Infections Associated With Immunosuppression
For immunosuppressive disorders, immunosuppressive drugs, and AIDS patients.
Infection Risk by CD4 Count
CD4 >500 (or >32%): Acute Retroviral Syndrome, Pulmonary Tuberculosis
CD4 <500: Bacterial Pneumonia, Pulmonary Tuberculosis, Zoster, Thrush, Kaposi’s
Sarcoma (KS), Candida vaginitis.
CD4 <200 (or <14%): PCP, Histoplasmosis, Tuberculosis (extrapulmonary)
CD4 <100: Recurrent HSV, Toxoplasmosis, Cryptococcosis, Candida esophagitis, Progressive Multifocal Leukoencephalopathy (PML)
CD4 <50: Cytomegalovirus, Mycobacterium avium complex
At <200, body no longer has adequate protection against opportunistic infection (OI).
Pneumocystis carinii Pneumonia (PCP)
The most common OI in patients with HIV. Caused by P. jiroveci.
Clinical manifestations
Interstitial pneumonitis. Gradual onset (5-14 days) of fever, nonproductive cough and dyspnea
(shortness of breath).
Diagnosis
The causative fungus can’t be cultured. Requires induced sputum, bronchoscopy with bronchoalveolar lavage, or transbronchial biopsy.
Treatment
SMX-TMP and adjunct corticosteroids.
Prophylaxis
Same as treatment. Use when CD4 <200 or a history of oropharyngeal candidiasis infection. Stop when on ART and CD4 >200 for 3-months.
Toxoplasma Gondi Encephalitis
Latent bacterial cysts can stay inactive in body and will reactivate once CD4 count drops. Caused by Toxoplasma gondii (protozoan parasite). Risk factors include eating contaminated meats and cat feces exposure.
In AIDs patient it reactivates in the brain. For cardiac transplant patients, it reactivates in the heart.
Clinical manifestations
Focal encephalitis with headache, confusion, motor weakness and fever. Neurological abnormalities can progress to altered mental status, coma, seizures without treatment.
Treatment
Pyrimethamine + Sulfadiazine + Leucovorin for at least 6 weeks.
Prophylaxis
Same as treatment if CD4 <200. Additionally, SMX-TMP if CD4 <100.
Progressive Multi-Focal Leukoencephalopathy
Characterized by focal demyelination of the white matter creating diffuse lesions in the brain. Caused by Human polyomavirus 2 (JC virus).
Immunosuppressive treatments like natalizumab, infliximab, and rituximab have been recognized as risk factors.
Clinical manifestations
Gradual onset and progression of neurological deficits. Location of lesion varies and so signs vary and can include speech difficulties and muscle weakness in one limb (which can evolve to hemiparesis).
Diagnosis
Clinical presentation, neurological imaging (MRI - typically white matter lesion), and lumbar puncture to test cerebral spinal fluid for JC.
Treatment
Antiviral therapy can be started to reverse immunosuppression. Otherwise, no treatment.
Cryptococcal Meningitis
Caused by Cryptococcus neoformans and gatii.
C. neoformans is a fungus found worldwide, typically found in the soil, decaying wood and in bird droppings. It is transmitted via inhalation.
Clinical manifestations
Subacute meningitis or meningoencephalitis: fever, malaise, headache, typical meningeal symptoms (neck stiffness and photophobia), encephalopathic symptoms (lethargy, altered mental status).
Disseminated disease: Any organ can be involved. Typically disseminated in patients with HIV.
Diagnosis
Lumbar Puncture. Blood and CSF cultures with India ink staining. Expect mildly elevated protein levels, low/normal glucose concentrations, pleocytosis consisting mostly of lymphocytes, many yeast.
Can also use Cryptococcal antigen detection.
Treatment
Amphotericin B + Flucytosine. Maintenance includes Fluconazole.
Cytomegalovirus (CMV) Retinitis
Caused by cytomegalovirus. Localized end organ disease.
Risk factor for patients with CD4 <50 or a previous CMV infection.
Clinical manifestations
Will progress to bilateral in most patients without therapy. May be asymptomatic or present with visual field defects and decreased acuity.
Diagnosis
The virus will cause necrosis creating a red tinged cottage cheese appearance. Can also do PCR detection of CMV DNA in vitreous/aqueous humor.
Treatment
Ganciclovir. May also consider Foscarnet or Cidofovir.
Mycobacterium Avium Complex Infection
Caused by atypical nontuberculous mycobacterium. Most commonly transmitted via ingestion and affects GI tract.
CD4 <50 is a risk factor.
Clinical manifestations
Fever, night sweats, unintentional weight loss, fatigue, weakness, rigors, abdominal pain, chronic diarrhea.
Diagnosis
Combination of clinical presentation and identification of virus in tissue. Can use Acid Fast Bacillus (AFB) of blood cultures or tissue.
Expect leukopenia, anemia, and elevated alkaline phosphatase.
Treatment
Should be about 12 months and should consist of at least 2 effective drugs.
Primary: Clarithromycin + Ethambutol
Alternative: Azithromycin + Ethambutol