sarcoma, invasive cervical cancer), wasting syndrome OR CD4 <200 (or <15%);thisis largely

historical because ART can reverse CD4 count decline

Seroconversion:Development of

detectable anti-HIV antibodies

Window Period: Time between infection

and development of anti-HIV antibodies:

when serologic tests (ELISA. Wcslern

blot) are negative

All infants born to HIV-infected

mothers have positive enzyme linked

Immunosorbent assay (ELISA) tests

because of circulating maternal anti-HIV

antibodies,which disappear by 18 mo:

early diagnosis is made by detection ol

HIV RNA in plasma

Table 21. Symptomatic Stage (CD4 count thresholds for classic clinical manifestations)

HLAB-S701Testing

Abacavir hypersensitivity reactions

usually only occur in individuals

carrying this HLA allele (

“

5-7% of White

individuals,lower prevalence in other

ethnic groups)

Routine screening for HIA-B'S701at

baseline and definitely prior to abacavir

CD4 Counts Possible Manifestations

<500 cells/mm 3 Often asymptomatic

Constitutionalsymptoms:fever, night sweats,fatigue, weight loss

Mucocutaneous lesions:seborrheic dermatitis. HSV, VZV (shingles),oral hairy leukoplakia (EBV). candidiasis(oral,

esophageal,vaginal). KS

Recurrent bacterial infections,especially pneumonia

Pulmonary and extrapulmonary tuberculosis

lymphoma

Pneumocystnitrorecl pneumonia (formerly PCP)

use

<200 cells/mm'

I.:

Oral thrush

Local and/or disseminated fungal infections:Cryptococcas neofoimans. Coccidioides immitis.Histoplasma capsulatum

Progressive multifocal leukoencephalopathy (PMl)

-JC virus

CHS toxoplasmosis

CMV infection: retinitis, colitis, cholangiopalhy, CNS disease

HIV Status

• CD4 count:progress and stage of

disease

• Viral load:rate of progression

<100 cells/mm*

*50 cclls/mm’

I '

-:

Bacillary angiomatosis (disseminated Bartonella)

Primary CHS lymphoma ( PCNSl)

HIV Non-disclosure Laws in Ontario

In 2017.Ontario changed HIV nondisclosure laws for people living with

HIV.where non-disclosure of HIV

status to a sexual partner Is no longer

considered a criminal offense if one of

the following criteria is met:

• On antiretroviral therapy with a viral

load <200 copies/mL for at least

6 mo

• Viral load between 200-1500 copies/

mland a condom is used properly

and does not break

Laboratory Diagnosis

• anti-HIV antibodies detectable after a median of 3 svk, virtually all by 3 mo (therefore 3 mo window

period)

• initial screening test (3rd generation antibody test): ELISA detects serum antibody to HIV; sensitivity

>99.5%

• increasingly, combination p24 antigen/HIV antibody tests (4th generation) used for screening;

improved sensitivity in early or acute infection and sensitivity/specificity approach 100% for chronic

infection

• confirmatory test:if positive screen, Western blot confirmation by detection of antibodies to at least

two different HIV protein hands (p24, gp41, gpl 20/160);specificity >99.99%

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•rapid ( point-of-care) antibody tests: higher false positives, therefore need to confirm positive results

with traditional serology

•p24 antigen: detection by ELISA may be positive during “window period"

r and 2“ prophylaxis may be

discontinued if CD4 count is above

Management of the HIV-Positive Patient threshold for >6 mo while on ART

•verify positive HIV test

•complete baseline history and physical exam, then follow-up every 3-6 mo

•laboratory evaluation

if non-stable and non-suppressed viral load, order routine CD4 count to measure status of the

immune system

I 1 V

Anti Retroviral Pie- Exposure Prophylaxisfor

PiexentiigHIV in High-RiskIndividsals

Cochrane 01Syrst lev 20V2;7:CDOOP189

Purpose: lo evaluate the efficacy of ora etretrowal prophylactic therapy n preietteg HR

efection.

Stidy.Syste-nabc review of 12 recteaiotrc- ed

CrabwiDi S trialsforming the tore aslyss.

Population: 9849 HIV-urrnfected oatetts at»gi

rsx or'

mnCrecting HIV including HSUsnwfcortenf

cooples.and others.

Outcome: New infection with HR.

Results: Daily oral tenofonir disoproiJ f.rjice

(TOP) pi us emtricitabi ne (fit) reduced the rsk of HIV

acquishoc tom pared lo place ho|!I O.ft95t0

028-0.8S). lOf alone also showed sign huut nsh

reduction in trials with fewer patentsft

*

033:951

Q020-0.55).Iherewas no sgnS

adierse Clients in any of the treafreetgetas.Sexual

practces and adherence did not drier between

beacmert and placebo arms.

Conclusions: Pre-exposure prophylais with TOP

nrQ or without fIC effectively reducesthe rsx of

HR acgulsition inhjgh-risk. HR-ucinfeded patents

wr Chou!causing significao!adverse effecs.

• routine HI V-RNA levels (viral load) also important indicator of effect of ART

• baseline HIV resistance testing to guide ARV therapy

• HLA-B'5701 genetic test to screen for abacavir hypersensitivity if considering abacavir in

treatment regimen

CCR5 tropism testing if considering CCR5 antagonist in treatment regi

baseline tuberculin skin test (PPD):induration greater than 5 mm is positive

baseline serologies (hepatitis A, B, and C,syphilis,toxoplasmosis,CMV, VZV)

routine biochemistry and hematology, OCR, urinalysis

annual fasting lipid profile and fasting glucose (due to ART side effects)

•education

:v. r.

• regular follow-up on viral loads (q3-6 mo) as well asstrict adherence to AR T improves prognosis;

routine monitoring of CD4 counts until consistently over 500 cells/uL with suppressed viral load

• prevention of further transmission through safer sex and clean needles for 1DU

• HIV superinfection (transmission of different HIV strainsfrom another H1V+ person) can rarely

occur so barrier protection during sex isstill recommended

discuss importance of disclosing HIV statusto partnersincluding risk of criminal prosecution of

non-disclosure in jurisdictions where applicable

connect to relevant community groups and resources

•health care maintenance

assessment of psychosocial concerns and referral to psychiatry orsocial work if appropriate

• vaccines: influenza annually, 23-valent pneumococcal every 5 yr, HBV (if not immune), HAV (if

seronegative), HPV

annual screening ( PAP smear), regular ST1 screening

• management of comorbid conditions and provision of general primary care

castixtas m

Reasonsfor Deterioration of a Patient

with HIV/AIDS

• Opportunistic infections

• Neoplasms

. Medication-related toxidties

. Co-infections(e.g. HBV. HCVSTIs)

• Non-AIDS-related comorbidities

(e.g.cardiovascular, renal, hepatic,

neurocognitive. bone disease)

Table 22. Prophylaxis Against Opportunistic Infections in HIV-infected Patients

Pathogen Indication for Prophylaxis Preferred Prophylactic Regimen

CD 4 count Pneumocystis jirovecii «200 cells r.r

Toxoplasma gondii

TMP/SMX1SS or DS once daily

IgG antibody to Toxop. IMP.'SMX1 DS once daily '

osrcjand CD4 count

<100 cells/mm1

PPD reaction >5mm or contact with case of INH * pyntome daily x 9 mo

active IB

CD4 count <50 cells/mm5

Mycobacterium tuberculosis

Urcobocterivm avium complex No propbylaxs if patients are started on ARTs

See

SS

from

=

:

USPHS

single

http:/

strength

/

/aidsinfo

IDSA guidelines

.

:

nih

DS

.gov

= double

/

for preventing

strength

opportunistic infections among HIV-infected persons (Re levantSections updated 2013.2015).Available

Treatment

o

Failure

• Assess adherence

• Assess drug Interactions

. Resistance testing

• Rule out opportunistic infections

• Rule out marrow suppression

• Construct new combination drug

regimen

Anti-Retroviral Treatment

Overall Treatment Principles

• recommended that all HIV-positive patients initiate combination ART to restore and preserve

immune function,reduce morbidity, prolong survival,and prevent transmission

• patientsstarting ART should be committed to treatment and understand the importance of

adherence; poor compliance can lead to viral resistance;may defer treatment on the basis of clinical

and psychosocial factors on case-by-case basis

• consider results of baseline resistance testing and complete ART history before initiating or reinitiating ART

• goal: keep viral load below limit of detection i.e. <40 copies/mL (undetectable); viral load should

decrease 10-fold within 4-8 wk, be undetectable by 6 mo, and restore immunological function

• strong evidence against intermittent ART'

or‘

drug holidays’

• patient with undetectable viral load adhering to ART does not transmit HIV to sexual partners

ART Recommendations for Treatment of Naive Patients

• 2 NRTIs + 1 1NSTT or “boosted” PI (combined with ritonavir or cobicistat for improved

pharmacokinetics)

• note:guidelines are subject to frequent change.Combination therapy is suggested, preferably with

single pill regimens

Treatment Failure

• defined primarily by viral load (persistently >200 copies/mL)

• ensure that viral load >40 is not just a transient viremia or ‘blip’; confirm medication adherence,

assess drug interactions, perform resistance testing

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Table 23. Anti-Retroviral Drugs

Class Drugs Mechanism Adverse Effects

Nucleoside reverse abacavir (ABC)

transcriptase inhibitors emtricltabine|FTC)

(hails)

Incorporated into the growing viral DNA Lacbc acidosis (often secondary lo

chain,thereby compettnrely inhibiting mitochondrial toxicity)

lamivudine (3TC) reverse transcriptase and terminating Lipodystrophy

lenofovir disoproxil fumarate (IDF) viral DNA growth

tenofoviralafenamide (TAF)

zidovudine (AZT)

Lactic Acidosis

• Occurs secondary to mitochondrial

toxicity

• Symptoms include abdominal pain,

fatigue,nauseavomiting,muscle

weakness

Bash

Nausea.'

vomiting/diarrhea

Bone marrow suppression (AZT)

Peripheral neuropathy (ddl. d4!)

Orug induced hypersensitivity (ABC)

Pancreatitis (ddl.'dAT)

Myopathy (AZT)

drdanosine (ddl)

stavudme (d41)

Combination Tablets:

AZTilTC (Combivir '

l

AZT/3TC/ABC (Trizivir

*

)

ABC/3TC (Kivexa‘

)

TDFi

'TIC (Truvada'

)

TAF ’FTC (Oescovy :

)

Non-nucleoside reverse delavitdine (DLV)

transcriptase inhibitors doravinne (DOR)

efavirenz (£FZ)

etravirine (ETR)

nevirapine (NVP)

rilphririne (RPV)

Non-competitively inhibit function

of reverse transcriptase,thereby

preventing viral RNA replication

Rash.Stevens-Johnsonsyndrome

CNS:dizziness,insomnia,somnolence,

abnormal dreams (efavirenz)

Hepatotoxicity (nevirapine -avoid

in females with CD4>250.men with

CD4»400)

CYP3A4 interactions

Lipodystrophy,metabolic syndrome

Nausea.1

vomiting/diarrhea

Nephrolithiasis (indinavir)

Rash (APV)

Hyperbilirubinemia (atazanavir.

Indinavir)

CTP3A4 interactions

Hyperlipidemia

Lipodystrophy

Body fat redistribution (mainly with old

ARVs)

• Lipohypertrophy (e.g.dorsal fat

pad.breast enlargement increased

abdominal girth) thought to be

caused primarily by protease

inhibitors

• Lipoatrophy (e.g.facial thinning,

decreased adipose tissue in the

extremities) is thought to be caused

by thymidme analogue NRTIs such as

d4T andAZT

• Metabolic abnormalities:lipids

(ixreased LDL increased TGs).

glucose (insulin resistance.T2DM).

increased risk of CVD

(NNRTIs)

Protease inhibitors

(Pis)’

atazanavir (ATV)

amprenavir (APV)

darunavir (DRV)

darunavi' cobicistat (DRV/c)

Iopinavir.ritonavir (LPV/f)

nelfinavir|NFV)

ritonavir (RTV)

tipranavir (TPV)

indinavir

bictegravir

cabotegravir

dolutegravir (DIG)

ehritegravir (EVG)

raltegravir (RAL)

enfuvirtide (T-20)

Prevent maturation olinfectious

virions by inhibiting the cleavageof

polyproteins

Integrase strand

transfer inhibitors

(INSTIs)

Inhibits integration olHIV DNA mlo the

human genome thus preventingHIV

replication

Fusion inhibitor

(only usedif resistance)

CCR5 antagonist maraviroc (MVC)

Inhibit viral fusion with T-celts by Injection site reactions,rash,

inhibiting gp41.prevelling cell infection infection,diarrhea,nausea,fatigue

Inhibit viralentryby biockung host OCRS Fever,cough,dizziness

co-receptor

'Standard of care ts topharracologically boost most Pis with ritonavir to increase concentrations

Single Tablet ART Regimens

• reduces pill burden and increases adherence

• generally better tolerated

Table 24. Single Tablet ART Regimens

Name Contents Common Side Effects

bictegravirI'emtricitabinehenofovii alafenamide good side effect profile

lenolonr '

emtricilabine/elvilegravirfcobicistal

rilphrirmei'emtricitabineiTenofovir

nlprnrinei'emlricitabineilenofovir alafenamide

elxritegravir.'cobicista(/emIricilabine/tenofovir

dolategraviriabacavir.lamivudine

efamreni'tenofovir.

'

emtricitabine

Biktanry ‘

Genvoya5

Complera:

Odefsey:

Stribild'

Triumeq:

Atripla;

good side effectprofile

good side effectprofile

good side effect profile

good side effect profile

good side effeetprofile use only in HLAB*5701negative patients

psychiatric events,vivid dreams

Recommended ARV Regimens for Treatment-Naive HIV-infected Adults

• initial regimensfor treatment (most include an integrase inhibitor and a pair of NRTTs):

1. bktegravir/TAF/FTC

2.Dolutegravir/ABC/3TC (in patients confirmed to be HLB‘5701 negative)

3.dolutegravir + (TAF or TDF)/(FTC or 3TC)

4.raltegravir + TAF (or TDF)/FTC

5.DTG/3TC

• note: not all regimens are available in all regions

Recommended ARV Regimens for Individuals of Childbearing Potential

• there is an increased risk of neural tube defects in infants born to women on dolutegravir at time of

conception

• it is not known if other INSTIs also increase risk of neural tube defects

• therefore,before beginning an INSTl-containing treatment regimen in individuals of childbearing

potential,the following should be considered:

completing a pregnancy test

• a discussion on risks and benefits of dolutegravir, and lack of information on other INSTIs

« for individuals attempting to conceive:RAL + TDF/FTC,TDF/3TC,or ABC/3FC are preferred

regimens; D IG regimens to be used as an alternative only

• for individuals not attempting to conceive but are sexually active and not using contraception,

consider effectiveness/tolerability, patient preferences in decision

for individuals using effective contraception, treatment approach issimilar to that of individuals

in the general population with HIV

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TARGETSITES FOR ANTIRETROVIRAL DRUGS

(A) Fusioninhibitor

IBICCR5 antagonist Early identification of HIV is essential for

patients to receive the maximal benefit

from ART

ICINucleosidereverse transcriptase inhibitors (NRTIsl

(ClNucleotidereverse transcriptase anhibitors

(ClNon-nucleosidereverse transcriptase inhibitors INNRTIs)

101Integrase strand transfer inhibitors (INSTIs)

IEIProteaseinhibitors (Pis)

PROCESS OF Efficacy. Safety, and Elfect on Sexual Behaviour

of On -Demand Pre-Exposure Prophylaxis for HIV

iiMen who have Sex with Men: An Observational

Cohort Study

Lancet HIV 2017:4:402-410

Purpose: Assessthe efficacy,safety,ard effect of

on-demand pre-exposure prophylaxis (Pr(P|on sexual

behaviour.

Methods: Men and transgender women who have

sex with men.previously enrolled in the placebocontrolled ANRSIPERGAU trial. On demandtenofovir

dsopioail fumarate (300 mg) and emlricitabine (200

mg) to be taken before and after sexual intercourse

and participants assessed for incidence of HIV. PrtP

adherence,safety,and sexual behaviour.

Jesuits: if IV incidence was 0.19.'100 person-years

(95% Cl 0.01-1.081 vs.6.60,1100 person-)*

a>s(95%

Cl 3.60-11.05) in the placebo group,relative risk

reduction of 97%. Drug -related 61events were

reported in 14% of participants buiwete sen-limiting.

Parte pants reporting condomlesssexattheir last

receptive anal intercourse increased from 77 to86%

at 18 mo follow-up.

Conclusions:On-demand oral PiEP is highly effective

a1preventing HIV infeebon among high-risk MSM.Ibis

represents an alternative to daily PrEP.

MULTIPLICATION

1.Binding

2.Fusion and uncoating

3 Reverse transcription

4.Integration

5 Translation

6 Assembly and budding

7. Maturation

2 FUSIONAND

UNCOATING

1 BINDING

3.REVERSE

TRANSCRIPTION

^

TRANSLATION

Use of a Vaginal Ring Containing Dapivirine for

HIV-1 Prevention inWomen

HEIM 2016:375:2121-2132

Purpose:Toevaluate whether longer-acting

methods of anti-retroviral therapy (i.e. vaginal rings)

may sim pi ify use of medications an d provide HIV-1

protection.

Methods: Phase 3. randomized, double-blind,

placebo-cnntrolled trial of monthly vaginal ring

containing dapivirine In women (aged 18-45)

,n

Malawi.South Africa, Uganda, and Zimbabwe.

Results: Among 2629women enrolled, tne Incidence

of HIV-1infection was 3.3/100 person-years in

dapivirine group and 4.&T00 person-years in placebo

group.Post hoc analysis identified higher rales of

HIV-1 protection in women >21 yr (56%, 95% Cl 31-71)

but notamong those <21 yr (-27%,95% Cl -133- 311.

which correlated with reduced adherence.

Conclusions: Monthly vaginal ring containing

dapivirine reduced risk of HIV-1infection among

African women.

6.ASSEMBLY AND

BUDDING

7 M A

'

- R A V U '

.

'Stuart Januen 2012

Figure 9. Mechanism of HIV replication

Prevention of HIV Infection

• education, including harm reduction

• safer sexual practices:condomsfor vaginal and anal sex, barriers for oral sex

• harm reduction for 1VDU: avoid sharing needles

prevention of vertical HIV infection:treatment with ART should be initiated prior to pregnancy or

as early as possible during pregnancy.The risk of vertical HIV transmission can be reduced to <1%

if maternal AR T is started in a timely manner and the maternal viral load is undetectable prior to

delivery

• universal blood and body precautionsfor healthcare workers

• post-exposure prophylaxis(PEP) after occupational (e.g. needle-stick injury) and nonoccupational (e.g. consensual sex,sexual assault) exposure to HIV:2- or 3-drug regimen initiated

immediately (<72 h) after exposure and continuing for 4 wk

• recent data has demonstrated efficacy of pre-exposure prophylaxis (oral PrtP or topical microbicides)

in preventing HIV

• ART associated with 96% reduction in risk of transmitting HIV to sexual partners

• screening of blood and organ donation

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Types of Testing

1. Nominal/Name-Based HIV Testing

• person ordering the test knows the identity of the person being tested for HIV

• HIV test is ordered using the name of the person being tested

• person ordering the test islegally obligated to notify Public Health officialsif test results are positive

for HIV

• test result is recorded in the healthcare record of the person being tested

2. Non-Nominaf Non-Identifying HIV Testing

• similar to nominal/name-based testing on all points except:

• HIV test is ordered using a code or the initials of the person being tested

3. Anonymous Testing

• available atspecialized dinics

• person ordering the HIV test does not know the identity of the person being tested

• HIV test is carried out using a unique non-identifying code that only the person being tested for HIV

knows

• test results are not recorded on the healthcare record of the person being tested

• patient identification and notification of Public Health required to gain access to ART

HIV Pre- and Post-Test Counselling

• a diagnosis of HIV can be overwhelming and is often associated with stigma and discrimination

• consider pre- and post-test counselling, regardless of the results

• goalsinclude: assessing risk,making informed decision to be tested,education to protect themselves

and othersfrom virus exposure,where to go for more information and support

• HIV-positive individualsshould be connected with local supportsendees

FUNGAL INFECTIONS

Skin and Subcutaneous Infections

Superficial Fungal Infections

. see Dermatology. D32,D33,D37,D45D46,and D49

Dermatophytes

• see Dermatology. D31

Subcutaneous Fungal Infections

Etiology

• subcutaneousinoculation by fungi that naturally reside in the soil,including Sporothrix schenckii,

which usually occursin gardeners injured by a rose thorn orsplinter

Clinical Features

• causessubcutaneous nodules at the point of entry,may develop into an ulcer

• fungi may migrate up lymphatic vessels creating nodules along the way -

“nodularlymphangitis”

Treatment

• oral azole

• IV'amphotericin B forsevere or disseminated infection

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Endemic Mycoses

Etiology

• fungal infection that occurs through the inhalation of spores (from soil,bird droppings, vegetation) or

inoculation injury

• thermally dimorphic organisms: mould in cold temperature (e.g.soil),and yeast at higher

temperature (e.g. tissue)

• in North America, the three major endemic mycoses are: histoplasmosis, blastomycosis,and

coccidioidomycosis

Clinical Features

• maybe asymptomatic

• all can cause pneumonia and may disseminate hematogenously

• may reactivate or disseminate during immunocompromised states

Histoplasmosis is commonly associated

with exposure to chicken coops,bird

roosts,and bat caves

Table 25. Endemic Mycoses

Disease Endemic Region Clinical Features Investigations

Histoplosma capsulatum Ohio and Mississippi River Asymptomatic (in most people)

valleys in central USA, Primary pulmonary

Ontario,Ouebec;widespread Fever,cough,chest pain,headache,myalgia,anorexia

CXR (acute):pulmonary infiltrates T hilar lymphadenopathy

CAR (chronic):pulmonary infiltrates,cavitary disease

Disseminated (rate)

Occurs primarily inimmunocompromised patients

Spread to bone marrow (pancytopenia).Gl tract (ulcers),lymph nodes (lymphadenitis),skin,

liver,adrenals, CNS

Blastomycesdermotitidis States east of Mississippi May be asymptomatic

River,Northern Ontario,and Primary:acute or chronic pneumonia

along the Great Lakes Fever,cough,chest pain,chills,night sweats,weight loss

CXR (acute):lobar or segmental pneumonia

CAR (chronic):lobar infiltrates,fthronodular interstitial disease

Disseminated

Spread to skin (verrucous lesions that mimic skin cancer,ulcers,subcutaneous nodules),bones

(osteomyelitis,osteolytic lesions),genitourinary tract (prostatitis,epididymitis)

Primary

"Valley fever":subacute fever,chills,cough,chest pain,sore throat,fabgue that lasts for wk

to mo

Can develop hypersensitivity with arthralgias,erythema nodosum

Disseminated

Rare spread to skin (ulcers),joints (synovitis),bones (lytic lesions),meninges (meningitis)

Common opportunistic infectionin patients with HIV

Fungal culture,fungal stain

Antigen detection (urineand serum)

Serology

Sputum smear and culture

Direct examination of clinical

specimens for characteristic broadbased budding yeast (sputum,tissue,

purulent material)

Cocddioides immitis Deserts in southwest USA.

northwest Mexico

Sputum culture

Direct examination of clinical

specimens forcharacteristicyeast

(sputum,tissue,purulent material)

Opportunistic Fungi

Pneumocystis jirovecii (formerly P. carinii ) Pneumonia:PJP

or PCP

Etiology

• respiratory exposure to unicellular fungi (previously classified as a protozoa)

• can be transmitted from person to person

• without prophylaxis,HIV-positive patients with a CD-I count <200 cells/mm 'have an 80"u lifetime

risk of PIP

• most cases of PJP occur in patients who are unaware of their HIV infection, do not seek medical care

for HIV, or who do not use prophylaxis

• in HIV-negative patients, PJP occurs almost exclusively in immunocompromised patients (e.g.organ

transplant patients,inflammatory conditions,hematological malignancies)

Clinical Features

• symptoms of pneumonia:fever, non-productive cough, progressive dyspnea (and hypoxia)

• classic CXR findings of interstitial pneumonia

• most clinical disease is due to reactivation of latent infection or reinfection by a different genotype in

immunocompromised patients (steroid use,HIV)

Investigations

• CXR: bilateral symmetrical interstitial infiltrates

• ABG:reduced pO:and elevated alveolar-arterial (A-a) gradient

• serum LDH: elevated (>2201U/L)

• induced sputum or lower airway sampling: positive for Pneumocystis, traditional test was

immunofluorescence however many labs using quantitative PCR

CXR inP.provedi

• Bilateral,diffuse opacities

• CXR may be normal (20-30% cases)

• CT shows cysts (hence the name

Pneumocystis) but almost never

pleural effusions

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Treatment and Prevention

• oxygen to keep SaO’ >90%

• antimicrobial options

TMP/SMX (PO or IV) is preferred therapy

dapsone and TMP

• clindamycin and primaquine

pentamidine (IV ) issecond line in severe disease

atovaquone

• corticosteroids used as adjuvant therapv in those with severe hvpoxia ( pO:<70 mmHg or A-a gradient

OB >35 mmHg)

• prophylactic TMP/SMX for those at high-risk of infection (HIV patients when CD4 <200 cells/mm Jor

non-HIV immunocompromised patients under specific conditions)

Cryptococcus spp.

•

Etiology

inhalation of airborne encapsulated yeast from soil contaminated with pigeon droppings(C. O

neoformans) or certain tree speciessuch as Eucalyptus or Douglasfir (C. gatti )

• C. neoformans tends to affect immunocompromised hosts vs.C. gatti which tends to affect

immunocompetent hosts

Clinical Features

• asymptomatic

• pulmonary

• usually asymptomatic or self-limited pneumonitis

only 2% of HIV+ patients present with pulmonary symptomsincluding productive cough, chest

tightness, and fever

• disseminated

frequently disseminatesin HIV+ population

CNS: meningitis(leading cause of meningitis in patientssvith HIV)

skin: umbilicated papules that resemble large lesions of MoDuscum contagiosum

other:bone, lymph nodes,bone marrow,soft tissues, eyes,prostate

Investigations

• serum cryptococcal antigen

• CSF for meningitis:India-ink stain or cryptococcal antigen test, culture to confirm

• lateral flow'cryptococcal antigen assay from serum and CSE

• LP with measurement of opening pressure

Treatment

• in patients with HIV' who have cryptococcal meningitis or severe pulmonary disease:

amphotericin B (+ flucytosine) is used in the first 2 wk for induction therapy;limited duration

due to side effects

• switch to fluconazole for at least 8 wk as consolidation therapy,then continue at lower dose for

prolonged maintenance

serial lumbar puncture or other method of managing increased ICP an important adjunct to

therapy

C. gottii has a limited geographical

distribution including Vancouver Island.

Northern Australia,and Papua New

Guinea

India

o-ink sensitivity for Cryptococcus is

only 50% (higher in HIV patients);now

replaced by cryptococcal antigen test in

most laboratories

Candida albicans a

Etiology

• overgrowth ofC albicans (normally found as part of the microbiome of the skin, mouth, vagina, and

G1 tract)

• risk factors for overgrowth:

immunocompromised state (DM, corticosteroids)

critically ill patients(broad-spectrum antibiotic use, central venous catheters, total parenteral

nutrition)

obesity: maceration and moisture in intertriginous areas, pannus. under breasts

Clinical Features

• mucocutaneous

oral thrush, esophagitis (chest pain, odynophagia), vulvovaginitis (see Gynaecology, GY26),

balanitis, cutaneous (diaper rash,skin folds,folliculitis), chronic mucocutaneous

small satellite lesions beyond the margin of the rash

• invasive

candidemia, endophthalmitis, endocarditis,UTI (upper tract), hepatosplenic disease

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1D35 Infectious Disease Toronto Notes 2023

Treatment

• thrush: clotrimazole troches, miconazole mucoadhesive buccal tablets,or nystatin suspension or

pastilles for mild disease, fluconazole forsevere or refractory disease

• vulvovaginal candidiasis: topical agents (imidazole or nystatin), oral fluconazole for recurrent disease

• cutaneous infection: topical imidazole

• opportunistic infections in HIV'

, other systemic infections:fluconazole or echinocandin

• chronic mucocutaneous: azoles

Aspergillus spp.

Etiology

• infection with Aspergillus fungi ( A. fumigatus, A. flavus) which isfound ubiquitously in the air and

the environment

• Aspergillus produces a toxin called aflatoxin that contaminates nuts, grains, and rice

Clinical Features

• allergic bronchopulmonary aspergillosis (ABPA)

lgE-mediated asthma-type reaction with dyspnea, high fever, and transient pulmonary infiltrates

occurs more frequently in patients with asthma and allergies

• aspergilloma (fungus ball)

ball of hyphae in a pre-existing lung cavity

symptoms range from asymptomatic to massive hemoptysis

CXR:round opacity surrounded by a thin lucent rim of air, often in upperlobes (“air crescent”

sign)

« invasive aspergillosis

associated with prolonged and persistent neutropenia or transplantation

• pneumonia -most common

may disseminate to other organs:brain,skin

severe symptoms with fever,cough, dyspnea, cavitation;fatal if not treated early and aggressively

CXR:local or diffuse infiltrates ± pulmonary infarction, pulmonary nodules with surrounding

ground glass(“halo"sign)

• mycotoxicosis

aflatoxin produced by A.flavus(nuts, grains, rice)

results in liver hemorrhage, necrosis, and hepatocellular carcinoma formation

Treatment Options

• voriconazole or amphotericin B for invasive aspergillosis

• surgical resection for aspergilloma

• corticosteroids ± itraconazole for ABPA

See Undnart InfectittssOsease InaStablefat mare

ieforaatm wfie loricotazolets.aspiotenas Bfar

arasnreaspergrilosstraLIt compared toricotezole

wiBasptofarts Bfor pitman therapjof imras*

aspergikisoPARASITIC INFECTIONS

Protozoa -Intestinal/Genitourinary Infections

Brain abscess 0,

> Ingestion of

]

.marcreevst

Entamoeba histolytica (Amoebiasis)

Etiology

• infection with E.histolytica occurs when the cysts are transmitted via the oral-fecal route in areas of

poor sanitation that have been contaminated by other infected humans,or via sexual activity

• seen in migrants, travellers, institutionalized individuals, Indigenous peoples,MSM

Clinical Features

1. asymptomatic carriers

2. amoebic dysentery

• abdominal pain, cramping, colitis, dysentery, low grade fever with bloody diarrhea secondary’to

local tissue destruction, and ulceration of large intestine

3. amoebic abscesses (liver abscesses,see General and Ihoracic Surgery, GS52)

most common in liver (hematologic spread); presents with right upper quadrant pain, weight loss,

fever, hepatomegaly

• can also occur in lungs and brain

Investigations

• serology, fecal/serum antigen testing, stool microscopic exam (for cysts and trophozoites), colon

biopsy,single stool for multiplex enteric parasite PCR

• E.histolytica indistinguishable microscopically from the non-pathogen E.dispar (distinguish byspecific stool antigen detection or multiplex stool PCR assay)

<g>

1

Lung abscess

Liver abscess

03/

i

lonmotile

cyst i

(infective)

J

4

%trophozoite

Motile +

Inotmlectivel s

Figure10.Entamoeba life cycle

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ID36 Infectious Disease Toronto Notes 2023

Treatment and Prevention

• metronidazole

• for invasive disease or cyst elimination:follow with iodoquinol or paromomycin

• aspiration of hepatic abscess if risk of abscess rupture, poor response to medical therapy,or diagnostic

uncertainty

. asymptomatic cystshedding:iodoquinol or paromomycin alone

• good personal hygiene, purification of watersupply by boiling,filtration ( not chlorination )

Giardia lamblia

Etiology

• infection with (i. lamblia occurs via the fecal-oral route with the ingestion of cystsfrom water/food

contaminated by infected humans and other mammals(especially in the Rockies)

• risk factors: travel, camping, institutions,daycare centres, MSM

Clinical Features

• giardiasis (“beaver fever")

symptoms vary from asymptomatic toself-limited mild watery diarrhea to malabsorption

syndrome (chronic giardiasis where the parasite coatsthe small intestine and thus prevents fat

absorption)

nausea,malaise, abdominal cramps,bloating,flatulence,fatigue,weight loss,steatorrhea

no hematochezia (no invasion into intestinal wall),no mucousin stool

Investigations

• multiple stool samples (daily x 3d) for microscopy;single stool for multiplex enteric parasite PCR;

stool antigen used occasionally

• occasionally small bowel aspirate or biopsy

Treatment and Prevention

• metronidazole; nitazoxanide ifsymptomatic

• good personal hygiene and sanitation, water purification (iodine better than chlorination),outbreak

investigation

Trichomonas vaginalis

Etiology

infection with T. vaginalis occurs via sexual contact

Clinical Features

• often asymptomatic (10-50%), especially males(occasionally urethritis,prostatitis)

• Trichomonas vaginitis (see Gynaecology.GY26)

• vaginal discharge (profiise, malodorous, yellow-green or grey,frothy), pruritus,dysuria,dvspareunia

Investigations

• wet mount (motile parasites), antigen detection, culture

• urine PCR to detect in males

Trichomonas causes 2S% of vaginitis

Treatment

• metronidazole for patient and partner(s)

Cryptosporidium spp.

Etiology

• infection with Cryptosporidium spp. via the fecal-oral route occurs with the ingestion of cysts from

water contaminated by infected humans and other animals(including cows)

• risk factors:summer and fall, young children (daycare), MSM, contact with farm animals,

immunodeficiency

Clinical Features

• range from self-limited watery diarrhea (immunocompetent) to chronic,severe, non-bloody

diarrhea with nausea/vomiting, abdominal pain, and anorexia resulting in weight loss and death

(immunocompromised)

Investigations

• modified acid-fast stain ofstoolspecimen,microscopic identification of oocystsin stool or tissue,stool

antigen detection by direct fluorescent antibody,single stool for multiplex enteric parasite PCR

Treatment and Prevention

• supportive care

• in HIV+ patients, (reinitiate ART and try to increase their CD-I count to >100;if fails, try

nitazoxanide or macrolides

• good personal hygiene, water filtration

n

L J

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ID37 Infectious Disease Toronto Notes 2023

Blood and Tissue Infections

Mtfluquinr lor Prerenting Malaria during Travel

to EndemicArras

Gxhrant Ot Spt ler 2O1);CD0OW91

Purpose losuinmarne efficacy and siletycrf

mefloquine used as propterlastsloi malaria in

trartlltts.

Methods tandomned control Inals|l«elficacgr

and saletrl and noo tandonsiied cohoit studies(lor

saleIf) to compere prophflattie meflciqiune with

placebo, no treatment, or alternathre antimalarlal

agent.

lesnlts: Participants weie mote likeif to discontinue

mefloquine (ft)rs.asouaquoiiepioguaml p%|

due toeditrsf effects (including nausea,vomiting,

abnormal dreams, insomnia, ancetf, and depressed

mood during travel). Do difference in seriousadverse

effects or discontinuation due toedveise effects

wasioond between mefloquine anddoifCfdlne or

mefloquine and cMoroquine.

Conclusions: Absolute ns

*

ol malaria during

short term travel appearslow with mefloqune.

doiftfClme.and atovaguoneprognaml therapy.

Choice ol agent depends on how individual travellers

assessimportance olspecific adverse effects, pill

burden,and cost.

Plasmodium spp. (Malaria)

Etiology

• transmission of Plasmodium spp. ( P. falciparum, P. vivax, P. ovale, P. malariac, P. knowlesi) primarily

occurs during the blood meal of an infected female Anopheles mosquito

• sporozoites injected during the blood meal then infect human liver cells, where they multiply and are

released as merozoites; merozoites infect RBCs and cause disease

• infection with malaria parasites can also occur via vertical transmission (rare) or blood transfusion

• occurs in tropical/subtropical regions (sub-Saharan Africa, Oceania, South Asia,Central America,

Southeast Asia.South America)

Clinical Features

• flu-like prodrome (may include fever, chills, fatigue, diaphoresis, cough, rash, arthralgias, myalgias,

headache,Gl symptoms)

• paroxysms of high spiking fever and shaking chills (due to synchronous systemic lysis of RBCs) that

can last several hours

P. vivax and P. ovale: chills and fever x 48 h but can be variable

P.malariac: chills and fever x 72 h but can be variable

P. falciparum: less predictable fever interval, can be highly variable

• abdominal pain,diarrhea, myalgia, headache, and cough

• hepatosplenomegalv and thrombocytopenia without leukocytosis

• >90% of patients infected with P.falciparum are ill within 30 d

• relapsing malarial attacks may occur after many months due to the reactivation (entering the

erythrocytic cycle) of dormant liver hypnozoites of either P.ovale or P. vivax

• complications:

P.falciparum (most common and most lethal):CNS involvement (cerebral malaria = seizures and

coma),severe anemia,acute kidney injury, ARDS,primarily responsible for fatal disease

P.knowlesi,and rarely P. vivax,can be fatal

Investigations

• CBC screen (assessfor triad of:thrombocytopenia, elevated LDH, and anemia)

• microscopy: blood smearql2-24 h (x3) to rule out infection

thick smear (Giemsa stain) for presence of organisms

thin smear (Giemsa stain)forspecies identification and quantification of parasites

• rapid antigen detection tests

. RCR

$

Malaria isthe most common fatal

infectious disease worldwide

Treatment and Prevention

• allspp. of malaria can lead to severe infection (P. falciparum most likely to cause severe disease and

death)

• markers of severity:clinical features + parasitemia

in any patient with clinical evidence of severe disease: parenteral treatment (artemisinin

combination therapy)

• P. falciparum: most areas of the world show chloroquine resistance - check local resistance patterns

artemisinin combination therapy (e.g. artesunate i doxycydine or artemether-lumefantrine)

atovaquone/proguanil combination (Malarone*)

quinine i doxycydine or clindamycin

• mefloquine and artemisinin resistance increasing in southeast Asia (check local resistance)

• P. vivax, P. ovale: chloroquine (and primaquine to eradicate liver forms)

• P. vivax,chloroquine resistant: atovaquone/proguanil + primaquine or quinine and doxycydine +

primaquine

• P. malariac, P. knowlesi: chloroquine

• prevention with antimalarial prophylaxis (although quality may vary regionally), covering exposed

skin, insecticide-treated bed nets, insect repellent

• prevention of relapse for P. vivax: primaquine or the newly FDA-licensed tafenoquine (in patients £16

y/o who are receiving appropriate antimalarial therapy for acute R vivax infection)

I Sporozoites enter blood via mosquito bile,

inlect iver

l Hepatic infiltration

3 Inlect red blood cells

4 Trophozoite divides asexually many

timesto produce schizont(contains

merozoites)

3 Red blood cell tyses and merozoites

attack other red blood cells(chills and

fever)

6. Male and female gametocytes (from

merozoitesl ingested by mosquito during

bite

7. Male and female gametocytes(from

merozoites)fuse m mosquito gut;

produce ookinete

8. Ookinete matures into an oocystwhich

containsindividualsporozoites;migratesto

mosquito salivary glands

ri

(

_ J

Figure11. Life cycle of Plasmodium

' +

spp.

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ID38 Infectious Disease Toronto Notes 2023

Trypanosoma cruzi

Etiology

• found in Mexico,South America,and Central America

• transmission by reduviid insect vector (

“

Kissing Bug"

), which defecates on skin and trypomastigotes

in the stool are rubbed into bite siteorintact mucous membranes by host

trypomastigotes can penetrate intact buccal mucosa when orally inoculated (e.g.via sugar canesweetened unpasteurized juices)

• also transmitted via placental transfer, organ transplantation, blood transfusion,and ingestion of

food or drink contaminated by an infected triatomine

congenital acquisition increasingly recognized as a risk factor for Chagas disease being detected

in non-endemic areas

Clinical Features

• American trypanosomiasis (Chagas disease)

acute:usually asymptomatic,local swelling at site of inoculation (Chagoma) with variable fever,

lymphadenopathy, cardiomegalv,and hepatosplenomegaly

if inoculation via conjunctiva:

“Romana’

ssign:

"

usually unilateral

acute myocarditis, pericardial effusion,meningoencephalitis in severe cases

chronic indeterminate phase:asymptomatic but increasing levels of antibody in blood;most

infected persons(60-70%) remain in this phase, and do not go on to manifest a determinate form

of Chagas disease

chronic determinate:leads to chronic dilated cardiomyopathy,esophagomegaly.and megacolon

10-25 yr after acute infection in 30-40% ofinfected individuals

Investigations

• wet prep and Giemsa stain of thick and thin blood smear,serology, PCR

Treatment and Prevention

• acute: benznidazole or nifurtimox

• indeterminate:increasing trend to treat as acute infection for children and adults under age 50

• chronic determinate:sy mptomatic therapy,surgery as necessary including heart transplant,

esophagectomy, and colectomy; there is unlikely a clinical benefit to antiparasitic treatment at the

determinate stage of disease

• insect control, bed nets

See Landmark Infectious D isessc Trials table lot more

information on the 8MEFIT trial. It details the role

of trypanocidal thera py in patientswith established

Chagas cardiomyopathy.

Classic Triad of Congenital

Toxoplasmosis

• Chorioretinitis

• Hydrocephalus

• Intracranial calcifications

;v.

(required for

completion of

sexual cycle)

Cat \

ingests

mouse Toxoplasma gondii '

.I :

Sheds resistant

oocysts in stool paras te

J

Etiology

• infection with 21 gondii occursthrough exposure to cat feces(oocysts),ingestion of undercooked

meat (tissue cysts),transplacental transmission,organ transplantation,gardening without gloves (cat

oocyst exposure),whole blood transfusions,contaminated watersources

Sporozoites

Mouse

(intermediate host)

Clinical Features Direct ingestion

• (handling kitty congenital

result of acute primary infection of mother during pregnancy (TORCH infection)

stillbirth (rare), chorioretinitis, blindness,seizures,severe developmental delay,microcephaly

• initially asymptomatic infant may develop reactivation of chorioretinitis as adolescent or adultblurred vision,scotoma, ocular pain, photophobia, epiphora, hearing loss, developmental delay

Livestock

(ingestion of poorly

cooked meat!

• acquired

• usually asymptomatic or mononucleosis-like syndrome in immunocompetent patient

infection remainslatent for life unless reactivation due to immunosuppression

• immunocompromised (most commonly AIDS with CD4 <200)

• encephalitis with focal CNS lesionsseen assingle or multiple ring-enhancing masses on CT

(headache and focal neurologicalsigns)

lymph node, liver,spleen enlargement, and pneumonitis

• chorioretinitis

Investigations

• serology, CSF Wright-Giemsa stain, antigen or DNA detection ( PCR); pathology provides definitive

diagnosis

• immunocompromised patients: considerCT scan ( ring-enhancing lesion in cortex or deep nuclei) and

ophthalmologic examination

Treatment and Prevention

• no treatment if:immunocompetent, not pregnant,no severe organ damage

• immunocompromised: pyrimethamine + sulfadiazine + folinic acid

• pregnancy:spiramycin if fetal status unknown, pyrimethamine + sulfadiazine + folinic acid if

confirmed or highly suspected fetal infection, avoid undercooked meat and refrain from emptying cat

litter boxes

. HIV:TMP/SMX

• proper hand hygiene, cook meat thoroughly to proper temperature

n

u

Figure12. Life cycle of Toxoplasma

gondii

+

1/3 of Ontario's population is infected

with Toxoplasmagondii

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ID39 Infectious Disease Toronto Notes 2023

Helminths =

E

Roundworms - Nematodes ©

Table 26. Nematodes (Roundworms) l

T

Nematode Epidemiology Transmission Clinical Presentation Treatment

Human feces,ingestion Often asymptomatic,abdominal

discomfort

Heavy infections may cause

intestinal blockage,growth

Impairment

Cough,dyspnea,pulmonary

infiltrates from larval migration

through lungs (Loffler's syndrome)

Diarrhea|

*

mucous,blood),

abdominal pain,rectal prolapse,

stunted growth

River blindness (onchocerciasis). Ivermectin * doiycydine

dermatitis

Mebendazole OR

albendazole OR

pyrantel pamoate OR

ivermectin

to: :e ~:st

common in tropical and of contaminated food

Ascaris

lumbricoides

or water containing

eggs

subtropical areas)

Trichuris

trichiura

(whipworn)

Onchocerca

volvulus

Wuchererio

boncrolti

Ingestion of eggs

in soil

Worldwide (most Mebendazole OR albendazole

common in tropical

areas)

Sub-Saharan Africa.

Latin America

Tropics

Blackfly bite

Mosquito bite Oamage to lymphatics causes Diethylcarbamazine * doiycydine

lymphadenopathy.lymphedema,

lymphatic filariasis (elephantiasis),

hydrocele

Tropical pulmonary eosinophilia

loiasis is mostly asymptomatic. Surgicalremoval of adult worms,

Symptomscan include episodic diethyrlcarbamazme.albendazole

angioedema (Calabar swellings)

and subconjunctival migration

resulting in eye pain and ifching

1. Embryonated eggs ingestedbytunns

2 Larvae hatchinsmall intestine

3. Females migrate out anus at night

West and Central

African rainforest (e.g.

Cameroon.Central

African Republic)

Loo loo Deerfly bite

Figure 13. Life cycle of Enterobius

Enterobius

vermiculoris

(pinworm)

Human host:fecal-oral Asymptomatic earners or severe

self-inoculation and

fomiteperson-to- ani)

person transfer

Adult worms live in

Sticky tape test eggs adhere to tape

nocturnal peri-anal itching (pruritus applied toperianal skin (need S-7

tests to rule out)

Eiammabon of perianal skin at night

may revealadult worms

Usually no eosinophilia as no tissue

invasion

Mebendazole,albendazole;pyrantel

inpregnancy

Change underwear,bathe in

morning,pajamas to bed.wash

hands,trim fingernails

Treatall family members

simultaneously

Reinfection common

Worldwide

Occasional vaginitis,ectopic

migration to appendix or other

cecum and deposit pelvic organs

eggs in peri-anal skin Abdominal pain,nauseaVomiting

withhigh worm burden

Strongytoides

stercorolis

(threadworm)

Subtropical,tropical. Fecal contamination ol One of few worms able tomultiply

and temperate soil:transmission via in human host

(mclud ng southern US) unbroken skin,walking Mostly asymptomatic infection or

can have pruritic dermatitis at site

of larval penetration

Transient pulmonary symptoms

during pulmonary migration of

larvae|eosinophilicpneumonrtis ^

Loffler's syndrome)

Abdominal pain,diarrhea,pruritus

ani.larva currens (itchy rash)

Hyperinfection:occasionalfatal

cases caused bymassive autoinfection in immunocompromised

host;immunoablative therapy,

including high-dose corticosteroids,

is the most common risk factor for

disseminated infection

Ivermectin anchor albendazole

barefoot

Autoinfection:

penetration of larvae

through Gl mucosa or

perianal skin

Adult worms live

in mucosa of small

intestine

vv-v

^

'

V© V

1. Larvae penetrate intact skin of host

2.Larvae migrate to lungs via

bloodstream

3. Larvae crawl up trachea and down to

Gl tract (cough/swallow)

4.Adult worms in intestine

5.Eggs produced in bowel

6.Larvae

7.Bowel movement containing larvae

Figure 14. Life cycle of Strongyloides

r ~i

L J

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ID10 Infectious Disease Toronto Notes 2023

Flatworms- Cestodes/Trematode

Table 27. Cestodes/Trematodes (Flatworms)

Epidemiology Transmission Clinical Presentation Treatment

CEST00ES

Taeniasolium

( pork tapeworm}

Corticosteroids albendazole * praziquantel for most

cysticercosis

Antiepileptics if seizures

Praziquantel for adult tapeworm in gut (taeniasis)

Praziquantel

Worldwide,but more common Undercooked pork (larvae), Taeniasis:mild Gl symptoms

in places with poor sanitation human leces(eggs} Cysticercosis: masslesions in CNS.eyes,skin,seizures

Taeniasaginota Worldwide,but more common Undercooked beef (larvae) Taeniasis: mild Gl symptoms

(bed tapeworm) wherever contaminated raw

beelis eaten

Diphyllobothrium Europe. North America, Asia Raw fish

latum

Ichinocoecus

granulosus

Vitamin Bit deficiency leading to macrocytic anemia and Praziquantel

posterior column deficits

Liver/lung cysts (enlarge between 1-20 yr; may cause

mass effect or rupture)

Risk ol anaphylaxis if cystic lluid released during surgical Percutaneous aspiration * perioperative albendazole

evacuation

Rural areas.sheep- raising

countries

Dog feces (eggs) Albendazole t praziquantel alone

Surgery » perioperative albendazole

TREMATODES

Japan,Taiwan.China.

Southeast Asia

Schistosoma spp. Africa,Southeast Asia,focal In Fresh water exposure

Western Hemisphere

Raw fish Exists In bile ducts, causes inflammation and sometimes Praziquantel

cholanglocardnoina

Chronic sequelae secondary lo long term infection|c.g. Praziquantel

chronic liver disease, squamous cell carcinoma|SCC) ol

the bladder)

Clonorchis

sinensis

Schistosoma spp.

Etiology

infection with Schistosoma spp. (S. niattsonl,.S'

, hcniatobitim, S. iaponicum) occurs following

penetration of unbroken skin by their larvae (cercariae) which are found in infested fresh water

• adult worms live in terminal venules of bladder/bowel passing eggs into urine/stool

• schistosomes cannot multiply in or pass between humans

• more common in individuals from sub-Saharan Africa,South America, Asia,Caribbean, Eastern

Mediterranean /North Africa

Clinical Features

• most asymptomatic;symptoms seen in travellers ( nonimmune)

• swimmer’s itch: pruritic skin rash at site of penetration (cercarial dermatitis)

• acute schistosomiasis (Katayama fever): hypersensitivity to migrating parasites (4-8 wk after

infection)

fever, hives, headache, weight loss, cough, abdominal pain, chronic diarrhea, high-grade

eosinophilia

• chronic schistosomiasis (can persist for years):

S. mattsoni, S. japonicum

• worms in mesenteric vein, eggs in portal tracts of liver and bowel

heavy infections: intestinal polyps, portal and pulmonary HIN,splenomegaly (2° to portal HTN ),

hepatomegaly

S. hcinatobiiiiii

T . Eggs released into water

2. Snail (intermediate host)

releases infective larvae

3. Infective cercariae

4 Penetrate skin

5 Migrate to portal

blood stream;

mature in liver

6. Migrate to

Gl and GU

- worms in vesical plexus, eggs in distal ureter and bladder induce granulomas and

fibrosis

- hematuria and obstructive uropathy; associated with squamous cell bladder cancer

neurologic complications:spinal cord neuroschistosomiasis (transverse myelitis), cerebral or

cerebellar neuroschistosomiasis (increased ICP, focal CNS signs,seizures)

pulmonary complications: granulomatous pulmonary endarteritis, pulmonary H TN, cor

pulmonale; especially in patients with hepatosplenic involvement

Investigations

• serology (high sensitivity and specificity), CBC (eosinophilia, anemia, thrombocytopenia), loopmediated isothermal amplification, circulating serum antigen test

• S. mansoni, S. japonicum: eggs in stool,liver U/S shows peri-portal fibrosis,rectal biopsy

• S.hematobium: bladder biopsy, eggs in urine and occasionally stool, kidney and bladder U/S

Treatment and Prevention

• praziquantel

• add prednisone if acute schistosomiasis or neurologic complications develop

• proper disposal of human waste, molluscicide (pesticide against molluscs), avoidance of infested fresh

water while travelling

r-»