HIV opportunistic infections
Why does CD4 count decrease over time in HIV infected persons?
1) HIV causes cytopathologic effects 2) CD8 cells exert cytotoxic effects on infected CD4 cells
MAC treatment
2-3 drug combination Macrolides: clarythromycin Others: rifabutin, ethambutol, quinolones, injectable aminoglycosides
HHV-8 Kaposi's sarcoma associated herpesvirus treatment
ART, chemo
Treatment of OI diarrheal illness
ARTs--> most useful Cystoisospora: TMP-SMX
AIDS
Acquired Immune Deficiency Syndrome- a consequence of untreated late stage HIV infection Defined as: CD4<200
Diarrheal illnesses: Cryptosporidiosis, Microsporidiosis, Cystoisosporiasis
All can cause prolonged non-bloody diarrheal illness, abdominal symptoms, poor oral intake, fever
HHV-8 Kaposi's sarcoma associated herpesvirus
Associated with Kaposi's sarcoma--> vascular malignancy Skin lesions--> violaceous irregular plaques
Other OIs
Bacillary angiomatosis, Reactivation of herpes simplex virus, Reactivation of varicella zoster virus "shingles"
Risk stratification of opportunistic infections
Based on CD4 counts--> most important Based on affected organ(s) Based on exposure (endemic infections, latent infections) Based on class of organism: virus, bacteria, mycobacteria, fungi
At what CD4 count are patients at an increased risk for opportunistic infections?
CD4 count of 200 Stage 3: systemic immunodeficiency
OIs associated with CD4 <50
CMV reactivation Mycobacterium-intracellular complex
CMV diseases
CMV retinitis: infarction and necrosis- patient can't see. CMV esophagitis and colitis: pain swallowing, diarrhea, abdominal pain, fever. Dx by endoscopy CNS disease: ementia, ventriculoencephalitis, radiculopathy
Endemic Mycoses
Caused by Histoplasmosis, coccidioidomycosis
Type of immunity affected by HIV
Cell-mediated
OIs associated with CD4 <250
Coccidioidomycosis- in endemic areas
Prophylaxis for CD4 <200, >100
Cover for PCP TMP-SMX (preferred)-->daily or three times weekly (double strength tablet)
Cryptosporidiosis, Microsporidiosis, Cystoisosporiasis are found...
Cystoisospora-->mostly in tropical and subtropical regions Cryptosporidium--> contaminated water/food, infected animals, and raw oysters Microsporidia--> actually many species
OIs associated with CD4 <150
Disseminated histoplasmosis- in endemic areas
PCP physical exam
Drop in oxygenation on exertion Normal lung exam
OI and malignancy
EBV,HHV-8, HPV, JC virus
PCP symptoms
Fever Nonproductive cough Accelerated dyspnea (shortness of breath) on exertion
Mucocutaneous Candidiasis
HIV patients: tend to cause oropharyngeal and/or esophageal infection
HPV
HIV-infected women have several fold higher risk of cervical cancer than non-infected women
Toxoplasmosis symptoms
Headache, altered mental status, seizures, personality changes, focal neurologic deficits
Histoplasmosis diagnosis
Histoplasma antigen biopsy culture fungal blood culture
CMV treatment
IV gancyclovir Oral valgancyclovir
EBV diagnosis
Imaging, EBV PCR of CSF
Toxoplasmosis diagnosis
Imaging: CT or MRI showing multiple ring enhancing lesions Serology Brain biopsy
EBV
In HIV infected patients, has increased oncogenic potential primary central nervous system (CNS) lymphoma
MAC clinical presentation
Insidious onset of fever, weight loss, night sweats, diarrhea Several weeks of symptoms Predominantly affects bone marrow and lymph nodes: enlarged lymph nodes, enlarged spleen/liver Anemia, neutropenia, elevated alkaline phosphatase
Cryptococcal diagnosis
LP: elevated intracranial pressure (>20), cryptococcal antigen, cell counts NOT elevated, elevated protein, india ink showing yeast capsules Skin infection: skin biopsy
Mycobacterium Tuberculosis infection
Lungs
PCP site of infection
Lungs. Causes intense inflammatory reaction in alveoli-->interstitial pneumonitis Alveoli fill with frothy honey combed material
Secondary prophylaxis
Maintaining patients with prior infection on medication. Can stop if CD4 count is above threshold for 6 mons
AIDS defining illnesses
Most are caused by infectious agents EXCEPT dementia, wasting, and lymphoma
Pneumocystis jiroveci Pneumonia (PCP)
Most common OI in HIV patients
Mycobacterium Tuberculosis
Most common in developing countries
MAC diagnosis
Mycobacterial blood culture (BACTEC)- takes 8 weeks Biopsy of affected organ- usual sites include lymph node, bone marrow. Culture, and pathology
Do opportunistic infections occur in people with normally functioning immune systems?
No
Cryptococcal infection
Occurs mostly in CNS Also causes skin infections- papule with umbilicated center from disseminated infection, pneumonia, skeletal system
OIs associated with CD4 <200
Pneumocystis jiroveci pneumonia (PCP)- most common OI seen in AIDS patients
Mucocutaneous Candidiasis treatment
Preferred: fluconazole oropharyngeal disease: clotrimazole troches, nystatin suspension Resistant infections: echinocandins, amphotericin
Toxoplasmosis
Presents as reactivation of prior infection in HIV patients- in CNS
EBV presentation
Presents with CNS symptoms (lethargy, confusion, seizures) and constitutional symptoms
JC virus
Progressive multifocal leukoencephalopathy
Mycobacterium Tuberculosis presentation
Pulmonary disease-->cavitary "miliary" tuberculosis-->hematogenous seeding of lung tissue. small micro nodules Bone marrow and lymph nodes-->can see pancytopenia Brain, bone, peritoneum, etc.
Role of CD4 cells normally
Release cytokines to activated other members of cell mediated immunity: CD8, macrophages
Route of MAC infection
Route of infection: inhalation, ingestion, inoculation ubiquitous in nature
When to start prophylaxis?
Start OI prophylaxis when CD4 <200
Diagnosis of OI diarrheal illness
Stool studies: ova and parasite. Acid fast stain showing: cryptosporidium: 5-7 μm, cystoisospora: 25 μm, microsporidia species: 1- 2μm ELISA, PCR Biopsy of small intestine
Why do we need to do a CT scan prior to an LP in HIV patients?
There is a risk of brain hernation. OIs can lead to mass lesions in the brain. Any change in pressure can cause brain herniation. LPs cause a change in pressure.
Mucocutaneous Candidiasis clinical presentation
Thrush: painless, creamy white plaques/patches on mucosa (buccal, tongue, palate) Esophageal odynophagia, retrosternal pain
OIs associated with CD4 <100
Toxoplasmosis-central nervous system Cryptococcosis (usually CD4<50) Diarrheal illness caused by cystoisosporiasis, cryptosporidiosis, microsporidiosis
Mycobacterium avium complex (MAC)
Usually presents as disseminated infection
Cryptococcal treatment
amphotericin B PLUS flucytosine monitor creatinine plenty of fluid hydration with each daily dose Maintenance: Fluconazole 400 mg daily LP: can releave headache
PCP x-ray
bilateral (usually) reticular/interstitial infiltrate
PCP diagnosis
bronchoalveolar lavage (camera) Gomori methamine silver stain Induced sputum: less invasive, but lower sensitivity Lactate dehydrogenase (LDH): usually elevated, but is not specific
Prophylaxis for CD4 <50
cover for MAC AND Toxo AND PCP TMP-SMX DS daily or thrice weekly Azithromycin 1200 mg once weekly
Prophylaxis for CD4 <100, >50
cover for Toxoplasmosis AND PCP TMP-SMX DS daily or thrice weekly—preferred
Prophylaxis not needed for
cryptococcus, candida, CMV, cryptosporidium, cystoisospora, microspora
Histoplasmosis presentation
fever, weight loss, fatigue, night sweats, enlarged lymph nodes, liver, spleen Infection in lungs: shortness of breath, cough
Coccidioidomycosis presentation
focal or diffuse pneumonia, skin lesions, meningitis, liver and lymph node involvement
PCP therapy
high dose TMP-SMX (15-20 mg/kg in divided doses daily) If there is severe O2 impairment, administer steroids
Prophylaxis should be considered for
histoplasmosis, coccidioidomycosis
Loss of CD4 cells causes...
increased risk of infection by organism that is unchecked by cell mediated immunity, especially intracellular organisms.
Opportunistic infection
infection that occurs in person with an impairment in their immune system (i.e. immunosuppression)
Stop prophylaxis if...
patient is on ART and CD4 count rises above threshold for organsism
Toxoplasmosis treatment
pyrimethamine PLUS sulfadiazine PLUS leucovorin
CMV
reflects reactivation of prior infection
Cryptococcal symptoms
subacute meningoencephalitis without classic signs Encephalitis gradually worsening headache fever, malaise
Type of opportunistic infection acquired depends on...
the part of the immune system that is impaired
Coccidioidomycosis diagnosis
ulture from clinical specimens, histopathology on tissue specimens, blood cultures (low yield), and serology (IgM, IgG)
