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
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
31
Q
Cytomegalovirus
Infection in the Immunocompromised Host
A
- 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
Q
CMV Retinitis
A
White, fluffy retinal infiltrate or granular white area w/ hemorrhage
Leads to blindness in 3-4 months
34
Q
Cytomegalovirus
Diagnosis
A
- 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
39
Q
Kaposi’s Sarcoma (KS)
A
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
Q
Primary CNS Lymphoma
A
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
46
Q
Toxoplasmosis
vs
Primary CNS Lymphoma
vs
PML
A
