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D-Infectious Diseases

D-Infectious Diseases. 2008. Sepsis. PIRO severity staging TLR 4 – LPS (Gm-) TLR 2 – PGN, LTA (Gm+) Fever, inflammation, DIC, ARDS, azotemia, olyguria, cellulitis, purpura, GI bleeding, jaundice Procalcitonin diagnostic? Tx: ATB, supportive, Activated Protein C (Xigris).

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D-Infectious Diseases

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  1. D-Infectious Diseases 2008

  2. Sepsis • PIRO severity staging • TLR 4 – LPS (Gm-) • TLR 2 – PGN, LTA (Gm+) • Fever, inflammation, DIC, ARDS, azotemia, olyguria, cellulitis, purpura, GI bleeding, jaundice • Procalcitonin diagnostic? • Tx: ATB, supportive, Activated Protein C (Xigris) • SIRS – systemic response • Temp >38C (<36C) • HR >90bpm, RR >20bpm (PaCO2<32mmHg) • WBC >12k or >10% bands • Sepsis = SIRS + Infection • Severe Sepsis = Sepsis + Organ Dysfunction • Septic Shock = Sepsis + Hypotension

  3. Fever / Hyperthermia Hyperthermia Fever • Hypothalamic setpoint shifted up by PGE2 stimulating EP-3 • Pyogenic cytokines • Pneumonia, drugs, PE, DVT, C. difficile, fungal infection, MI, NG tubes, IV catheters • Hypothalamic setpoint unchanged • Does not respond to NSAIDS • Heat stroke, hyperthyroidism, atropine, ecstasy, malignant hyperthermia, serotonin syndrome

  4. Bioterrorism Botulism (Inhalation) Bacillus antracis Anthrax (Cutaneous) Bacillus antracis • Direct contact with spores • Jet black lesions (eschars) on skin within 7-10d • Incubation 1d • Tx: Cipro or Doxy q 60d • Vaccine: attenuated Ag • Inhaled spores, no person-to-person transmission • Incubation: 1w to 2 months • Mediastinal widening, pleural effusion, infiltrates • Initial symptoms improve, abrupt onset of fever/ARDS, shock/death within 24-36h • Tx: Penicillin or Cipro/Doxy

  5. Bioterrorism Botulism Clostridium botulinum Anthrax (GI) Bacillus antracis • Ingested spores, no person-to-person transmission • N/V, severe abd pain, bloody diarrhea, possibly mediastinal widening, rebound tenderness, ascites • Incubation: 1-7d • Tx: Penicillin or Cipro/Doxy • Most poisonous toxin on earth • Not contagious, spread by aerosol/food • 12-72 h incubation • N/V, diff see, swallow, speak • Muscle weakness/paralysis

  6. Bioterrorism Glanders Burkholderia mallei Cholera Vibrio cholerae • Rice-water diarrhea, dehydration, shock • Incubation 12h-5d • Food/water spread • Affects horses, mules, donkeys • Enters cut skin, mucous membranes, inhalation

  7. Bioterrorism Q Fever Coxiella burnetii Plague Yrsinia pestis • “Black Death”, infected fleas • Bubonic – 1-10 cm buboes on skin w/ edema, flu-like symptoms w/ abd pain • Septicemic - secondary septicemia, thromboses in acral v. leading to necrosis • Penumonic – acute fulminant symptoms, nearly 100% mortality rate • Tx: Streptomycin or Doxycycline • Nonspecific febrile syndrome, pneumonia • Hepatitis, endocarditis, granulomatous complications • Tx: Doxycycline 14-21d

  8. Bioterrorism Tularemia Francisella tularensis Smallpox Variola major • Officially eradicated • Incubation 10-14d • High fever, HA, backache, vomiting, rash on palm/sole • Highly contagious • No tx, vaccine within 3-5d • One of most infectious bacteria in world • Tick/insect bites • Incubation 10-14d • Fever, chills, HA, cough, lethargy, skin ulcers, lymph-adenopahty

  9. Bioterrorism VX GB Sarin • Binary weapon – two non-lethal reagents mix to form sarin gas • Inhibit ACHe, phosphonate esters, light brown oil • If mild: dim vision, salivation, chest tightness • Tx: Atropine and 2PAMCl • 1000x more toxic than GB • Persists in soil for 6d • Binary weapon • Inhibits ACHe, phosphonate esters, light brown oil • If severe: stop breathing, paralysis, seizures, LOC

  10. Bioterrorism Ricin • Waste leftover from processing castor beans • V/D, dehydration, hypotension, hallucinations, seizures, hematuria, multiple organ dysfunction • No tx available

  11. Bioterrorism • Needs Immediate Treatment, Suspect … • Respiratory Symptoms • Acute: Cyanide • Also nerve agents, mustard, lewisite, phosgene, SEB • Delayed: Anthrax, Plague, Tularemia • Also Q Fever, SEB, ricin, mustard, lewisite, phosgene • Neurological Symptoms • Acute: Nerve agents • Also cyanide • Delayed: Botulism • Also VEE-CNS

  12. Bioterrorism • “Secretly” Developing • China • Russia • “Former” Programs • Canada • France • Germany • Japan • S. Africa • UK, US • “Active” Research • Algeria • Egypt • India • Iran • Israel • N. Korea • Pakistan • Syria • Taiwan

  13. Immunocompromised • Clues • Recurrent Neisseria inf • Recurrent pneumonia • Severe presentation • Pneumocystis jiroveci • Burkholderia cepacia • Non-TB Mycobacteria • Aspergillus • Deficiencies in • Complement • IG/B-Cell • Phagocyte • T-cell

  14. Complement Deficiency • DAF and CD59 • Paroxymal nocturnal hemoglobinuria • C1, C3, C4 deficiency • Recurrent pyogenic sinus and respiratory infection • C1q deficiency • 90% have SLE • Hereditary angioedema • C1 inhibitor deficiency • Overactive complement • Minor stressors trigger attacks • C5-9 Deficiency • MAC lysis defect • Neisseria bacteremia

  15. Ig/B-Cell Deficiency • CVID • Low Ig, normal B-cell • Recurrent sinus, respiratory infections • Chronic infections with Giardia, Campylobacter • Tx: ATB, IVIg • IgA deficiency • Associated with CVID • Compensated by others • Secondary Ig deficiencies • Multiple myeloma, leukemia, skin burns • (Bruton’s) X-Linked Agammaglobulinema • Btk defect, no B-cells, Ig • Multiple pyogenic infections • No live vaccines! • Tx: IvIg • Hyper IgM Syndrome • X-linked, normal B-cell • Low Ig but high IgM • Pneumocystis infections • T-cells lack CD40L

  16. Neutrophil Deficiency • Hereditary Cyclic N. • AD, ELA2 mutation • Predictable cycles • Aphtous stomatitis • Tx: G-CSF, steroids • Chediak-Higashi Syndrome • AR, LYST mutation • Giant lysosomes, ineffective granulopoiesis • Oculocutaneous albinism • Neutropenia • Causes • Blacks have lower counts • Chemotherapy patients • Post-infection, sepsis • Sulfa-drugs, β-lactams • Infections • Mucositis • Ecthyma gangrenosum • Disseminated candidiasis • Aspergillosis

  17. Neutrophil Deficiency • CGD • Defective NADPH oxidase, no respiratory burst, no killing • Infections with catalase positive organisms • NBT test • Job’s Syndrome • Hyper IgE, impaired chemotaxis • STAT3 gene mutation • Facies, scoliosis, skin abscesses, sinusitis • Myeloperoxidase (MPO) • Makes pus green • Converts H2O2 to HOCl • Deficiency impairs this

  18. Spleen “Deficiency” • Decrease in circulating activated B-cells (75%) • Risk of thalassemia > hodgkins > sphero-cytosis > ITP > sepsis • Infections • S. Pneumoniae (mostly) • Haemophilus, GNR, Neisseria (less common) • Splenectomy • Trauma, ITP, Hairy cell leukemia, abscess • Hyposplenism • Autoimmune (Graves, Hashimoto, SLE) • Neoplasia (Hodgkin, CML, Sezary) • Amyloidosis • Alcoholism, elderly, Crohn’s, Sickle cell

  19. T-Cell Deficiency • Wiskott-Aldrich • WASP protein • Pyogenic infections, purpura, eczema • High IgA, IgE, low IgM • Infections • Mycobacteria, norcardia, legionella, cryptococcus, histoplasma, pneumocystis, herpesvirus, cryptosporidium, toxoplasma • DiGeorge’s • Deletion 22q11.2 • No T-cells, hypocalcemia, velocardiofacial defects • SCID • Combined B/T-cell deficiency, lymphopenia, hypogammaglobulinemia • ADA, PNP, RAG1/2, Jak3 gene deficiencies • CD4 T-cell Deficiency • HIV, <300 CD4+/mL

  20. Food Safety • Milk pasteurization: 72C for 15s or 63C for 30m • Botulism spores: kill with high heat + acidic • Preservatives: weak acids, nitrites, sulfites, spices • Radiation: γ-irradiation for spices, meats • Survival: Cold – Listeria; Chlorine – Giardia, Cryptosporidum cysts; Anything home processed • Outbreaks: Listeria (microwaved hot dogs), Cyclospora (raspberries), Salmonella, ETEC

  21. TuberculosisMycobacterium tuberculosis, bovis, africanum • Acid-fast, aerobic non-motile bacillus, reduce nitrates, produce niacin, slow growing • BACTEC blood culture, DAT tests using PCR • PPD (Mantoux) is killed tuberculin, positive if >15 mm, indicates prior infection (LTBI), need CXR • Risks: (normal) 1st year: 3-4%, lifetime: 5-15%(HIV infected) 1st year: 40%, +10% every year • Tx: test susceptibility, give multiple drugsINH + RIF + ETH (+ PZA), INH prophylaxis, hepatotoxicity

  22. TuberculosisMycobacterium tuberculosis, bovis, africanum • Infected aerosolized droplets, milk (M. bovis), replicates in middle/lower lobes alveolar space, Rasmussen’s aneurysm (pulmonary a.), pleural effusion, sputum with PMNs • Spread to hilar lymph nodes in macrophages • Reactivate in upper lobes, cavities form • Can disseminate through blood (military TB), skin lesions, HA, abd pain, osteomyelitis

  23. LeprosyMycobacterium leprae Tuberculoid Leprosy Lepromatous Leprosy • Poor TH1 response • Large # of bacteria in tissue • Infectious, non self-limiting • Tx: rifampicin (monthly)and dapsone (daily) - FREE • Thickened peripheral nerves • Loss of sensation, lesions, peripheral nerve damage, hair loss, disfigurement • Strong TH1 response • Small # of bacteria • Self-limiting • Form granulomas

  24. AIDSHIV infection • Lenti- retrovirus, persistent viremia, infects T-cells and macrophages (CD4 + CCR5/CXCR4) • CD4 >500 asymptomatic, 200-500 increased thrush, shingles, <200 opportunistic infections, <50 MAI, CMVCD4 drops 10/month on average • Transmitted by breast milk (acute), blood, semenRisk: blood 95%, pregnancy 20-33%, MSM 10%, needlestick 1 in 300 (1 in 2400 with therapy) Acute infection “mono”-like w/ rash, ulcers, and w/o tonsil hypertrophy and exudate.

  25. AIDSHIV infection • Presents with unexplained anemia, leukopenia, recurrent pneumococcal pneumonias, Kaposi’s sarcoma, thrush, wasting, STD, fever • Screen: ELISA, Confirm: Western Blot, Viral Load: PCR, Severity: CD4 Count • HAART Treatment: NRTI (AZT, 3TC), NNRTI (nevirapine, efavirenz), protease inhibitors (ritonavir, nelfinavir) • Opportunistic Infections: CMV, MAC, PCP, Toxoplasmosis, Cryptococcosis, Candida, PML

  26. GonorrheaNeisseria gonorrhoeae • Gm- diplococci • Infect columnar/cuboidal epi, PMN response, pharynx, anorectal, conjunctivitis • Spread via sex and perinatally • Dysuria w/o frequency or urgency, pain, discharge, cervicitis (PID complication) • Dx by culturing swab for diplococci • Tx with Ceftriaxone IM/cefixime PO

  27. ChlamydiaC. trachomatis, psittaci, pneumoniae • Intracellular membrane-bound inclusions • Dx with culture, DFA (MicroTrak), ELISA, annual screen sexually active women <25 yo • Tx Azithromycin x 1 or Doxycycline bid x 7d, abstinence x 7d after treatment

  28. ChlamydiaC. trachomatis, psittaci, pneumoniae Urethritis LGV (STD) • Endemic in Africa/SE Asia/ India/S. America • Painless ulcer (heals) to lymphadenopathy (scars) to ulceration of genetalia • Tx: Doxycycline po bid x 21d • NGU • 7-14d incubation • Dysuria, scant discharge • Complications • PID, ectopic pregnancy • Reiter’s syndrome (arthritis)

  29. Trichomonas Vaginalis • Flagellated motile protozoa • Yellow, purulent, frothy, foul-smelling vaginal discharge, itch, dysuria, lower abd pain • Tx: Metronidazole (ok in pregnancy)

  30. Bacterial VaginosisGardnerella or Mobiluncus • Mild to moderate thin, gray, adherent vaginal discharge with odor, itch • Clue cells (squamous cells stippled with bacteria) • +Whiff test (fishy smell in KOH) • Tx: Flagyl/Clindamycin (+Metronidazole in pregnant women)

  31. Herpes SimplexHSV-1/2 • Vesicular lesions, grouped, painful ulcers • Incubation 6 days, primary disease lasts 3wks • Recurrence in 90% of patients • Dx by Tzanck smear (Wright stain) showing multinucleated giant cells • Tx: Acyclovir

  32. SyphilisTreponema pallidum • 1⁰ - localized painless chancres (ulcerated, non-tender, hard, smooth clean base) • 2⁰ (25% untreated) – 3-6 wks after chancre, generalized rash on palms/soles, condylomata lata (flat warts), minimally pruritic • Latency – High Ab titers, 30% progress to 3⁰ • 3⁰ - “gummas” (granulomatous lesions)neurosyphilis: general paresis (insanity),tabes dorsalis (demyelination of posterior columns - sensation), Argyll Robertson pupil (non-reactive to light), gun-barrel sight

  33. SyphilisTreponema pallidum • Congenital: affects muscle, skin, bones; saber shins, saddle nose, Hutchinson’s teeth • Dx: non-specific VDRL, RPR (negative in 1⁰, 3⁰), specific FTA-ABS test (confirmatory) • Tx: (1⁰, 2⁰) Benzathine – Penicillin G IM x 1(late latent) Benzathine PCN G q week x 3(neurosyphilis) IV PCN G q 4h

  34. ChancroidH. ducreyi • Painful ulcer/ragged edges, painful inguinal lymphadenopathy • Often associated with HIV infection • Incubation 4-7d • Tx: Azithromycin x 1 or Ceftriaxone IM x 1

  35. DonovanosisKlebsiella granulomatis • Painless destructive ulcers • No lymphadenopathy • Tx: Doxycycline (+aminoglycoside)

  36. TORCH Syndrome • Mother asymtomatic but baby has: small size, hepatosplenomegaly, rash (thrombocytopenia), CNS defects (encephalitis, seizures), jaundice • Toxoplasma • Other (syphilis, HIV) • Rubella • CMV • HSV

  37. TORCH Syndrome Other (syphilis) Toxoplasmosis • Detect IgG for previous infection, positive immunity • If not immune: monitor for IgM (acute), avoid undercooked meat, garden soil, wash fruits and vegetables, handwashing • Treat infected infants aggressively • Test all pregnant mothers • If positive, treat monther with penicillin, if allergic to PCN then desensitize • Infected babies commonly show bone lesions, screen CSF for neurosyphilis

  38. TORCH Syndrome Rubella Other (HIV) • Reduce transmission by • Anti-HIV therapy (zidovudine) during pregnancy and at birth • Give infant antiretroviral therapy for 16 weeks • Cesarean delivery • No breast feeding • Vaccinate mother • Highest risk when mother infected in 1st trimester, no risk after 16 weeks • Infected infant has patent ductus arteriosus

  39. TORCH Syndrome HSV CMV • Dangerous if mother not immune before pregnancy • If mother not immune, 40% transmission • 15% infected infants have neurological symptoms (hearing loss, MR) • Education, handwashing, no vaccine • Perinatal infection by reactivated herpes lesions • Reduce transmission by Cesarean section • Can treat mother with acyclovir around birth time to reduce transmission • Treat infected infants with antiviral therapy

  40. Other Congenital • GBS • Perinatal infection (50%), anogenital screening • Concern in newborn (meningitis), infant (sepsis) • VSV • Primary infection during pregnancy very serious, especially during first 20 weeks (later is mild) • VZV Ig given within 96h of exposure, no vaccine • Fetal infection results in short limbs, skin scars, CNS • B19 • Most maternal infections do not lead to fetal infection • Infant symptoms: death, anemia w/ blueberry rash

  41. Endocarditis • Infection of the endocardial surface or valves • Surface disrupted, platelets/fibrin deposit on exposed collagen forming sterile thrombus, transient bacteremia infect sterile thrombus on low pressure side (Venturi effect), thrombus grows, Ab cannot clear infection • Once established, require ATB to cure • Two types, native or prosthetic valve endoc.

  42. Endocarditis PVE NVE • Native Valve Endocarditis • Viridans strep most common (followed by S. aureus, Strep, Entero) • If culture negative, can be HACEK, intracellular pathogens, fungi • Prosthetic Valve Endocarditis • Coagulase negative Staph most common in early PVE • Late PVE similar to NVE but coag neg staph still common • Platelets still deposit • Infection of surgical site leads to ring abscess

  43. Endocarditis • Fever + murmur, persistent bacteremia • Insidious onset of non-specific symptoms • History of heart disease, dental work • Small red lesions on palms/soles, Janeway are non-tender, Osler’s is tender • Roth spots – retinal hemorrhage w/ central pallor • Splinter hemorrhages under nails • Anemia, elevated ESR, TEE echo

  44. Endocarditis • Dx: Duke – microbes on valve OR 2 major OR1 major & 3 minor OR 5 minor • Tx: IV Bactericidal for >4 weeks(Viridans) IV PCN + aminoglycoside(Culture-neg) IV Ceftriaxone(MRSA) Vancomycin + Gentamycin + Rifampin(Entero) Ampicillin + Gentamycin(Fungi) Amphotericin B + SURGERY(2+ embolic event) SURGERY • Prophylaxis: Amoxicillin

  45. Respiratory Diseases Influenza Rhinitis • Rhinovirus, parainfluenza, RSV, coronavirus, others • Rhinorrhea, little cellular damage, self-limiting • Symptoms peak days 3-4, persist 1-2 weeks • Late August to early spring, unrelated to temp • Leading infectious cause of death in US • Type A shifts H+N antigens easily, B less so • Vaccine: 2 A strains, 1 B • Amantadine resistance is prevalent

  46. Respiratory Diseases Atypical Pneumonia Mycoplasma pneumoniae Typical Pneumonia Streptococcus pneumoniae • Rusty sputum, unilobar • Aspirated into alveolar space, fills with fluid and PMN, then fills with blood (2-3d), then fill with fibrin, then resolve w/o scarring • Asplenic, sickle-cell, agammaglobulinemia at risk • Vaccine has 23 serotypes • Dry cough, myringitis • Inhaled, attaches to respiratory cell, bronchitis infiltrated by plasma cells, lasts 2-6 wks • Similar to Chlamydophila • Unusual over age 40 • IgM cold agglutinins

  47. Respiratory Diseases Aspiration Pneumonia • Chronic, foul sputum • Polymicrobial anaerobic, microaerophilic aspirated into lung • Alcoholics, seizures, tracheoesophageal fistula are risk factors • Tx: Clindamycin PO x 3wks

  48. Acute Bacterial Meningitis • Stiff neck, Kernig’s sign (leg extension resisted when supine), Brudzinski’s sign (neck flex causes hip flex) • Dx: CNS leukocytosis, positive culture • Tx: Ceftriaxone (+Vanco if community acquired) (+ampicillin if immuno-compromised)+ Dexamethasone • S. pneumoniae • vaccine covers most types • N. meningitidis • B cause half infections • vaccine does not have B • H. influenzae • type b vaccine • L. monocytogenes • neonates + elderly • <4w GBS, <18y H.flu, 18-50y S.pneu, >50y L.mono

  49. Acute Viral Meningitis • Mucosal to viremia to BBB crossing to subarachnoid space to CSF to inflammation • Dx: LP <1000, mostly lymphocytes • Tx: (enterov) nothing(HSV-2) acyclovir(HIV) HAART • Enterovirus • Kids > 2 wks old • Summer months • Hand-foot-mouth disease, herpangina • HSV-2 • Aseptic meningitis • Genital warts • HIV • Aseptic meningitis

  50. Chronic Meningitis • Chronic symptoms with gradual neurologic decline • Dx: history, PE, LP • Tx: most likely diagnosis • Fungal • CSF glucose normal, protein >60, WBC <500 • Tuberculosis • CSF protein >>100 • AFB smear, +culture

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