Tuesday, August 30, 2011

Hospital Acquired Infections and Hematological Malignancies

Patients with hematological malignancies are high risk group for nosocomial infections because of many factors as impaired immunity, high parenteral exposure, and administration of cytotoxic chemotherapy or receiving bone marrow transplantation. They are vulnerable to infections including viruses, mainly herpes viruses and respiratory viruses (Pizzo, 2007).
Viral infections are important causes of morbidity and mortality for patients with hematological malignancies. However the true incidence and consequences of viral Infections for these patients who undergo conventional nontransplant therapy are poorly defined. Differences in incidence and outcome of viral infections among these patient groups are based on intensity and duration of T-cell-mediated immune suppression (Wade, 2006).
Respiratory Viruses:
Respiratory viruses, including RSV, PIV and influenza virus, are wide spread in the community and easily transmitted to patients with hematological malignancy (England, 2001).
Infection control measures are critical and should consist of hand washing, annual influenza vaccination, early detection for infection and both respiratory and contact isolation of infection health care workers and patients. Patients, who develop respiratory virus infection prior to the initiation of treatment or transplantation, should if possible, have their therapy delayed. Respiratory virus infection among patients with hematological malignancy are associated with a more prolonged infection, higher frequency of nosocomial infection (55-83 % of exposed immunocompromized patients will become infected), a higher rate of pneumonia, co-pathogens and death. The risk of death from pneumonia has ranged from 9% to 82%, and appears to vary little between the different groups of patients with active hematological malignancy (Peck et al., 2004).
Other Viral Infections
• Adenovirus:
Primary infection is acquired from either a respiratory droplet or oral-fecal route. Most infection among compromised hosts is postulated to be viral reactivation (Kojaoghlanian et al., 2003). Clinical manifestations vary with serotype and include viremia, pneumonia, hepatitis, gastrointestinal disease, cystitis, nephritis and conjunctivitis (Bruno et al., 2004). Control of adenovirus appears T-cell mediated, and allogenic SCT recipients appear to be at greatest risk of infection and disease. However fatal adenovirus infections have been reported in patients with B-cell lymphoma, multiple myeloma and AML (Fianchi et al., 2003).
Risk factors for infection and disease include unrelated donor transplantation, GVHD, T-cell depletion, younger patient age, total body irradiation, and viremia. The incidence of infection in SCT recipients has been reported to range from 5-29% with disease occurring in 5-8% of patients. Death secondary to adenovirus disease range from 30-50% (Lion et al., 2003).
Severe disseminated disease can develop following BMT. Typical presentations in immunocompromised include pneumonitis, enterocolitis, hemorrhagic cystitis, hepatitis, encephalitis, and disseminated disease. In one study, 46% of BMT patients with adenovirus infections died; seven patients with pneumonia and six with disseminated disease (Slatter et al., 2005).
• Human Metapneumovirus ( hMPV ):
hMPV is newly discovered RNA Paramyxovirus. Most children by age 5 years are seropositive. Infection occurs primarily during winter and manifests as both upper and lower respiratory tract disease (Williams et al., 2004).
More serious disease has been reported among immunosuppressed patients. It could be an important cause of idiopathic pneumonia syndrome after SCT; Five out of 200 tested patients had hMPV detected in archived bronchial alveolar lavage specimens. All 5 positive patients had upper respiratory tract prodromes that preceded their pneumonia, and 4 of 5 patients died. Lung tissue of the died patients had histologic picture of idiopathic pneumonia syndrome at autopsy. Prospective studies of the role of hMPV as a cause of infection for patients with hematological malignancy are needed. There is no established treatment for hMPV infections although Ribavirin appears to have antiviral activity (Englund, 2001).
Herpes simplex virus:
HSV infections in patients with hematological malignancy are almost exclusively reactivation Infections (Lungman, 2004). They are common, ranging from 15% among chronic leukemia patients treated with Fludarabine, to 90% of patients with acute leukemia or stem cell transplant recipients. HSV infections and disease occur early after therapy, and frequently recur with future treatment. Mucocutaneous HSV disease will frequently present with an atypical appearance and can mimic other pathogens (i.e., Candida) or treatment induced mucositis. HSV infections among immunocompromised patients are characteristically more invasive, heal more slowly, are associated with prolonged viral shedding and may disseminate (Sandherr et al., 2006).
Varicella-Zoster virus:
The majority of VZV infections in adult patients with hematological malignancy are reactivation infections and 80% present with localized disease. The incidence of VZV infection ranges from 2% among patients with CML receiving Imatinib; to 10-15% in patients with CLL receiving Fludarabine; to 25% of patients with Hodgkin lymphoma or autologous stem cell transplantation (SCT) recipients; and to 45-60% among allogenic SCT recipients (Mattiuzzi et al., 2003).
Infection risk is greatest within the first 12 months following treatment or transplant, but late onset disease occurs because of persistent immunosuppression. Patients who are VZV naive are at risk for primary infection with either wild type or vaccine strains and should be counseled about the risk of developing such infection. Primary VZV infection can be very severe, and measures to prevent exposure and intervene early are recommended (Weinstock et al., 2004).
Unusual VZV syndromes of importance include trigeminal zoster with keratitis and yeast infections, and post–zoster pain. Hepatic or gastro-intestinal VZV disease is an important entity, and may present with few or no skin lesions. This presentation may result in delayed diagnosis, and has been associated with significant mortality (David et al., 1998).
Human herpes virus – 6 (HHV-6):
HHV-6 is ubiquitous Herpes virus that infects most persons early in life. Two major viral variants have been identified (A and B), but the B variant is most frequently associated with disease among immunocompromised patients. Longitudinal studies in SCT recipients found that viral reactivation occurred a median of 20 days after transplantation, and that viral shedding for some patients was prolonged, and correlated poorly with clinical improvement. HHV-6 viremia among allogenic transplant recipients is associated with an increased mortality, and increased when patients are transplanted for disease other than first remission, when donor and recipient are sex mismatched and among younger patients (Zerr et al., 2005).
Wade (2006) treated 4 patients for HHV-6 viremia who developed CNS dysfunction and delayed platelet recovery; three of them had autologous transplant for myeloma following Melphalan, and the fourth was treated with Imatinib for relapsed ALL. All 4 responded to prolonged antiviral therapy.
Quantitative real-time PCR analysis on blood and CSF is the method of choice for diagnosis. Foscarnet and Ganciclovir, alone or in combination, have been used as treatment for HHV-6 infection. Prospective studies are needed to better understand the importance of HHV -6 infections among patients with hematological malignancy, and to define disease spectrum, and appropriate therapy (Zerr et al., 2005).
BK Virus:
BK virus is DNA polygonal virus that is believed to cause nephropathy and graft loss among renal transplant recipients and also may cause pneumonia (Boeckh et al., 2005). There is increasing evidence that BK virus plays an important role in renal impairment in patients with hematological malignancy, but viral tissue invasion has only recently been demonstrated (Erard et al., 2005). BK virus was reported up to 95% of SCT recipients, with the onset of viral shedding occurring a median of 41 days after transplant, BK viruria may be prolonged, can be severe and some patients remain symptomatic for more than one month. Highly sensitive PCR assay for BK virus detection in blood and urine is now available (Bridges et al., 2006).
T-cell function is paramount in the control of CMV and T-cell depleting agents as Alemtuzamab and aggressive chemotherapy e.g. CVAD and acute leukemia induction appear to increase the risk of CMV infection and disease. In the absence of effective antiviral prophylaxis, the incidence of CMV infection in patients with hematological malignancy ranges from 5-75% (Boeckh and Nichols, 2004). Patients undergoing an autologous stem cell transplant have a low risk of CMV infection but CD 34 selection of the autologous stem cell product increases the risk of CMV disease and death (Holmberg et al., 1999).
CMV attributable mortality for patients with hematological malignancies who receive conventional therapy ranged from 30% -57%. CMV disease in patients with acute leukemia was associated with the use of high dose Fludarabine, Cyclophosphamide, or Alemtuzumab. CMV viremia occurred in 15% of these patients with a median 28 days after starting therapy, and a similar incidence was reported for patients with lymphoid malignancies who were treated with Alemtuzumab or Rituximab (Faderl et al., 2003).
Late CMV infection after stem cell transplant is common (3-17%) of allogeneic transplant recipients and is associated with 13-fold increase in post transplant mortality. The primary risk factor for late CMV infection is specific T-cell dysfunction (Hakki et al., 2003). Late CMV disease have a varied presentation, with retinitis, sinusitis, encephalitis and marrow failure being more common than in early CMV disease (Ayala et al., 2006).
Hepatitis B Virus:
HBV infection in diffuse large B-cell lymphoma (DLBCL) patients is a common complication in China. However, the clinical relevance of HBV infection with respect to DLBCL disease stages and patient survival remains unclear. Compared with HBsAg negative patients, the HBsAg positive DLBCL patients had earlier onset and more advanced stage. The disease stage and hepatic dysfunction during chemotherapy were two significant prognostic factors in the HBsAg positive DLBCL patients. This study suggests that the prophylactic treatment of HBV may be of great importance in the cases of HBsAg-positive patients (Wang et al., 2008).
Hepatitis C Virus:
HCV infection is frequent among patients with hematological malignancies, especially those with lymphoproliferative disorders. The molecular data suggest patient-to patient nosocomial HCV transmission. A series of preventive measures should be adopted as screening for Anti-HCV search for HCV-RNA in newly admitted patients and at fixed intervals during follow up and isolation of patients during neutropenic phases and avoidance of multidose vials (Silini et al., 2002).

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