OrganismsIn bold arc lltc moil common isolates

1. Streptococcus includes mainly vitidans group streptococci

2. Other Includesless common organismssuch ns:

•Streptococcus gattofytKui (previously known asS. bows; usually associated with underlying 61malignancy and cirrhosis)

•Ciilturc-ncydtlvt:organism

*

including Ablotroplua. GrunuiiiulvHu. Ban

•Hoomophlhn.Aggn jpf boettt Cotdioboctorium.BfkonoilQ,andKfngt to (HACItQ

•Candida

3. IVDU endocarditis pathogens depend on substance used to dilute the drugs(i.e.tapwater = Pseudomonas,saliva = oral llora.toilet water « 61flora) +

Clinical Features

• systemic

fever (80-90%), chills,weakness, rigors, night sweats, weight loss, anorexia

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•cardiac

dyspnea, chest pain, clubbing (subacute)

• regurgitant murmur (new onset or increased intensity)

• signs of CHI-

'

(secondary to acute mitral regurgitation (MR), atrial regurgitation (Alt))

•embolic/vascular

• petechiae over legs, splinter hemorrhages (linear, reddish-brown lesion within nail bed )

laneway lesions (painless, 5 mm, erythematous, hemorrhagic pustular lesions on soles/palms)

focal neurological signs(CNS emboli), headache (mycotic aneurysm)

splenomegaly (subacute)

microscopic hematuria,flank pain (renal emboli) ± active sediment

•immune complex

Osier’s nodes(painful, raised, red/brown, 3-15 mm on digits)

• glomerulonephritis

arthritis

Roth'

sspots(retinal hemorrhage with pale centre)

Diagnosis

•Modified Duke Criteria

• definitive diagnosis if: 2 major,OR 1 major + 3 minor,OR 5 minor

• possible diagnosis if: 1 major + 1 minor, OR 3 minor

(§)

Clinical Features of Infective

Endocarditis

FROM JANE

Fever

Roth'sspots

Osier'

s nodes

Murmur

Janeway lesions

Anemia

Nail- bed hemorrhages(i.e.splinter

hemorrhages)

Emboli

Table 17. Modified Duke Criteria

Major Criteria (2)

1.Positive blood culturesfor IE

•typical microorganismsfor IE from 2 separate blood cultures(Streptococcus viridans.HACEK group,Streptococcus gallolyticus.Staphylococcus

aureus,community-acquired enterococci) OR

•Persistently positive blood culture,defined asrecovery of a microorganism consistent with IE from blood drawn >12 h apart OR

•All of 3 or a majority of 4 or more separate blood cultures, with first and last drawn >1h apart OR

•Single positive blood culture for Coxiello burnetii or antiphase1IgG antibody tiler >1:800

2.Evidence ol endocardialinvolvement

• Positive echocardiogram for IE (oscillating intracardiac mass on valve or supporting structures, or in the path ol regurgitant jets, or on

implanted material in the absence ol an alternative anatomic explanation OR abscess OR new partial dehiscence ol prosthetic valve); and new

valvular regurgitation (insufficient ifincrease or change in pre-existing murmur)

TEE

Q

Transesophageal echo

TTE Transthoracic echo

Minor Criteria (5)

1. Predisposing condition (abnormal heart valve, IVDU)

2.Fever (38.0“C/100.4“F)

3.Vascular phenomena:major arterial emboli,septic pulmonary infarcts,mycotic aneurysms, intracerebral hemorrhage (ICH), conjunctival

hemorrhages.Janewaylesions

4. Immunologic phenomena:glomerulonephritis,rheumatoid lactor, Osier's nodes. Roth'

sspots

5. Positive blood culture but not meeting majoi criteria OR serologic evidence of active inlection with organism consistent with IE

Investigations

• serial blood cultures:3 sets (each containing one aerobic and one anaerobic sample) collected from

differentsites >1 h apart

persistent bacteremia is the hallmark of an endovascular infection (e.g.IH)

• repeat blood cultures (at least 2 sets) after 48-72 h of appropriate antibiotics to confirm clearance

• blood work: CBC and differential (normochromic, normocytic anemia), HSR (increased), rheumatoid

factor (RP)(i ),urea/Cr

• urinalysis (proteinuria, hematuria, red cell casts) and urine C&S

• EGG: prolonged PR interval may indicate perivalvular abscess

• echo findings:vegetations, regurgitation, abscess

- TTE (poor sensitivity) indicated for all suspected IE, inadequate in 20% (obesity,COPD,chest

wall deformities)

THE indicated if TTH is non-diagnostic in patients with at least possible endocarditis or if suspect

prosthetic valve endocarditis or complicated endocarditis (e.g. paravalvular abscess/perforation)

(

-90% sensitivity)

Treatment

• medical

usually non-urgent and can wait for confirmation of etiology before initiating treatment unless

patient isseptic

empiric antibiotic therapy if patient is unstable;administer ONLY after blood cultures have

been taken. Generally,.S

'

, aureus,coagulase-negative Staphylococcus(CNST), and GN coverage is

important

* first line empiric treatment for native valve: vancomycin t ceftriaxone OR gentamicin

first line empiric treatment for prosthetic valve: vancomycin + gentamicin t rifampin

targeted antibiotic therapy: antibiotic and duration (usually 4-6 wk) adjusted based on valve,

organism, and susceptibilities

monitor for complications of IE (e.g. heart failure (HE),conduction block, newemboli) and

complications of antibiotics (e.g. renal disease)

post-treatment prophylaxis only recommended for high-risk individuals listed above with dental

procedures that may lead to bleeding OR invasive procedure of the respiratory tract that involves

incision or biopsy of the respiratory mucosa,such astonsillectomy and adcnoideclomy OR

procedures on infected skin,skin structure, or musculoskeletal tissue

+

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• dental/respiratory procedures: amoxicillin single dose 30-60 min prior; clindamycin if truly

penicillin-allergic

infected skin/soft tissue procedures: cephalexin single dose 30-60 min prior;clindamycin if truly

penicillin-allergic (modify based on etiology ofskin/soft tissue infection)

Set Lanamark Iniectious DiseasesInals1« note

nfotmationon the POEf tnal.which imestigated

the efficacy and safety of slatting from IV to oral

antibiotics in patients with IE.

•surgical

most common indication is refractory CHT

• other indications include: valve ring abscess, valve perforation, unstable prosthesis, large

vegetation >lcm, recurrent emboli despite adequate antimicrobial treatment, antimicrobial

failure (persistently positive blood cultures), fungal etiology, S. aureus on a prosthetic valve

Corticosteroids lor Acute Bacterial Meningitis

Cochiare OB Syst Rev 20IS:C000440S

Purpose: loeiamine the effect of adjuvant

corticosteroid therapy vs. placebo on mortality,

hearing loss, and neurological segue lae with acute

bacterial meningitis.

Methods: RCls ol corticosteroids loracute bacterial

meningitis.

Results: 25 studies. 4121 participants.

Corticosteroids were associated with non -significant

morSa irty reductions(RR 0.90.95% Cl 0.80-1.01).

Corticosteroids were associated with tower rates

of hearing toss(88 0.24, 95% Cl 0.63-0.87) and

neurological sequelae (RR 0.83.9S% CI 0.69-1.00).

Corticosteroids were associated with increase m

recurrent fever (881.27. 95% Cl1.09-1.47).

Conclusions: Corticosteroids sign hcantly reduced

hearing loss and neurologicalsequelae butdid not

reduce mortality.Data supports use in high-income

countries but no benefit in low- mcomecountries.

Prognosis

•adverse prognostic factors:CHT,prosthetic valve infection, valvular/myocardial abscess,

embolization, persistent bacteremia, altered mental status

•mortality: prosthetic valve It (25-50%), non-IV'DU S. aureus It (30-45%), IVDU .S

'

, aureus or

streptococcal It (10-15%)

CNS Infections

Meningitis

• see Paediatrics, P65

Definition

• inflammation of the meninges

Etiology $

Brudzinski's Sign

Passive neck flexion causes involuntary

flecion of hips and knees

Table 18. Common Organisms in Meningitis

Bacterial Viral Fungal Other

Age 0- 4 wk Age 1-3 mo Age >3 mo Kernig's Sign

Resistance to knee extension when hip

is flexed to 90”

S. pneumoniae

Af. meningitidis

L. monocytogenes

(likely if age »50 and

comorbidities)

HSV-1.2 Crypfococcus

Coccidroides

GB5 GBS tyme disease

[.coll m Hvurosyphrlis

L. monocytogenes

Klebsiella

l. coli

5. pneumoniae

It. meningitidis

H.influenzae

Enteroviruses

Parechoviruses

West Kile

IB

Jolt Accentuation of Headache

Headache worsens when head turned

horizontally at 2-3 rotations:more

sensitive than Brudzinski Risk Factors 's and Kernig's

• lack of immunization against H. influenzae type B, .S

'

, pneumoniae, and N. meningitidis in children

• most cases of bacterial meningitis are due to hematogenous spread from a mucosal surface (nasopharynx)

• direct extension from a parameningeal focus (otitis media,sinusitis) less common

• penetrating head trauma or iatrogenic

• anatomical meningeal defects-CST leaks

• immunodeficiency (corticosteroids, HIV, asplenia, hypogammaglobulinemia, complement deficiency, etc.)

• contact with colonized or infected persons

Clinical Features

• neonates and children:fever, lethargy, irritability, vomiting, poor feeding

• older children and adults:fever, headache, neck stiffness, confusion, lethargy,altered LOC,seizures,

focal neurological signs, nausea/vomiting, photophobia, papilledema

• petechial rash in meningococcal meningitis (purpura fulminans),seen more frequently on trunk or

lower extremities

CSF Gram Stain Findings

• S. pneumoniae -GP diplococci

. N. meningitidis - GN diplococci

• H. influenzae - Pleomorphic GN

coccobadlli

• t. monocytogenes - GP rods

Doesthis Adult Patient have Acute Meningitis!

JAMA »99:281:175-181

Study Systematic review ol literature inalyung the

accuracy and precision of the clinical examination m

the diagnosis ol adult meningitis.

Results: Clinical history items nave a low accuracy fur

the diagnosis of meningitis in adults.Ihe sensitivity

for headachesis 50% and the sensitivity lor nausea/

vomiting is 30%. On physical elimination, absence

of fever,neck stiffness, and altered mentalstatus

ehm nates meningitis with a sensitivity of 99%.

Conclusions: Ihe clinical elimination aids In

eidudmg a diagios s of meningitis in adults with a

tow-fish clinical presentation.In high-risk patients,

clinicians need tn proceed directly to lumbar puncture

given the serious implications of the infection.

Investigations

• blood work:CBC and ditferential, electrolytes (for S1ADH), blood C&S

CST:opening pressure, cell count + differential, glucose, protein,Gram stain,bacterial C&S

ATB,fungal C&S, cryptococcal antigen in immunocompromised patients,subacute illness,

suggestive travel history or TB exposure

PCR for HSV, VZV, enteroviruses; in infants <6 mo, parechoviruses

• West Nile virusserology in blood and CST during summer and early fall if viral cause suspected

• imaging/neurologic studies:CT,MR1, EEC if focal neurological signs present

Table 19. Typical CSF Profiles for Meningitis r

L J

CSF Analysis Bacterial Viral

Glucose (mmol/l)

Protein (gfl)

Decreased

Markedly increased

500-10000/pl

Heutrophils

Normal

Increased

10-500/pl

lymphocytes

WBC

Predominant WBC +

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Treatment

• bacterial meningitis is a medical emergency: do not delay antibioticsfor CT or LP

• empiric antibiotic therapy

age £28 d: ampicillin H cefotaxime

age 29 d-3 mo:ceftriaxone/cefotaxime t vancomycin ± ampicillin

age >3 mo: ceftriaxone i vancomycin

add ampicillin IV if risk factorsfor infection with L. monocytogenes present:age >50, alcohol

use disorder,immunocompromised

• steroidsin acute bacterial meningitis:dexamethasone IV within 20 min prior to or with first dose of

antibiotics

continue in those patients with proven pneumococcal meningitis

not recommended for patients with suspected bacterial meningitis in some resource-limited

countries

• not recommended for neonatal meningitis

Prevention

• see Paediatrics. P65

• immunization

children:immunization against H.influenzae type B (Pentacel*),S. pneumoniae (Synflorix*,

Prevnar-13*), N. meningitidis (Menjugate*, Menactra*, Nimenrix*, Menveo*,Bexsero*)

adults:immunization against iV. meningitidis in selected circumstances (immunocompromised,

outbreaks, travel, epidemics) and S.pneumoniae (Pneumovax*) for high-risk groups

• prophylaxis:close contacts of patients infected with H. influenzae type B should be treated with

rifampin if they live with an inadequately immunized (<4 vr) or immunocompromised child (<I8 yr);

ciprofloxacin, rifampin, or ceftriaxone if close or household contact of a patient with N.meningitidis;

meningococcal vaccines are also recommended for post-exposure prophylaxisfor close contacts and

in outbreak control

Public Health Agency of Canada

Indicationsfor Adult Immunization

Pneumococcal Polysaccharide Vaccine

(i.e. Pneumova*

)

>65 yr (option to also give pneumococcal

conjugate vaccine;if so.to give

polysaccharide vaccine8wk after

conjugate vaccine)

Pneumococcal Polysaccharide Vaccine

(i.e. Pneumovax ) and Pneumococcal

Conjugate Vaccine

Chronic cardiovascular/respiratory/

hepatic/renal disorders, asplenia,

sickle cell, or immunosuppression

(polysaccharide vaccine to be given 8 wk

after pneumococcal conjugate vaccine)

Meningococcal Ouadrivalent Vaccine

(Menactra ’ or Menomune '

)

Healthy young adults

Asplenia

Travellers to high-risk areas

Military recruits or laboratory personnel

Complement factor D. or properdin

deficiency or acquired terminal

complement deficiency through receipt

of eculizumab

Prognosis

• complications

death, headache,seizures, cerebral edema, hydrocephalus, S1ADH, residual neurological deficit

(especially CN VIII).deafness

Multicomponent Meningococcal

Serogroup B Vaccine (Bexsero'

)

Asplenia

Military recruits or laboratory personnel

Complement,factor D. or properdin

deficiency, or acquired terminal

complement deficiency through receipt

of eculizumab

• mortality

• S. pneumoniae 25%;N.meningitidis 5-10%; H. influenzae 5%

worse prognosisif:extremes of age,delaysin diagnosis and treatment,stupor or coma,seizures,

focal neurologicalsigns,septic shock at presentation

Encephalitis

Meningitis and encephalitis patients

can be distinguished based on their

cerebral function.Cerebral function is

abnormal in encephalitis patients(e.g.

altered mentalstatus, motor orsensory

deficits, altered behaviour,speech

or movement disorders), but may be

normal In patients with meningitis. Note

however, that there is considerable

overlap between the two syndromes

("meningoencephalitis")

Definition

• inflammation of the brain parenchyma

Etiology

• identified in only 40-70% of cases

» when cause is identified, the most common etiology is viral: HSV, VZV, EBV,CMV, enteroviruses,

parechoviruscs, West Nile and other arboviruses, influenza and other respiratory viruses, HIV,

mumps, measles, rabies, polio

bacteria: L.monocytogenes, mycobacteria,spirochetes(Lyme,syphilis), Mycoplasma pneumoniae

• parasites: protozoa (e.g. Toxoplasma) and helminths (rare)

fungi: e.g.Cryptococcus

post-infectious(e.g. acute disseminated encephalomyelitis(ADEM))

Pathophysiology

• acute inflammatory disease of the brain due to direct invasion or pathogen-initiated immune response

viruses may reach the CNS via peripheral nerves (e.g. rabies, HSV)

• herpessimplex encephalitis

acute, necrotizing, asymmetrical hemorrhagic process with lymphocytic and plasma cell reaction

which usually involves the medial, temporal, and inferior frontal lobes

associated with HSV-1,less likely caused by HSV-2

• influenza and other respiratory viruses are associated with acute necrotizing encephalopathy (ANE);

likely mediated by pathogen-initiated immune response

Clinical Features

• constitutional:fever, chills, malaise, nausea /vomiting

• meningeal involvement (meningoencephalitis): headache, nuchal rigidity

• parenchymal involvement:seizures, altered mental status,focal neurological signs

• herpessimplex encephalitis

acute onset (<1 wk) of focal neurological signs: hemiparesis, ataxia, aphasia,focal or generalized

seizures

temporal lobe involvement:behavioural disturbance

usually rapidly progressive over several days and may result in coma or death

• common sequelae: memory and behavioural disturbances

rare complication: development of encephalopathy and Kluver-Bucy syndrome characteristics I

mo after completion of treatment for HSV encephalopathy

n

L J

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Investigations

• CSE:opening pressure; cell count and differential;glucose; protein; Gram stain; bacterial C&S; PGR

for HSV, VZV, EBV, enteroviruses/parechoviruses, M. pneumoniae,and selectively for other less

common etiologies

• serology: may aid diagnosis of certain causes of encephalitis(e.g. EBV, West Nile virus, rabies,

Bartonella henselae)

• imaging/neurologic studies;CT, MRl, EEG to define anatomical sites affected

• invasive testing:brain tissue biopsy may be required for culture, histological examination, and

immunocytochemistry (if diagnosis not clear via non-invasive means)

• findingsin herpessimplex encephalitis(must rule out due to high mortality)

CT/MRI:medial temporal lobe necrosis

EEG:early focal slowing, periodic discharges

Treatment

• general supportive care

• monitor vital signs carefully

• IV acyclovir empirically until HSV encephalitis ruled out

Generalized Tetanus

Etiology and Pathophysiology

• caused by Clostridium tetani:motile, spore forming, anaerobic GP bacillus

• found in soil,splinters, rusty nails, Gl tract (humans and animals)

traumatic implantation ofspores into tissues with low oxygenation (e.g. puncture wounds,burns, nonsterile surgeries or deliveries)

upon inoculation,spores develop intoC.tetani bacilli that produce tetanus toxins

toxin travels via retrograde axonal transport to the CNS where it irreversibly binds presynaptic

neuronsto prevent the release of inhibitors’neurotransmitters (e.g.GABA)

• net effect is the disinhibition ofspinal motor reflexes which results in tetany and autonomic

hyperactivity

Clinical Features

• generalized tetanus

initially present with painful spasms of masseters (trismus or “lockjaw")

sustained contraction of skeletal muscle with periodic painful muscle spasms (triggered by

sensory stimuli, e.g. loud noises)

• paralysis descends to involve large muscle groups(neck, abdomen)

• apnea,respiratory failure,and death secondary to tonic contraction of pharyngeal and respiratory

muscles

• autonomic hyperactivity

diaphoresis, tachycardia, HT'

N,fever asillness progresses

Antimicrobial therapy (e.g.

metronidazole) may fail to treat C.tetani

unless adequate wound debridementis

Investigations performed

• primarily a clinical diagnosis, often although not always with a history of a traumatic wound and lack

of immunization

• culture wounds,CK may be elevated

Treatment

• stop toxin p

wound <

• antimicrobial therapy: IV metronidazole;IV p

• neutralize unbound toxin with tetanus immune globulin (Tig)

• supportive therapy: intubation,spasmolytic medications (benzodiazepines), quiet environment,

cooling blanket

control autonomic dysfunction:o- and (5-blockade (e.g. labetalol), magnesium sulfate

roduction

debridement to clear necrotic tissue and spores

cnicillin G is an effective alternative

Prevention

• infection with C. tetani does not produce immunity - vaccinate patients on diagnosis

• tetanustoxoid vaccination (see Paediatrics, P5 and Emergency Medicine, ER17)

Rabies

Definition

• acute progressive encephalitis caused by RNA virus (genus Lyssavirus of the Rhabdoviridae family)

Etiology and Pathophysiology

• any mammal can transmit the rabies virus

most commonly transmitted by raccoon,skunk, bat,fox,cat, and dog; monkeys also a risk in the

tropics and sub-tropics

• transmission: breaching ofskin by teeth or direct contact of infectious tissue (saliva, neural tissue)

with skin or mucous membranes

• almost all cases due to bites

animals can be carriersfor several days before manifest signs of disease

r -t

LJ

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•virus travels via retrograde axonal transport front PNS to CNS

•virus multiplies rapidly in brain, then spreads to other organs, including salivary glands

•development of clinicalsigns occurs simultaneously with excretion of rabies virus in saliva

infected animal can transmit rabies virus as soon as it shows signs of disease

Clinical Features

•five stages of disease

1. incubation period

1-3mo on average (can range from daysto years, depending on distance from bite site to CNS)

2. prodrome (<1 wk)

low-grade fever, malaise, anorexia, nausea/vomiting,

pain, pruritus, and paresthesia may occur at wound site

once prodromal symptoms develop, there is rapid, irreversible progression to death

- progression from prodrome to coma and death may occur without an intervening

neurologic syndrome

3. acute neurologic syndrome: 2 types (<1 wk)

a. encephalitic (most common): hyperactivity, fluctuating LOC, hydrophobia, aerophobia,

hypersalivation, fever,seizures

- painful pharyngeal spasms on encountering gust of air or swallowing water cause

aerophobia and hydrophobia,respectively

b.paralytic:quadriplegia, loss of analsphincter tone, fever

4. coma

headache,sore throat

acute

complete flaccid paralysis, respiratory, and cardiovascular failure

5. death (within days to weeks of initialsymptoms)

Investigations

•purpose of diagnosis by investigations is to limit patient contact with others and to identify others

exposed to the infectioussource

•antemortem:direct immunofluorescence or PCR on multiple specimens:saliva,skin biopsy,serum,

CSF

•post-mortem: direct immunofluorescence in nerve tissue, presence of Negri bodies (inclusion bodies

in neurons)

Treatment

•post-exposure prophylaxis depends on regional prevalence and circumstancessurrounding injury

•mandatory to report animal bite/contact that may result in rabies to Public Health Authority

•if not previously immunized:

wound care: clean wound promptly and thoroughly with soap and running water for 15 min

• passive immunization:rabies immunoglobulin (RIG) infiltrated into wound site, with any

remaining volume administered IM in anatomical site distant from vaccine administration. Due

to variable response rates, vaccine should not be administered into gluteal muscle

active immunization: inactivated human diploid cell rabies virus vaccine (HDCV )

-series of 4

shots post-exposure on d 0, 3, 7 and 14. Vaccine administered into deltoid

•if previously immunized:

•wound care: clean wound promptly and thoroughly with soap and running water for 15 min

•two doses of HDCV into deltoid on d 0 and 3

•no RIG administered

•treatment is supportive once victim manifestssigns and symptoms of disease

Prevention

•pre-exposure vaccination

recommended for high-risk persons:laboratory'staff working with rabies, veterinarians, animal

and wildlife control workers,long-term travellers to endemic areas

Systemic Infections

Sepsis and Septic Shock

• see Respiroloav, R32

SOFA score >2 -10% mortality risk in

patient with suspected infection

Hospital mortality with septic shock

>40%

Definitions

• bacteremia: bacteria in blood from primary bloodstream infection orsecondary to infection of

another body system

• sepsis:severe organ dysfunction resulting from dysregulated host response to infection

• organ dysfunction identified via acute change in SOFA score >2 points

qSOFA score used initially to screen patients for suspected sepsis using three criteria:

1. respiratory rate 222/min

2.sBP <100 mrnHg

3. altered mentation (GCS <15)

• septic shock:subset ofsepsis with circulatory and cellular/metabolic dysfunction; clinically defined in

cases where despite adequate volume resuscitation there is both

1. persistent hypotension requiring vasopressors to maintain MAP 65 mrnHg AND

2.serum lactate >2 mmol/L

[]

qSOFA score

1.Respiratory rate >22/min

2.sBP <100 mrnHg

3.Altered mentation (GCS <15)

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Pathophysiology

• causative agents are identified in only 50-70% of cases

• when organisms are identified, GP and GN organisms are the cause in 90% of cases

• bacteremia -> local immune response -> pro-inflammatory cytokine release -> spread of immune

response beyond local environment > unregulated, exaggerated systemic immune response >

vasodilation and hypotension > distributive shock and reduced 0: delivery to tissues -> anaerobic

metabolism and lactic acid production -> metabolic acidosis -> multiple organ failure

Clinical Features

history:symptoms and signsspecific to an infectioussource (e.g. cough, headache, dysuria, purulent

exudate, rash)

• general symptoms of infection:fever, chills, pain, dyspnea, cool extremities,fatigue, malaise, anxiety,

confusion

physical:abnormal vitals (e.g. fever,tachypnea,tachycardia, hypotension),flushed skin, altered mental

status, local signs of infection (e.g. pharyngitis,septic arthritis, neck stiffness,skin wounds/ulcers, or

murmurs)

Investigations

• CBC and differential, electrolytes, urea, creatinine,liver enzymes, ABG,lactate,1NR, PTT,troponin,

blood C&S x2, urinalysis, urine C&S, and cultures of any wounds or lines

• CXK (other imaging depends on suspicion of focus of infection)

• nasopharyngeal swab/stool/sputum cultures, throat swabs, genital swab, LP as indicated

Treatment (see Respiroloav,R33)

• respiratory support:O’

± intubation

• cardiovascular support: IV fluids ± blood transfusion i vasopressors + ICU

• IV antibiotics (empirical, guided by suspected source)

consider broad spectrum antibiotics (e.g. piperacillin/tazobactam or meropenem) ± additional

agents depending on patient risk factors,suspected etiology or focus of infection, and local

microbialsusceptibilities(± aminoglycoside for drug-resistant Gram-negatives or vancomycin for

MRSA)

breadth of empiric coverage should take into account i) estimated adequacy of spectrum of

activity and ii) degree of instability or severity of infection

narrow once organism and susceptibilities are known

• source control: procedure to control focus of infection (catheter removal, abscess drainage)

• hydrocortisone IV may be added in patients with septic shock unresponsive to fluid resuscitation and

vasopressors

The Third International Consensus

Definitionsfor Sepsis and SepticShock

(Sepsis-3) in 2016 re-defined sepsis

using the Sequential Organ Failure

Assessment (SOFA)score for diagnosis

and Ouick-SOFA (qSOFA) forscreening

of end-organ failure.The terms

severe sepsis and systemic response

inflammatory response syndrome

(SIRS) arc no longer part of the sepsis

definition

Leprosy (Hansen’s Disease)

Etiology

• Mycobacterium leprae: obligate intracellular bacteria,slow-growing (doubling time 12.5 d),survives

in macrophages

• bacteria transmitted from nasalsecretions, potentially via skin lesions

• invades skin and peripheral nervesleading to chronic granulomatous disease

Clinical Features

• lesions involve cooler body tissues(e.g.skin,superficial nerves, nose, eyes,larynx)

• spectrum of disease determined by host immune response to infection

i. paucibacillary “tuberculoid” leprosy (intact cell-mediated immune response)

S hypoesthetic lesions, usually hypopigmented, well-defined, dry

early nerve involvement, enlarged peripheral nerves, neuropathic pain

may be self-limited,stable,or progress over time to multibacillary "lepromatous"

form

ii.multibacillary “lepromatous"

leprosy (weak cell-mediated immune response)

>6 lesions,symmetrical distribution

leonine facies (nodular facial lesions, loss of eyebrows, thickened ear lobes)

extensive cutaneous involvement, late and insidious nerve involvement causing sensory loss

at the face and extremities

iii.borderline leprosy

lesions and progression lie between tuberculoid and lepromatousforms

Investigations

• skin biopsy down to fat orslit skin smears for Al-

'

B staining, PCR

• histologic appearance:intracellular bacilli in spherical masses (lepra cells), granulomas involving

cutaneous nerves

LJ

Treatment

• regimens based on WHO recommendations

• paucibacillary: dapsone daily + rifampin monthly + clofazimine monthly AND low dose clofazimine

once daily x 6 mo

• multibacillary: dapsone daily + rifampin monthly + clofazimine monthly x 12 mo AND low dose

clofazimine once daily for 12 mo

+

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ID22 Infectious Disease Toronto Notes 2023

•treatment of leprosy (along with other precipitants of immune responsivenesssuch as viral illness,

immunization, hormonal fluctuations of pregnancy and parturition) can cause an immune reaction

to killed or dying bacteria (e.g. erythema nodosum leprosum [a type of antigen-antibody complex

deposition panniculitis] and reversal reaction [upgrading cell-mediated immune response!):

symptomatic management with NSAlDs if mild, prednisone with 12-24 wk taper ifsevere;

thalidomide for erythema nodosum leprosum

Prognosis

•curable with WHO approved treatment regimens

•complications: muscle atrophy, contractures, blindness, trauma/superinfection of lesions, crippling/

loss of digits and limbs, erythema nodosum leprosum,social stigmatization due to clofazimine

hyperpigmentation

•long post-treatment follow-up warranted to monitor for relapse and immune reactions

Lyme Disease s

Etiology/Epidemiology

• spirochete bacteria: Borrelia burgdorferi (North America), B.garinii,B. afzelii (Europe and Asia)

• transmitted by Ixodes tick

• reported in 49 of the 50 U.S.states, but most cases occur in the Northeast, the Midwest, and Northern

California

• as a result of climate change, Lyme disease has spread into higher latitudes. In Canada, reported

in southern and southeastern Quebec,southern and eastern Ontario,southeastern Manitoba, New

Brunswick, and Nova Scotia,as well assouthern British Columbia

• small rodents(mice)serve as primary reservoir, while larger animals (white-tailed deer) serve as hosts

for ticks

• human contact usually May-August in fields with low brush near wooded areas, but may start earlier

in the spring or later in the fall as a result of warmer winters due to climate change

• infection usually requires >36 h tick attachment

• as a result of climate change,other tick-borne diseases are expected to increase in prevalence:

Anaplasmosis,Babesiosis, Powassan virus, and B. miyamotoi disease

Clinical Features

• stage 1 (early localized stage: 7-14 d post-bite)

malaise,fatigue, headache, myalgias

erythema migrans:expanding, non pruritic bulls-eye (target) lesions(red with clear centre) at

site of tick bite

• stage 2 (early disseminated stage: weeks post-infection)

CNS: aseptic meningitis, CN palsies (CN VII palsy), peripheral neuritis

cardiac: heart block or myocarditis

• stage 3 (late persistentstage: months to years post-infection)

may not have preceding history of early-stage infection

MSK:chronic monoarticular or oligoarticular arthritis

• acrodermatitis chronicum atrophicans(due to B.afzelii)

• neurologic:encephalopathy, meningitis, neuropathy

Investigations

• order Public-Health-Lab-approved Lyme disease testing and interpret results on basis ofsymptoms

• a negative test for Lyme Disease does not preclude a tick-borne disease;further testing may be

indicated ifsymptoms are present

Prevention

• early identification, investigation of symptoms, and reporting of tick-borne illnesses

• use of protective clothing (tuck pantsinto socks), insect repellent, inspection for ticks, and prompt

removal of tick

• doxycydine single dose prophylaxis within 72 h of removal of an engorged Ixodesscapularis tick in

hyperendemic area (local rate of infection of ticks S20%) for patients >8 yr who are not pregnant or

lactating

Treatment

• stage 1:doxycycline/amoxicillin/cefuroxime

• stage 2-3:ceftriaxone or doxycydine

BAKE a Key Lyme Pie

Bell's palsy

Arthritis

Kardiac block

Lyme

Erythema chronicum migrans

r n

LJ

Toxic Shock Syndrome

Etiology

superantigens produced by some strains of S.aureus or GAS cause widespread T-cell activation and proinflammatory cytokine release (1L-1, IL-6,TNF)

• course of disease is precipitous and leads to acute fever,shock, multiorgan failure

• staphylococcal Toxic Shock Syndrome (TSS) involves the production of superantigen toxic shock

syndrome toxin I (TSST-I)

• streptococcal TSS involves the production of superantigens SPEA,SPEB, SPEC

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Risk Factors

• staphylococcal:tampon use, nasal packing, wound infections(e.g. postpartum vaginal or cesarean or

surgical infections)

• streptococcal:minor trauma,surgical procedures, preceding viral illness (e.g. chickenpox), use of

NSAlDs

Clinical Features and Investigations

• acute onset

• staphylococcal TSS

• T>38.9°C

sBP 290 mmHg

• diffuse erythroderma with subsequent desquamation, especially on palms and soles

• involvement of 3 or more organ systems:Gl (vomiting, diarrhea), muscular (myalgia, increased

CK), mucous membranes(hyperemia), renal, hepatic, hematologic (thrombocytopenia),CNS

(disorientation)

isolation of S.aureusis not required for diagnosis ( S.aureusis rarely recovered from blood in

TSS)

• streptococcal T SS

• sBP <90 mmHg

isolation of GAS from a normally sterile site (e.g. blood, pleural, tissue biopsy, or surgical wound)

>2 of coagulopathy, liver involvement, ARDS,soft tissue necrosis (necrotizing fasciitis,myositis,

gangrene), renal impairment, erythematous macular rash that may desquamate

Treatment

• supportive care, fluid resuscitation,surgical debridement of infected tissue

• streptococcal:IV penicillin and clindamycin and ± IVIG

• staphylococcal:for methicillin-susceptible S. aureus:clindamycin + doxacillin (IV);for MRSA:

clindamycin + vancomycin x 10-14 d

Cat Scratch Disease

Etiology

• Bartonella henselae: intracellular bacteria

• cat-to-human transmission via cat scratch/bite

Clinical Features

• skin lesion appears 30 d post-inoculation

• may be followed by fever, malaise,tender regional lymphadenopathy

• in some patients,organism may disseminate causing 1 UO, hepatosplenomegaly, retinitis,

cncephalopathy, infective endocarditis, uveitis

• in patients with advanced HIV, can present with violacious nodularskin lesions t underlying bone

involvement, known as “bacilliary angiomatosis”

• usually self-limited

Investigations

• serology, PGR, lymph node biopsy

Treatment

• the disease may be self-limited but treatment is recommended by the Infectious Disease Society'of

America with a 5d course of azithromycin for immunocompetent patients with mild to moderate

illness

• needle aspiration of painful suppurative lymph nodes may hasten the relief of symptoms

• combination therapy consisting of doxycycline or azithromycin plus rifampin often used for

disseminated disease (neuroretinitis, hepatosplenic involvement)

Rocky Mountain Spotted Fever

Etiology

• Rickettsia rickettsii:obligate intracellular GN organism

• reservoir hosts:rodents,dogs

• vectors: Dermacentor ticks in North America; Rhipicephalus ticks in Mexico and Central America

• organisms cause inflammation of endothelial lining of small blood vessels, leading to small

hemorrhages and thrombi

• can cause widespread vasculitisleading to headache, and CNS changes;can progress to death if

treatment is delayed

Clinical Features

• usually occurs in summer following tick bite

• influenza-like prodrome: acute onset fever, headache, myalgia, nausea/vomiting, anorexia

• macular rash appearing on d 2-4 of fever

begins on wrists and ankles, then spreads centrally to arms/legs/trunk/palms/soles

• occasionally “spotless” (10% of patients)

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Investigations

• skin biopsy and serology (indirect fluorescent antibody test)

Treatment

• empiric doxycycline, usually 5-7 d (treat for 3 d after defervescence)

West Nile Virus

Epidemiology

• virus has been detected throughout the United States and much ofsouthern Canada (Ontario and

Manitoba)

• case-fatality rates in severe cases are -10%

Transmission

• primarily from mosquitoes that have fed on infected birds (crows, blue jays)

• transplacental, blood products(rare), organ transplantation

• rising temperatures linked to increased mosquito survival and geographical range, increased biting

rates, increased replication of virus within mosquitoes,shorter reproduction rates, and longer

transmission seasons. Climate change also affects bird migration patterns and timing, causing

changes in virusspread

Clinical Features

• 80% are asymptomatic

• mostsymptomatic cases are mild (West Nile fever):acute onset of headache,back pain, myalgia,

anorexia, maculopapular non-pruritic rash involving chest, back,arms

• severe complications: encephalitis, meningoencephalitis, and acute flaccid paralysis(especially in

those >60 yr)

Investigations

• IgM antibody in serum or CS1

:

is the best test (cross reactivity with yellow fever and lapanese

encephalitis vaccines, and with dengue fever and St. Louis virus infection); may not reflect current

illness as IgM antibody can last for >6 mo

• viral isolation by PCR from CSF,tissue, blood, and fluids (all have low sensitivity due to transient

viremia)

• CS1-: elevated lymphocytes and protein if CNS involvement

Treatment and Prevention

• treatment:supportive

• prevention: mosquito repellant ( DLL I

'

, picaridin), drain stagnant water, community mosquito control

programs

Syphilis

Etiology

• Treponema pallidum: thick motile spirochetes historically detectable by dark-field microscopy

• transmitted sexually, vertically, or parenterally (rare)

Clinical Features Argyll Robertson Pupil

Accommodates but does not react to • see Dermatology. D38 and Gynaecology. CiY30

• multi-stage disease

1. primary syphilis (3-90 d post-infection)

painless chancre at inoculation site (any mucosalsurface)

regional lymphadenopathv

acute disease lasts 3-6 wk, 25% progress to secondary syphilis without treatment

2.secondary syphilis

= systemic infection (2-8 wk following chancre)

maculopapular non-pruritic rash including palms and soles

generalized lymphadenopathy, fever, malaise, headache, aseptic meningitis, ocular/otic

syphilis

condvlomata lata: painless, wart-like lesion on palate, vulva, or scrotum (highly infectious)

3.latentsyphilis

asymptomatic infection that follows untreated primary/secondary syphilis

early latent (<1 yr post-infection) or late latent/unknown duration (>l yr post-infection)

increased transmission risk with early latent; longer treatment duration required for late

latent

4.tertiary syphilis(1-30 yr post-infection)

gummatoussyphilis: nodular granulomas ofskin, bone, liver, testes, brain

• aortic aneurysm and aortic insufficiency

5.congenitalsyphilis

causes spontaneous abortions,stillbirths, congenital malformations, developmental delay,

deafness

most infected newborns arc asymptomatic

clinical manifestations in early infancy include rhinitis(snuffles), lymphadenopathy,

hepatosplenomegaly, pseudoparalysis (bone pain associated with osteitis), and rash (usually

maculopapular and involving palms and soles)

light

Those with Untreated 1* or 2° Syphilis

1/3Cure

1/3 L atent indefinitely

1/33°syphilis

<§>

Causes of False Positive VDRL and

RPR Tests

Vi (uses(mononucleosis, hepatitis)

Drugs and substance misuse

Rheumatic fever

Lupus and leprosy

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late onset manifestations (>2 yr of age) include saddle nose,sabershins, Glutton joints,

Hutchinson’

steeth, mulberry molars, rhagades, CN VIII deafness, interstitial keratitis, juvenile

paresis

6. neurosyphilis

headache, dementia, difficulty in coordination, paralysis, sensory deficits, personality

changes, Argyll-Robertson pupils, tabes dorsalis

can occur from secondary stage onward

Patients with 2° or 3°syphilistreated

with penicillin may experience a

JarischHerxheimer reaction, lysis ol

organisms releases pyrogens thought to

cause fever, chills,myalgia, and flu-like

symptomsthat may last up to 24 h

Investigations

•syphilis tests are conducted by Public Health labs. Thus, order set for syphilis is simplified and does

not require specification of which test to complete. Below are details on what tests are conducted at the

Public Health lab VDRL Venereal Disease Research

Laboratory

RPR Rapid Plasma Reagin

EIA Enzyme Immunoassay

CHA Chemiluminescent

ImmunoAssay

CMIA ChemiLuminescent

Microparticle ImmunoAssay

FTA-ABS Fluorescent Treponema

Antibody-Absorption

MHA-TP Microhemagglutination

Assay T. pallidum

T. pallidum Particle

Agglutination Assay

T. pallidum immobilization

•initialscreening tests:traditionally non-treponemal tests (RPR, VRDL), or treponemal tests in some

jurisdictions(EIA,CMIA,CL1A)

'

.confirmatory tests: treponemal tests (TPPA, FTA-ABS, MHA-TP,T PI)

•LP for neurosyphilis if:seropositive and symptoms of neurosyphilis or treatment failure/other tertiary

symptoms,or with HIV and late latent/unknown duration syphilis; consider in others

•for congenital syphilis, LP is essential;long bone x-rays may also be helpful

Treatment

•for r, 2", early latent: benzathine penicillin (i 2.4 million units IM x I

•for 3", late latent: benzathine penicillin G 2.4 million units IM weekly x 3

•if truly allergic to penicillin: doxycydine 100 mg PO BID x 14 d is a second line therapy (x 28 d in late

disease)

•for pregnant patients allergic to penicillin, oral desensitization techniques are considered safe

• neurosyphilis: aqueous penicillin G 16-24 million units/d IV x 14 d ± single dose ofhenzathine penicillin

•for congenitalsyphilis, penicillin GIV x 10 d

•see Family Medicine, FM46 for generalized ST1 workup

TPPA

TPI

test

Tuberculosis

Etiology,Epidemiology, and Natural History

• 1/3 of the world’

s population is infected with TB

• contracted by aerosolized inhalation of Mycobacterium tuberculosis, a slow growing aerobe (doubling

time 18 h) that can evade innate host defenses,survive, and replicate in macrophages

• inhalation and deposition in the lung can lead to one of the following outcomes

1. immediate clearance of the pathogen

2. latent TB: asymptomatic infection contained by host immune defenses (represents 90% of

infected people)

3. primary TB:symptomatic, active disease (represents 5% of infected people)

4.secondary TB:symptomatic reactivation of previously dormant TB (represents 5-10% of those

with latent TB, most often within the first 1-2 yr of initial infection) at a pulmonary or extrapulmonary site

Tuberculous Polyserositis

Pleural

*

pericardial * peritoneal

effusions (usually from granuloma

breakdown thatspills TB into pleural

cavity-very rare)

Risk Factors

• social and environmental factors

travel or birth in a country with high TB prevalence (e.g.Asia, Latin America,Sub-Saharan

Africa, Eastern Europe)

• the incidence of TB is 25 times higher in Canadian-born Indigenous peoples (highest in lnuit)

compared to Canadian-born non-lndigenous peoples

• personai/occupational contact, crowded living conditions, low socioeconomic status(SES), people

experiencing homelessness,1VDU

• host factors

• immunocompromised (especially HIV), including extremes of age

• immunosuppressed (TNF-a inhibitors, glucocorticoids)

silicosis

chronic kidney disease requiring dialysis

diabetes

• malignancy and chemotherapy

substance use (e.g. drug use, alcohol use disorder, smoking)

Clinical Features

• primary infection usually asymptomatic, although progressive primary disease may occur, especially

in children and immunosuppressed patients

• secondary infection/reactivation usually produces constitutional symptoms (fatigue, anorexia, night

sweats, weight loss) and site-dependent symptoms

1.pulmonary TB

chronic productive cough f hemoptysis,fever, night sweats, weight loss, chest pain, anorexia

CXR consolidation or cavitation, lymphadenopathy, predominantly upper lung findings but

variable +

non-resolving pneumonia despite standard antimicrobial therapy

2.miliary'TB

widely disseminated spread especially to lungs, abdominal organs, marrow, CNS

CXR: multiple small 1 -5 mm millet seed-like lesions throughout lung

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3.extra-pulmonary TB

• can occur in any organ • lymphadenitis, pleurisy, pericarditis, hepatitis, peritonitis, meningitis,

osteomyelitis (vertebral = Pott disease), adrenal (causing Addison disease), renal,ovarian

Investigations

•screening for latent TB may be done via TST or IFN-y release assay (1GKA)

both can be used to diagnose prior TB exposure. IGRA has fewer false positives as it does not

detect antigens In B(Xi vaccine or most types of non-tuberculosis mycobacteria

neither should be used for active TBdiagnosis or monitoring anti-TB treatment response

• TST preferred when repeat testing planned to assess risk of new infection (e.g.serial testing in

healthcare)

•IGRA preferred when BCG vaccine after 1 y/o, vaccination more than once, or unable to return for

reading

•diagnostic tests/investigations for active pulmonary TB

• sputum specimens (eitherspontaneous or induced) should be collected for APB smear and

culture;the three specimens can be collected on the same day,a minimum of 1 h apart

BAL if other lung pathology (e.g.lung cancer) also suspected,or TB suspected despite negative

sputum samples

• CXK

Positive TST Test

If induration at 48-72 h

>5 min if immunocompromised, dose

contact with active TB

>10 mm all others; positive PPD: CXR;

decision to treat depends on individual

risk factors

False(

-) : poor technique, anergy.

immunosuppression, infection <10 wk

or remotely

False(f): BCG after12 mo of age in a

low-risk individual, nontuberculous

mycobacterial (NTM)

Booster effect:initially false(

-) result

boost to a true)*) result by the testing

procedure itself (usually if patient was

infected long ago so had diminished

delayed type hypersensitivity reaction or

if history of BCG)

classic triad: apical-posterior infiltrates, lung volume loss, cavitation

atypical features: hilar/mediastinal lymphadenopathy, non-cavitary infiltrates

si

G

gns of complications:endobronchialspread, pleural effusion, pneumothorax

hon complex: a parenchymal granuloma, indicating a previous tuberculosis infection, and

an involved hilar lymph node on the same side

Prevention

•primary prevention

airborne isolation for active pulmonary disease

BCG vaccine

~80% effective against paediatric miliary and meningeal TB

effectiveness in adults debated (anywhere from 0-80%)

recommended in high-incidence communities in Canada for infants in whom there is no

evidence of HIV infection of immunodeficiency; widely used in other countries

•prevention of reactivation of latent infection

rifampin (R11-) (10 mg/kg (600 mg maximum)) daily for 4 mo (active disease must be ruled out)

isoniazid (INH) (15 mg/kg (900 mg maximum)) + pyridoxine (B6) and rifapentine (RPT) (dose by

weight) weekly for 3 mo

• INH (5 mg/kg (300 mg maximum)) + pyridoxine (B6) daily for 9 mo (previousstandard regimen,

recommended when rifamycin regimens cannot be used)

INH (5 mg/kg (300 mg maximum)) + pyridoxine (B6) daily for 6 mo

INH (5 mg/kg (300 mg maximum)) + pyridoxine (B6) and RIF (10 mg/kg (600 mg maximum))

daily for 3 mo

Treatment of Active Infection

•given the nuances of TB treatment, active TB infection should be managed by an experienced TB

clinician

pulmonary TB:INH + rifampin + pyrazinamide + ethambutol x 2 mo (initiation phase), then INH +

rifampin x 4 mo in fully susceptible TB (continuation phase), total 6 mo. Extend continuation phase

to 7 mo if >65 y/o, pregnant, or risk of hepatotoxicity

•exlrapulmonary TB:same regimen as pulmonary TB but increase to 12 mo in bone/joint,CNS, and

miliary/disseminated TB + corticosteroidsfor meningitis, pericarditis

•for patients taking INH,pyridoxine should be added in cases of diabetes, renal failure, malnutrition,

substance use disorders,seizure disorders, pregnancy/breastfeeding, risk of neuropathy

•empiric treatment of suspected MDR or extensively drug-resistant (XDR) TB requires referral to a

specialist

• MDR = resistance to INH and rifampin ± others

XDR = resistance to INH t rifampin i fluoroquinolone + >1 of injectable,second-line agents

very difficult to treat, global public health threat, 5 documented casesin Canada from 1997-

2008

suspect MDR TB if previous treatment failed, exposure to known MDR index case, or

immigration from a high-risk area

•note:TB is a reportable disease to Public Health (please see Public Health Agency of Canada website

for more information)

TB Treatment

RIPE

Ri tampln

INH

Pyrazinamide

Ethambutol

ri

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ID27 Infectious Disease Toronto Notes 2023

HIV and AIDS

w

p24 - capsid protein

gp41 *

fusion and entry

gp120 Epidemiology -

attachment to host Tcell

Canadian Situation (Public Health Agency of Canada, 2016)

• estimated 65040 Canadians living with HIV infection at the end of 2016, 20% unaware of HIV-positive

status

• 2090 new infections were reported in 2013: MSM account for 53% of cases, PWID 19%

Global Situation (WHO and UNAIDSCore Epidemiology Slides, July 2018)

• estimated 36.7 million people living with HIV/AIDS at the end of 2016

« estimated 1.8 million newly infected in 2016

• estimated 1 million AIDS-related deaths in 2016

Homozygosity

m

for A32 mutation in CCR5

gone confers relative resistance to HIV

infection

Heterozygosity for A32 mutation in CCR5

gene associated with slower disease

course

Etiology gpi20

gp4l p17 matrix

• HIV is a retrovirus that causes progressive immune system dysfunction, predisposing patients to

various opportunistic infections and malignancies

• HIV virion includes an envelope (gp41 and gpl20 glycoproteins), matrix (pl7),and capsid (p24),

enclosing 2 single-stranded copies of RNA plus enzymes in its core

• virion glycoproteins bind CD4 and CCR5/CXCR4 on CD4+ Tlymphocytes (T-helper cells) to fuse and

enter the cells

• RNA converted to dsDNA by viral reverse transcriptase; dsDNA is integrated into host genome by

viralintegrase

• virus DNA transcribed and translated using host cell machinery, post-translational modifications

include proteolytic activity of virally encoded protease enzymes

• newly produced virions bud out of host cell, incorporating host cell membrane;additional maturation

steps are required before virion is considered infectious

• exact mechanisms of CD4 depletion incompletely characterized but likely include direct viral

cytopathic effects, apoptosis, and Increased cell turnover

Lipid -

bilaycr

-p24 capsid

Reverse

transcriptase

Integrase —.

Modes of Transmission

Table 20, Modes of Transmission in Adolescents and Adults by Site and Medium

Sub-Location Transmission Medium Transmission Probability

per Exposure Event

1in 200 to1 in 2000

HIV Invasion Site

<R>

Female genital tract

Male genital tract

Vagina, edocervix. endocervix Semen

Inner foreskin, penile urethra Cervicovaginal and rectal

secretions and desquamations

Semen

1in 700 to1in 3000

Pi

Intestinal tract Rectum 1in 20 to1in 300

Upper Cl tract Semen

Maternal bioodlgemtalsecretions 1in S to1in 10

(intrapartum)

Breastmilk

1in 2S00

1in S to1in 10

p7 INA Chorionic villi 1in10 to1in 20

95 in 100 to1in 150

Placenta

Blood stream

Maternal blood (intrauterine)

Contaminated blood products

Sharp/needleslick injuries

nucleocapstd

Protease

p24 capsid

Adapted with permission horn Macmillan Publishers Ltd. , triad Ik F. McEMhMJ, Setting Uie stage: host Invasion by HIV. Nat Rev Immunol

2008:8:447-457.

NOTE:these estimates are lor'

all comers'i.e. they estimate Uansinission risk lor anyone with HIV Inlcction and do not take into account treatment

status of the HIV* person (In contrast to results ol PARTNER study)

iPStuort Janlzen 2012 J

Figure 7. HIV viral particle

r

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ID28 Infectious Disease Toronto Notes 2023

Natural History

Sciual Activity without Condoms a ltd Ink ol

HIV Ttansmissioa in Scrodiffcrcnt Couples when

t he HIV- Positive Partner is using Suppressive

Antiretroviral therapy

JAMA 2016:316f 2):171-181

Purpose:toevaluate the rate ot withsi-coupte HIV

transmission (tieteroseiual and MSM) during periods

of se« wthoutcondoms and when the HIV* partner

had HIV-1 IHA «200 topes/ml.

Methods Prospective, observational PAIINIR study,

enrolled 1IWHIY serodifferent couples(in which the

HIV* partner wastakng ART|who reported having

condomlessso.Primary outcome was risk of with in -

couple HIVtransmtssion to HIV- partner.

Results: Enrol led couples p'ovded 1238 elghie

couple-years olfollow-up.Couples reported

condomlesssev for a median ol 2 yr and condon ess

set with other partners was reported by 108 HIV- MSM

and 21 heteroseicais.While 11 HIV - partners became

HIV* (10 MSM;1 ireteiose» ual|, no phylogeneticaiiy

linked transmissions occurred over eligible coupleyears ol fo ow - up (within -couple HIV transmission *

0,95% Cl 0.30-0.71 pei100 couple-years).

Conclusions: A-ong serodrfferer.t heteroseual end

MSM couples in which HIV* partner was usi-g ART a-d

who reported cordomlesssev, during median 1.3pf

couple follow-up.there weie no documented cases of

wilhui-coupSe transmission.

C04cell count

Anti-HIVI antibodies

Viral loads

Figure 8. Relationships between CD4 T-cell count, viral load, and anti-HIV1antibodies

Acute (Infection) Retroviral Syndrome

• -10-90% experience an acute non-specific illness (may include fever, pharyngitis, lvmphadenopathy,

rash,arthralgias, myalgias, headache, Cil symptoms, oral ulcers, weight loss) 2-6 wk post-exposure

lasting 10*15 d

• hematologic disturbances (lymphopenia, thrombocytopenia)

• 10-20% present with aseptic meningitis,CN palsies, or other neurological presentations; HIV RNA

and/or p24 may be detected in CST

• associated with a high level of plasma viremia and therefore high-risk of transmission

Asymptomatic (Latent) Stage

• during latent phase, HIV infects and replicates in CD4 t T lymphocytes (lymph nodes)

• normal CD4 count in adults: 500-1100 cells/mm3

• CD4 count drops 60-100 cells/mm3 per yr but is variable

• by 10 yr post-infection, 50% have advanced HIV (i.e. AIDS), 30% demonstrate milder symptoms, and

<20% are asymptomatic if untreated

Definition of AIDS

• HIV-positive AND one or more of the clinical Illnesses that characterize AIDS, including:

opportunistic infections (e.g. Pneumocystis jiroveci pneumonia (P|P, previously PCP), esophageal

candidiasis,CM V, Mycobacterium avium complex (MAC), TB, toxoplasmosis), malignancy (Kaposi'

s