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10-28-c: Immune deficiencies
- Saying someone is immunocompromised does not really help, you need to know the type of deficit!:
- Each type of immune deficiency is associated with a special set of organisms that are dependent on the corresponding branch of the immune system for eradication of the organisms
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Immune defects
- Cell-mediated immunity:
- Humoral Immunity:
- Innate immunity: neutrophils, complement, antimicrobial peptides
- (skin, mucosal epithelium)
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Defective cell-mediated immunity
- AIDS:
- Many types of lymphomas and transplant patients suffer from defects in cell-mediated immunity:
- Organ transplant recepients, patients on corticosteroid therapy: and lymphomas are at high risk for these infections
- Severity and the rapidity of the presentations may differ
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Transplant patients and T-cell immunity
- Type of transplant: (renal, cardiac, lung, liver, and bone marrow) and
- The type and frequency of these infections varies with the type of transplant:
- Different immunosuppressive regimens will give different responses
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T-Cell pathogens
- Common pathogens include
- Listeria:
- Salmonella:
- M. tuberculosis:
- Nocardia:
- Cryptococcus, histoplasmosis, coccidiomycosis, and
- Pneumocystitis: poster child for immune-mediated immune responses
- Cytomegalovirus and varicella-zoster virus: can also get reactivation
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HIV
- Not all HIV patients have the same risk of infection
- CD4 > 200 S. Pneumoniae, H. influenzae, M. Tuberculosis, S. aureus (IDU), Influenza:
- CD4 count 50-200 Above + P. jiroveci, Cryptococcus, histoplasmosis, coccidioidomycosis, nocardia, M. kansasii, Kaposi’s sarcoma:
- CD4 count <50 Above + P. aeruginosa, aspergillus, MAC, CMV:
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Pneumocystis jiroveci (pneumocystis carinii)
- Opportunistic pathogen:
- Compromised host:
- T-cell immune defect: Pneumocystis jiroveci (pneumocystis carinii)
- Originally classified as a protozoan, molecular studies clearly place it as a fungus:
- Cell wall lacks eldosterol
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Pathogenesis Pneumocystis jiroveci (pneumocystis carinii)
- High risk HIV: central role for the CD4 cell, dormant for years
- Immunosuppressive therapy:glucocorticoids:
- Organ transplantation:
- Children with primary immunodeficiency
- Premature malnourished infants
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Clinical Features Pneumocystis jiroveci (pneumocystis carinii)
- Dyspnea:
- Fever:
- Nonproductive cough:
- In non-HIV associated changes in the glucocorticoid dose
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Dx - Pneumocystis jiroveci (pneumocystis carinii)
- Tachypnea, tachycardia, and hypoxia are prominent: like regular bacterial pneumonia
- Chest examination: is frequently normal but no rales.
- ABG’s show hypoxia ans respiratory alkalosis
- LDH values are frequently elevated in HIV infected individuals: NON-SPECIFIC, NOT A SENSITIVE INDICATOR
- Disease progression in HIV is generally slower than in other forms of immunosupression
- Organisms can be seen on silver stain, but..
- ***FLUORESCENT MONOCLONAL ANTIBORY IS MUCH MORE SENSITIVE:
- Sputum for DFA is the best diagnostic choice: can also be done on lung tissue
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Chest X-Ray
- Diffuse bilateral infiltrates in the perihilar region: classic look of pneumocystis
- Other findings may be seen and failure to see a classic CXR does not rule out the disease
- Patients with HIV increased pneumothorax
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Therapy Pneumocystis jiroveci (pneumocystis carinii)
- Trimethoprim-sulfamethoxazole: first drug of choice, second line
- Second line clindamycin/primaquin, atovaquone, dapsone/primaquin, pentamidine, trimetrexate
- Patients with HIV frequently develop worsening of their symptoms on initiation of antibiotic therapy:
- PAO2 of 70 mmHg or an A-a gradient of 35 mmHg benefit from corticosteroids within 72 hours!: IN PATIENTS WITH SEVERE DISEASE, GIVING STEROIDS MAY HELP WITH THE COMPLICATIONS OF TREATMENT
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Prophylaxis for Pneumocystis jiroveci (pneumocystis carinii)
- Primary prophylaxis: prevention of 1st episode; in HIV and patients at known high risk – use cut-off of 200 to decide who’s at high risk
- Secondary prophylaxis is indicated ifor HIV – prior history of PCJ
- Regimens: TMP/SMX preferred: dapsone or dapsone pyrimethamine
- Inhaled pentamidine:
- Or atovaquinone are alternatives
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Nocardia
- Higher bacteria, somewhat intermediate between bacteria and fungi
- Microbiology: worldwide in soil
- Epidemiology: e.g. 53 y o patient with a non-Hodgkins lymphoma, think T- cell mediated disease
- Risk is associated with deficient cell-mediated immunity – AIDS, lymphoma, transplantation
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Clinical manifestations of Nocardia
- Nocardia may spread locally in the chest cavity to adjacent structures but has a predilection for extrapulmonary spread to the brain.
- Pulmonary and CNS disease in a patient with deficient T-cell immunity should raise the suspicion of Nocardia!!: when see lung and brain involvement, and T-cell mediated immunity deficiency, think Nocardia!!
- Transcutaneous inoculation leads to a cutaneous form of Nocardia
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Dx of Nocardia
- The lab should be alerted
- Organism may take more time to grow and may be difficult to differentiate
- Branching Gram-positive hyphae that is acid-fast on a MODIFIED acid-fast stain!!!: if on exam, think Nocardia!
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Treatment
- Sulfonamides:
- Minocycline, imipenem others second choice
- Patients with pulmonary disease and impaired T-cell immunity should probably have a CT or MRI to inverstigate the CNS as dissemination is common:!! Look for it
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***Humoral Immune Deficiency:
- Severe hypogammaglobulinemia(unable to produce antibodies): encapsulated bacteria – streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningititus
- Asplenia: (can’t remove Ab labeled cells) encapsulated bacteria - Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningititus
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Innate Immune Deficiency: Neutrophils Deficiency
- Seen mainly in pts with cancer chemotherapy
- Severe neutropenia, early: gram-negative rods
- Pseudomonas aeruginosa, Enterobacteraceae, Staphylococcus aureus, esp with catheters, Aspergillus
- Severe neutropenia, Late: think Fungi
- Aspergillus, Mucomycosis – because have been treated with many antibiotics by this point
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Severe Neutropenia
- Gram-negative pathogens, including Pseudomonas aeruginosa are common
- Classic skin manifestation – ecthyma gangrenosum
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Neutrophil deficiency
- Infections may rapidly progress and rapid institution of appropriate antibiotic therapy is essential in preventing overwhelming sepsis in the absence of the primary pagocytic cell line: risk of death is very high, so give antibiotics, which should cover pseudomonas
- A recent increase in gram positive infections has been associated with highly active gram-negative therapy and IV acess lines
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Fever with no white cells = antibiotics
But the antibiotics have to cover pseudomonas
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Severe Neutropenia
- White candida is a common pathogen outside of the pulmonary tract, it is an uncommon agent of pneumonia:
- Bone marrow translplants have a high degree of marro suppression and are at risk for many opportunist pathogens with a wide variety of clinical syndromes:
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Neutrophil defects:
- Chronic granulomatous disease: STAPH AUREUS, Aspergillus, Nocardia, Gram-negative rods, and other catalase-positive bacteria
- Other neutrophil defects – diabetes?
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Complement deficiencies
Terminal complement deficiencies (C6-C9) high frequency of Neisserial infections, especially Neisseria meningitides
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