Opportunistic Infections Flashcards
1
Q
HIV Opportunistic Infections (OIs)
General Principles
A
- Low CD4 count is the major risk factor for many OIs
- Many pts w/ HIV dx w/ OIs
- Many people living w/ HIV who are being diagnosed w/ were not aware of HIV or not engaged in care
- Many OIs have similar or overlapping signs and sx
- Multiple OIs may be present at the same time
- Treatment does exist for most OIs w/ good prognosis
2
Q
Opportunistic Infections
Overview
A
- Select infections:
- Toxoplasmosis
- Pneumocystis pneumonia
- Cryptococcosis
- Cytomegalovirus
- All AIDS defining illnesses
- Requires deficient CMI for fulminant disease
- CD4+ T-cell count < 200 cells/μl
3
Q
Toxoplasmosis
A
- Systemic disease caused by obligate intracellular Protozoan parasite T. gondii
- #1 Food borne illness
- Most infections are asymptomatic
- Mild disease in the immunocompetent host
- Devastating in immunodeficient hosts or if passed congenitally
4
Q
Toxoplasma gondii
Epidemiology
A
-
Ubiquitous worldwide
- Prevalent in warm, humid, low altitude environments
- France
- Central America
-
50% of adults seropositive for T. gondii
- 1% will be dx w/ disease
5
Q
Toxoplasma gondii
Lifecycle
A
Complex life cycle:
- Oocyst ⇒ formed during the sexual cycle in the cat & excreted in feces
- Tachyzoite ⇒ replicating form which disseminates through blood to tissue
- Bradyzoite ⇒ dormant form contained within cysts in tissue
6
Q
Toxoplasma gondii
Transmission
A
- Reservoir: house cat
- Intermediate hosts: sheep, cattle
- Ingest the oocysts → dormant tissue cysts containing bradyzoites
-
Methods of transmission:
- Ingestion of undercooked meat from intermediate hosts
- Oral contact with oocytes (cat feces)
- Drinking unfiltered water
- Transfusion and transplantation
- Congenital
7
Q
Toxoplasma gondii
Pathogenesis
A
- Ingestion → trophozoites released from oocysts → penetrate gut wall → hematogenous spread → can invade all nucleated cells
- Prefers heart, lung, brain, lymphoid tissues, and eyes
- Replication within MΦ
-
Self-limiting mononucleosis-like symptoms:
- Cervical or generalized lymphadenopathy
- Pharyngitis, low grade fever, fatigue
- Activated MΦ can kill the organism
- Within several weeks of infection, once host mounts CMI response → infection controlled
- Immune pressure → formation of dormant cysts in body tissues
8
Q
Toxoplasma gondii
Reactivation Disease
A
- Immunocompromised individuals, esp. AIDS pts
- Type II strains
- Cysts rupture releasing tachyzoites
- Uncontrolled tachyzoite replication ⇒ necrosis and intense inflammatory response
- Disease manifestations include:
- Encephalitis, cerebral mass lesions, pneumonitis, systemic toxoplasmosis and chorioretinitis
- Hemiparesis, seizures, lethargy, confusion, visual impairment
- Highly lethal
9
Q
Toxoplasma gondii
Congenital Disease
A
-
Pregnant woman acquires a primary infection w/ T. gondii
- 1st trimester ⇒ usually causes spontaneous abortion or stillbirth
- > 70% of congenitally acquired toxoplasmosis manifests months to years after birth
- Mental retardation
- Visual impairment
- Hearing loss
- Learning disabilities
- Hydrocephalus
- Chorioretinitis
- Hepatosplenomegaly
- Thrombocytopenia
10
Q
Toxoplasma gondii
Diagnosis
A
-
Congenital Infection or Symptomatic Primary Infection
- Dx by serology
- ↑ IgG titers (4-fold) & specific lgM
-
Latent infection
- Variable IgG titers, no IgM
- Presumptive dx of encephalitis based on clinical and radiographic findings
- Brain MRI ⇒ multiple ring enhancing lesions
- Ocular toxoplasmosis ⇒ retinal changes
- Biopsy specimens ⇒ visualize organisms in tissue
11
Q
Toxoplasma gondii
Treatment
A
-
Active disease
- 1° disease in immunocompetent host usually self-limiting ⇒ requires no treatment
- Congenitally acquired infection, damage is done in utero ⇒ tx after birth ineffective
- AIDS pts w/ toxoplasmosis tx ⇒ Pyrimethamine + Sulfadiazine (synergistic)
- High dose therapy for 4-6 weeks
- Low dose maintenance therapy due to high relapse rate
-
Chemoprophylaxis for toxo-seropositive HIV pts (< 100 CD4 count)
-
Trimethoprim/sulfamethoxazole
- Active vs tachyzoites form
-
Trimethoprim/sulfamethoxazole
12
Q
Toxoplasma gondii
Prevention
A
- Cook meat to 165°F
- Wash hands after gardening
- Wash all fruits and vegetables
- Avoid cat litter – or change daily
- Screen women for anti-toxoplasma Ab during early pregnancy
- Women who are seropositive (indicating previous infection) have no risk of producing a congenitally infected child
- Seronegative women can be given preventative advice
- Seroconvert during pregnancy can be further counseled and treated
- Risk of drug toxicities to the fetus
13
Q
Cryptococcus neoformans
Characteristics
A
- Causes Cryptococcosis
- Oval budding yeast at both 25° and 37° (not-dimorphic)
- Large acidic mucopolysaccharide capsule ⇒ ⊗ phagocytosis
- Asexual
14
Q
Cryptococcus neoformans
Epidemiology and Transmission
A
- Nitrogen rich environments ⇒ pigeon droppings
- Found worldwide
- Acquired by inhalation of aerosolized fungal elements
- Person to person transmission does not occur
15
Q
Cryptococcus neoformans
Clinical Diseases
A
- Immunocompetent ⇒ usually asymptomatic
-
1° infection in the lung ⇒ Pulmonary Cryptococcosis
- Mild to fulminant PNA
- CXR may show a solitary nodule or focal infiltrate
- Hematogenous spread from lungs → meninges
-
Cryptococcal meningitis (most common clinical manifestation)
- Causes meningitis, meningo-encephalitis, space occupying lesions
- Behavioral changes, fever, HA, seizure, AMS
- Leading cause of fungal meningitis
- Highest mortality occurring in AIDS pts and transplant recipients
- Meningitis due to mild disease w/ C. neoformans also seen in pts w/o underlying disease
- Brain abscesses
- Skin and bone lesions
16
Q
Cryptococcus neoformans
Diagnosis
A
-
Examination of CSF for budding yeast cells w/ capsules using India Ink staining ⇒ ⊕ in 50% of cryptococcal cases
- Clear halo around organisms d/t dye exclusion by the capsule
-
Latex agglutination and EIA tests for cryptococcal Ag ⇒ rapid, sensitive, and specific tests
- False ⊕ reactions may be caused by rheumatoid factor
- Dx confirmed by culture on SDA
17
Q
Cryptococcus neoformans
Treatment
A
-
Pulmonary cryptococcosis
- Frequently self-limiting
- When symptomatic, can usually be cured by excision of the nodule
-
Cryptococcal meningitis
- Long term, combination antifungal agents
- Amphotericin B + Flucytosine (induction therapy)
- Then 8 wks of fluconazole
- AIDS pts may need lifelong maintenance therapy
- Long term, combination antifungal agents
18
Q
Pneumocystis jiroveci
Characteristics
A
Previously P. carinii
- Primitive fungus
- Lack ergosterol in cell membrane
- Poorly defined cell wall
- Extracellular trophozoite ⇒ divides by binary fission
- Cyst form ⇒ contains intracystic bodies
19
Q
Pneumocystis jiroveci
Epidemiology
A
- Ubiquitous
- 75% seropositive by age 4
- Infants infected after maternal Ab wanes
- Almost always asymptomatic
20
Q
Pneumocystis jiroveci
Transmission
A
- Person to person by respiratory secretions
- Droplet inhalation
- Inhalation from the environment
- Infants colonized
- Exogenous reinfection
21
Q
Pneumocystis jiroveci
Risk Factors
A
-
Symptomatic disease in immunosuppressed
- AIDS pts: CD4 count < 200 cell/ml
- Cancer chemotherapy
- Organ recipients
- Malnourished children who live in overcrowded conditions
- Usually manifest after a debilitating illness → ? reactivation or carrier state
22
Q
Pneumocystis jiroveci
Pathogenesis
A
- Inhaled as sporozoites
-
In the host, sporozoites → trophozoites
- Binds Type I cells in alveolus
- Remains extracellular
- Eventually transform back into cysts (probably d/t sexual mating)
- Each cyst can release 2 to 8 sporozoite forms (spore like)
- CMI (Alveolar MΦ and CD4+ T cells) kill organisms
- Alveolar damage through host and pathogen mediated mechs.
23
Q
Pneumocystis jiroveci
Diagnosis
A
-
ID organism in a tissue specimen or lavage fluids
- Gomeri stain ⇒ thick-walled cystic forms
- Giemsa staining ⇒ trophozoite forms
- Serology is not useful
- Wide prevalence of seropositive individuals
- Titers rise several weeks after the onset of symptoms
24
Q
Pneumocystis Pneumonia
(PCP)
A
AIDS defining illness
- Sx: dry cough, fever, rapid breathing, SOB, progressive respiratory insufficiency
- Develops over weeks-months in AIDS pts
-
Bilateral diffuse interstitial pneumonitis w/ plasma cell infiltrates
- Stays in air spaces
- CXR ⇒ ground glass appearance
- Usually responds to treatment but recurring bouts common
- Rarely disseminates ⇒ extrapulmonary disease in pts w/ AIDS
25
Pneumocystis jiroveci
Treatment/Prevention
* P. carinii is **resistant to antifungal drugs**
* Sensitive to a number of **antibacterial and anti-protozoal drugs**
* Organism is ubiquitous ⇒ avoiding exposure is not possible
26
Cytomegalovirus
Characteristics
**Herpesviruses family /** **beta-herpesvirus subfamily**
* **Large linear dsDNA viruses, enveloped**
* Transcription and translation highly regulated and consist of three phases:
* Immediate early proteins ⇒ DNA binding proteins that regulate transcription
* Early proteins ⇒ including the DNA polymerase
* Late proteins ⇒ structural proteins
* _Replication and assembly_ occur in the **nucleus**
* Virus _buds_ from the **nuclear membrane**
* Release from the cell occurs by **exocytosis and cell lysis**
* Tendency to establish **latent and recurrent infections**
* Manifestations of disease vary w/ age and immunocompetency
27
Cytomegalovirus
Epidemiology & Transmission
* Ubiquitous
* No seasonal incidence
* Transmission:
* **Direct person to person contact w/ virus containing secretions**
* **Sexually**
* **Blood transfusions**
* **Tissue transplants**
* **Vertically from mother to infant before**, **during and after birth**
* Virus can be isolated from **tears, saliva, pharynx, semen, cervical secretions, peripheral blood leukocytes, amniotic fluid and urine**
28
Cytomegalovirus
Pathogenesis
* **4-8 wk incubation**
* Initial infection usu. **asymptomatic**
* Virus replicates in **epithelial cells** of respiratory and GI tract
* Viremia
* Infection of all organs and lymphoid tissue
* **Shed from most body fluids:** pharynx, urine, genital tract
* **Latent infection** in _lymphocytes and MΦ and organs like the kidney and heart_
* **Reactivation** d/t profound immunosuppression ⇒ AIDS, prolonged corticosteroid use, chemotherapy
29
Cytomegalovirus
Immune Response & Evasion
* **CMI critical to control infections**
* **CMV blocks Ag presentation via MHC class I and II**
* ⊗ Transport to cell surface
30
Cytomegalovirus
Infection in Children and Adults
* Usually asymptomatic
* May show a **mononucleosis like syndrome** w/ _atypical lymphocytes_
* No heterophile antibody
31
Cytomegalovirus
Infection in the Immunocompromised Host
* May be due to **reactivation** or **acquisition** of primary infection
* **Interstitial pneumonia (15%), retinitis, esophagitis, chronic colitis (10%), and weight loss**
* CMV retinitis: white, fluffy retinal infiltrate or granular white area w/ hemorrhage, leads to blindness in 3-4 months
* CMV is also _frequently reactivated in transplant recipients_ ⇒ cause of transplant loss
* Avoid seropositive → seronegative transplants
32
CMV Retinitis
White, fluffy retinal infiltrate or granular white area w/ hemorrhage
Leads to blindness in 3-4 months
33
Cytomegalovirus
Congenital or Perinatal Infection
* **1% of live births are infected in utero**
* Usu. d/t 1° infection of the mother during pregnancy
* 10-20% are diagnosed w/ **mental retardation or deafness**
* Transmission from **passage through the birth canal** and postnatally by **ingesting virus containing breast milk**
* Most term infants who acquire infection during or after birth have **asymptomatic infections**
* _Preterm infants_ at higher risk for **interstitial pneumonia or hepatitis**
34
Cytomegalovirus
Diagnosis
* _In immunocompetent individuals_, **serology** is a sensitive dx method
* **Seroconversion** and **IgM** usually indicates a primary infection
* Lymphocytosis w/ \> 10% atypical lymphocytes
* _Immunodeficient individuals_ ⇒ **Viral culture** d/t presence of high titers of virus
* Histological identification in tissues of the **“owl’s eye”, basophilic intranuclear inclusion body** is a hallmark of CMV infection
35
Cytomegalovirus
Treatment
Anti-CMV agents
**Ganciclovir, Cidofovir and Foscarnet**
⊗ Viral DNA pol
36
Cytomegalovirus
Prevention
* Transplant organs between seronegative pts
* Deplete leukocytes from transplanted organs
* **HAART for AIDS pts (CD4 counts \< 50)**
* At risk for retinitis and esophagitis
37
Mtb and MAC
* **Tb** can occur w/ only mild immune impairment
* Pulmonary Tb
* May disseminate widely
* Lymphadenitis, meningitis, hepatitis
* **MAC** more commonly causes disseminated disease
* Frequently of the GI tract & lymphoreticular organs
38
Other Infections of Immunocompromised
* Systemic candidiasis
* Nocardia
* Aspergillus
* Histoplasma
* Coccidiodes
39
Kaposi’s Sarcoma (KS)
Caused by **human herpes virus – 8 (HHV8)**
* More common w/ **CD4 \< 200 cells/mm3**
* May occur at any CD4 count
* _Clinical Appearance:_
* **Non-tender, purple-reddish maculopapular skin lesions**
* Indistinguishable from Bacillary angiomatosis caused by *Bartonella henselae*
* Can have similar lesion in the **oropharynx**
* May also involve **lymph nodes, lungs, digestive tract**
* _Diagnosis_:
* **Biopsy**
* _Treatment_:
* **Antiretroviral therapy (ART) for mild-moderate KS**
* **ART plus chemo for disseminated KS**
40
Primary CNS Lymphoma
A **diffuse, large-cell non-Hodgkin lymphoma of B-cell origin** which is caused by **Epstein-Barr virus**
* _Clinical presentation:_
* Generally w/ **CD4 \< 100 cells/mm3**
* Symptoms include **lethargy, headache, personality changes, memory loss, confusion**
* Often have focal neurologic symptoms: **weakness, seizures, cranial nerve involvement**
* _Diagnosis:_
* **EBV PCR in CSF** w/ compatible **lesion** on imaging
* CT or MRI generally shows a **single lesion which is enhancing w/ contrast**, but can be multiple lesions
* Brain biopsy for definitive dx
* _Treatment:_
* **Chemo and radiation therapy + ART**
41
Progressive Multifocal Leukoencephalopathy (PML)
Overview
**Central nervous system infection** caused by the **polyoma JC virus**
* Belongs to papovavirus family
* **Naked circular dsDNA genome**
* Replicated and assembled in the **nucleus**
42
Progressive Multifocal Leukoencephalopathy (PML)
Epidemiology
* **~65% of the population is seropositive**
* 20-30% of adults w/ a normal immune system have JC DNA in urine
* Most individuals acquire **asymptomatic infection during childhood**
* Disease remains **latent in kidney** afterwards
* Profound immunosuppression permits renewed viral replication, dissemination of virus to CNS, and progressive disease
43
Progressive Multifocal Leukoencephalopathy (PML)
Clinical Presentation
* Characterized by **focal demyelination**
* Present w/ **focal neurologic deficits** w/ _insidious onset and steady progression_
* Starts as a **partial deficit that worsens over time as lesions expand**
* Symptoms progress over several weeks
44
Progressive Multifocal Leukoencephalopathy (PML)
Diagnosis and Treatment
* _Diagnosis:_
* MRI for **white matter lesions**
* Confirm w/ CSF testing for **JC virus PCR**
* _Treatment:_
* No specific treatment
* Initiation of ART may help
* Generally poor prognosis
45
Immune Reconstitution Inflammatory Syndrome (IRIS)
* IRIS usually occurs within **weeks to a few months after starting ART**
* Antiretroviral therapy initiated ⇒ ↓ HIV viral load ⇒ ↑ CD4 count ⇒ improved immune function
* Can have a **dramatic immune response if an opportunistic infection is present**
* Most common w/ **mycobacterial infections** (Tuberculosis or *M. avium* complex) or **disseminated fungal infections**
* Most common sx: fever, lymphadenopathy, worsening respiratory sx
* Treatment is **supportive** and symptoms resolve w/ time
* Continue ART
* May need to start **steroids** for inflammation if symptoms are severe enough
46
Toxoplasmosis
vs
Primary CNS Lymphoma
vs
PML
