Oppurtunistic infections Flashcards
“Pneumocystis pneumonia
(PCP ping pong)”
Features:
“* Disc shaped yeast or cysts containing dark oval bodies
Previously classified as protozoa
Targetoid/cup-shaped w silver stain”
Location:
Transmission:
“ Inhalation of spores affecting lungs bilatereally
cyst –> trophozoite forms
*OI: HIV w CD4 < 200”
Symptoms:
“Diffuse interstitial pneumonia: intense inflammatory rxn in alveoli of lungs that impairs O2 exchange
*Non-productive cough, accelerated dyspnea (decreased O2 on RA), fever, no consolidations/ lung sounds may be normal (symptoms worsen over weeks)
* Frothy honeycombed/eosinophilic exudate in alveolar spaces
* AIDS-defining illness: Most common OI in AIDS pts”
Diagnosis:
“ Bronchoalveolar lavage (BAL): bronchoscopy w lung samples through fluid rinses
*Methamine silver stain: disc/ovoid shaped, stains for walls of cyst
Giemsa stain: identifies cysts & trophozoites
* CXR: ground glass appearance, diffuse, bilateral reticular or interstitial infilitrate
* LDH Blood Test: NOT specific, usually elevated”
Treatment:
“TMP-SMX (ppx & treatment)
* Atovaquone or Pentamidine (w sulfa allergies)
* Steroids (reduce inflammation if significant)
- HIV PPX: TMP-SMX (CD4 = 50-100)”
CD4 < 200
“Coccidioidomycosis
(presidio san joaquin)”
Features:
“Coccidioidomycosis
(presidio san joaquin)”
Location:
“Southwest US
* San Joaquin Valley, CA
* Dust storms & earthquakes increase spread”
Transmission:
“ Resp transmission (inhale dust with arthrospores)
* NOT contagious person to person
*OI: HIV CD4 < 250”
Symptoms:
“Acute: Mostly asymptomatic
* Vague symptoms: chest pain, fever, cough, fatigue
* Erythema nodosum (painful nodules on legs/shins)
* Self-limited acute pneumonia w fever, cough, arthralgia that lasts a couple weeks
* CXR may show nothing OR cavities & nodules
Chronic:
* Commonly targets skin & lungs
* Necrotizing granuloma formation
*Disseminates to bone & meninges (meningitis)
HIV: focal or diffuse pneumonia, skin lesions, meningitis, liver/LN involvement”
Diagnosis:
“*KOH stain
*Culture (takes VERY long)
Serology (ab titers, IgM indicates recent infection)”
Treatment:
“ Systemic: Amphotericin B
* Local: conazoles
- HIV PPX (TMP-SMX) in those living in endemic areas”
CD4 < 200
“Histoplasma capsulatum
(historian’s cave)”
Features:
“Smaller than RBC
* Dimorphic
* Yeast lives in macrophages”
Location:
“ Midwestern/Central US
* MI & OH Rivers”
Transmission:
“*Airborne/Resp transmission (spores inhaled & ingested by macrophages)
*Bird/bat feces
* Spelunking in caves
* Chicken coops
*OI: HIV CD4 < 150”
Symptoms:
“Acute:
* Vague symptoms: fever, chills, sweats, fatigue
* Erythema nodosum (painful nodules on legs/shins)
Chronic: disseminates to liver, spleen, bone marrow
* Lung granuloma that becomes calcified
*Cavitary lesions in upper lobes, calcified nodules, fibrotic scarring; resembles TB –> SOB, cough
Hepatosplenomegaly w calcifications “
Diagnosis:
“ KOH Stain: Macrophages containing several oval bodies
* Urine rapid antigen test
*Serum rapid antigen test
*Culture of biopsy (takes VERY long)
Serology (ab titers, IgM indicates recent infection)”
Treatment:
“ Systemic: Amphotericin B
* Local: Conazoles
- HIV PPX (TMP-SMX) in those living in endemic areas”
CD4 < 150
Toxoplasmosis (Toxoplasma gondii)
Features:
Location:
Transmission:
“* ingestion of cat oocyst from feces, cysts in meat, crosses placenta (greatest risk during 3rd trimester, but most symptoms if contracted during first semester), blood transfusion/ transplant
* OI: HIV w CD4 < 100”
Symptoms:
“* Immunocompetent: flu like symptoms, self limited
* Immunocompromised: reactivation of infection –> brain abscesses that cause HA, altered mental status, seizures, personality changes, focal neuro deficits
Congenital:
* Chorioretinitis (unlikely w CMV), hydrocephalus (Not seen w CMV, enlarged ventricles), intracranial calcifications (more diffuse than CMV which is along ventricles)
* Petechiae, lymphadenopathy, jaundice, muscular-papular rash, small for gest age, microcephaly”
Diagnosis:
“* Brain biopsy (cysts in tissue)
* CSF (tachyzoite)
*PCR
* Brain CT/MRI: multiple ring-enhancing lesions
*Serology (IgM/IgG)
Congenital:
During pregnancy: US (growth delay, hydrocephalus, calcifications, ascites)
* 18 wk: Fetal blood sample, amniotic fluid sample for PCR
* Newborn: IgM screening”
Treatment:
“Pyrimethamine + Sulfadiazine + Leucovorin (mitigates effects of pyrimethamine)
* Clindamycin (against only tachyzoites, not cysts)
- HIV PPX: TMP-SMX (CD4 = 50-100)
Congenital:
* Spiramycin: reduces transmission by 50%; does NOT tx infected fetus
* Pyrimethamine & Sulfadiazine: 1 yr for infected NB (stops active disease and restores normal functioning)”
CD4 < 100
Cryptosporidium
Features:
“*Low infectious dose
* Long survival in moist environments
Protracted communicability
* Extreme chlorine tolerance”
Location:
Transmission:
“Fecal-oral route: ingestion of oocysts from contaminated drinking water or lakes/water parks, infected animals, raw oysters
OI: HIV w CD4 < 100”
Symptoms:
“ Watery diarrhea within 2 wk of travel that is self-limited
AIDS: prolonged non-bloody diarrhea, abdominal symptoms, poor oral intake, fever, wasting/malabsorption”
Diagnosis:
“Acid fast stain of stool (oocysts)
* Biopsy of sm intestine: cysts on brushborder
ELISA, PCR”
Treatment:
“Supportive
* Nitazoxanide in immunocompetent hosts (inconsistent evidence, but ART should help)
*No PPX for HIV pts”
CD4 < 100
Cystoisoporia (Isospora belli)
Features:
Location:
Transmission:
“*Fecal-oral route: ingestion of oocysts
* Tropical/subtropical areas
* OI: HIV w CD4 < 100”
Symptoms:
AIDS: prolonged non-bloody diarrhea, abdominal symptoms, poor oral intake, fever, wasting/malabsorption
Diagnosis:
“Acid fast stain w stool (oocysts)
ELISA, PCR
* Biopsy of sm intestine”
Treatment:
“ TMP-SMX
*No PPX for HIV pts”
CD4 < 100
Microsporidia
Features:
“* Many species with many presentations
* Smallest one”
Location:
Transmission:
“*Fecal-oral route: ingestion of spores
* OI: HIV w CD4 < 100”
Symptoms:
“Can be systemic or involve eyes, muscles, intestine, biliary tree; chronic diarrhea in immunocompromised (esp AIDS)
AIDS: prolonged non-bloody diarrhea, abdominal symptoms, poor oral intake, fever, wasting/malabsorption”
Diagnosis:
“Modified trichrome stain
*Acid fast stain w stool: oocytes/spores in stool
* ELISA, PCR
* Biopsy of sm intestine”
Treatment:
benzimidazole
*No PPX for HIV pts”
CD4 < 100
“Cryptococcus neoformans
(crypt for cryptococcus)”
Features:
“Urease +
* Capsule w thick proteoglycan capsule (mucicarmine stain)
* Yeast w wide capsular halos on india ink stain
Narrow based, unequal budding”
Location:
Transmission:
“ Inhalation of spores from soil or pigeon droppings
* OI: HIV w CD4 < 100”
Symptoms:
“Early symptoms: cough, chest pain, weight loss, fever, dizziness
* Pneumonia (cough, dyspnea, fever)
*Tropism for CNS: Most common cause of fungal meningoencephalitis (lethal, can cause permanent deficits)
* Skin infections: papule with umbilicated center usually due to disseminated disease (skin biopsy for dx)”
Diagnosis:
“LP: elevated ICP
* CT scan prior (to ruleout any lesions that could precipitate herniation with LP)
*Cryptococcal antigen (specific)
*Low WBC count is a negative prognostic sign
*Elevated protein
*India Ink: visualize capsules as halos
* Culture of CSF
Other tests:
*Latex Agglutination Test: detects repeat polysaccharide capsular antigen & causes agglutination (more sensitive)
* Bronchopulmonary washing
*Tissue sample w mucicarmine (red) or methanamine silver stains
* India Ink Stain: shows yeast with wide capsular halos (less sensitive)
Brain CT: soap bubble lesions in gray matter”
Treatment:
“Induction therapy: Amphotericin + Flucytosine
*Maintenance dose of fluconazole
*Manage high ICP with repeat lumbar punctures to alleviate HA
*No PPX for HIV pts”
CD4 < 100
“CMV
(cyto mega-lo virus)”
Features:
“* dsDNA
* Owl’s eye inclusion bodies
Icosahedral shape”
Location:
Transmission:
“ Binds cellular integrans (heparan sulfate)
*Transmitted via sexual contact, organ transplant, vertically (placenta, TORCHES)
- Primary infection to upper resp & GI tract mucosal surfaces
- Spread during acute phase & in asymptomatic hosts for mo-yrs
* Latent in bone marrow stem cells (B/T lymphocytes & macrophages)
- Blocks MHC-I express –> inhibits CTLs
- Reactivated with immunosuppression
- OI: HIV w CD4 < 50 –> reactivation”
Symptoms:
“Congenital: Greatest risk during 1st trimester - # 1 cause of congenital infection (1-2% infected at birth, 10% infected during birth)*MR DICS - Microcephaly, Retardation, Deaf, Intracranial calcifications, Seizures
*Other symptoms: Jaundice, hepatosplenomegaly, ventriculomegaly (head CT), anemia, pneumonitis - Hydrops fetalis: heart failure –> edema –> spont abortion
- Blueberry muffin rash: thrombocytopenia, petechial rash (similar to rubella)
Immunocompetent hosts: Mononucleosis w sore throat, lymphadenopathy, fatigue (mono spot test = neg, differs from EBV mono)
Immunocompromised hosts: Organ transplant & AIDS pt (CD4 count < 50)
* Interstitial pneumonia: HSCT complication within first 120 days; rapid onset resp symptoms that last < 2 wk, fever, non-productive cough, dyspnea that can progress to hypoxia
*Retinitis: full thickness necrotizing infection that has pizza pie appearance & cotton wool spots on fundoscopy (retinal lesions with intraretinal hemorrhages)
* Esophagitis: Singular/deep linear ulcers (differs from HSV which has multiple shallow ones)
Colitis w ulcerated walls (diarrhea, abdominal pain, fever)
* CNS manifestations: dementia, ventriculoencephalitis, radiculopathy”
Diagnosis:
“Buffy Coat Culture: Tests transplant pts for lg cells w prominent owl’s eye inclusions
*Fundoscopy (retinitis)
* Endoscopy with biopsy: (esophagitis & colitis) large cells w intracellular & intracytoplasmic inclusions
Congenital
* Viral isolation from urine/saliva sample during first 3 wk of life
* PCR on serum, urine or CSF”
Treatment:
“* Ganciclovir (IV): Nucleoside analog that inhibits viral DNA Pol; initial phosphorylation step catalyzed by viral enzyme & final steps by host enzymes; half-life > 24 hr; myelosuppression
*Valganciclovir (PO): Pro-drug of ganciclovir (same MOA & spectrum) but allows for oral dosing; myelosuppression
*Foscarnit in those with resistance to ganciclovir due to mutated UL97 gene (phosphotransferase) & UL54 (viral DNA Pol)
*Prevent interstitial pneumonia in HSCT pts using antivirals 90-120 days post-transplant
*No PPX for HIV pts
Congenital
* Ganciclovir or oral valganciclovir”
CD4 < 50
Mycobacterium avum (MAC, NTB)
Features:
“* Acid fast
*Rod shaped
*Non-motile
catalase +”
Location:
Transmission:
“Inhalation or ingestion
OI: CD4 < 50”
Symptoms:
“ Lung infection similar to TB symptoms
* Insidious onset of fever, weight loss, night sweats, diarrhea (several wks)
Disseminates into bone marrow (anemia, neutropenia, elevated alkaline phosphatase-high turnover of bone marrow) & LNs (lymphadenopathy, hepatosplenomegaly)”
Diagnosis:
“ Blood culture (takes up to 8 wk to grow)
* Biopsy affected organ with culture & pathology”
Treatment:
*2-3 drug combo including at least 1 macrolide (clarithromycin)
CD4 < 50
Mycobacterium tuberculosis
Features:
* Acid fast
Location:
Transmission:
Symptoms:
“Pulmonary TB: cavitary
Miliary TB: hematogenous seeding of lung tissue
- bone marrow/LN: pancytopenia
- brain, bone, peritoneum, pericardium, etc.”
Diagnosis:
Treatment:
Risk with decreased CD4 count
“HSV-1 & HSV-2
(Hermes, the god of herpes)”
Features:
“Herpes Virus Family
* dsDNA, linear
*Enveloped
*Cowdry bodies: Intranuclear eosinophilic inclusion bodies (also in CMV/VZV)
* Tzank smear w multinucleated giant cells (same as VZV)”
Location:
Transmission:
Symptoms:
“Above the waist (1) symptoms vs below the waist (2)
Herpetic whitlow: painful hand vesicle/wart; common in dentists
Genital Herpes:
* Most with HIV-2 have not been diagnosed with genital herpes, but shed virus in genital tract
*HSV-1 increasing in first episodes of anogenital herpes (MSM, young women)
Cervicitis: discharge, intermenstrual bleeding
HIV –> Reactivation of HSV: esophagitis, recurrent mucocutaneous & genital ulcers”
Diagnosis:
“Above the waist (1) symptoms vs below the waist (2)
Herpetic whitlow: painful hand vesicle/wart; common in dentists
Genital Herpes:
* Most with HIV-2 have not been diagnosed with genital herpes, but shed virus in genital tract
HSV-1 increasing in first episodes of anogenital herpes (MSM, young women)
Cervicitis: discharge, intermenstrual bleeding
HIV –> Reactivation of HSV: esophagitis, recurrent mucocutaneous & genital ulcers”
Treatment:
“First episode: Acyclovir, Famcyclovir, or Valacyclovir (10 day course, extend if healing incomplete)
*Recurrent: Higher doses of above antivirals for shorter courses
* Suppressive therapy: reduces frequency of recurrence”
Risk with decreased CD4 count
HSV-1
Features:
* dsDNA, linear
Enveloped
Cowdry bodies: Intranuclear eosinophilic inclusion bodies (also in CMV/VZV)
* Tzank smear w multinucleated giant cells (same as VZV)”
Location:
Transmission: “ Vertical transmission (TORCHES)
Latent in trigeminal ganglia & reactivated by stress/immunosuppression”
Symptoms:
“First sign is gingivostomatitis (inflammed lips/tongue)
* Rash: dew drops on rose petal appearancen on upper body
Erythema multiform: target-shaped rash w pink-red ring around pale center that appears 1-2 wk post-infection
* Serpiginous/dendritic corneal ulcers seen on slit lamp exam of Keratoconjunctivitis (red eyes)
*Temporal lobe encephalitis (#1 cause of sporadic encephalitis in US) –> hemorrhage/necrosis of tissue –> personality changes, hallucinations
* Esophagitis with volcano-like ulcers (immunocompromised)
* Herpes labialis (cold sores) result from reactivation of virus from stress”
Diagnosis:
“ PCR (gold standard)
* Cell culture has low sensitivity that declines as healing occurs
* Cowdry intranuclear inclusion bodies”
Treatment:
“First episode: Acyclovir, Famcyclovir, or Valacyclovir (10 day course, extend if healing incomplete)
*Recurrent: Higher doses of above antivirals for shorter courses
* Suppressive therapy: reduces frequency of recurrence”
Risk with decreased CD4 count
HSV-2
Features:
* dsDNA, linear
Enveloped
Cowdry bodies: Intranuclear eosinophilic inclusion bodies (also in CMV/VZV)
* Tzank smear w multinucleated giant cells (same as VZV)”
Location:
Transmission: Lies dormant in sacral ganglia
Symptoms:” Aseptic meningitis in adolescents/adults
* Painful inguinal lymphadeopathy
Vesicular genital lesions”
Diagnosis: Tzank smear w multinucleated giant cells (old test, now use PCR)
Treatment:
“* NO cure
* Prevent with acyclovir or valcyclovir”
Risk with decreased CD4 count
“EBV
(ye olde epstein bar)”
Features:
“* dsDNA (linear)
* Enveloped
Atypical CTLs (Downey type II): basophilic, vacuolated cytoplasm & lobulated nucleus
* Reed-Sternberg Cells: Hodgkin’s lymphoma; binucleate w prominent nucleoli (owl eyes)”
Location:
Transmission:
“ Mainly saliva transmission
* Virus envelope gp binds CD21 to infect B cells (CD21 is a receptor & binds gp350) –> spread to lymphoid system
* Latent in B cells (episome)
*Incubation period = 30-50 days
* More common in adults/adolescents in developed countries & in kids in developing countries
Compromised hosts include:
*X-linked lymphoproliferative syndrome: genetic inability to mount normal immune response to EBV
*Infection associated Hemophagocytic Syndrome: CTL/NK cells inability to regulate EBV proliferation; hypercytokinemia
*Post transplant Lymphoproliferative Disorder: risk due to immunosuppression highest in first year after
*HIV infection –> Primary CNS Lymphoma: Lethargy, confusion, seizures, constitutional symptoms (dx: imaging, EBV PCR on CSF if possible)”
Symptoms:
“Heterophile-positive Mononucleosis (agglutinates with non-human RBCs)
* Initial symptoms: 3-5 days of headache, malaise & fatigue; fevers (high as 40’C & last 7-14 days)
* Major symptoms: generalized lymphadeopathy, fever, splenomegaly (T cell proliferation), pharyngitis (sore throat) & tonsilar exudate
*Confused w Strep (which is more common in kids); when given amox/ampicillin for suspected strep –> maculopapular rash
* Periorbital edema
Complications:
* Neuro: meningitis, encephalitis, optic neuritis, cranial nerve palsy, myelitis, psychosis
* Heme: hemolytic anemia, thrombocytopenia, aplastic anemia, leukopenia
Associated Conditions:
* Lymphocytic Interstitial Pneumonitis: pulmonary condition that causes chronic wheezing (very rare)
*Non-Hodgkin’s Lymphoma: VERY common
*Oral Hairy Leukoplakia: seen in HIV pts; non-cancerous lesion usually on lateral tongue similar to candida/oral thrush (But CANNOT be scraped off)
* Leiomyosarcoma: soft tissue tumors that can occur anywhere in body (common in those with AIDS)
*Hodgkin’s Lymphoma: Mediastinal mass/non-tender lymphadenopathy
- Reed-Sternberg cell: binucleate B cells w nucleoli (owl eyes)
- mixed cellularity & lymphocyte depleted subtypes
*Endemic/African Burkitt Lymphoma: large jaw lesion & swelling (non-endemic/sporadic form presents w abd mass)
Nasopharyngeal Carcinoma: Asian ancestry”
Diagnosis:
“ Heterophile Ab: IgM Abs produced by B cells that are reactive against sheep, horse RBCs & do NOT react with specific EBV proteins (non-specific); Monospot test
* EBV Viral Capsid Antigen:
- IgM Ab peaks during 2-6 wks & declines 2-3 mo
- IgG Ab perists for life
* Early Antigens (EA): IgG Ab that appears while symptomatic & indicates ACUTE infection
EBV Nuclear Antigen (EBNA): Abs that indicate LATENT infection (maintains virus in episome)
“
Treatment:
“ Heterophile Ab: IgM Abs produced by B cells that are reactive against sheep, horse RBCs & do NOT react with specific EBV proteins (non-specific); Monospot test
* EBV Viral Capsid Antigen:
- IgM Ab peaks during 2-6 wks & declines 2-3 mo
- IgG Ab perists for life
* Early Antigens (EA): IgG Ab that appears while symptomatic & indicates ACUTE infection
*EBV Nuclear Antigen (EBNA): Abs that indicate LATENT infection (maintains virus in episome)
Risk with decreased CD4 count
