Lecture 8: Immunocompromised Flashcards
Cryptococcus neoformans
4 serotypes
– serotypes 1 and 4 named Cryptococcus neoformans variety grubii and variety neoformans respectively.
– Serotypes 2 and 3 form a new species Cryptococcus gattii
Cryptococcal meningoencephalitis: HIV patients
- Rarely occurs with CD4>100
- Indolent onset usually over a period of one to two weeks
Dx
- Definition: >20 cm CSF opening pressure
- Common
- – recent case series showed 2/3 of pts have opening pressure >20 – 1/4 of pts have pressure >35
- Unclear mechanism - ? Crowding of arachnoid villi with fungal antigen
Management
- Wait at least 5 wk before starting CART in Pt with HIV and C. neoformans co-infection
- If persistently elevated pressures in spite of serial LPs after 4 weeks of Rx consider shunt
Pneumocystis jirovecii
Etiopath
- CD4 lymphocyte depletion increases risk of PCP (<200/cubic millimeter)
- Act to orchestrate host’s inflammatory response
- Produce cytokine mediators
- Aid in clearance of Pneumocystis
- Inflammatory responses (cytokines and chemokines) do most of the damage to the alveolar epithelial cells.
- Surfactant D causes aggregation and decreased macrophage uptake
- Macrophages uptake and degrade organisms. Function decreased in HIV and malignant disease.
- Sustained propagation outside host lung not possible.
- Infected animal model is the only source for organisms to date for study.
- Alveolar pathogen that doesn’t invade host unless severe underlying immunosuppression or overwhelming infection. (Severe CD4 depletion AIDS)
- Surface glycoprotein A
- Immunologically and antigenically distinct. Contains beta-1,3-glucan (fungal cell wall component)
- Responsible for marked inflammatory response in the lungs of the host
- Trophic forms adhere to alveolar epithelium and signal mating and proliferation in fungal organisms.
- Severe Pneumocystis pneumonia associated with neutrophilic lung inflammation leading to diffuse alveolar damage, impaired gas exchange, and respiratory failure.
- Degree of lung inflammation more associated with risk of death than organism burden.
- Neutropenic patients occasionally get PCP but are not inordinately predisposed as compared to other groups of immunosuppressed patients.
Sx
– Subtle onset increased dyspnea
– Nonproductive cough
– Low grade fever
– Physical exam tachypnea, tachycardia, normal lungs on auscultation.
– More organisms, fewer neutrophils, higher diagnostic yield on bronchoscopy and induced sputum than non HIV patients.
– Mortality rate 10-20% but increases if intubation required.
– Abrupt onset respiratory insufficiency associated with taper of immunosuppressant.
– Likely related to immune reconstitution – More neutrophils and fewer organisms. – Higher mortality rates 30 -60%.
Candida
- Superficial (mucosal as opposed to skin for S. aureus) and invasive infection
- Local infection: vulvovaginal, oropharyngitis,, eosophagitis,
- Focal invasive infection secondary to medical devices (Central line catheters, prosthetic valves, Central Nervous System shunts)
- Febrile neutropenic: disseminated disease
- Community versus nosocomial infections may affect species
Risk for Invasive Disease (Candidemia)
- – Immunosuppressed
- Hematologic malignancy: Neutropenic, central lines, mucosal damage
- from chemotherapy, glucocorticoids, broad spectrum antibiotics
- Stem cell or solid organ transplants
- – ICU patients
- TPN
- Anastamotic leak GI tract
- Central lines
- GI tract surgery
- Renal failure especially dialysis
Presentation
- Fever to full blown sepsis syndrome
- Multi-organ failure from microabscesses
Candidemia: Management
- +ve blood cultures. Never assume contaminant
- Pull central line if line culture positive
- Get endophthalmoscopy (if positive effects duration of therapy); indicator for longest duration of rx
- Search for disseminated foci
- Candida endocarditis is an indication for surgery
- Duration of therapy for line related infection 2 weeks after 1st
- negative blood culture. Do daily blood cultures to determine
- Treat for minimum 6 weeks for endophthalmitis. Ophthalmologist must be involved for possible surgery and diagnosis
- Mortalityhigherwithdelayedinitiationoftherapyandretained infected catheter (up to 41% mortality if untreated by day 3 fungemia)
Infections in the Immunocompromised Host: Aspergillus infections
- Allergic Bronchopulmonary Aspergillosis
- Aspergilloma
- Invasive Aspergillosis
- Pulmonary aspergillosis
- Chronic Invasive Aspergillosis
- Disseminated Aspergillosis
- Sinus infection and associated structures
- Tracheobronchitis
- Cutaneous, cardiac, bone and joint, gastrointestinal, eye
- Occurs in the setting of severe immunosuppression
Prolonged neutropenia
Hematopoietic stem cell transplant
Advanced AIDS (CD4 < 50)
Etiopath
- Alveolar macrophages provide first line of defense against fungal conidia
- Ineffective if large inoculum or insufficient or poorly functioning macrophages (e.g. Post chemo)
- Fungal metabolic products and mycotoxins evade or inhibit host defense
- Invasion across tissue planes including walls of vessels
- Ischaemia and infarction of structures distal to invaded arteries
Dx
- Obtaining tissue may be a problem in the most at risk patient e.g. Pancytopenic AML patient
- BAL with + culture enough to initiate therapy
- Galactomannan assay
– Major constituent Aspergillus cell wall
– Released during growth phase
– Serum levels can be tested by ELISA
– Assay only validated for serum
Pulmonary Aspergillosis Risk Factors
- Prolonged and Severe Neutropenia
- Glucocorticoid Therapy
- Hematopoietic Stem Cell Transplant
- Early < 40 days associated with advanced age and HLA mismatch
- Late associated with CMV disease and Graft Versus Host Disease (GVHD)
- Solid Organ Transplant
- Advanced AIDS
- Chronic Granulomatous Disease
Sx
- Persistent fever in presence of antibacterial therapy in neutropenic patient
- Chest pain, cough, hemoptysis may occur
- Nodular, patchy or cavitary infiltrates. CT scan more sensitive. May show halo sign around nodule (Hemorrhage into tissue around infection)
- May worsen with recovery of neutrophil count
- Can disseminate to kidney, liver, spleen or CNS
Aspergillosis of Sinuses and Associated Structures
- May present like zygomycosis or mucormycosis (usually in diabetics) involving sinuses
- Nasal congestion, fever, facial pain including around eyes
- May extend to orbit then cavernous sinus with decreased LOC and cranial nerve abnormalities
Invasive Aspergillosis: Management
- Primary therapy: Voriconazole and amphotericin B deoxycholate (D-AMB)
- Salvage therapy: Lipid formulations of D-AMB, itraconazole, caspofungin
- Prophylaxis in Neutropenic patients with leukemia and myelodysplasia and allogeneic HSCT with GVHD: posaconazole
CMV
Most commonly occurs as CMV retinitis.
– Can be in GI tract (eosphagitis, colitis) or blood (viremia)
– Usually presents with CD4 less than 50. Has associated CMV viremia
– Presents with loss central vision, floaters, blind spots
– Diagnosed by ophthamologic exam (PCP, Cryptococcus and Syphilis in differential)
– Can get CMV immune recovery uveitis in patients on CART with good response
HSV
Eosophagitis is common presentation in solid organ and bone marrow recipients
– Dysphagia, odynophagia
– Often have coexistent herpes labialis or oropharyngeal lesions
– Diagnosis by histology or culture of brushings of edge of ulcer taken at endoscopy
– Responds well to IV acyclovir
