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Infectious Disease

Christopher Knox, Erika Nakajima, and Rachel (Hiu-Ki) Tran, chapter editors

Karolina Gaebe and Alyssa Li, associate editors

Wei Fang Dai and Camilla Giovino, LBM editors

Dr. Andrea Boggild, Dr. Paul Bunce,and Dr. Susan Poutanen, staff editors

Infectious Disease

Acronyms

Principles of Microbiology

Bacteriology

Virology

Mycology

Parasitology

Transmission of Infectious Diseases

Nosocomial Infections

Respiratory Infections

Influenza

COVID-19

Skin and Soft TissueInfections.

Cellulitis

Necrotizing Fasciitis

Acquired Oral Lesions

Gastrointestinal Infections.

Traveller's Diarrhea.

Chronic Diarrhea

Peptic Ulcer Disease(Helicobacterpylori)..

Bone and Joint Infections

Septic Arthritis

Diabetic Foot Infections

Osteomyelitis

Cardiac Infections

Infective Endocarditis

CNS Infections

Meningitis

Encephalitis

Generalized Tetanus

Rabies

Systemic Infections

Sepsis and Septic Shock

Leprosy (Hansen's Disease)

Lyme Disease

Toxic Shock Syndrome

Cat Scratch Disease

Rocky Mountain Spotted Fever

West Nile Virus

Syphilis

Tuberculosis

HIV and AIDS

Epidemiology

Etiology

Modes of Transmission

Natural History

Anti-Retroviral Treatment

Prevention of HIV Infection

Types of Testing

HIV Pre- and Post-Test Counselling

FUNGAL INFECTIONS

Skin and Subcutaneous Infections

Superficial Fungal Infections

Dermatophytes

Subcutaneous Fungal Infections

Endemic Mycoses

ID1 Op portunistic Fungi ID33

Pneumocystis jirovecii (formerly P. corinii) Pneumonia:PJP or ID2

PCP

ID2 Cryptococcus spp.

Candida albicans

Aspergillus spp.

PARASITIC INFECTIONS

Protozoa -Intestinal/Genitourinary Infections

Entamoeba histolytica (Amoebiasis)

Giardia lamblia

Trichomonas vaginalis

Cryptosporidium spp.

Blood andTissue Infections. .

Plasmodium spp. (Malaria)

Trypanosoma cruzi

Toxoplasma gondii

Helminths

Roundworms - Nematodes

Flatworms -Cestodes/Trematode

Schistosoma spp.

Ectoparasites

Travel Medicine

General Travel Precautions

Fever in the Returned Traveller

Fever of Unknown Origin

Infections in the Immunocompromised Host....

Febrile Neutropenia

Infections in Solid Organ Transplant Recipients

Immune Reconstitution Inflammatory Syndrome

A Simplified Look at Antibiotics

Antimicrobials

Antibiotics

Antivirals

Antifungals

Antiparasitics

Quick Reference: Common Infections and Their Antibiotic

Management .......

Landmark Infectious Diseases Trials

References

ID35

ID35

...ID6

ID11 _.ID37

. ..ID13 ID39

ID13

ID13

ID13 ID41

ID13 ID41

ID43

....ID15 ID44

ID17

ID46

..ID48

ID20

ID52

ID53

ID55

ID56

.ID56

...ID25 ID58

....ID27

...ID32

ID32

r T

L. J

ID33

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ID1 Infectious Disease Toronto Notes 2023

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Acronyms

GAS group A Streptococcus

GBS group B Streptococcus

gonococcus

GN Gram-negative

GNB Gram-negative bacilli

GP Gram-positive

HAART highly active anti retroviral

treatment

HAV hepatitis A virus

HBc HBV core antigen

HBeAg HBV envelope antigen

HBsAg HBV surface antigen

HBV hepatitis B virus

HCC hepatocellularcarcinoma

hepatitis C virus

HDV hepatitis D virus

HEV hepatitis E virus

HHV human herpesvirus

Haemophilus influenzae b

high power field

human papillomavirus

HRIg human rabiesimmunoglobulin

HSV herpessimplex virus

HTLV-1 Human T-lymphotropic virus1

HUS hemolytic uremic syndrome

infective endocarditis

interferon

immunoglobulin

isoniazid

INSTI integrase strand transfer

RT-PCR reverse transcription-PCR

SARS severe acute respiratory

syndrome

SCID severe combined

immunodeficiency

SIAOH syndrome of inappropriate

antidiuretic hormone secretion

sensitivity

Sp specificity

spp. species

severe respiratory illness

STEC Shiga toxin-producing £coli

Mycoplasma tuberculosis

triglycerides

Tig tetanus immune g

TMP/SMX trimethoprim-sulfi

TNF tumour necrosisfactor

toxoplasmosis,other,rubella,

cytomegalovirus. HSV

T. pallidum immobilization test

TPPA T. pallidum particle

agglutination assay

TSS toxic shock syndrome

TST tuberculin skin test

upper respiratory tract infection

VDRl venereal disease research

laboratory

VRE vancomycin-resistant

Enterococcus

VZV varicella-zoster virus

AFB acid-fast bacilli

ANC absolute neutrophil count

AOM acute otitis media

ARDS acute respiratory distress

syndrome

ARV anti-retroviral

ART anti retroviral therapy

BAL bronchoalveolar lavage

BCG Bacille Calmette-Guerin

BUN blood urea nitrogen

CFU colony forming units

CLIA ChemiLuminescent

immunoAssay

CLL chronic lymphocytic leukemia

CMIA ChemiLuminescent Microparticle HCV

ImmunoAssay

CMV cytomegalovirus

CNS central nervoussystem

COVID-19 Coronavirus disease 2019

DEET N.N-Diethyi-meta-totuamide HPF

DVT deep vein thrombosis

EBV Epstein-Barr virus

EHEC enterohemorrhagic£coli

EIA enzyme immunoassay

EIEC enteroinvasive£co/r

ETEC enterotoxigenic£coli

FDP fibrinogen degradation products IFN

FTA-ABS fluorescent Treponemo

antibody-absorption

FUO fever of unknown origin

inhibitor

IVOU intravenous drug use

KOH potassium hydroxide

KSHV Kaposi'

ssarcoma-associated

herpes virus

LDL low-density lipoprotein

LOC level of consciousness

LP lumbar puncture

MERS Middle Eastern respiratory

syndrome

MDR multidrug resistance

MHA-TP microhemagglutination assay

T.pallidum

MMR measles mumpsrubella

MRSA methidllin-resistant S.aureus

MSM men who have sex with men

MSSA methidllin-sensitive S.aureus

NRTI nudeoside/nudeotide reverse TORCH

transcriptase inhibitor

O&P ova and parasites

PCP Pneumocystis pneumonia

protease inhibitor

PJP Pneumocystis jirovecii

pneumonia

PMN polymorphonuclear leukocytes URTI

PNS peripheral nervoussystem

PPD purified protein derivative

rapid plasma reagin

RSV respiratory syncytial virus

respiratory tract infection

GC

Sn

SGI

TB

TG

lobulin

amethoxazole

Hib

TPI

H P:

PI

IE

H P

9

Plh

RTI

Principles of Microbiology

Bacteriology

Bacteria Basics

• bacteria are prokaryotic cellsthat divide asexually by binary fission

• Gram stain divides most bacteria into two groups based on their cell wall

• GP:thick,rigid layer of peptidoglycan

• GN:thin peptidoglycan layer + outer membrane composed oflipoproteins and lipopolvsaccharides

clinicalsignificance:Gram stain results are used to guide tailored empiric treatment prior to

availability of culture and susceptibility testing results

• acid-fast bacilli:high mycolic acid content in cell wall, “acid fast" as washout phase with acid-alcohol is

ineffective in acid-fast bacteria (e.g.Mycobacteria)

• partially acid-fast bacilli:some bacteria have moderate amounts of mycolic acid content that will

decolourize with the acid-alcohol used in A1

:Bstains but are considered partially acid-fast positive

using a modified acid-fast stain with a weaker acid during the washout phase (e.g.Socardia); note that

Nocardia will be acid-fast stain negative but modified acid-fast stain positive while mycobacteria will be

acid-fast stain positive and modified acid-fast positive

• “atypical"

bacteria: not seen on Gram stain and difficult to culture

• obligate intracellular bacteria: e.g. Chlamydia

• bacteria lacking a cell wall: e.g. Mycoplasma

• spirochetes:e.g. Treponema pallidum

• O:can be either vital or detrimental to growth

obligate aerobes:require 02

obligate anaerobes:require environment without 02

facultative anaerobes:can survive in environments with or without 02

0

Coccus Coccobacillus

Diplococci

&

Bacillus

Staphylococci Diplobacilli

Mechanisms of Bacterial Disease

•t/

1.adherence to and colonization ofskin or mucous membranes

fimbriae (pili):microfilaments extending through the cell wall attach to epithelial cells(e.g.E.coli in

the urinary tract)

2.invasion or crossing epithelial barriers

3.evasion of host defense system through:

inhibition of phagocytic uptake via polysaccharide capsule (e.g.S

'

, pneumoniae, S.meningitidis, H.

influenzae)

• presence ofsurface proteins(e.g. Staphylococcus,Streptococcus)

4.toxin production

exotoxins are secreted by living pathogenic bacteria and cause disease even if the bacteria are not

present (e.g.Clostridium)

endotoxins are structural components of GN bacterial cell walls and may be shed by live cells or

released during cell lysis

5.intracellular growth

• obligate intracellular: Rickettsia,Chlamydia

• facultative intracellular: Salmonella, Neisseria, Brucella, Mycobacteria, Listeria, Legionella

6.biofilm

• an extracellular polysaccharide network forming mesh around the bacteria (e.g.S

'

, epidermidis)

which can coat prosthetic devices such asIV catheters

Streptococci Spirochete

© Paul Kelly 2011

Figure 1. Bacteria morphology

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ID3 Infectious Disease Toronto Notes 2023

Table!Common Bacteria

GP Bacteria GN Bacteria Not Seen on Gram Stain

Cocci (round) Bacilli (rod-like) Diplococci Bacilli (rod-like) Acid-Fast Others

Staphylococcus

S.aureus

S.soprophyticus

S. epidermidis

S.lugdunensis

Streptococcus

S.pneumoniae

S. pyogenes (GAS)

J. ogaloctioe|GBS)

S. onginosus group

Interococcus

l.taecatis

Peptostrcptococcus

Obligate intracellular

Rickettsiae

Chlamydia

C.trachomatis

C. pneumoniae

Aerobes Bacillus

B. onthrocis

Listeria

A/ocordia(moditied acidfast positive)

Reisseria

H. meningitidis

A!,gonorrhoeae

Moroxella

M. coturrlmlis

Cnterobacterates

[. coli

Klebsiella

Salmonella

Shigella

Yersinia

Campylobacter

Legionella

Pseudomonas

Haemophilus

H. inlluemoe

Mycobacteria

M.tuberculosis

M. leprae

M. avium complex

Ho cell wall

Mycoplasma

Spirochete (spiral)

treponema pallidum

Clostridioidesditlicile

Clostridium

C.letoni

C. botulinum

C. perlringens

Cutibacterium

IPropionibacterium)acnes

Anaerobes Bocteroides

B, Itogilis

Table 2. Commensal Flora

Site Organisms

Coagulase- negative staphylococci.Corynebocterium. C. atnes. Bacillus. S. aureus

Vitidans group streptococci. Haemophilus, Heisserla, anaciobes (Peptoslreptococius. Bacteroides. Veillonello, fasobaclerium. Actinomyces, Prevotello)

l. coli, anaerobes (low numbers)

l coli. Klebsiella, Interobacter, Interococcus,anaerobes {8otleroides, Peplostreptococcus, Clostridium)

Lactobacillus acidophilus,vitidans group streptococci,coagulase negalive staphylococci,facultative anaerobes

Skin

Oropharynx

Small Bowel

Colon

Vagina

Bacteria

1

I T

Obligate intracellular bacteria Non-obligatc intracellular bacteria

i

I

I

Rickettsia rickcttsii Spiral shaped

Chlamydia trachomatis

Coxiclla burnetii

Cocci or bacilli

1

1

f J

Treponema pallidum *

Borretia burgdorferi

Leptospira spp.

Gram-positive Gram-negative Acid fast

V 4 4 4

Bacilli/Coccobacilli M tuberculosis

M. leprae

Cocci Bacilli COCCI

I

*

I

*

I

Aerobic Anaerobic Aerobic Anaerobic

1

r . i i i

Catalase tve Catalase -ve Pcptococcus

Peptostreptococcus

N. gonorrhoeae Vcillonclla

N. meningitidis

Moraxella spp. : :

Aerobic Anaerobic

4 4

Staphylococcus Spore forming Non-spore forming Bacteroides fragilis

I 1

; 4 4 4 4 4

Coagulase +ve Coagulase -ve Growth on sheep No growth on sheep

blood agar

Aerobic Anaerobic Aerobic Anaerobic

blood agar 4 4 4 4 4 4

S. aureus S. epidermidis 4

S. saprophyticus

Bacillus anthracis C. botulinum

Bacillus cereus C. tetani

C. perlringens

C. difficile

Listeria

monocytogenes

C.diphthcriac

Lactobacillus

Actinomyces

Cutibacterium Haemophilus influenzae

Legionella pneumophila

I 4 4

Enterococci Streptococci * Oxidase

*

ve Oxidase -ve

1

4

'

4 4 4 4 4 4 r“i

a-homolytic p-homolytic y-hcmolytic Glucose fermenter Non-glucose fermenter Lactose fermenter Non-lactose fermenter L J

4 4 4 4 4 4 4

S. pneumoniae Group A Strep S. gallolyticus

Vmdans group Strep IS. pyogenesI

Group B Strep

IS. agalacliael

Group C Strep

Group G Strep

Figure 2. Laboratory identification of bacterial species

Bold - commonly encoifrteied bacteria

Vibrio cholorao Bordatella pertussis

Cardiobacterium Campylobacter jejuni

Pastcurclla Pseudomonas aeruginosa

Eikcnclla

Moraxella

Escherichia coli Salmonella typhi

Klebsiella pneumoniae Shigella dyscntchac

Acromonas Proteus mirabilis

Yersinia pcstis +

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ID l Infectious Disease Toronto Notes 2023

Virology

Viral Basics

• viruses are infectious particles consisting of RNA or DNA covered by a protein coat

• infect cells and use host metabolic machinery to replicate

• nucleic acid can he double stranded (ds) or single stranded (ss)

can be enveloped or naked

• virions are mature virus particles that can be released into the extracellular environment

• host susceptibility is governed by the host cell and virus surface proteins (viral tropism) and cellular

immunity

Viral Disease Patterns

1 . acute infections (e.g. adenovirus)

• host cells are lysed in the process of virion release

some produce acute infections with late sequelae (e.g. measles virus-induced subacute sclerosing

panencephalitis)

2. chronic infections (>6 mo) (e.g. HBV,HIV)

host cell machinery is used to produce and chronically release virions

Helical

Icosahcdral

3. latent infections

viral genome remains latent in host cell nucleus

can reactivate (e.g. HSV,VZV)

Table 3. Common Viruses

Nucleic Acid Enveloped Virus Family Major Viruses Medical Importance

dsDNA No Adenoviridae Adenovirus URTI

Conjunctivitis

Gastroenteritis Complex

Papillomaviridae HPV1.4

HPV6.11

HPV16.18,etc.

No Plantar warts

Genital warts

Cervical/anal dysplasia and cancer

Oral, ocular, and genital herpes; encephalitis

Genital, oral,and ocular herpes: encephalitis

Chicken pox,shingles

Mononucleosis, viral hepatitis

Retinitis,pneumonitis,hepatitis,encephalitis

Roseola

Kaposi's sarcoma,multicentric Castleman’s disease,body cavity

lymphoma

Progressive multifocal leukoencephalopathy

Hepatitis

Monkeypox

Smallpox

HHV1-HSV1

HHV2-HSV2

HHV3-V2V

HHV4-EBV

HHV5-CMV

Ves Herpesviridae a

s

5

HHV6* Enveloped

HHV8-KSHV

Figure 3.Virus morphology

JC virus

Hepatitis 8

Monkeypox

Smallpox

Polyomaviridae

Kepadnavindae

Poxviridae

No

Yes

Yes

DNA Viruses: Families ssDNA No Parvoviridae Parvovirus 819 Erythema intectiosum (Filth disease)

Caticivindac Gastroenteritis

Acute hepatitis

Poliomyelitis

URIIs, viral meningitis

URIIs

Hand.

foot-and- mouth, viral meningitis,myocarditis

Acute hepatitis

URIIs.SARS. MERS.C0VID-19

Yellow lever

Dengue fever

Hepatitis

Encephalitis, flaccid paialysis

Zika virus disease

(v) ssRNA Noioviiuses

Hepatitis E

Poliovirus

Echoviius

Rhinovirus

Coxsackie virus

Hepatitis A

Coronavirus

Yellow lever

Dengue fever

Hepatitis C

West Nile

No HHAPPPPy

Hcpadnaviridae

Herpesviridae

Adenoviridae

Papillomaviridae

Parvoviridae

Polyomaviridae

Poxviridae

No Picomaviridae

Coionaviridae

Elaviviridae

Yes

Yes

2ika

Rubella (German measles)

Chikungunya

Yes Togaviridae Rubella

Chikungunya

( ) ssRNA-RT Yes Retroviridae HIV AIDS

HTLV-1 T cell leukemia and lymphoma

(-) ssRNA Lassa fever

Hemorrhagic fever

Influenza

Measles

Mumps

URIIs,croup,bronchiolitis

Bronchiolitis,pneumonia

Rabies

Yes Arenaviridae Lassa

Ebola.Marburg

Orthomyxoviridae Influenza A.B. C

Paramyxoviridae Measles

Mumps

Parainfluenza

Yes Filoviridae

Yes

r t

Yes .

( J

RSV

Yes Rhabdoviridae Rabies +

dsRNA No Reoviridae Rotavirus Gastroenteritis

Note: viridae = family. .virus *

genus./ = species (e.g.Retroviridae HIV-2)

'Roseolovirus.Herpes lymphotropic virus

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ID5 Infectious Disease Toronto Notes 2023

Mycology

Fungal Basics

• fungi are eukaryotic organisms, they can have the following morphologies

1. yeast (unicellular)

2. moulds,Le.filamentousfungi (multicellular with hyphae)

3. dimorphic fungi (found as mould at room temperature but grow as yeast-like forms at body

temperature)

a

S

i