; eggs are shed in cat feces - organsms are intracellular - caught from cat droppings or eating raw meat from an incidentally-infected animal - adults with normal immunity suffer only mild mono-like symptoms - this infection is devastating in the newborn and immunocompromised Other protozoans - babesiasis - trivial disease caused in the Martha's vienyard area by babesia microti - carried from its animal reservoir by ticks (ixodes dammini) which are active in summertime - grow in red cells but produce no pigment - African trypanosomiasis - sleeping sickness - dread infections caused by tsetse flies (glossina) - trypanosoma gambiense - West African sleeping sickness; humans are only reservoir - this leads to meningoencephalomyelitis and brain damage after several years - trypanosoma rhodesiense - East African sleeping sickness - cattle and antelopes - shorter course before brain damage - a red rubber chancre is common but not invariable, at the inoculation site - both T-cell and B-cell mediated immunity become impaired; there is an ineffective B-cell hyperplasia - at autopsy, a heavy chronic inflammatory infiltrate, with many plasma cells, is seen in the brain - prednisone therapy seems to help considerably - Chaga's disease - trypanosoma cruzi is carried by the reduvid kissing bug - poor homes of Latin America - the trypanosoma appears in the blood - causes cells to burst and release more trypomnastigotes to infect bugs - in both chronic and acute forms death results from cardiac involvement - disease can pass to unborn child - mechanism is unknown - leishmaniasis - carried by phlebotamine sand fly - kala-azar - black fever - involves infiltration of spleen, liver, nodes, marrow - cutaneous leishmaniasis - tropical sore - a mild, self-limiting lesion in warm countries of both worlds; organisms are controlled by granuloma formation ; mucucutaneous leishmaniasis is in South America - primarily chronic, non-healing ulcers; diffuse cutaneous leishmaniasis occurs when there is extreme T-cell dysfuntion - looks clinically like leprosy Worms - whenever ther are lots of eosinophils, look for Charcot-Leyden crystals, composed of a strongly alkaline protein from eosinophil granules Intestinal roundworms - ascariasis - ascaris lumbricoides is a big roundworm up to a foot long; larvae hatch in stomach, travel through the lungs, and settle in gut - can cause dyspnea, can occlude the gut, can plug bile duct - trichuriasis - whipworm - dwells in gut with head in crypt - eggs are ingested with fecal contamination - can be fatal under poor sanitation - enterobiasis - pinworms - enterobius vermicularis causes night-itch when migrates to anal area - lifecycle entirely within intestine; infection is contagious within households - scotch tape test demonstates diagnostic eggs - hookworm - necator and ancylostoma bite into duodenal mucosa and nibble on blood cells - acquired from soil - enter through soles of feet into the body - pass through the lungs and are coughed up and swallowed - usual problem is iron deficiency - strongyloidiasis - strongyloides stercoralis is endemic in much of the world - larvae mature in soil; in immunosuppressed patients can mature in gut and cause superinfection Tissue roundworms - visceral larva migrans - occult infection is produced when 1/2 mm larvae of toxocara travel among human viscera in a vain search for a place to develop into adults - abdominal and lungs are hit hardest - lots of circulating eosinophils - cutaneous larvae migrans - localized to skin - dacunculus medinensis - a big worm up to 12 cm long - fresh-water cyclops - results from exposure to contaminated water - humans are required for life cycle - causes painful nodule in the skin - one snake - asclepias - whose portfolio was healing and medicine - two snakes - Hermes - trichinosis - infection by trichinella spiralis follows ingestion of uncooked meat with live cysts - the worms encyst in individual striated muscle cells beyond the reach of the immune system - can cause myalgia and cardiac failure - prefer well-oxygenated muscle Filarias - lymphatic filariasis - infection by Wucheria bancrofti or Brugia malayi - carried as larvae by mosquitos - travel by bloodstream - plug lymphatics, can produce granulomas that obstruct lymphatic channels - most people mount a good response, which is the cause of tropical eosinophilia - onchocerciasis - river blindness - infection by onchocerca volvulus - worm whose larvae are transmitted by black flies in African and Latin America - vectors must breed in water - severe dermatitis results, elephatiasis in extreme cases - minor tropical filariae - rarely cause devastating illness, but can see Loa Loa worm travelling under conjunctiva - zoonotic filaria - dirofilaria - dog heartworm - can grow in human heart - can produce coin lesion in lung Tapeworms - intestinal tapeworm infections - taenia saginata - beef tapeworm - taenia solium - pork tapeworm - hymenolepis nana - dwarf tapeworm - diphyllobothrium latum - fish tapeworm - may plug the bowel or take up available vitamin B12 - cysticercosis - ingest egg of a pig tapeworm - prefers the brain - common cause of epilepsy in developing countries - echinococcus - hydatid disease - lives in intestines of dogs - larvae go into liver and other places and form large cysts - cysts compress organs and cause severe morbitity Trematodes - fascioliasis - sheep liver fluke - fasciola hepatica - people aquire it from eating watercress contaminated with eggs - worm live in biliary tree - produces fibrosis and obsrtuction - clonorchiasis - chinese liver fluke - clonorchiasis sinensis aquired from eating poorly-cooked fish - deformity and scarring of the liver - places patient at high risk of cholangiocarcinoma - fasciolopsiasis - pig is reservoir, reproduce in certain snails - paragonimiasis - oriental lung fluke - inhabits lung and causes morbidity in Far East - life cycle requires both snail and crustacean - cough up eggs are swallowed and passed into feces - schistosomiasis - blood flukes - inhabit veins of humans - infection from contact with contaminated water - eggs have razor sharp spines to cut through intestines - S. mansoni - Africa, Latin America - hepatic fibrosis and cirrhosis - S. hematobium - Egypt - bladder fibrosis and carcinoma - S. japoncium - China, Philippines - hepatic fibrosis and cirrhosis - when portal hypertension supervenes, the eggs will embolize to the lungs to produce pulmonary hypertension and a miserable death - kaytayma fever - an allergic illness that results when the schistosome larvae first penetrate human skin and enter the bloodstream - S. mansoni - oval egg, large lateral spine - S. hematobium - oval egg, large terminal spine - S. japonicum - round egg, small lateral spine