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An Overview of Infectious Disease

C. Stringer PA-C

Copyright 1996-98 © Dale Carnegie & Associates, Inc.

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Introduction Of diseases afflicting humans, most that

are curable and preventable are caused by infectious agents.

An understanding of infectious diseases offers insight into medicine as whole.

Infectious diseases remain a major cause of death and debility of many millions of people around the world (e.g.MTB).

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COURSE OBJECTIVES Identify the database needed to

evaluate infectious diseases. Understand the basic concept of

host parasite interactions. Acquire an understanding of

immunology and vaccinations. Demonstrate knowledge of the

principles of anti-microbial therapy.

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Innate immune response

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Cytotoxic T-cell

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Innate-Adaptive responses

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The Immune System The immune system: an organization

of cells and molecules with specialized roles in defending against infection.

Innate-acquired immunity are complementary systems.

Clinical manifestations seen in patients with either an infection, allergy, cancer or autoimmune disease.

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Innate immune response Key components in the innate immune

response include soluble and cellular factors,which are nonspecific, invariable and they lack immunologic memory.

The interaction of these factors allows the body to recognize and respond to foreign antigens with their elimination from the host without damaging host tissues.

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Adaptive responses Humoral immunity relies on B

lymphocytes Cell-mediated immunity relies on T

cells T cells are divided into helper

cells(CD4) and suppressor cells(CD8).

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Diagnostics of ID

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The Complement System The complement system enhances

phagocytosis, lyses of microbes-infected cells.

Microbes and acute phase proteins activate the complement system.

The classic pathway is activated by antigen-antibody complexes

The alternate pathway by microbial-cell walls

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Host Defense Mechanisms. For any infectious process to occur, the

parasite and host must first encounter each other.

The normal human body harbors a complex microbial ecosystem:

The skin Mucus membranes The gut (enteric bacteria) Generally these are commensal organisms

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Three levels of Defense Pathogens must overcome numerous

anatomic barriers: such as enzymes Mucus that’s directly antimicrobial or

inhibt the attachment of the microbe . breaches of anatomic barrier

unleashes specific host defenses; innate and acquired immune responses .

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Immunology The immune system has two arms:

innate immunity, which is nonspecific and immediately available; And acquired immunity, which develops over time (adaptive) to specific antigens.

The immune system consist of the immune cells, and the central and peripheral lymphoid structures.

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Immunology

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Innate immune response Key components in the innate immune

response include cellular and soluble factors,which are nonspecific, invariable and they lack immunologic memory.

The interaction of these factors allows the body to recognize and respond to foreign antigens with their elimination from the host without or with minimal damage to host (native) tissues.

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Immunology (Innate) The skin-mucosal surfaces serves

as the first line of defense of the innate immune system.

Complement, acute phase proteins, natural killer cells, phagocytic wbc’s and certain cytokines provide additional protection (second line of defense).

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Innate immune response. Nutrition Age: very young-old Fever Immunization Immunocompromised: Diabetes, pregnancy

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Host and the parasite

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Humans and the Environment

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Host and parasite

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The Febrile response Fever is defined as a state of

elevated body temperature that is mediated by hypothalamus (TRC).

Fever is usually a physiologic response to infection or inflammation

Malignancies Autoimmune disorders Allergies

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The febrile response Many immunologically disorders,

such as SLE-RA Many drug reactions are associated

with fever and/or rash Endocrine disorders like

thyrotoxicosis, adrenal insuffiency, pheochromoctyoma can also produce fever.

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Fever of unknown origin Nosocomial FUO: fever not manifest on

admission and requiring 3-days of evaluation, including blood cultures.

Neutropenic FUO: fever on several ocassions with absolute neutrophil count (ANC) < 500 with incubating blood cultures.

HIV-Associated FUO: fevers over a period > 4 weeks with outpatient evaluation or 3-day hospitalization.

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Diagnostic approach General lab workup includes: CBC with peripheral smears Cultures of urine, stool and blood PPD ANA, Rheumatoid factor

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Diagnostic approach Syphilis serology LFT’S Thyroxine-calcium level HIV test. Additional diagnostic test depend

on the clincal setting e.g CT scans, endoscopy, BX, echocardiograms, gallium scans, etc.

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Clinical Pathogens Mycobacterium are a group of obligate

aerobes, rod shape bacilli that stain weakly (acid alcohol) gram positive.

Atypical mycobacteria (MOTT) like MTB have high lipid cell wall content and are recognized by their growth and response to light

M. kansasii-Marinum, M. Scrofula, MAC complex, M. Fortuitum-Chelonei.

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Clinical Pathogens Chlamydiae obligate intracellular

parasites closely related to gram negative bacteria

The three chlamydial species known to cause disease:

C.trachomatis, C. pneumonia and C. psittaci.

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Clinical Pathogens Gram- bacteria contain a endotoxin,

a potent inducer of cytokines and are associated with fever, bacteremia, and septic shock.

Gram-negative cocci that cause disease in humans are N. menigitidis, N. gonorrhea (diplococci), and Moraxella catarrhalis species.

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Gram- rod (klebsiella)

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Clinical Pathogens H. influenzae and other haemophilus species

may cause sinusitis, otitis, bronchitis, epiglottis, pneumonitis, cellulitis, arthritis, and endocarditis.

Pneumonia is one of the more common infections of adults caused by H influenzae type b.

The enteric bacteria are large gram- rods that include E. coli, Klebsiella, Serratia, Salmonella, Shigella, Proteus and Enterobacter.

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Clinical Pathogens Most pseudomonas infections are

nosocomial, except for the peculiar risk of infection in IVDA.

P. Aeruginosa is the most commonly encountered nosocomial species and may cause osteomyelitis, Malignant external otitis, CNS infections, skin-soft tissue infections, and PVE.

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Pathogenic Organisms

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Infectious Organisms

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Clinical Pathogens Occasionally, important infections of

gram-positive rods include Anthrax, listeria, Tetanus, C. diphtheria Bacillus cereus and Clostridia.

Gram+ cocci are a much more common source of infections in particular the streptococci, e.g., pharyngitis, pneumonia, rheumatic fever, impetigo, and endocarditis.

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Clinical Pathogens Anaerobic bacteria are primarily

commensals, which inhabit the skin, the mouth, the gut and the female genital tract.

They usually cause infection when displaced from their normal sites into tissues or closed body spaces e.g lung, CNS, visceral “gut” perforation, bacteremia,or endocarditis.

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Clinical Pathogens Mycoplasmas smallest free-living

organisms, commonly found in plants, animals and humans.

The biologic properties of mycoplasmas, resistance to beta-lactam antibiotics, and their adhesion to host cells,result from the lack of a cell wall, in that they have a cell membrane.

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“The fungus among us”

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Mycoses

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Clinical Pathogens Fungi appear either as rounded,budding

forms (yeast like) or hyphae (molds). Most fungi that are pathogens for humans

are saprophytes in nature. Some pathogens e.g cryptococcus, candida,

pneumocystis, fusarium virtually never cause serious disease in the normal host.

Endemic fungi e.g histoplasma, aspergilla are more aggressive in the immunocompromised.

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Clinical Pathogens Rickettsia are small gram negative

obligate intracellular bacteria : Typhus group RMSF Ehrlichiosis Q FEVER.

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Clinical Pathogens

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“ I see something crawling”

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What’s that sore

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Clinical Pathogens Spirochetes of clinical importance Treponema (Syphilis) Leptospira (rat urine) Borrelia(tick-borne) species are

frequent causes of diseases.

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Pathogens

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If it’s crawling it’s alive

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Clinical Pathogens

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Laboratory Diagnosis Direct visualization: microscopy-

staining can diagnose bacteria, mycobacteria

Candida through KOH prep India ink cryptococci

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Laboratory Diagnosis Tzanck’s smear zoster or simplex. Diagnosis by microbial antigen

detection via serology e.g chlamydia, mycoplasma,legionella,syphilis

IFA or EIA for influenzae, Hep B, RSV and Adenovirus

PCR and BDNA can identify viruses-bacteria.

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Important Terms

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Antimicrobials

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Extended Spectrum PCN’s

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Fluoroquinolones

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Mechanism of Action

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Mechanism of Action

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The Bacteria Strike Back

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Site of Action of ATB agents

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Microbial Susceptibility

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ANTI-MICROBIALS/ANTI-INFECTIVES Augmentin (Amoxicillin/Clavulanate) Zosyn ( Piperacillin/Tazobactam) Ticarcillin, Nafcillin, Dicloxacillin Mezlocillin. Oxacillin, Methicillin Pipercillin Cloxacillin Qxacillin

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CEPHALOSPORIN 1st Generation-Kaflux. Valoof 2nd Cefixime, 3rd Rocephin, Fortaz 4th Omnicef, Suprax