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18 Cards in this Set
- Front
- Back
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General Principles of Viral Infection
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Obligate intracellular organisms
Utilize host cell machinery to replicate Tropism for specific cell type(s) Therapeutic window typically small Latency/chronic infection frequently part of the natural history of infection |
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Aplastic Crises in Patients with Chronic Hemolytic Anemia Historical Context
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Occurred only once in a lifetime
Could be life threatening, profound anemia Transfusions life saving and patients spontaneously recovered Often preceded by a nonspecific ‘viral’ illness Appeared to be outbreaks and even transmission to ‘roommates’ in the hospital |
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Parvovirus B-19
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DNA virus, discovered in 1974, but only associated with disease in the early 1980’s
Now clearly shown to be the causative agent of: hydrops fetalis erythema infectiosum (fifth disease) aplastic crises in hemolytic subjects seronegative RA syndrome chronic anemia in immunocompromised hosts |
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Parvovirus B-19 Epidemiology
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about half of all adults are antibody positive
prevalence rises rapidly during school years 20-60% of children in an outbreak situation will be symptomatic virus shed in respiratory secretions -patients with aplastic crisis and virtually no transmission once symptomatic (Erythema infectiosum) |
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Parvovirus B-19 Pathogenesis
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Infects erythroid progenitor cells
-thus marked anemia out of proportion to reductions in other cell lines w/infection Acute infection causes mild illness in most immunocompetent children (Erythema infectiosum) -onset of rash about the time of seroconversion -fever, myalgias, HA precede rash by a few days -No/little anemia due to RBC life span of 120 days |
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Parvovirus B-19 Additional Clinical Syndromes
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Arthropathy - mimics acute onset of RA, but seronegative; occurs with acute infection in ~60% of adults, but only 10% of children, women > > men
Aplastic crisis: due to high reticulocyte counts in chronic hemolytic anemias Chronic anemia due to inadequate immune response (Dx requires PCR, no Ab detectable); primarily seen in advanced HIV |
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Epstein-Barr Virus Antibody Studies
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IgM is present in the first 4-8 wks
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Cold vs warm hemolytic anemia
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cold IgM
warm IgG |
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Viral Causes of Pneumonia in Immunocompromised Hosts
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Cytomegalovirus:
particularly in allogeneic BMT patients Varicella Zoster or Herpes simplex: usually as part of dissemination Community acquired: Respiratory Syncytial Virus (RSV) Influenza Parainfluenza |
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Allogeneic BMT Patients vs. Chemotherapy Alone
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Allogeneic BMT patients very similar to leukemic patients early
bacteria, fungi if prolonged (> 2 weeks of neutropenia) After day +30, primary defect is T cell deficit CMV, Fungi, PCP, Idiopathic pneumonitis |
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Non-infectious Causes of Fever and Pulmonary Infiltrates in Immunocompromised Hosts
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Idiopathic pneumonia
ARDS Alveolar Hemorrhage Leukemic Infiltration Lymphoma Pulmonary Emboli Aspiration Drug Induced Lung Injury bleomycin cyclophosphamide busulfan ifosfamide methotrexate BCNU doxorubicin |
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Risk Factors of CMV in BMT Recipients
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Seropositive status (donor or recipient)
older age conditioning regimens with agents other than cyclophosphamide GvHD!!!!!!! |
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CMV Pneumonia
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Diagnosis is usually clinical, but BAL cytology and culture helpful
Very often found in presence of another pathogen CMV immunosuppressive in and of itself fungi (including PCP) and Pseudomonas most common |
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Therapy of CMV Disease
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IV GCV 5 mg/kg q 12h (dose adjusted for renal failure) is cornerstone
-duration unclear; personal style - - -> bid x 14 d, then qd x7d, then off -Can substitute valganciclovir 900 mg po bid as equivalent if tolerating/absorbing po meds Foscarnet for salvage/intolerance unclear if CMV Ig has any role in SOT, perhaps in unresponsive disease, but Either CMV Ig or IVIg is absolutely necessary for treatment in HSCT recipients |
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Treatment/Prophylaxis of CMV After Bone Marrow Transplantation
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MUST use combined therapy for 14-21 days to treat pneumonia
GCV 5 mg/kg q12h + IVIG 500 mg/kg qod Targeted prophylaxis strategies decrease CMV, but ? overall effect on survival -GCV if blood or BAL culture (+) at day 35 improves survival -survival benefit may be lost if prophylaxis given to all CMV (+) recipients -PCR/Antigenemia-guided |
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Two Major Strategies to Reduce the Risk of CMV Disease
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Prophylaxis
-anti-CMV therapy when either donor or recipient is CMV seropositive -easier to write into a protocol -no need for surveillance -may expose many to risks of drug for benefit of a few Preemptive Therapy -more targeted therapy for brief periods given with: ---‘induction’ therapy ---ALA therapy ---defined lab evidence of infection -fewer patients exposed -may improve reconstitution of immunity -requires sensitive and predictive lab tests |
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Therapies used for Prophylaxis and Preemptive Therapy
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Prophylaxis
-IV ganciclovir -PO valganciclovir -High dose (1 gm tid-2gms qid) valacyclovir ---Most of the data with this agent were generated with the surrogate endpoint of CMV reactivation, not the more definitive endpoint of preventing CMV disease Preemptive Therapy -IV GCV (5 mg/kg bid for 7-14 days or until PCR (-)) -? Need for suppression thereafter -Can probably substitute po VGCV for IV GCV |
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Bottom Line of Prophylaxis vs. Pre-emptive Therapy
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Prophylaxis
Avoids the issue of those that present with disease rather than shedding first Doesn’t require intensive diagnostic monitoring Exposes the greatest number of patients to drug (side effects?) May reduce reconstitution of immunity vs. CMV Risk of drug resistant virus? Pre-emptive Risk of disease before shedding is caught Requires intensive diagnostic monitoring Exposes less patients to drug (side effects?) Allows re-exposure of the virus to immune system to facilitate reconstitution Risk of drug resistance? |
