6/28/2011 Sepsis • SIRS –systemic response • PIRO severity staging – Temp >38C (<36C) • TLR 4 –LPS (Gm‐) – HR >90bpm, RR >20bpm • TLR 2 –PGN, LTA (Gm+) Infectious Diseases (PaCO2<32mmHg) – WBC >12k or >10% bands • Fever, inflammation, DIC, ARDS, azotemia, olyguria, • Sepsis = SIRS + Infection cellulitis, purpura, GI HIHIM 409 • Severe Sepsis = Sepsis + bleeding, jaundice Organ Dysfunction • Procalcitonin diagnostic? • Septic Shock = Sepsis + • Tx: ATB, supportive, Hypotension Activated Protein C (Xigris) Fever / Hyperthermia Bioterrorism Anthrax (Cutaneous) Botulism (Inhalation) Fever Hyperthermia Bacillus antracis Bacillus antracis • Hypothalamic setpoint • Hypothalamic setpoint • Direct contact with spores • Inhaled spores, no person‐ shifted up by PGE2 unchanged • Jet black lesions (eschars) to‐person transmission stimulating EP‐3 • Does not respond to NSAIDS on skin within 7‐10d • Incubation: 1w to 2 months • Pyogenic cytokines • Heat stroke, • Incubation 1d • Mediastinal widening, • Pneumonia, drugs, PE, DVT, hyperthyroidism, atropine, pleural effusion, infiltrates C. difficile, fungal infection, ecstasy, malignant • Tx: Cipro or Doxy q 60d • Initial symptoms improve, MI, NG tubes, IV catheters hyperthermia, serotonin • Vaccine: attenuated Ag abrupt onset of fever/ARDS, syndrome shock/death within 24‐36h • Tx: Penicillin or Cipro/Doxy Bioterrorism Bioterrorism Anthrax (GI) Botulism Cholera Glanders Bacillus antracis Clostridium botulinum Vibrio cholerae Burkholderia mallei • Ingested spores, no person‐ • Most poisonous toxin on • Rice‐water diarrhea, • Affects horses, mules, to‐person transmission earth dehydration, shock donkeys • N/V, severe abd pain, • Not contagious, spread by • Incubation 12h‐5d • Enters cut skin, mucous bloody diarrhea, possibly aerosol/food • Food/water spread membranes, inhalation mediastinal widening, • 12‐72 h incubation rebound tenderness, ascites • N/V, diff see, swallow, speak • Incubation: 1‐7d • Muscle weakness/paralysis • Tx: Penicillin or Cipro/Doxy 1 6/28/2011 Bioterrorism Bioterrorism Plague Q Fever Smallpox Tularemia Yrsinia pestis Coxiella burnetii Variola major Francisella tularensis • “Black Death”, infected fleas • Nonspecific febrile • Officially eradicated • One of most infectious • Bubonic –1‐10 cm buboes on syndrome, pneumonia bacteria in world skin w/ edema, flu‐like • Incubation 10‐14d symptoms w/ abd pain • Hepatitis, endocarditis, • High fever, HA, backache, • Tick/insect bites • Septicemic ‐ secondary granulomatous • septicemia, thromboses in vomiting, rash on palm/sole Incubation 10‐14d acral v. leading to necrosis complications • Highly contagious • Fever, chills, HA, cough, • Penumonic – acute fulminant • Tx: Doxycycline 14‐21d • lethargy, skin ulcers, lymph‐ symptoms, nearly 100% No tx, vaccine within 3‐5d mortality rate adenopahty • Tx: Streptomycin or Doxycycline Bioterrorism Bioterrorism GB Sarin VX Ricin • Binary weapon –two non‐ • 1000x more toxic than GB • Waste leftover from lethal reagents mix to form • Persists in soil for 6d processing castor beans sarin gas • Binary weapon • V/D, dehydration, • Inhibit ACHe, phosphonate • Inhibits ACHe, phosphonate hypotension, hallucinations, esters, light brown oil esters, light brown oil seizures, hematuria, • multiple organ dysfunction If mild: dim vision, • If severe: stop breathing, salivation, chest tightness paralysis, seizures, LOC • No tx available • Tx: Atropine and 2PAMCl Bioterrorism Bioterrorism • Needs Immediate Treatment, Suspect … • “Active” Research • “Secretly” Developing – Respiratory Symptoms – Algeria – China • Acute: Cyanide – Egypt – Russia – Also nerve agents, mustard, lewisite, phosgene, SEB – India • “Former” Programs • DlDelaye d: AhAnthrax, Plague, TlTularem ia – Iran – Canada – Also Q Fever, SEB, ricin, mustard, lewisite, phosgene – Israel – France – Neurological Symptoms – N. Korea – Germany • Acute: Nerve agents – Pakistan – Japan – Also cyanide – Syria – S. Africa • Delayed: Botulism – Taiwan – UK, US – Also VEE‐CNS 2 6/28/2011 Immunocompromised Complement Deficiency • Deficiencies in • Clues • Hereditary angioedema • DAF and CD59 – Complement – Recurrent Neisseria inf – C1 inhibitor deficiency – Paroxymal nocturnal – IG/B‐Cell – Recurrent pneumonia – Overactive complement hemoglobinuria – Phagocyte – Severe presentation – Minor stressors trigger • C1, C3, C4 deficiency – T‐cell – Pneumocystis jiroveci attacks – Recurrent pyogenic sinus – Burkholderia cepacia • C5‐9 Deficiency and respiratory infection – Non‐TB Mycobacteria – MAC lysis defect • C1q deficiency – Aspergillus – Neisseria bacteremia – 90% have SLE Ig/B‐Cell Deficiency Neutrophil Deficiency • (Bruton’s) X‐Linked • CVID • Neutropenia • Hereditary Cyclic N. Agammaglobulinema – Low Ig, normal B‐cell – Causes – AD, ELA2 mutation – Btk defect, no B‐cells, Ig – Recurrent sinus, • Blacks have lower counts – Multiple pyogenic respiratory infections – Predictable cycles infections – Chronic infections with • Chemotherapy patients – Aphtous stomatitis Giardia, Campylobacter • Post‐infection, sepsis – No live vaccines! – Tx: G‐CSF, stidteroids – Tx: IvIg – Tx: ATB, IVIg • Sulfa‐drugs, β‐lactams • • Hyper IgM Syndrome • IgA deficiency – Infections Chediak‐Higashi – X‐linked, normal B‐cell – Associated with CVID • Mucositis Syndrome – Low Ig but high IgM – Compensated by others • Ecthyma gangrenosum – AR, LYST mutation – Pneumocystis infections • Secondary Ig deficiencies • Disseminated candidiasis – Giant lysosomes, – T‐cells lack CD40L – Multiple myeloma, • Aspergillosis ineffective granulopoiesis leukemia, skin burns – Oculocutaneous albinism Neutrophil Deficiency Spleen “Deficiency” • Job’s Syndrome • CGD • Splenectomy • Decrease in circulating – Hyper IgE, impaired – Defective NADPH – Trauma, ITP, Hairy cell activated B‐cells (75%) chemotaxis oxidase, no respiratory leukemia, abscess • Risk of thalassemia > – STAT3 gene mutation burst, no killing • Hyposplenism hodgkins > sphero‐ – Facies, scoliosis, skin – IfInfec tions with catltalase – Autoimmune (Graves, cytosis > ITP > sepsis Hashimoto, SLE) abscesses, sinusitis positive organisms • Infections – Neoplasia (Hodgkin, – NBT test – S. Pneumoniae (mostly) • Myeloperoxidase (MPO) CML, Sezary) – Haemophilus, GNR, – Makes pus green – Amyloidosis Neisseria (less common) – Converts H2O2 to HOCl – Alcoholism, elderly, – Deficiency impairs this Crohn’s, Sickle cell 3 6/28/2011 T‐Cell Deficiency Food Safety • DiGeorge’s • Wiskott‐Aldrich • Milk pasteurization: 72C for 15s or 63C for 30m – Deletion 22q11.2 – WASP protein – No T‐cells, hypocalcemia, – Pyogenic infections, • Botulism spores: kill with high heat + acidic velocardiofacial defects purpura, eczema • Preservatives: weak acids, nitrites, sulfites, spices • SCID – High IgA, IgE, low IgM – Combined B/T‐cell • Infections • RditiRadiation: γ‐iditiirradiation for spices, meats deficiency, lymphopenia, – Mycobacteria, norcardia, • Survival: Cold –Listeria; Chlorine – Giardia, hypogammaglobulinemia legionella, cryptococcus, – ADA, PNP, RAG1/2, Jak3 histoplasma, Cryptosporidum cysts; Anything home processed gene deficiencies pneumocystis, herpesvirus, • Outbreaks: Listeria (microwaved hot dogs), • CD4 T‐cell Deficiency cryptosporidium, toxoplasma Cyclospora (raspberries), Salmonella, ETEC – HIV, <300 CD4+/mL Tuberculosis Tuberculosis Mycobacterium tuberculosis, bovis, africanum Mycobacterium tuberculosis, bovis, africanum • Acid‐fast, aerobic non‐motile bacillus, reduce • Infected aerosolized droplets, milk (M. bovis), nitrates, produce niacin, slow growing replicates in middle/lower lobes alveolar • BACTEC blood culture, DAT tests using PCR space, Rasmussen’s aneurysm (pulmonary a.), • PPD (Mantoux) is killed tuberculin, positive if >15 mm, indicates prior infection (LTBI), need CXR pleural effusion, sputum with PMNs • Risks: (normal) 1st year: 3‐4%, lifetime: 5‐15% • Spread to hilar lymph nodes in macrophages (HIV infected) 1st year: 40%, +10% every year • • Tx: test susceptibility, give multiple drugs Reactivate in upper lobes, cavities form INH + RIF + ETH (+ PZA), INH prophylaxis, • Can disseminate through blood (military TB), hepatotoxicity skin lesions, HA, abd pain, osteomyelitis Leprosy AIDS Mycobacterium leprae HIV infection Lepromatous Leprosy Tuberculoid Leprosy • Lenti‐ retrovirus, persistent viremia, infects T‐cells and macrophages (CD4 + CCR5/CXCR4) • Poor T 1 response • Strong T 1 response H H • CD4 >500 asymptomatic, 200‐500 increased • Large # of bacteria in tissue • Small # of bacteria • thrush, shingles, <200 opportunistic infections, Infectious, non self‐limiting • Self‐limiting <50 MAI, CMV • Tx: rifampicin (monthly) • Form granulomas and dapsone (daily) ‐ FREE CD4 drops 10/month on average • Transmitted by breast milk (acute), blood, semen • Thickened peripheral nerves Risk: blood 95%, pregnancy 20‐33%, MSM 10%, needlestick 1 in 300 (1 in 2400 with therapy) • Loss of sensation, lesions, peripheral nerve damage, Acute infection “mono”‐like w/ rash, ulcers, and hair loss, disfigurement w/o tonsil hypertrophy and exudate. 4 6/28/2011 AIDS Gonorrhea HIV infection Neisseria gonorrhoeae • Presents with unexplained anemia, leukopenia, • Gm‐ diplococci recurrent pneumococcal pneumonias, Kaposi’s sarcoma, thrush, wasting, STD, fever • Infect columnar/cuboidal epi, PMN response, • Screen: ELISA, Confirm: Western Blot, Viral Load: pharynx, anorectal, conjunctivitis PCR, Severity: CD4 Count • SdSpread via sex and perillinatally • HAART Treatment: NRTI (AZT, 3TC), NNRTI • Dysuria w/o frequency or urgency, pain, (nevirapine, efavirenz),