1. 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
  2. Immune defects
    • Cell-mediated immunity:
    • Humoral Immunity:
    • Innate immunity: neutrophils, complement, antimicrobial peptides
    • (skin, mucosal epithelium)
  3. 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
  4. 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
  5. 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
  6. 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:
  7. 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
  8. 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
  9. Clinical Features Pneumocystis jiroveci (pneumocystis carinii)
    • Dyspnea:
    • Fever:
    • Nonproductive cough:
    • In non-HIV associated changes in the glucocorticoid dose
  10. 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..
    • Sputum for DFA is the best diagnostic choice: can also be done on lung tissue
  11. 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
  12. 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
  13. 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
  14. 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
  15. 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
  16. 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!
  17. 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
  18. ***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
  19. 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
  20. Severe Neutropenia
    • Gram-negative pathogens, including Pseudomonas aeruginosa are common
    • Classic skin manifestation – ecthyma gangrenosum
  21. 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
  22. Fever with no white cells = antibiotics
    But the antibiotics have to cover pseudomonas
  23. 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:
  24. Neutrophil defects:
    • Chronic granulomatous disease: STAPH AUREUS, Aspergillus, Nocardia, Gram-negative rods, and other catalase-positive bacteria
    • Other neutrophil defects – diabetes?
  25. Complement deficiencies
    Terminal complement deficiencies (C6-C9) high frequency of Neisserial infections, especially Neisseria meningitides
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