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Opportunistic

Infections
In Acquired Immune Deficiency Syndrome

BY LAYLEE GHAFAR, OMS-III


Objectives

Review definition of AIDS


Discuss basic factors regarding Opportunistic
infections (Ois)
See the frequency with which these OIs occur
and their clinical features, diagnosis and
treatment
Discuss patient education messages for
preventing OIs
AIDS Definition

Most severe phase of HIV infection


CDC Definition of an HIV positive person as having
AIDS:
Has had at least 1 out of 21+ AIDS defining
opportunistic infections
And / or
Has had a CD4 cell count of 200 or less
Without treatment, people with AIDS typically
survive about 3 years
Common symptoms of AIDS: Chills, fever, sweats,
swollen lymph glands, weakness, and weight loss
HIV Related Infections and
Illnesses
Bacterial Viral Fungal Parasitic Other Illnesses

Tuberculosis Varicella Zoster Candidiasis Isosporiasis AIDS -dementia

Bacterial Resp. Oral Leukoplakia Cryptococcosis Microsporidiosis Invasive cervical


Infections cancer
(Strep. Pneumoniae)

Bacterial enteric HSV Penicilliosis Cryptosporidiosis Non-Hodgkins


infections Lymphoma
CMV

Pneumocystis Human Herpes Histoplasmosis Giardiasis Kaposis Sarcoma


Jiroveci pneumonia virus type 8
(PCP) Toxoplasmosis

Atypical Human papilloma Coccidiomycosis Strongyloidiasis


Mycobacteriosis virus
HIV-specific DDX based
on symptoms
Symptoms DDX

Constitutional mycobacterial infection (TB and MAC)


(fever, weight loss, fatigue) HIV wasting syndrome
Lymphoma
Bartonella
Visual changes, eye pain CMV retinitis
Ophthalmic varicella-zoster
Headache, mental status changes Toxoplasma encephalitis
CNS lymphoma
Cryptococcal meningitis
Progressive multifocal leukoencephalopathy
Cough, shortness of breath PCP
TB
Recurrent bacterial (strep pneumo) pneumonia
Influenza
Oral lesions Thrush
Oral hairy leukoplakia
Aphthous ulcers
HSV
HIV-specific DDX based
on symptoms
Symptoms DDX

Odynophagia, Dysphagia Candidal esophagitis


CMV esophagitis
HSV esophagitis
Chronic diarrhea Cryptosporidiosis
Isosporiasis
Genitourinary symptoms Recurrent HSV infection
Syphilis
Cervical cancer
Skin lesions Kaposi sarcoma
Molluscum contagiosum
Bartonella infection (bacillary angiomatosis)
Scabies
Enlarged lymph nodes Lymphoma
Mycobacterial infection
HIV lymphadenopathy
Bartonella infection
The Basics Of OIs

HIV infects the CD4 type of white blood cells in


the blood
When the immune system loses too many CD4
cells, OIs are more likely to develop.
Different type of OIs develop at different levels of
CD4 count, depending on the microbes or
pathogens endemic in that particular region.
Most common OIs by CD4+ count

400 Herpes zoster, TB

Oral Candidiasis
300

200 PCP
Esophageal Candidiasis
Mucocutaneous Herpes

Toxoplasmosis, Histoplasmosis
100

50 MAC, CMV, PML, cryptococcosis,


coccidioidomycosis
Tuberculosis
Major world wide co-infection
ALL HIV infected individuals regardless of CD4 count should be
screened for latent TB using either IFN-gamma release assay or
TB skin test.
Clinical features:Cough
Hemoptysis
Weight loss
Evening rise of temp.
Diagnosis: sputum for AFB, CXR, culture of specimen from the
site, IFN-gamma release assay, urine antigen detection
Negative PPD test results are frequent among AIDS patients due to
immunosuppression****
Patients with advanced immunosuppression have atypical chest
radiography: non-cavitary pulmonary infiltrates with no particular
preference for the upper lung fields and normal chest radiographs
Treatments: combination regiment of isoniazid, a rifamycin,
ethambutol, and pyrazinamide
Candidiasis

Oral candidiasis may be the initial sign of HIV infection


Clinical features: Oral thrush
Dysphagia
Diagnosis: Clinical diagnosis, KOH preparation or gram stain
of the scrapings
An alternative diagnostic approach that has been used in AIDS
patients is to treat with systemic antifungal agents on the basis of
the history. Symptoms d/t candidiasis should improve within
several days
Treatment: Gentian violet, clotrimazole, miconazle in mild
cases (oral cand.) & fluconazole in severe cases (esophageal
can.)
Extensive esophagitis The buccal mucosa is
due to Candida involved here in the
pseudomembranous form of
albicans in a patient oropharyngeal candidiasis.
with AIDS.
Cryptosporidiosis

Found in about 35% of AIDS diarrheal cases


Clinical features: Watery diarrhea
abdominal bloating
profound weight loss
Diagnosis: Microscopic identification of oocysts, PCR testing,
or enzyme immunoassays. Organisms may be present in
stool, duodenal aspirates, bile secretions, etc.
Treatment: paromycin/azithromycin.
Response is poor with all available therapies. Prevention of
malnutrition & symptomatic relief vital in management
Pneumocystis Pneumonia
(PCP)
Occurs in patients with CD4 < 200
Risk without prophylaxis is 40-50% per year in those with CD4 below 100
Leading cause of death in patients with AIDS
Clinical features: Fever
Dry cough
Chest pain
Shortness of breath
Diagnosis: Diffuse interstitial infiltrates on CXR (negative radiographs in 25% of
patients with PCP Order CT chest!)
Identification of organism in respiratory secretions, often through induced sputum or
broncheoalveolar lavage, which is more sensitive
Serum (13)-beta-D-glucan is also highly sensitive for the diagnosis of PCP
Elevated LDH shown in 90% of HIV patients with PCP between 300-600!!!!
If the diffusion lung capacity for carbon monoxide (DLCO) is normal PCP is highly
unlikely!!!!
Treatment: TMP-SMZ (co-trimoxazole)
Chest radiograph shows diffuse ground glass opacification
without air bronchograms and without obliteration of the
pulmonary vessels.
Cytomegalovirus (CMV)
Retinitis
Rarely occurs unless CD4 cell count less than 50
Most typically affects the eyes
Clinical features: Blurry or loss of central vision
Scotomata (blind spots), floaters,
photopsia (flashing lights)
Respiratory, CNS & GI complications
Diagnosis: retinal changes examined by ophthalmologist
yellow-whtie, fluffy, or granular retinal lesions, often located
close to retinal vessels and a/w hemorrhage
Testing for CMV by DNA PCR, blood antigen or culture is not helpful
diagnostically. Poor S/S for determining CMV end-organ disease
Treatment: Gancyclovir, Foscarnet
Prevention: Yearly eye exams with HIV patients
Cryptococcal Meningitis
Most common cause of meningitis in AIDS
Vast majority of cases occur among patients with CD4 < 100
Clinical features:headache, fever, malaise
N/V
Confusion, impaired consciousness
signs of meningism (only in about 40%)
Diagnosis: CSF examination (antigen, culture, or India ink
staining)
Sensitivity of serum antigen testing is comparable to CSF testing and
is useful diagnostic modality in patients who cannot undergo LP
Treatment: Amphotericin B/Fluconzaole with or without 5-
flucytosine
Toxoplasmosis
Most common cause of focal cerebral lesions in HIV/AIDS
CD4 < 100 increases risk of reactivated toxoplasmosis by 30%
HIV infected individuals who are seropositive for toxoplasma
and have CD4<100, probability of reactivated toxoplasmosis is
about 30% per year
Clinical features: Focal neuro deficit
seizures
intracranial hemorrhage
AMS and coma
Diagnosis: clinical syndrome + positive T. gondii IgG antibody +
ring enhancing lesions on CT/MRI
Treatment: Sulfadiazine PLUS pyrimethamine & folinic acid is
preferred
Mycobacterium Avium
Complex (MAC)
Usually occurs only if the CD4 < 50
For patients with CD4 <50, the risk of developing disseminated MAC
can be as high as 40% per year. Risk increases with decreasing CD4
count
Clinical features: Flu-like fever
chills, sweats
abdominal pain, diarrhea, weight loss
anemia, fatigue
Diagnosis: CT abd can be helpful as patients typically demonstrate
mesenteric/abdominal lymph node enlargement, but recent study
showed CT normal in 25% of pts with positive blood culture
Culture of blood or lymph node is best , but can take up to 7-10 days.
Treatment: Macrolide (clarithromycin or azithromycin) + ethambutol
for at least 12 months in addition to ART
For patients failing ART add rifabutin as third agent.
Treatment & Prophylaxis of Major OIs
Pathogen Treatment Indications for 1o Prophylaxis 2o prophylaxis
[alternatives] prophylaxis [alternatives] [alternatives]
PCP TMP-SMZ CD4 <200 or oral Same as treatment Same as
[dapsone aerosolized candidiasis treatment
pentamidine, dapsone +
pyrimethamine]

TB Isoniazid + pyridoxine + TB test >5 mm or Isoniazid + pyridoxine None


rifampin + ethambutol history of +test without [rifampin]; rifampin or
(adjust with sensitivity results) treatment or contact rifabutin (if suspected
with active case of TB isoniazid resistance)
Toxoplasma Sulfadiazine + IgG antibody to TMP-SMZ Same as
pyrimethamine + Toxoplasma and [dapsone + pyrimethamine + treatment
leucovorin]
leucovorin CD4 <100
[clindamycin as alternative to
sulfa]

MAC Clarithromycin or CD4 <50 Clarithromycin or Same as


azithromycin + one more Azithromycin treatment
of rifabutin, ethambutol, [rifabutin]
clofazimine, ciprofloxacin
Influenza No recommendation All patients Influenza vaccine None
[oseltamivir, zanamivir, [oseltamivir, zanamivir, rimantadine,
rimantadine, amantadine] amantadine]

Hepatitis B None All susceptible (i.e. hep Hepatitis B vaccine None


[Lamivudine for chronic acitve] B core antigen neg)
Treatment & Prophylaxis of Major OIs
Pathogen Treatment Indications for 1o Prophylaxis 2o prophylaxis
[alternatives] prophylaxis [alternatives] [alternatives]
Hepatitis A None All susceptible and Hepatitis A vaccine None
those at high risk or
with chronic liver
disease
Strep Penicillin, All patients Penumococcal Pneumococcal vaccine
pneumo Cephalosporins vaccine
CMV IV Ganciclovir IgG antibody to CMV Oral ganciclovir IV ganciclovir
[foscarnet] and CD4 <50 [IV foscarnet, oral ganciclovir,
cidofovir]

HSV Acyclovir Not recommended Not recommended Acyclovir or famciclovir


[famiclovir] [valacyclovir] for frequent
and/or severe relapses
Herpes Acyclovir Exposure to person Varicella-zoster Acyclovir [famiclovir] for
(varicella) [famiclovir] with acute chicken immune globulin frequent and/or severe
zoster virus pox or zoster relapses
Candida Fluconazole CD4 < 50 Fluconazole If frequent or severe
species [Ketoconazole] [Ketoconazole] fluconazole [ketoocnazole]
Crypto- Fluconazole CD4 < 50 Fluconazole Fluconazole [itraconazole, weekly
coccus [Ketoconazole] [Ketoconazole] IV amphotericin]

Histo- Itraconazole CD4 < 100 and Itraconazole Itraconazole [weekly IV


plasma [fluconazole] endemic area [fluconazole] amphotericin]
Patient Education

Best way to prevent OIs is to keep immune system strong


antiretroviral therapy!
Appropriate medication at certain CD4 cell levels can
prevent many OIs (prophylaxis)
Keep up to date with vaccinations
Treatment options available if OIs develop
After recovery from OIs, on-going maintenance treatment is
still needed
Can stop prophylaxis or maintenance treatment if CD4 cell
count goes up
Should not discontinue any treatment without discussing first
with doctor
Patient Education

Prevent exposure to ill patients


Personal hygiene (washing hands etc.)
Avoid contact with raw food, soil, cats, bird
excreta, litter boxes etc.
Wash vegetables before cooking, avoid raw
meat intake, drink boiled water
Use condoms during sexual contact reduce
exposure to CMV, HSV and other STDs
Also prevent transmission of HIV to others
Thank You
LAYLEE GHAFAR, OMS-III