1. Infectious Diseases 2008

2. Sepsis • 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 • 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)

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

4. Bioterrorism Anthrax (Cutaneous) Bacillus antracis Botulism (Inhalation) Bacillus antracis 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 • Direct contact with spores • Jet black lesions (eschars) on skin within 7-10d • Incubation 1d • Tx: Cipro or Doxy q 60d • Vaccine: attenuated Ag

5. Bioterrorism Anthrax (GI) Bacillus antracis Botulism Clostridium botulinum Most poisonous toxin on earth Not contagious, spread by aerosol/food 12-72 h incubation N/V, diff see, swallow, speak Muscle weakness/paralysis • 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

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

7. Bioterrorism Plague Yrsiniapestis Q Fever Coxiellaburnetii Nonspecific febrile syndrome, pneumonia Hepatitis, endocarditis, granulomatous complications Tx: Doxycycline 14-21d • “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

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

9. Bioterrorism GB Sarin VX 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 • 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

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

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

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

15. Ig/B-Cell Deficiency • (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 • 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

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

17. Neutrophil Deficiency • 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 • CGD • Defective NADPH oxidase, no respiratory burst, no killing • Infections with catalase positive organisms • NBT test

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

19. T-Cell Deficiency • 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 • Wiskott-Aldrich • WASP protein • Pyogenic infections, purpura, eczema • High IgA, IgE, low IgM • Infections • Mycobacteria, norcardia, legionella, cryptococcus, histoplasma, pneumocystis, herpesvirus, cryptosporidium, toxoplasma

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 Lepromatous Leprosy Tuberculoid Leprosy Strong TH1 response Small # of bacteria Self-limiting Form granulomas • 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

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

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

33. SyphilisTreponemapallidum • 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. DonovanosisKlebsiellagranulomatis • 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 Toxoplasmosis Other (syphilis) 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 • 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

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

39. TORCH Syndrome CMV HSV 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 • 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

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 NVE PVE 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 • Native Valve Endocarditis • Viridans strep most common (followed by S. aureus, Strep, Entero) • If culture negative, can be HACEK, intracellular pathogens, fungi

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 Rhinitis Influenza 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 • 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

46. Respiratory Diseases Typical Pneumonia Streptococcus pneumoniae Atypical Pneumonia Mycoplasmapneumoniae 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 • 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

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 • 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 • 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

49. Acute Viral Meningitis • Enterovirus • Kids > 2 wks old • Summer months • Hand-foot-mouth disease, herpangina • HSV-2 • Aseptic meningitis • Genital warts • HIV • Aseptic 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

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