How to use these notes: I would suggest reading through comprehensively only if you have oodles of time before

your exam or if you are still in stages of learning microbiology from the ground up. After all, I wrote these notes for myself, in my own shorthand, so your time invested in reading FA or CMMRS an extra time would be infinitely better spent. Having said that, a quick skim over the bolded points or sections/pathogens you are weak in may help fill in some gaps or give a new perspective. The format of the notes is Naths Problem-Based Micro + FA mnemonics + CMMRS + Wikipedia filling. The bolded points are things that were asked on my school exams + things that were asked in qbanks I used + things that were asked on my COMLEX and USMLE exams + things I felt were worth emphasizing. To learn RNA viral structures in one night and cold, I used this mneumonic:
[Link]/mmsa/Documents/[Link]

(Note: combine it with the FA virus table; take note that all viruses above coronavirus are SS + sense icosahedral, and all viruses under it are SS - sense helical; coronavirus is mixed) Oh yeah, and know meningococcus inside and out. It made an appearance half a dozen times on both COMLEX and USMLE. Good luck.

Random points: HACEK endocarditis (Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella) ToRCH3S-List perinatal (Toxoplasmosis, Rubella, CMV, HSV, HIV, HBV, Syphilis, Listeria. Also B19) Silver stains: PCP and other fungi, legionella Giemsa: campylobacter, leishmaniae, malaria, chlamydia Replication machinery: (-)RNA viruses bring RNA-depdendent RNA polymerase and convert (-)RNA > (+)RNA. Retroviruses bring reverse transcriptase, integrase, protease. Poxvirus brings its own DNA-dependent RNA polymerase. C3 complement deficiency causes predisposition to infection by enteric Gram- rods, such as E. coli.

C6 (C5-C9) complement deficiency (late-acting component) causes susceptibility to encapsulated organisms, such as Neisseria meningitis. Neutrophil dysfunction leads to infection with Gram+ organisms and Pseudomonas. Cell-mediated (T-cell) deficiency leads to intracellular (viral, mycoplasma), parasitic, and fungal infection. Can only use IgM to diagnose disease in infant, since IgG may have come from mother.

Compendium
Respiratory Tract Bugs Viruses are by far the most common cause of URIs, whereas bacteria more common in pneumonia. Most common URI is the common cold (rhinovirus in adults, coronavirus in children). Pharyngitis most often a virus (rhino, corona, adeno, entero, influenza, EBV), although older children (5-15) prone to S. pyogenes, which is the only cause that should be treated. Laryngitis typically viral, self-limiting. Sinusitis viral or bacterial, in latter presenting with fever, purulent discharge, and sinus tenderness; otitis media can be primary, but usually secondary bacterial following a viral URI (bacterial causes for both: S. pneumoniae, H. influenzae, M . catarrhalis). Tracheobronchitis in patients without COPD mostly viral; with COPD usually bacterial (S. pneumonia, H. influenzae, M. catarrhalis). Croup (laryngotracheitis) is seen in children < 3 with a primary viral infection, usually parainfluenza virus. Typical pneumonia marked by sudden onset of chills, fever, dyspnea, and productive cough with purulent sputum (may be blood tinged), and possibly pleuritic pain. PE reveals fever, tachypnea, tachycardia, and rales. CXR shows consolidation. Usual cause is S. pneumoniae, Klebsiella pneumoniae, H. influenzae, M. catarrhalis, and S. aureus. S. pneumoniae and S. aureus most common cause of post-viral (influenza) pneumonia. Atypical pneumonia has a gradual onset of nonproductive cough and dyspnea, with extrapulmonary signs such as HA, sore throat, and diarrhea. PE reveals fever, tachypnea/tachycardia. CXR shows no consolidation; may show interstitial infiltrates. It does not produce bacteria on smear or respond to beta-lactams. Mycoplasma, Chlamydophila, and Legionella are the major causes. In the very young, RSV and influenza may be the cause. In the immunocompromised, CMV, Pneumocystis jiroveci, and Aspergillus fumigatus. In patients with suppressed cell-mediated immunity (steroids), Nocardia asteroides. In adults, adenovirus and VZ can cause ARDS. Adenovirus naked ds linear DNA virus; fever and pharyngitis, with various serotypes also causing conjunctivitis (especially by waterborne route), lower respiratory syndromes (especially by aerosolized droplet route), gastroenteritis (in daycare infants, fecal-oral route; serotypes 40 and 41), and hemorrhagic cystitis. Ad14 is emerging lethal serotype. No Tx.

Epstein-Barr virus ds DNA herpesvirus. Causes fever, pharyngitis, lymphadenopathy (esp posterior cervical), as well as fatigue, loss of appetite, malaise, hepatitis, and hepato/splenomegaly. CBC: leukocytosis, with lymphocytosis and monocytosis exceeding 50% (with atypical cells > 10%). Infect epithelial cells of pharynx, followed by B cell infection (CD21); become part of memory B-cell population, and occasionally rotate back to pharynx for another round of viral amplification. Hosts immune system strength is directly proportionate to suppression of clinical symptoms of IM. Response yields CD8 atypical lymphocytes (Downey cells). Associated with Burkitt lymphoma (Africa), nasopharyngeal carcinoma (Asia), oral hairy leukoplakia (HIV), and Non-Hodgkin lymphoma (HIV). Monospot test (heterophile antibodies cause agglutination of sheep RBCs) is dx. Disease self-limiting; NSAIDs/steroids may help pharyngeal pain; (val)acyclovir lowers presence of virus. Ampicillin and amoxicillin cause rash. Streptococcus pyogenes Gram + cocci found in chains, catalase-negative, betahemolytic, and bacitracin-sensitive. Pharyngitis, especially with petechiae and tonsillar exudates, and cervical lymphadenopathy. Transmitted by respiratory droplets. Using streptolysin O and S may spread through tissue planes and cause an abscess. Erythrogenic toxin (lysogenic toxin) causes Scarlet fever: sandpaper rash starting on trunk and spreading outward, especially in skin creases (armpits/inguinal); face less affected, though circumoral pallor and strawberry tongue characteristic; although palms/soles not affected by rash, desquamation occurs a week later. Major virulence factor, M protein (dictates serotype), protects from complement activation and facilitates antibody reaction, which may become rheumatic fever: Subcutaneous nodules (like RA), Polyarthritis, Erythema Marginatum, Chorea, Carditis (SPECCulate; ASO test confirms). Dx: throat culture, RADT test. Tx: PCN. Corynebacterium diphtheria Gram + club-shaped bacteria with metachromatic granules, non-spore forming, aerobic, non-motile. Mostly eradicated, but still occurs in less-developed countries. Transmitted via respiratory droplets and direct contact. Toxin acquired by lysogeny ADP-ribosylates (inhibits) EF2 > stops mRNA>protein, causing necrosis in pharynx and forming a gray-brown pseudomembrane. DTaP vaccine available. Tx: diphtheria antitoxin neutralizes toxin. Abx reduce infection only. Mumps virus enveloped ss RNA paramyxovirus. Causes Parotitis, Orchitis, aseptic Meningitis (POM-poms) as well as submaxillary gland inflammation. Acquired via rerspiratory secretions. Can cause sterility, esp. after puberty. Has F (fusion) protein and so produces multinucleated giant cells. Prevention: MMR vaccine. No tx. Parainfluenza virus (PIV type 1 > 3 > 2 > 4) enveloped ss RNA syncytial paramyxovirus. Acquired through inhalation of infected droplets, affecting mainly larynx, and often trachea and bronchi, causing edema and narrowing of upper

airway and vocal cords, leading to stridor and barking cough (croup). Dx: Neck XR to rule out epiglottitis, rapid antigen detection, and viral cultures. Tx: nebulized epi, nebulized glucocorticoids. Bordetella pertussis Gram rods, non-motile, aerobic. Transmission by respiratory route, usually from older persons to nonimmunized infants. Bacteria noninvasive, but produce tracheal cytotoxin that paralyzes the cilia and kills mucosa (as well as pertussis toxin, which inactivates Gi protein > increases cAMP > PKA > CFTR > mucus), and end up in the bronchi and bronchioles. A muco-purulo-sanguineous exudate is formed, compromising small airways and leading to paroxysmal cough with whooping, and sometimes post-tussive vomiting. Prevention: DTaP vaccine. Tx: Mucus suctioning; macrolides. Haemophilus influenzae Gram coccobacillary rods. Cultured on chocolate agar, requiring factors X (hematin) and V (NAD+); falls into two groups: encapsulated (type b, or Hib) and unencapsulated (nontypable, or NTHi). Although Haemophilus species are normal URT flora, NTHi often cause disease in adults, particularly COPD patients. IgA protease allows NTHi to colonize respiratory mucosa, especially bronchi to cause chronic bronchitis, otitis media and sinusitis. Hib cause disease in children (6 mo 3 yrs), namely epiglottitis, meningitis, otitis media, pneumonia (EMOP), and bacteremia (septic shock). Prevention: Hib vaccine - polyribosyl ribitol phosphate of capsule conjugated to protein. Tx: ceftriaxone (with steroids 20 mins prior if for meningitis). Moraxella Catarrhalis Gram rods; pneumonia, acute exacerbation of COPD, otitis media in children. Streptococcus pneumoniae Gram + diplococci. Encapsulated, alpha-hemolytic (pneumolysin), Optochin-sensitive. Transmitted via aerosolized droplets; IgA protease aids in colonization of the upper airway; it is then aspirated into lower airways, where failure of normal defenses leads to proliferation and inflammation. S. pneumoniae is the most common cause of pneumonia, especially with sickle cell anemia, smoking, asplenia, and post-viral infection; often produces a sudden onset of symptoms and rusty sputum, and can have empyema and bacteremia as complications. Also a cause of acute exacerbation of chronic bronchitis, and common cause of Meningitis, Otitis media in children, (Pneumonia) and Sinusitis (MOPS). Exudates spread rapidly between alveoli (by pores of Kohn) to involve whole lobe. Empirical tx of CAP: 3rd gen cephalosporin + macrolide, or quinolone. Tx: PCN; vancomycin if resistant. A vaccine of 23 most common serotypes is available. Klebsiella pneumoniae Gram rod of the Enterobacteriacea family. Nonmotile, encapsulated, urease-positive, lactose-fermenting. It is a common nosocomial pathogen, including nosocomial UTI (due to catheter), nosocomial URI (due to airway manipulations), and post-surgical intra-abdominal infections, and

wound infections, any of which may cause subsequent bacteremia from any point of entry. May be part of normal oropharyngeal or intestinal flora in alcoholics and diabetics, and gain access to LRT after aspiration. Presents with bronchopneumonia (patchy opacity) on CXR; lung abscess in polymicrobic infections results in necrotic damage of alveoli, cavity formation, and thick currant jelly or mucoid" sputum. Tx: broad-spectrum PCN (piperacillin, ticarcillin), aminoglycosides, quinolones. Mycoplasma pneumoniae (walking pneumonia) bacteria without cell wall (doesnt Gram stain), but containing sterol in membrane. Grown on Eatons agar. Presents as fever, headache, and nonproductive cough. CXR may reveal patchy infiltrates (almost always bilateral). Transmission via aerosolized particles, often occurs with 2-3 week intervals between family members or in schools, prisons, military, etc. Bacteria deposits and adheres in lower respiratory tracts and inhibits ciliary movement, resulting in prolonged cough. High titer of IgM autoantibodies may cause agglutination or lysis of RBCs. Young males may develop an extensive rash known as erythema multiforme (Stevens-Johnson syndrome). Dx: serologic tests - cold agglutination > 1:32; IgG titers rise in 2-3 weeks. Tx: erythromycin or tetracycline. Chlamydophila pneumonia, TWAR strain causes atypical pneumonia similar to mycoplasma. Legionella pneumophila (legionellosis) flagellated, Gram rods. Causes high fever, cough, diarrhea, and severe headache. CXR: consolidation. Organism survives in water for months and is often associated with whirlpools, spas, cooling towers, humidifiers, etc. When aerosolized or aspirated, the bacteria are inhaled, adheres to epithelium, is phagocytosed, but prevents phagosome-lysosome fusion, and multiplies in the macrophages, destroying them. Pontiac fever is the milder version of legionellosis, a flu-like illness occurring shortly after exposure. Dx: fluorescence antibody staining of BAL or silver stain of tissue (Gram stains poorly); hyponatremia/hypophosphatemia often seen; antigen present in urine; cultures on charcoal yeast extract agar with iron and cysteine. Tx: macrolide, quinolone, or doxycycline. Influenza ss RNA enveloped orthomyxovirus. A, B, and C types exist, further subtyped on basis of surface antigens H (hemagglutinin, used to attach to cells) and N (neuraminidase, used to sever budding viral vesicles from membrane). A(H1N1) and A(H3N2) are current human types (+ B = vaccine); swine and avian types also transmissible. H5N1 = next pandemic. Antigenic shift = genetic reassortment that results in new surface epitopes and strains. Antigenic drift occurs when a point mutation results in a change of a specific epitope. Transmission by coughing/sneezing; virus uses neuraminidase to degrade mucus and enter URT/LRT epithelium, where it replicates. Sudden presentation of fever, chills, muscle aches, and cough. Desquamation of bronchial/alveolar epithelium causes loss of

primary defense, and predisposes to secondary bacterial pneumonia (esp. staph). Tx: amantadine or rimantadine for type A if within 48 hours of onset > ? Zanamivir or oseltamivir (neuraminidase inhibitors) for types A and B. Reye syndrome: childhood hepatoencephalopathy associated with VZV and influenza B treated with aspirin. RSV (bronchiolitis) ss RNA enveloped paramyxovirus. Contains a fusion (F) protein, which leads to fusion of epithelial cells into a syncytium. Common in winter months. Infects mucous membranes of nasopharynx and spreads to bronchioles, where inflammation (IgE and type III HS) restricts airways, leading to wheezing and hyperinflation of chest. Premature infants, infants with congenital heart and lung problems, and children on chemotherapy are at high risk for pneumonia and encephalitis. Dx: rapid antigen detection. Tx: palivizumab (neutralizes F protein); salbutamol for spasm; contact isolation. All mycobacterium species are acid-fast and Gram + bacilli. When any organ infected, TB in DDx! Mycobacterium tuberculosis acid-fast (stains mycolic acid) bacteria spread by respiratory aerosol. Bacteria are obligate aerobes, and therefore tend to cause disease in upper lobe. Once ingested by macrophages, they inhibit phagolysosome fusion, proliferate, and eventually burst the macrophages. Granulomas form to wall off infection, which may heal by fibrosis or calcification, visualized on CXR as lobar granulomas (Ghon focus) in the lower upper lobe or upper lower lobe, and perihilar lymph nodes (together called Ghon complex), reflecting primary infection. 90% of TB infections are latent, in which bacterial replication in granuloma is balanced by killing. Decline of cell-mediated immunity (due to age, illness, or overwhelming exposure) leads to reactivation and post-primary infection. Granuloma (now apical) becomes caseous and necrosis may break into a bronchus, discharging bacteria into exhaled air. Presentation may include cough with blood-tinged sputum, weight loss, night sweats. If untreated, may progress to miliary TB, an uncontrolled blood-borne disseminated spread, involving CNS (meningitis), T/L vertebral bodies (Potts), liver, pleura and pericardium, etc. Tx: empirical therapy with 4 drugs: isoniazid, rifampin, pyrazinamide, ethambutol. Prevention: BCG vaccine may be useful. Mycobacterium kansasii pulmonary TB-like disease Mycobacterium avium-intracellulare cause disseminated disease in AIDS, often drug-resistant. Mycobacterium leprae (Hansens disease) bacilli which are uncultivable in vitro, and prefer cool temperatures (infects skin and superficial nerves). Reservoir is US armadillos. Leprosy may be tuberculous (limited to a few hypoesthetic nodules) and lepromatous (diffuse nodules; cell-immunity fails to contain it). Tx: long-term dapsone.

Aspergillus fumigates (aspergillosis) mold, appearing as thin septate hyphae that branch at a V-shaped (45 degree) angle, with rare fruiting bodies; not dimorphic; secretes aflatoxin. Inhalation of airborne conidia (spores) is the major route of infection, followed by invasion; phagocytes destroy hyphae in normal hosts, but granulomas develop in neutropenic and CGD patients, with fungal hydrolases causing endothelial damage. Cytotoxic drugs that lead to neutropenia greatly increase susceptibility. Sometimes associated with building reconstruction or renovation. Presents as fever, dry or bloody cough, dyspnea, and pleuritic chest pain. Hematogenous dissemination often occurs (brain, kidneys, etc.) Aspergillus grows profusely in TB cavities, producing a fungus ball visible on CXR, which may lead to massive hemoptysis. Also, may cause allergic broncho-pulmonary aspergillosis asthma-like (Ige-mediated type I HS reaction) caused by an immune response to hyphae colonizing the airways which may progress to bronchiectasis. Tx: voriconazole. Recovery from neutropenia is necessary. Systemic mycoses: next 3 cases are dimorphic fungi, growing as mold in environment (mold = cold), but converting to yeast form at body temperature in the host. Tx: fluconazole, ketoconazole, or itraconazole for local infection (inhibit lanosterol>ergosterol). Amphotericin B (binds ergosterol and forms membrane pores) and flucytosine (converts to 5-FU) for systemic. Histoplasma capsulatum (histoplasmosis) dimorphic fungus, visualized as thinwalled, oval yeasts. Endemic in Midwest, esp Ohio and Mississippi river valleys. Grows in soil contaminated with bird (starlings) or bat droppings; becomes airborne when disturbed, gets inhaled, and is endgulfed by macrophages in alveoli, where it transforms into budding yeast form, growing within the macrophages (only yeast to do that). In the immunocompromised or COPD patients, caseous granulomas may form, resembling TB, and infection may disseminate to lymphatic organs. Presents as fever, night sweats, cough; fatigue and weight loss due to cytokine response. Blastomyces dermatitidis (blastomycosis) dimorphic fungus, visualized as a yeast with broad-base budding in biopsies. Associated with decaying vegetation and endemic in states SE of Mississipi River. After inhalation, forms granulomatous nodules, some of which may cavitate, visible on CXR. In some patients, lymph/blood spread to other organs occurs, primarily skin and bones. Skin shows hyperplasia with microabscesses in dermis, presenting as verrucous skin lesions with pustular features. General symptoms include fever, productive cough, pleuritic pain and weight loss. Coccidioides immitis (coccidioidomycosis) - dimorphic fungus, visualized as thickwalled, nonbudding spherules, not yeasts. Associated with disturbance of soil (esp. earthquakes) and endemic in SW United States (esp San Joaquin Valley). After inhalation of arthroconidia, it develops into a spherule and prompts chronic

granulomatous inflammation similar to TB, with possible caseation. Cavitation may also occur. Dissemination may travel to skin, causing erythema nodosum (HS reaction in fat), and to bone and meninges. General symptoms include fever, dry cough, night sweats, HA, and weight loss. Nocardia asteroids (nocardiosis) filamentous (beaded) Gram + and weakly acidfast aerobic rod. Associated with immunosuppression or immunosuppressive drugs (esp. steroids). Inhalation of contaminated dust from soil is major route, and following engulfment bacteria grow within phagocytes. In the immunocompromised, the infection is not contained and inflammatory endobronchial masses and abscess formation follow, sometimes with cavitation. Presents with chronic fever, night sweats, cough, myalgia, and weight loss. Enlarged hilar and medistinal nodes and nodular infiltrates on CXR. CNS involvement is common, presenting with HA, lethargy, confusion, and seizures, but any organ can be infected. Tx: Sulfonamides (sulfa) Actinomyces israelii (thoracic actinomycosis) filamentous Gram + anaerobic rod?. Normal oral and GI flora, which can cause cervicofacial abscesses with poor oral hygiene, abdominal/pelvic infection with IUDs, or thoracic actinomycosis with aspiration. A. israelii requires synergistic presence of other commensals, usually anaerobes, to cause infection. Once infection is established, a chronic suppurative abscess spreads by direct extension to nearby tissues, including chest wall. Presents with chronic fever, productive cough, dyspnea, weight loss, and sometimes oral/facial/chest abscesses. In infected tissue, organism forms yellow dense masses known as sulfur granules that may drain through sinus tracts in skin. Cultures resemble molar teeth. Tx: Penicillin G. Pneumocystis jiroveci (pneumocystis pneumonia) opportunistic yeast causing interstitial pneumonia in the immunosuppressed. Fairly ubiquitous in nature; present in latent state in most people. HIV alters the mannose receptor-mediated binding and phagocytosis of P. jiroveci by macrophages. Although organism remains extracellular, colonization of lung results in deficiency of surfactant secretion and interstitial pathology. Dx: BAL; visualized by methenamine silver stain. Interstitial markings on CXR. Tx: TMP-SMX, pentamidine, or dapsone. Prophylaxis with one of these should be started once CD4 < 200. Pseudomonas aeruginosa Gram rod. Strictly aerobic and non-lactose fermenting, oxidase positive. Produces pyocyanin pigment; has a grapelike odor. Ubiquitous, especially in water, and an important nosocomial pathogen. Transmission by ingestion of contaminated water or food, by aerosolization, or insertion of infected medical equipment. CF patients colonized early in life. Organism becomes mucoid inside the body, by a production of an alginate capsule (cough with green, thick sputum). Produces endotoxin, which stimulates chronic inflammation in airways, disturbing pulmonary function and causing most of morbidity in CF. Also acquires exotoxin A, which, like diphtheria, ADP-ribosylates (inhibits) EF2. Causes

Burn/wound infection, Endocarditis (right-sided in IV drug users, same as S. aureus) Pneumonia, Sepsis, characterized by ecthyma gangrenosum, or black skin lesions; External otitis (swimmers ear); UTIs (complicated, esp. with hospital catheter use), Drug-use/Diabetic Osteomyelitis, and hot-tub folliculitis. Tx: aminoglycoside plus extended-spectrum PCN (piperacillin, ticarcillin). Staphylococcus aureus Gram + cocci appearing in grapelike clusters. Coagulase positive and catalase positive. Secretes protein A (binds Fc of Ig). Humans nasal and skin carriers are the reservoir, and transmission can be by aspiration or hematogenous (IV drug use). S. aureus is often a postviral disease (esp influenza), owing to the virus destroying the ciliary defense and mucociliary ladder, allowing S. aureus to colonize the lung. The hallmark of staph infection is the abscess, consisting of a fibrin wall that encloses a central core of pus containing organisms and leukocytes. Also associated with purulent conjunctivitis, spread from nasopharynx during influenza. Tx: nafcillin, or vancomycin. GU bugs Lower UTI (cystitis) associated with dysuria, frequent urination, and suprapubic pain. Upper UTI (pyelonephritis) associated with fever, flank pain, dysuria, and n/v. UTI uncommon in children, often being anatomic or functional abnormalities, or in men, often being tract abnormalities such as an enlarged prostate. Most common causes are E. coli and S. saprophyticus; also seen are Gram rods (Proteus, Klebsiella) and Gram + cocci (Enterococcus, S. aureus); nosocomial E. coli, Klebsiella, and Pseudomonas seen in catheterization. Lab findings include pyuria (10 neutrophils per HPF; alternatively, gives positive leukocyte esterase dipstick test) and bacteriuria. White cell casts suggest pyelonephritis. STDs in men characterized by urethritis (painful urination or penile discharge) or penile ulcers. STDs in women characterized by cervicitis, or, if asymptomatic, may progress to PID. Purulent discharge usually N. gonorrhea; C. trachomatis is clear discharge and can also cause painful adenopathy (lymphogranuloma venereum). Both chlamydia and gonorrhea should be treated when either is detected (ceftriaxone + azithromycin). Most common cause of painful genital ulcers is HSV; Haemophilus ducreyi (chancroid) can also cause them; T. pallidum (syphilis) causes an ulcer that is painless. Symptoms of vaginitis (caused by Trichomonas vaginalis or Candida albicans) and vaginosis (Gardnerella and Mobiluncus) are nonspecific and require pH and direct microscopy. Escherichia coli Gram rods displaying typical enterobacteriaceae group antigens: O antigen carrying LPS, H antigen on flagella (except shigella), and K antigen of the polysaccharide capsule. Mostly a result of intercourse. Attachment to uroepithelium stimulates desquamation and inflammation; mucosal invasion is rare. If untreated, pathogens ascend to ureters/kidneys by using the flagella. Tx: amoxicillin, TMP-

SMX, or fluoroquinolone. Aminoglycosides are heavy duty but toxic. E. coli may also cause neonatal meningitis/sepsis, pneumonia, intra-abdominal infections, and enteritis. Treponema pallidum (syphilis) spirochetes containing axial filaments (endoflagella) visible by darkfield microscopy; detectable by RPR and VDRL tests; confirmed by FTA-ABS, specific to treponemal antibodies (turns + first, stays + the longest). Transmitted either sexually or transplacentally. Following penetration of mucous membrane or dermis (where microabrasions present), painless chancre appears at site. Because outer membrane is rich in lipid, organism evades immune recognition and opsonization, entering blood and lymphatics. Plasma cell-rich dermal infiltrates occur within 6 months, appearing as a maculopapular copper penny rash (esp. on palms/soles), lymphadenopathy, condylomata lata (pale painless warts), fever, and fatigue. Secondary syphilis may become latent or progress to tertiary (15% of cases), in which type IV HSR to organism results in gummatous ulcerations (granuloma > necrosis), heart lesions (aortic aneurysm), and CNS lesions: meningitis, sometimes involving vasculature > stroke; tabes dorsalis, which destroys posterior column and dorsal root > ataxia and Charcot joints; general paresis, or weakness; disease of neurons > psychosis; and Argyll-Robertson pupils. Tx: Penicillin G. Congenital syphilis occurs within 2 years of birth; 8th CN deafness, periosteal inflammation destroys cartilage in nose/palate, giving nose a sunken appearance (saddle nose), and bowed tibia (saber shins). Upper incisors widely spaced with a central notch, and molars have many cusps (mulberry molars). T. pertenue, a related spirochete, causes yaws (infection of skin and bones, appearing as painless nodules or warts), endemic in tropical countries. HSV ds DNA enveloped virus. Infected host cells reveal presence of multinucleated giant cells on a Tzanck smear (along with VZV). HSV-2 mainly sexually transmitted, either through mucous membrane or abraded skin. Itchy, painful lesions called ulcers, blisters, or vesicles; cause is cytolytic effect of replicating virus on epithelium. Virus then travels to dorsal sensory ganglia, where it becomes latent. Transient suppression of cell immunity, as in stress, fever, UV light, and tissue damage allows virus to be transported down the axon to replicate again at or near original site of entry. Tx: acyclovir; foscarnet. Neonatal HSV mostly HSV-2, may be localized to skin, eyes, and mouth, or may involve CNS (encephalitis), hepatitis, pneumonitis, etc. Tx: acyclovir. HPV ds circular DNA nonenveloped virus. There are over 100 types, which may be classified as genital (16 and 18 associated with cancer) or cutaneous. Spread is sexual, and most infections are asymptomatic. HPV infects squamous epithelial cells of basal layer of skin or mucous membrane (where proliferation leads to cervical dysplasia and appearance of a wart), replicate in nucleus (infected cells exhibit

nuclear atypia), and are released with normal desquamation of cells. PE may reveal genital warts (condylomata acuminata), and lesions on/erythema of the cervix. Tx: mainly the removal of wart. Neisseria gonorrhoeae Gram nonencapuslated diplococci, spread primarily by sexual contact. Glucose-fermenting (gonococci = glucose) Binds to columnar mucosal epithelial cells (using pili), creates IgA protease to hydrolyze antibodies, and outer membrane proteins protect against phagocytosis and neutrophil degranulation. Reaching the subepithelial matrix initiates inflammation, resulting in dysuria and urethral discharge in men (possibly leading to epidydimitis), and cervicitis with lower abdominal pain and cervical discharge in women (possibly leading to PID). In both, gonorrhea can cause pharyngitis in oral sex, gonococcal conjunctivitis in newborns, and disseminated gonococcal infection, settling in joints (septic arthritis, in sexually active patients) and skin (rash). Tx: single injection of ceftriaxone. Chlamydia trachomatis obligate intracellular bacteria, dependent on host to produce ATP for them. Types D-K (dick) cause urethritis in men and PID in women (leading cause of infertility), as well as neonatal pneumonia and conjunctivitis. After infection through abrasions on mucosal surface, organism in its inert elementary body form attaches to columnar epithelial cells on cervix and stimulates uptake. It can be visualized as a vacuole called a cytoplasmic inclusion with Giemsa stain. Here the organism turns to active reticulate bodies, multiply, convert back to elementary bodies, and get released from cell for another round of reinfection, eventually reaching endometrium and endosalpinx. Other syndromes include trachoma (leading cause of blindness worldwide), caused by serotypes A, B, and C; serotypes L1-L3 cause lymphogranuloma venereum (painful inguinal lymphadenopathy following painless genital lesion, which in homosexual males can cause granulomatous proctitis). Reiter syndrome can manifest within 6 months of infection, owing to autoimmunity (HLA B-27). Tx: doxycycline or oral erythromycin. Trichomonas vaginalis pear-shaped flagellated protozoan that causes vaginitis with yellow or greenish foamy/frothy vaginal discharge with foul odor, and vulvar irritation/itching; easily identified in wet mount by their motility. Cervix may have macular erythematous lesions (strawberry cervix). Vaginal pH usually > 4.5. Transmission by direct contact; men usually asymptomatic; women asymptomatic or have inflammatory reaction after an incubation period of 4-28 days. Treat both. Tx: metronidazole. Candida albicans yeast, appearing in secretions and tissue as pseudohyphae, with budding. C. albicans differentiated from other Candida species by germ tubes (short hyphal filaments) after 2 hours of cultivation at 37 degrees in human serum. Organism is normal commensal of mouth, GI tract, and female genital tract. Vaginosis occurs when vaginal flora is imbalanced, such as with antibiotic use.

Other syndromes include oral thrush, candidal esophagitis, skin infection where moist or rubbing (under breasts, perianal, diaper rash), nosocomial UTI, and systemic infection (via central line), disseminating to any organ. Tx: nystatin for superficial infections, amphotericin B for systemic. Gardnerella and Group B strep are most common organisms in female genital tract. Gardnerella / Mobiluncus cause vaginosis and are associated with a strong fishy odor. Presence of vaginal epithelial cells with attached microorganisms (clue cells) in wet mount is diagnostic. Tx: metronidazole. HIV ss RNA retrovirus; sore throat, fever, lymphadenopathy, possibly a maculopapular rash 3-6 weeks after exposure. Transmitted through sexual contact, IV drug use, and across placenta. Infects APCs and CD4s by binding its envelope protein gp120 to lymphocytes CD4 and either CCR5 or CXCR4 (CXCR5 on macrophages); gp41 allows membrane penetration. Reverse transcriptase makes ss DNA (-vudine and tenofovir); DNA polymerase (native) makes ds DNA; integrase inegrates. After RNA > DNA, and integrated into hosts, activation of lymphocyte translates it. Finally, protease cleaves viral proteins/enzymes (-navir). Gradually destroys lymph node residents over a latent period, until T count low enough (AIDS = <200). In AIDS, patient susceptible to opportunistic infections (candida albicans, pneumocystis jiroveci, and atypical mycobacteria), reactivation of latent infections (EBV, CMV, TB), and cancers (B cell lymphoma due to EBV and Kaposis sarcoma due to herpesvirus-8). Antibodies ineffective against lipid glycoproteins because gp120 mutates. PPD negative in HIV patients. Proteus mirabilis very motile Gram -, urease + rod; common cause of UTI, esp nosocomial. Produces alkaline urine, due to urease splitting urine > NH3. Urease production of Proteus promotes the formation of struvite kidney stones by increasing alkalinity of urine. Tx: ampicillin. Serratia Gram rod; causes UTI and wound infections; produces bright red pigments. Haemophilus ducreyi Gram rod causing chancroid painful genital ulcer with unilateral swollen, painful inguinal nodes. DDx is syphilis (painless ulcer and nodes), herpes (start off as vesicle), Chlamydia (lymphogranuloma venerum is painless, ulcer of LGV disappears before nodes enlarge). Tx: azithromycin Ureaplasma Urealyticum non-Gram-staining bacteria, part of normal GU flora, which may cause urethritis. Urease-positive. Tx: macrolide or tetracycline.

GI bugs

All transmitted by fecal-oral route, minus Strongyloides and Schistosoma, which enter through skin, and bloodborne hep B and C. Illnesses can be divided into several syndromes: - Gastritis is the result of H. pylori infection. - Food poisoning (pre-formed toxin): affects upper GI; nausea/vomiting; can have explosive diarrhea. Rapid onset (1-3 hours) and resolution (12-36 hours); botulism, in contrast, can be fatal without supportive care, and should be considered in any patient with descending paralysis. - Acute infectious diarrhea (gastroenteritis) may be: Secretory - affects proximal small intestine, causing watery diarrhea by stimulating fluid and electrolyte secretion (enterotoxic E. coli and V. cholerae); no WBCs in stool; typically self-limiting. Viral causes are the most common (rotavirus in kids, norovirus in adults, adenovirus in both; stool viral antigen test diagnostic). Prolonged diarrhea, foul-smelling shit and flatulence particularly associated with protozoa (Giardia, Cryptosporidium, and Cyclospora). Dysentery invasion of colon, causing fever, pain/cramps, and bloody mucopurulent diarrhea with heavy WBCs. Bacterial causes are the most common (most common invasive bacteria in U.S. are Campylobacter, followed by Shigella, Salmonella, Yersinia and C. difficile). Usually preceded by 1-2 days of watery diarrhea. SSYC may cause B27 syndromes, especially Reiter syndrome. Hemorrhagic colitis - affects colon; pain/cramps, frank bloody diarrhea (few or absent WBCs). Caused by Enterohemorrhagic E. coli. Secretory and osmotic diarrheas should be differentiated from invasive right away by fecal smear for neutrophils. If inflammatory cells present, have to do stool culture (esp. for SSCY). O & P helps diagnose amebic dysentery, giardia, or helminths. - Chronic diarrhea due to immune compromise Cryptosporidium (self-limited in healthy patients), microsporidia, CMV (ischemic ulcer), Cyclospora. Once CD4 count is < 50, mycobacterium avium may involve any region of GI. C. difficile should be considered as most AIDS patients on antibiotics. - Typhoid (enteric) fever is a systemic febrile illness of 3-5 week duration, caused by Salmonella typhi, marked by bacteremia, metastatic spread and leading to multipleorgan dysfunction. -Hepatitis may be caused by bacteria (Leptospira spp), viruses (A, B, C) or parasites (S. mansoni). Helicobacter pylori Gram rod, causing severe gastritis (which > profound reduction in acid secretion). Occurs in as many as 30% of adults in US. With adequate immune response, gastritis becomes less severe following infection and most remain asymptomatic their entire life, but in susceptible individuals (advanced age, low SES, stress) may develop into peptic ulcer disease, atrophic gastritis, adenocarcinoma (via cagA factor), and B-cell lymphoma. The bacteria secretes urease, which creates a cloud of ammonia (buffer) that protects it against stomach

acid. Elicits chronic gastritis, characterized by mononuclear cell infiltration. Dx: Urea-breath test, fecal antigen test, and serology. Tx: metronidazole, bismuth and amoxicillin; or (more expensive) metronidazole, omeprazole and clarithromycin. Food poisoning: latex agglutination may help detect toxin. Staphylococcus aureus heat-stable enterotoxin, causing mostly n/v. Often from purulent discharges of infected finger or eye, or nasopharyngeal secretions from food preparer. Meats and mayonnaise. Bacillus cereus has heat-stable enterotoxin, causing n/v, and heat-labile enterotoxin produced in the gut, causing diarrhea. Reheated rice. Clostridium perfringens boxcar-shaped, heat-labile enterotoxin, with incubation time of 8-12 hours, causing watery diarrhea. Meats and gravy. Clostridium botulinum Gram + rod; spore-forming, obligate-anaerobe. Presents with decreased activity, descending flaccid paralysis, decreased oral intake, sluggish papillary response, hypotonia. Consider sepsis/bacterial meningitis, but both would have fever; botulism is afebrile. Usually caused by ingestion of spores in honey by infants (which then germinates in GI tract and produce toxin), or ingestion of pre-formed toxins (as from canned fruit) by adults. Attaches to cholinergic synapses and internalized into cytosol, irreversibly preventing release of Ach into neuromuscular junction. Tx: supportive therapy with mechanical ventilation. Equine antitoxin serum should be given as soon as possible, but antibiotics (in infants) are contraindicated, as bacterial lysis will increase level of toxin. Rotavirus naked ds RNA Reovirus with segmented genome. Most common cause of diarrhea, but affects mainly pediatrics. Common in winter months and associated with daycare. Transmitted by fecal-oral route, infects villi epithelium, and renders it unable to absorb nutrients, resulting in osmotic diarrhea, fever, and sometimes vomiting. Stool viral antigen assay is dx. Norovirus naked ss RNA Calcivirus, associated with explosive outbreaks; n/v occurs in most cases; diarrhea in about half. Virus occurs year-round, by fecal-oral route from contaminated food or water. Adenovirus and astrovirus also cause watery diarrhea, although less commonly. Giardia lamblia protozoa passed by fecal-oral route in cyst form, and living in upper small intestine in trophozoite (face) form. Usually from contaminated water supplies (campers/hikers) or recreational water (hot tubs/pools). Symptoms are gas, cramps/upset stomach, nausea, diarrhea with greasy, foul-smelling shit, and possibly dehydration and weight loss down the road. Symptoms begin in 1-2 weeks; last 2-6 weeks. Giardia neither invasive nor toxogenic; disrupts bush border by microvilli injury, causing villus atrophy and malabsorption diarrhea. Stool O & P and stool antigen tests are dx. Tx: metronidazole.

Cryptosporidium parvum protozoa existing as an oocyst containing four sporozoites. Spread by fecal-oral route, but mainly waterborne transmission. Upon ingestion, sporozoites released and infect GI tract, especially jejunum, by being vacuolated within and disrupting the microvilli. Watery diarrhea develops due to impaired absorption. In healthy individuals life cycle takes place only a few times, but in AIDS patients chronically repeated. Dx: tiny cysts appearing to lay on top of the brush border on acid-fast stain. Tx: Prevention and HAART. Cyclospora and Isospora acid-fast protozoa causing diarrhea in immunocompromised. Campylobacter Gram comma-shaped or S-shaped rods. Major virulence factor is flagella. Most common bacterial cause of diarrhea, associated with poultry and salads. Organism invades across epithelial surface, causing nonspecific neutrophilic and monocytic inflammation, especially in jejunum, similar to Crohns or UC. Presents as abdominal cramping and diarrhea, which become bloody. May cause reactive arthritis in HLA-B27, and Guillain-Barre. Self-limiting. Dx: grow at 42 degrees C. Tx: rehydration; erythromycin, if needed. Salmonella Gram motile rods; a non-lactose-fermenting facultative anaerobe; unlike Shigella, has flagella and produces H2S. Only S. typhi is encapsulated. Associated with poultry, beef, eggs, peanut butter, milk. Patients with reduced stomach acid at risk. Organism invades distal small intestine, causing neutrophil reaction. Damage to mucosa is self-limited but often yields cramping and bloody diarrhea. Being motile, may disseminate into bloodstream, where LPS and cytokins mediate sepsis; especially so in sickle cell patients, since sickling can cause infarcts in intestine. Tx: Fluoroquinolones (may prolong). Salmonella typhi Gram encapsulated rods (capsular antigen Vi is virulence). Associated with travel to South Asia. Acquired by fecal-oral route, bind to M cells, and invade Peyer patches. There is prominent infiltration ofmononuclear cells in colonic mucosa, although organism survives in macrophages. Bacteria eventually get into blood, causing bacteremia, where LPS causes sepsis. Monocyte delivery to liver and spleen causes hepatosplenomegaly. Presents as shaking chills and high fever, HA, diarrhea, bradycardia and rose spots on trunk, caused by thrombocytopenia. May survive in gall bladder, causing biliary tract damage, gall stones, and causing chronic carrier state. Tx is fluoroquinolones. Vaccine available. Shigella Gram nonmotile rods; facultative anaerobe. Grown on Hektoen agar. Humans are the only reservoir; fecal-oral transmission. Very virulent; as few as 10 organisms needed. Penetrate M cells in colon, and engulfed by macrophages, but survive and invade mucosa, causing it to slough off (pseudo-membrane) and ulcerate. Fever, abdominal pain, and watery diarrhea ( absorption) > mucoid

diarrhea with blood and pus (WBCs), and tenesmus. May cause Reiter syndrome. Tx: cipro, TMP-SMX. Yersinia enterocolitica Gram rod, more common in Canada. Associated with pet feces (puppies), contaminated milk, cheese, or pork. Invades M cells and penetrates epithelium of small intestine (esp terminal ileum), causing diarrhea and prominent RLQ pain (mimics appendicitis). Secretes heat-stable toxin. Iron raises virulence (people with hemolytic anemia/hemochromatosis likely to develop sepsis). E. coli O157:H7 (enterohemorrhagic) Gram rods; indole-positive, lactose-positive, sorbitol-nonfermenting, and + for agglutination of O157-specific antibodies. Associated with ground beef and unpasteurized milk. Attach to and efface brush border of intestine by producing phage-encoded Shiga toxins, lethal to colonic (and renal endothelial) cells. Not invasive. Presents as severe cramping followed by bloody diarrhea, but afebrile. Complications include hemolytic uremic syndrome (triad of anemia, thrombocytopenia and acute renal failure), occurring in the very young and very old, due to Shiga toxin binding to endothelial cells in kidney > swelling causing mechanical hemolysis, and endothelial damage consuming platelets . Tx: self-limiting; fluid and electrolyte replacement; abx contraindicated. E. coli O:6 (enterotoxic) Cholera-like illness with copious, watery diarrhea. Largely travelers diarrhea. Toxins ADP-ribosylate adenyl cyclase > cAMP (heat-labile; Cholera-like) and guanylate cyclase > cGMP (heat-stable toxin); both > increased activity of CFTR > diarrhea. No invasion. E. coli O:29 (enteroinvasive) dysentery-causing strand (milder than shigellosis). Scant bloody stools with fever. Invades and secretes Shiga-like toxin, causing inflammation and necrosis of large intestine. E. coli O26:H111 (enteropathogenic) childhood diarrhea. Organism adheres to apical surface, effaces microvilli, flattens villi, and prevents absorption. No invasion or toxins. Vibrio cholerae Gram mobile, comma-shaped rods; nonspore-forming, oxidasepositive facultative anaerobes, predominating in Asia, Africa and Latin America. Ingestion of contaminated water and food is major route. In US, mostly associated with raw shellfish consumption along Gulf coast. Individuals with reduced gastric acidity for any reason are at risk. Colonizes small intestine and stimulates fluid and electrolyte secretion by secreting cholera toxin (CTX), which ADP-ribosylates the Gs protein > increasing cAMP > PKA > CFTR, inhibiting Na+ absorption in villi / increasing Cl- excretion in crypt cells > rice-water diarrhea. Dx: thiosulfate citrate bile salt media growth. Tx: fluid & electrolyte replacement; doxycycline.

Clostridium difficile Gram + rod; spore-forming anaerobe, prevented from growth by normal flora, thus is almost always related to earlier antibiotic use. Produces exotoxin, which is detected in stool - the mainstay of diagnosis. The toxin binds to GTP-binding proteins, inactivating them, and causing depolymerization of actin in colonic mucosa, which leads to damage of cellular lining (erythematous and friable colonic mucosa), ulceration, and hemorrhagic necrosis. Presents as abdominal cramping and frequent diarrhea. May progess to pseudomembranous colitis and toxic megacolon. Tx: metronidazole. Entamoeba histolytica protozoan, prevalent in developing countries. Transmitted via cysts (fecal-oral), which are spherical with four nuclei; excystation occurs in small intestine, followed by migration to colon. Feed on WBCs, RBCs, and mucosa, giving rise to colitis. Micro: trophozoites with intracellular RBCs. Lesions in colon range from inflammation to flask-shaped ulcers (rupture of submucosal abscess). Causes abdominal pain and bloody diarrhea with tenesmus. WBCs consumed by amebae and may not be present in stool. Stool antigen test/microscopic O & P is dx. Trophozoites may enter portal circulation and travel to liver, which is of grave concern, due to irreversible hepatocyte damage and abscess formation (RUQ pain, fever, hepatomegaly) Tx: metronidazole + iodoquinol. Chronic diarrhea due to immune compromise cryptosporidium (self-limited in healthy patients), microsporidia, cytomegalovirus, cyclospora. Once CD4 count is less than 50, mycobacterium avium may involve any region of GI. C. difficile should be considered as most AIDS patients are on antibiotics. Notes: Transmission is fecal-oral for most. Most episodes are self limiting. Microscopic examination of stool for RBCs and WBCs can differentiate between invasive bacterial pathogens from noninvasive ones, viruses, and protozoa. Stool cultures and examinations for ova and parasites (O & P) can help diagnose amebae, giardiasis, and helminth infections. Enterics form metallic colonies on eosin methylene blue (EMB) agar Hepatitis Viral hepatitis is a febrile illness of prolonged duration, marked by fatigue, abdominal pain, loss of appetite, nausea, and gradual jaundice. Risk factors include seafood (hep A), multiple sex partners or unprotected sex (hep B), IV drug use (hep C). Dx by LFTs and virus serology. LFT: in viral hepatitis, hepatocytes are damaged and rupture, causing very high AST/ALT. The duct cells which make Alk Phos and GGT are gradually damaged, and will be mildly elevated; they rise later in the course, as the liver is swollen enough and ducts damaged enough for bilirubin to back up into blood > jaundice. In contrast, a stone blocks the duct, raising Alk Phos / GGT and bilirubin drastically, while AST/ALT are mildly elevated. Enteric hepatitis: Hep A and E (Anus and Enteric). Serum hepatitis: Hep B, C, D (BlooD). A most common.

Hepatitis A ss, + sense, linear picornavirus, transmitted by fecal-oral route. AntiIgM forms at time of active infection; anti-IgG rises shortly thereafter, and by itself signifies old infection, protecting against recurrence. Tx: serum globulin. Vaccine available. Hepatitis B ds, partially circular DNA hepadnavirus, transmitted sexually (major) or via bloodborne exposure (including during delivery). In active infection, virus present in all bodily fluids. Presence of HBsAg always means having infection (acute, chronic, or carrier). Having surface antigen antibodies (anti-HBsAg) means immunity. Core antibodies (anti-HBcAg) are not protective, but indicate length of infection (IgM new, IgG old). Part of the core, the HBeAg is a marker for active disease and highly infectious state. Anti-HBeAg low infectivity or recovery. Chronic hepatitis has several forms: asymptomatic carrier, chronic-persistent hepatitis (low-grade), and chronic active hepatitis (active hepatitis without recovery). Complications: primary hepatocellular carcinoma, cirrhosis, coinfection with HDV. Tx: IFN alpha or peg-IFN alpha; nucleoside analogs (lamivudine, adefovir, entacavir) take longer than IFN but ~ same efficacy (30%). Hepatitis C ss, + sense, linear flavivirus transmitted sexually and by injection (major route). Up to 85% develop chronic hepatitis. Tx: IFN and ribavirin. Hepatitis D can only replicate with help of HBV, by using HBVs envelope, HBsAg. Co-infections transmitted together end in same way as HBV, by anti-HBsAg antibodies protecting against both. Superinfection in HBV chronic state, however, causes active hepatitis, often > fulminant or cirrhosis. Hepatitis E ss, + sense, linear calcivirus enterically transmitted; causes acute hepatitis in India, where it exceeds HAV in incidence. Causes high mortality among pregnant women. Schistosoma mansoni (hepatosplenomegaly and portal hypertension) fluke (trematode), found in freshwater; penetrates the skin, travels to hepatic portion of portal venous system, and matures here. Evades immune system by molecular mimicry. The eggs laid travel in bloodstream to liver, lung, brain, etc., where immune system walls them off as granulomas. Deposition of eggs in veins leads to fibrosis > portal HTN. Dx: stool has large eggs with lateral spine. Tx: praziquantel. Ascaris lumbricoides (ascariasis) roundworm (nematode), transmitted by ingestion of eggs from soil/produce contaminated by human feces. The larvae hatch, invade intestinal mucosa, and are carried to the lungs, where they mature, penetrate alveolar walls (causing cough, hemoptysis, dyspnea, etc), ascend the bronchial tree to the throat, and are swallowed. Upon reaching the small intestine, they grow and produce eggs. Often recent immigration from a developing country. Mostly asymptomatic until bolus of worms causes obstruction (nausea, abdominal

distention and pain, and absence of bowel movements). Eosinophilia and elevated IgE. Tx: -bendazole, pyrantel. Necator americanus (hookworm) roundworm (nematode), penetrates skin of feet, travels to lungs and grows, then coughed up and swallowed. Attaches in small intestine and sucks blood, potentially causing iron-deficiency anemia. Tx: -bendazole, pyrantel. Strongyloides stercoralis roundworm (nematode), penetrates skin, travels to lungs (causing pulmonary symptoms), then coughed up and swallowed. Adult female lives in mucosa of small intestine and makes ova > larvae, not eggs. Burrow into mucosa, causing fever, abdominal pain, and diarrhea. Some larvae reinfect host by entering body through intestinal mucosa or the skin of perianal area (causing maculopapular rash and itching on groin and buttock area). In immunocompromise, disseminated infection may occur. Dx: O & P. Eosinophilia and elevated IgE. Tx: - bendazole, ivermectin. Necator americanus and Strongyloides stercoralis may both cause cutaneous larval migrans, an intensely pruritic creeping eruption, caused by larvae moving through skin. Same tx. Trichuris trichuria whipworm (whip-shaped) rectal prolapse, appendicitis, anemia. Clonorchis sinensis fluke causing inflammation of biliary tract > pigmented gallstones. Tx: praziquantel Paragonimus westermani crab meat > inflammation of lung / hemoptysis. Tx: praziquantel

Nervous system bugs Meningitis develops in subarachnoid space. Signs/symptoms depend on age of the patient. Anorexia and n/v occur in all, but infants and elderly have primarily altered mental status whereas older children and adults have typical fever, HA, photophobia, and nuchal rigidity. Altered mental status is suggestive of bacterial meningitis and is rare in viral. Occasionally leads to seizues. Most common cause of meningitis is viruses, leading to aseptic meningitis; primarily enterovirus, but also mumps, herpes and HIV; rarely fatal and no tx. On the other hand, bacterial meningitis is life-threatening; Group B strep, E. coli and Listeria common in neonates; N. meningitides and H. influenzae take over 6 months - 3 years, after maternal antibodies wane but before new ones are made. N. meningitides is main cause in children and young adults (in addition to S. pneumoniae); S. pneumonia, Klebsiella, and Listeria in older adults.
Properties Normal Viral Bacterial

CSF opening pressure WBCs PMNs Protein Glucose Gram stain

< 180 mm H2O < 10/microliter None < 30-40 mg/dL > 50 mg/dL Negative

180 250 200-600 < 50% < 100 > 50 Negative

> 250 > 1000 > 50% > 100 < 40 Positive

The model for infection is similar for all bacteria: colonization of nasopharynx > invasion of mucosa > entry into blood-stream and evasion of complement, antibodies and phagocytic killing via capsule > crossing choroid plexus into CSF > induction of inflammation, with subsequent edema and increased ICP. Pts with compromised immunity (no antibodies) or asplenia (physical or sickle-cell) rely on alternative complement pathway. AIDS predisposes to TB and mycoses, particularly Cryptococcus meningitis. Principles of treatment: dexamethasone + Gram + cocci (S. pneumoniae): 3rd gen cephalosporin (cefotaxime) + vancomycin Gram cocci (N. meningitidis): 3rd gen cephalosporin (cefotaxime) Gram + rod (Listeria monocytogenes): Penicillin G or Ampicillin + aminoglycoside (gentamicin) Gram rod (E. coli or Pseudomonas): 3rd gen cephalosporin (ceftazidime) + aminoglycoside (gentamicin) Infection of brain parenchyma may be local (abscess) or diffuse (encephalitis). Fever, HA and altered mental status. Mostly viral, of which only HSV, VZV, and possibly CMV are treatable. HSV main cause of viral encephalitis. Brain abscess presents as fever, HA and focal neurodeficits due to mass effect of abscess; mostly bacterial and diagnose by CT. Beware of performing a lumbar puncture in presence of papilledema or lateralizing neurologic findings. Neisseria meningitides encapsulated Gram diplococci (occurring in pairs or tetrads); capsule and endotoxin are virulence factors. Oxidase positive, ferment both maltose and glucose (MeninGococci). Children under 5 and people with C5-C9 deficiency and asplenia particularly at risk. Transmission via respiratory droplets. After nasopharyngeal colonization (with aid of IgA protease), bacteria invades blood, penetrates blood-brain barrier, and enters CSF. The diapedesis of leukocytes into CSF causes exudation of albumin through opened intercellular junctions of meningeal venules, which causes brain edema, increased ICP and altered cerebral blood flow. Most damage caused by IL-1 and TNF in response to endotoxin. Presents as meningeal symptoms (fever, n/v, HA, mental changes, nuchal rigidity); in blood infection, hypotension, low WBCs/platelets, and purpuric rash, caused by release of LOS into bloodstream > thrombocytopenia > DIC, and may result in ischemic necrosis. Acute adrenal gland failure due to bleeding into adrenal gland (Waterhouse-Friderichsen syndrome) presents with profound shock. Tx: Penicillin G. Prophylaxis: rifampin. Vaccine against Y, W135, C, A (YWCA) capsules exists.

Streptococcus agalactiae (group B strep) Gram + cocci, encapsulated (type III capsular polysaccharide = major virulence factor) and occurring in chains. Leading bacterial cause of death in newborns, since ~40% of pregnant women have it in genital tract. Prematurity and early membrane rupture increase risk. Enters newborns mucosa (eyes, nasopharynx) during delivery and colonizes in 2448 hours. Causes meningitis, pneumonia and sepsis (MPS). Pneumonia usually early-onset (first week) and meningitis late-onset (after a week). Same morbidity (MR, deafness). Dx: direct antigen testing in urine or CSF. Tx: Penicillin G or ampicillin; administration at the onset and throughout labor interrupts transmission. Listeria monocytogenes Gram + rod with endotoxin, beta-hemolytic, facultatively anaerobic, and motile (tumbling motility in wet mounds). Intracellular pathogen, which will not show up in CSF and need to be cultured; body relies on cell-mediated immunity to eliminate. Produces listeriolysin O (betahemolysin) and phospholipases to escape from phagosome into cytoplasm. Typically food-borne illness (soft cheese and processed / partially-cooked meat). At-risk groups are pregnant women (may experience febrile flu-like illness; may have fetal loss due to transplacental transmission; may carry vaginal/bowel Listeria until delivery > sepsis/meningitis occurs in newborns) and the immunocompromised (patients on steroids, with AIDS, and elderly > gastroenteritis or meningitis). Tx: penicillin or amoxicillin, plus aminoglycoside. Picornaviridae family naked, ss, + sense RNA (can serve as mRNA) viruses, falling into 3 groups: 1. Enterovirus (polio and nonpolio): Poliovirus (now eliminated) caused aseptic meningitic, encephalitis, and paralysis. Nonpolioviruses include: Coxsackie A: acute hemorrhagic conjunctivitis (type 24), hand-foot-mouthdisease, aseptic meningitis, and myopericarditis. Coxsackie B: pleurodynia, myopericarditis, aseptic meningitis, and exanthem/hepatitis/diarrhea. Echovirus: Aseptic meningitis, exanthema, hand-foot-mouth disease, myoperidcarditis, URI/LRI. 2. Hepatovirus (Hepatitis A) 3. Rhinovirus (common cold) Aseptic (viral) is the most common type of meningitis, 90% being enteroviral. Typically demonstrate seasonal pattern; enteroviruses often cause outbreaks in summer and fall months. Person-to-person transmission, including fecal-oral route. Presents with fever, HA, malaise, and mild or no nuchal rigidity. Arboviral disease leading cause of encephalitis. Fall into three families: 1. Bunyaviridae enveloped, triple-segmented, cicular ss, sense RNA. California and LaCrosse encephalitis, Hantavirus (Sin Nombre). 2. Togaviridae enveloped ss RNA. Includes Eastern and Western equine encephalitis, Rubella. 3. Flaviviridae enveloped ss RNA. Includes St. Louis encephalitis, Japanese

encephalitis, West Nile Virus (most asymptomatic; some have aseptic meningitis/encephalitis with motor weakness) HCV, and hemorrhagic fevers: dengue (break-bone fever: rash, extreme muscle and joint point; on reinfection, hemorrhagic shock syndrome) and yellow fever (hemorrhagic fever, hepatitis > jaundice, GI hemorrhage > black vomit; vaccine available). Most transmitted by blood-sucking arthropods, in summer months, in regions proximal to marshy lands, or woodland habitat, passing between mosquitos and vertebrate hosts (birds, rodents). In urban areas, vectors may be in trash-filled drainage, dumped tires, etc. Complications of encephalitis include CN palsies, hemiparesis, and convulsions; altered mental status points to it; worse in elderly. No tx. HSV-1 (HSV encephalitis) - ds DNA enveloped virus. Virus-infected tissues reveal presence of multinucleated giant cells. Virus latent in trigeminal ganglion or autonomic nerve roots; after reactivation, travels to brain via trigeminal nerve and causes direct damage to brain parenchyma by cytolysis; T-cell response causes perivascular inflammation resulting in hemorrhage, especially in right temporal lobe. Presents as fever, HA, seizures, confusion, neuro deficits. Dx: MRI, CSF PCR. Tx: acyclovir. Cryptococcus neoformans (cryptococcosis) encapsulated yeast (wide capsular halo); not dimorphic; narrow-based budding. Found in soil and pigeon droppings. Causes cryptococcal meningitis (soap bubble lesions in brain) and pulmonary cryptococcosis, especially in people with AIDS (main fungal infection) or on longterm steroids. Presents as fever, fatigue, dry cough, pleuritic pain, or meningeal symptoms (HA, n/v, mental changes, meningeal irritation signs). Culture on Sabourauds agar. Stains with India ink. Latex agglutination test detects polysaccharide capsular antigen. Tx: fluconazole (crosses blood-brain barrier). Tx for meningitis is amphotericin B and flucytosine followed by fluconazole. Mucor, Rhizopus (Mucormycosis) - irregular, broad, nonseptate hyphae branching at wide angles. Disease mostly in ketoacidotic diabetics and leukemic patients. May proliferate in walls of blood vessels and cause infarction/necrosis of distal tissue. Rhinocerebral mucormycosis: sinusitis with purulent discharge > orbital and front lobe abscesses. Rhizopus has roots, mucor does not. Tx: amphotericin B. Toxoplasma gondii obligate intracellular parasite found in two forms: resting cyst form of bradyzoites, found in muscle and brain during asymptomatic chronic infection, and active banana-shaped tachyzoites of acute infection or reactivation. Cats are hosts (80% infected), and cattle/pigs feeding on cat feces are intermediate hosts. Human infection by undercooked meat or ingestion of things contaminated with cat feces. Crosses placenta. Following ingestion of oocysts, sporozoites are released in GI tract, penetrate mucosa and disseminate into various organs. As an immune response is mounted, dormant bradyzoites develop and remain sequestered in brain matrix as long as host is immunocompetent; reactivates as T

count drops below 200, rupturing cells and resulting in focal necrosis. Ringenhancing lesions on MRI. Congenital infection is asymptomatic at birth, but later develops into chorioretinitis (same with AIDS patients), epilepsy, hydrocephalus, and intracranial calcifications. Tx: Sulfadiazine and pyrimethamine. C. tetani drumstick/tennis raquet-shaped; ubiquitous in soul; retrograde transport of toxin (tetanospasmin) from motor endplate > CNS, where it blocks Renshaw inhibitory interneurons, preventing GABA/glycine release. May develop from infected umbilical cord (neonatal tetanus). Trismus, clamped jaw, hyperresponsiveness to stimuli. DTaP vaccination available. Tx: anti-tetanus IgG. Naegleria fowleri fresh-water amoeba that penetrates nasal mucosa and enters cribiform plate, causing rapidly fatal meningoencephalitis. Presents as fever, HA, neck stiffness, and n/v; history of swimming a week earlier. Tx: intrathecal amphotericin B.

Skin/wound/multisystem bugs Rubeola (measles) ss, sense, linear RNA paramoxyvirus. Transmitted by respiratory droplets, infecting epithelial cells of URT, then entering blood and spreading to skin and respiratory tract. Multinucleated giant cells characteristic. Symptoms of 4 Cs - cough, conjunctivitis, coryza, and Koplik spots (red spots with blue-white centers, on buccal/palate mucosa), a day or two before rash. Rash spreads head to toe; disappears in same sequence, like paint poured over you. After febrile stage, virus-specific T cells attack infected endothelial cells of dermal capillaries (resulting in rash and Koplik spots). In immunocompromised, measles can progress to giant cell pneumonia, or subacute sclerosing panencephalitis (SSPE), years later. No Tx; MMR vaccine available. Rubella (German measles) enveloped ss RNA togavirus, Presents with fever, lymphadenopathy, maculopapular truncal rash, spreading forehead-down. Although eradicated in US, it is often imported. Infection either by droplet spread, or across placenta. Upon entry, it infects nasopharynx and lung epithelium, spreads to blood and lymphatics, causing febrile stage. Virus-specific T cells kidfaf ll infected vascular endothelial cells of dermal capillaries, which causes skin rash, lasting 3 days. Congenital transmission results in infant cataract formation, PDA, deafness; +/- blueberry muffin rash. No tx; MMR vaccine available. Varicella-zoster virus enveloped ds DNA herpesvirus. Causes varicella (chickenpox in children) and herpes zoster (zoster in adults). Chickenpox is a febrile rash disease, with vesicular rash starting on face and trunk, and spreading outwards (includes mucous membranes). Vesicles have red base, and filled with fluid, which turns cloudy and vesicle ruptures and scabs over. Vesicles present in different stages. Zoster is a reactivation of latent VZV and occurs mostly in people > 50. Spread primarily by inhalation of respiratory aerosol; infects mucosa and spreads via blood to skin. After primary infection, VZV may become

dormant in dorsal root ganglia for life. Reactivated VZV descends down sensory nerve to skin, causing vesicle eruption in a dermotomal distribution. Multinucleated giant cells seen in base of skin lesions. In immunosuppressed, virus may spread to lung to cause interstitial pneumonia and to CNS to cause encephalitis. May cause Reye syndrome. Tx: acyclovir. Viridans streptococci general grouping of Gram +, alpha-hemolytic chained cocci, including S. oralis, S. sanguis, S. salivarius, S. mutans, etc., which are normal inhabitants of oral cavity and GI tract. May cause infective endocarditis, especially with recent dental procedures. Produces dextran to adhere to enamel and heart valves. Tx: penicillin G (high doses) Bacterial endocarditis valves of the heart prone to infection, due to lack of dedicated blood supply. Risk of infection is increased by previous damage, such as rheumatic fever, or malformation. Produces fever, malaise and fatigue, as well as new heart murmur, night sweats, rigors, anemia, splenomegaly, splinter hemorrhages (under nails), glomerulonephritis (allowing blood and albumin to enter urine); Roths spots (retinal hemorrhage with white center (coagulated fibrin), Oslers nodes (painful red subcutaneous lesions on hands and feet) and Janeway lesions (painless red to black hemorrhagic papules on palms or soles) are characteristic of bacterial endocarditis, resulting from septic emboli. Acute BE: S. aureus, associated with IV drug use/surgery/catheterization; has a fulminant course. Subacute with native valve: Strep viridians, HACEK organisms (often culturenegative), due to colorectal cancer (mostly Streptococcus bovis - S. bovis in the blood = cancer in the bowel), or UTI (mostly enterococci (Enterococcus faecalis or faecium; Tx: ampicillin + gentamycin). Subacute with prosthetic valve: Staph epidermidis (Tx: vanco). CMV enveloped ds DNA herpesvirus; causes sore throat, fever, lymphadenopathy, as well as mild hepatitis. Following infection via body fluids (including saliva), virus becomes latent in T cells, and overt disease rarely occurs unless immunity is suppressed. Histologically, infected cells develop into cytomegalic (giant) cells with nuclear and cytoplasmic inclusions containing viral particles forming a surrounding halo called owls eye. Common cause of post-transplant infection. Targets several organs, causing pneumonia, colitis, esophagitis, and retinitis, as well as congenital infection of fetus (Hearing loss, MR, seizures due to periventricular calcifications, microcephaly). Tx is gancyclovir, or foscarnet in gancyclovir-resistant strains. C. perfringens Gram +, spore-forming, anaerobic, non-motile boxcar-shaped rod found in colon; secretes alpha toxin (lecithinase), which lyses lecithin in cell membrane > cell death > tissue destruction and gas gangrene (via release of enzymes that ferment carbohydrates). Tissue is discolored; palpation reveals crepitus. Tx: radical surgery, beta-lactams, hyperbaric oxygen. Other strep/staph infections: S. pyogenes most common cause of impetigo - vesicular eruption of epidermis that break to form a raw, weeping surface, and cause flaky honey-colored crusts;

most common cause of erysipelas streptococcal infection of dermis that has raised erythema with sharp border; cellulitis subcutaneous involvement; necrotizing fasciitis strains producing M protein (resistant to phagocytosis) are able to traverse fascial planes. S. aureus secretes exfoliatin, which lyses epithelial cells (scalded skin syndrome exfoliatin cleaves middle epidermis, with peeling to expose red inflamed layer of skin), TSST-1 superantigen, Protein A. Causes acute bacterial endocarditis (rapid, unlike subcute viridans). Causes impetigo (large vesicles to bullae) and cellulitis, like strep; also causes boils (furuncle), a deep folliculitis. TSS (S. aureus, by TSST-1) and TSLS (S. pyogenes, by erythrogenic toxin): high fever, n/v, watery diarrhea (due to heat-stable toxin), diffuse erythematous rash (like scarlet), desquamation of palms and soles, and may > septic shock. S. epidermidis may cause osteomyelitis following hip replacement. Tx: Vanco Rabies after a bite, virus replicates at wound site, then migrates slowly (over weeks) up nerve axons to CNS, causing fatal encephalitis. Brain cells have virions called Negri bodies. Brainstem infection causes cranial nerve dysfunction, causing painful spasms of pharynx when swallowing liquids. Inability to swallow saliva foaming at the mouth. If animal is observed and discovered to have rabies, rabies immune globulin is given. If known right away, prophylaxis with human diploid vaccine is given. Bacteroides fragilis Gram rod without endotoxin and low virulence, important during intestinal breach, due to trauma, surgery, or rupture due to infection (appendicitis). May cause peritoneal abscesses, which have to be drained. Synergistic presence of facultative anaerobe (such as Klebsiella) is required (to utilize oxygen and reduce redox). Tx: metronidazole, clindamycin, etc. Zoonotic bacteria Gram rods, mostly facultative intracellular (except pasteurella), treated with aminoglycoside (gentamicin or streptomycin) or doxycycline. Yersinia pestis safety-pin shaped; resides in wild rodents, squirrels, and pairie dogs of Southwest U.S., while fleas are vectors. Carries F1 (prevents destruction after phagocytosis), V, and W antigens (F1 VW). Francisella tularensis (tularemia) rabbits, ticks and deerflies. Cause ulceroglandular tularemia hole in skin with black base following bite, and swelling of local lymph nodes (bubo); and pneumonic tularemia. Brucella (brucellosis) domestic animals, especially goats, cows, pigs and dogs. Patient likely a meat-packer, veterinarian, farmer, or someone drinking unpasteurized milk. Symptoms strictly systemic, with undulant fever (slowly rises during the day, declining at night), chills, backache, and headache. Pasteurella follows cat or dog bite/scratch. Swelling of site, lymph node swelling, and high fever. Borrelia burgdorferi spirochete transmitted by Ixodes tick. Erythema chronicum migrans - a red, flat, round lesion, which spreads out over time appears within 10 days at site of tick bite. Outer border remains red, while center clears. This is followed by dissemination (same way as syphilis) to skin (other smaller erythema migrans), brain (meningitis, cranial nerve palsies, especially bilateral Bells

palsy), peripheral nerves (neuropathy), heart (AV heart block, myocarditis, etc), and joints (brief, migratory arthritis in large joints, esp knee). Dx: Giemsa stain or dark-field microscopy. Tx: doxycycline. Borrelia recurrentis/hermsii in US (relapsing fever) spirochete transmitted by a louse, causing a high, recurring fever, with headaches and muscle aches. Symptoms remain for 3-6 days, go away for about 8 days, then relapse, due to antigenic variation of surface proteins, which occurs within this span, necessitating production of new antibodies. Dx: Giemsa stain or dark-field microscopy. Tx: doxycycline. Leptospira interrogans long spirochete with characteristic hooked end, found in urine of rodents and domestic animals; infects by direct contact with urine or swimming in contaminated water (boating, watersports). Initial stage involves high fever, headache and muscle ache; this is followed by immune-complex vasculitis (rash, conjunctivitis). May then > to even more severe disease, Weils disease, which entails hepatitis with jaundice, renal failure, altered mental status (aspetic meningitis), and hemorrhage in many organs. Tx: doxycycline. Rickettsia, like Chlamydia, are obligate intracellular bacteria that scavenge host ATP. Predilection for endothelial cells of blood vessels > causes small hemorrhages and thrombi (rash). Causes classic triad of headache, fever, and rash (vasculitis). Weil-Felix antigens to diagnose. Has several arthropod vectors: Tick in Rocky Mountain spotted fever (Rickettsia ricketsii). Rash starts on hands/feet > wrists/ankles > trunk (Rocky Mountain fever rash = wRists). Vascular leakage due to endothelial damage may lead to hypotension / hypoproteinemia (protein loss) > organ hypoperfusion. Endemic to East Coast. Louse in epidemic Typus (Rickettsia prowazekii). Rash starts centrally (Trunk). Flying squirrels reservoir. Flea in endemic Typhus (Rickettsia typhi). Rash starts centrally (Trunk). Coxiella burnetti (Q fever) does not require a vector and causes no rash; transmitted by aerosol and causes mild, mycoplasma-like pneumonia. Grows in ticks and cattle; forms spores, which remain viable in dried tick feces deposited on cattle hide. Inhaling spores causes pneumonia. Weil-Felix negative. Tx for all: doxycycline. Bartonella henselae (cat-scratch disease) cat scratch or bite. Regional lymph node swelling and fever. Causes bacillary angiomatosis in AIDS. Fungi have cell membrane with ergosterol as essential sterol (amphotericin B and nystatin bind to ergosterol and make hole in cell wall; azoles and echinocandins interfere with ergosterol synthesis). Fungal cell wall is major antigen to human immune system. Superficial infections: Malassezia furfur (pityriasis versicolor) - produces acids that damage melanocytes and cause hypo- or hyperpigmented patches. "Spaghetti and meatballs" appearance on KOH slide. Tx: topical azole or selenium sulfide (Selsun).

Exophiala werneckii (tinea nigra) - superficial black patches on palms and soles. Cutaneous: Microsporum canis, Trichophyton floccosum, Epidermophyton spp (dermatophytoses) - cause infections of superficial keratin; secrete keratinase, which causes scaling of skin, loss of hair, crumbling of nails. Tinea corporis (ringworm), tinea cruris (jock itch), tinea pedis (athlete's foot), tinea capitis (hair/scalp), tinea unguium (onychomycosis). Tx: topical azole; griseofulvin for tinea unguium. Subcutaneous: Sporothrix schenckii (sporotrichosis) ovoid (cigar-shaped) yeast found in soil and on plants (thorns/splinters). Pt usually gardener. Formation of subcutaneous nodule > ulceration, and pustules spread along lymphatics. Tx: itraconazole, potassium iodide. Plasmodium spp. (malaria) protozoa endemic in equatorial tropics, with Chloroquine resistant P. falciparum in most of Africa, South America, and India. Proliferates within anopheles mosquito salivary gland, injected upon feeding. Injected form is the spindle-shaped sporozoite, which travels to liver and forms a schizont, producing many nuclei, which eventually separate into individual merozoites. Liver cells burst and release merozoites into blood, which bind RBC Duffy blood group antigen / glycophorin, enter, and feed on RBC hemoglobin, maturing into trophozoites (looks like diamond ring). Trophozoites > schizont > merozoites, which burst the cell > reinfect. RBCs burst at the same time, causing relapsing fever with chills or sweats, hepatosplenomegaly, and anemia / thrombocytopenia due to both increased clearance by spleen and hematopoiesis suppression. Protozoal use of glucose > hypoglycemia and lactic acidosis. Recurrence: P. vivax and P. ovale q 48 hours; Shuffner dots present. P. falciparum - approximately q 48 hours or continuous. P. malariae - q 72 hours. Infection with P. falciparum forms knobs on RBCs and may cause sequestration (due to increased adhesion) in microvasculature > hemorrhage/infarction of CNS (seizures, coma), kidneys (renal failure), and lungs (pulmonary edema). Tx: Vivax/ ovale chloroquine and primaquine; Falciparum chloroquine in Central America only, otherwise mefloquine, quinine, atavaquone-proguanil, or artemisinin. Prophylaxis: doxycycline. Babesia protozoa spread by bite of Ixodes tick (same as Lyme), causing malarialike fever and mild hemolysis. No effect on liver. Visible inside RBCs as crossshaped tetrad of merozoites. Tx: quinidine. Leishmania spp protozoa transmitted by sandfly bite, amastigote form in host. Disease proportional to immune system strength: isolated ulcer at site of bite in immunocompetent pt; in immune deficiency, disseminated nodular lesions or mucocutaneous ulcers spread across the body, depending on species. Visceral leishmaniasis (Kala-azar): caused by L. donovani or L. chagasi; infect reticuloendothelial cells and cause massive hepatosplenomegaly > anemia and leukopenia. Macrophages full of Leishmania. Tx: stibogluconate. Trypanosoma brucei (African sleeping sickness) protozoa transmitted by a painful bite of tsetse fly. Spreads to lymph nodes and CNS; fever and headache last a week,

subside for several weeks, and recur (due to variable surface glycoproteins, which, similar to Borrelia recurrentis, recombine and evade antibodies). Months later, CNS symptoms develop, with drowsiness, behavioral changes, slurred speech, and finally coma and death. Tx: suramine and melarsoprol. Trypanosoma cruzi found only in Americas; rodents and armadillos are reservoir; reduviid bug (kissing bug) is vector. The bug feeds on humans, defecating while it eats, and depositing the trypomastigotes found in feces. Organism invades local skin, forming a hardened red area (chagoma), followed by systemic spread via lymph nodes, causing fever and malaise. Acute illness resolves within a month; years to decades later some develop chronic Chagas disease: heart infection causes tachycardia, EKG changes (block, VT), and later, dilated cardiomyopathy; CNS infection may cause severe meningoencephalitis; esophagus and colon infection destroys enteric plexis > megaesophagus/megacolon. Tx: nifurtimox. Trichinella spiralis roundworm (nematode), present in pork as cysts; upon ingestion, larvae emerge and invade intestine, spreading to organs and muscle; produces muscle aches, elevated CPK & LDH, eosinophilia, periorbital edema, and subconjunctival hemorrhage. Tx: -bendazole. Onchocerca volvulus roundworm (nematode), transmitted by blackflies, cause fibrous black skin nodules (intraepithelial granulomas), migrate through CT, and may travel to eyes, causing blindness (river blindness, since black fly breeds on rivers). Tx: ivermectin. Wuchereria bancrofti roundworm (nematode), transmitted by mosquitos; matures in lymphatic vessels and nodes; repeated infections causes fibrous tissue within nodes that plugs up lymphatics. Organism circulates only at night, thus dx requires blood drawn at night. Tx: diethylcarbamazine. Taenia solium (pork tapeworm) tapeworm (cestode) acquired by eating undercooked pork containing cysts, which attach to intestine. Ingesting eggs instead of cysts causes cysticercosis: larvae hatch, penetrate gut mucosa, migrate through body and encyst within brain and skeletal muscle. Evoke little reaction until cyst degenerates. Tx: praziquantel; -bendazole for neurocysticircosis. Echinococcus granulosus (hydatid cyst disease of liver) flatworm (cestode), prevalent in developing countries; dogs and sheep are reservoirs. Following ingestion of eggs, larvae penetrate intestine and cause extraintestinal infections (lesions of liver, lung, etc.). Each larva forms a single, round fluid-filled hydatid cyst. Causes anaphylaxis if antigens released from liver. Tx: Surgical excision; ethanol injected prior to removal, to neutralize antigens. bendazoles used adjunctively.

Bioterrorism and emerging bugs

Variola (smallpox) linear ds DNA virus; eradicated infection. Transmitted by inhalation of respiratory droplets and contact with body fluids. Characterized by flulike symptoms and high fever, followed by peripheral rash consisting of papulovesicular lesions at same stage of development, mostly on face and extremities, and often have central depression (contrast with VZV);eventually scab over and resolve. Sin Nombre virus (hantavirus pulmonary syndrome) enveloped circular ss, - sense RNA virus. Infection associated when dried rodent urine or droppings are disturbed and inhaled. Begins with fever, HA, and severe myalgia with cramps that extends into legs, following by pulmonary edema and effusion due to plasma leakage into lungs, where CD8 cells destroyed infected pneumocytes (with resultant hemoconcenration in vessels). A left shift and thrombocytopenia are seen as well. No tx. SARS-associated coronavirus enveloped ss + sense RNA coronavirus. Coronaviruses 1-2 are typical mammalian, and 3 is typical avian virus. SARS-CoV is considered the 4th coronavirus. Transmission by droplet aerosolization and contact. Whereas normal coronavirus stays localized to upper respiratory epithelium, SARS extends to LRT, causing a viral (atypical) pneumonia with diffuse alveolar damage, inflammatory infiltrate, and multinucleated giant cells with no inclusions. Dx: PCR; antibodies. No tx. Bacillus anthracis Gram +, aerobic, spore-forming, box-shaped rod arranged in chains. Secretes edema factor, which is itself an adenylate cyclase and increases cAMP in cells > impairs neutrophil function and disrupts water homeostasis > mass edema (mediastinal widening). Also secretes lethal factor, which inactivates protein kinase > macrophages release TNF/IL-1. Protein capsule. Affects wool/hide workers; causes local necrosis in cutaneous infection (black lesions). Tx: cipro.

Prions Creutzfeldt-Jakob disease PrPc (cellular) is normal isoform of PrP found in brain. PrPSc (scrapie)is PrP in abnormal conformation, induced by anther PrPSc. Results in microscopic spongiform changes (small, apparently empty vacuoles of varying sizes within neural tissue), amyloid plaques, and accumulation of prion protein (PrP); no inflammation. Presentation is dementia, ataxia, myoclonus, and death. May have several etiologies: inherited (including fatal familial insomnia, which is presaged by sleep disturbances), infectious (including kuru, mad cow, corneal grafts and cadaveric pituitary hormones), and sporadic (spontaneous mutation).