HIV opportunistic infections

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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)


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