Prevalence and risk factors for viral blipping in chronic hepatitis B patients treated with nucleos (t) ide analogues.

The clinical relevance of viral blipping during nucleos (t) ide analogue (NA) treatment is unclear in chronic hepatitis B (CHB). We investigated the prevalence, risk factors and clinical outcomes for those with viral blipping during NA treatment. A retrospective cohort study investigated consecutively treated CHB patients from May 2008 to February 2015 on the NAs such as entecavir (ETV), tenofovir (TDF) and lamivudine (LAM). Included patients were previously treatment naive. Viral blipping was defined as serum HBV DNA >20 IU/mL on one occasion, and not >200 IU/mL, with subsequent measurement returning to undetectable levels, that is <20 IU/mL. A total of 242 treatment-compliant CHB patients were included with 44 (18.2%) experiencing viral blipping. In multivariable Cox regression, Asian race (HR=7.40, 95% CI 1.01-54.29, P<.049), LAM therapy (vs ETV/TDF, HR=2.53, 95% CI 1.29-4.95, P<.007), higher creatinine (per SD, HR=1.47, 95% CI 1.21-1.79, P<.001), HBeAg positivity (HR=2.68, 95% CI 1.39-5.03, P<.003) and longer time to achieve undetectable HBV DNA (per month, HR=1.05, 95% CI 1.02-1.08, P=.001) were associated with an increased risk of viral blipping. Viral blipping did not show any significant association with viral breakthrough, HBsAg loss, ALT flares or disease progression. Viral blipping is a frequent event during NA therapy; however, it did not lead to any clinically significant outcomes. Thus, it may not require more frequent blood work and patient visits in clinical practice.

Rate of cyp51A mutation in Aspergillus fumigatus among lung transplant recipients with targeted prophylaxis.

OBJECTIVES: The most common mechanism of azole (itraconazole and voriconazole) resistance in Aspergillus fumigatus is a mutation at the cyp51A locus. The aim of our study was to determine the rate of cyp51A mutations in lung transplant recipients (LTR) undergoing targeted antifungal prophylaxis with 12 weeks of voriconazole. METHODS: We conducted a prospective study that included 22 LTR with A. fumigatus between October 2008 and November 2011. Of those, 10 LTR were colonized with A. fumigatus and 12 had invasive pulmonary aspergillosis. RESULTS: Four patients were found to have A. fumigatus isolates with a cyp51A mutation, two had colonization and two had invasive pulmonary aspergillosis. The remaining 18 LTR had WT cyp51A A. fumigatus isolates. All A. fumigatus isolates (except one due to mixed growth) were tested for antifungal susceptibility. A total of nine LTR were exposed to azoles prior to A. fumigatus isolation for a median duration of 249 (IQR 99-524) days. Azole exposure preceded the isolation of two mutant isolates and seven WT isolates. None of the cyp51A mutant isolates conferred phenotypic resistance to azoles. CONCLUSIONS: Targeted antifungal prophylaxis in LTR did not lead to cyp51A resistance mutations in this cohort. Data on larger cohorts who receive universal antifungal prophylaxis are needed.

Human albumin eye drops as a therapeutic option for the management of keratoconjunctivitis sicca secondary to chronic graft-versus-host disease after stem-cell allografting.

BACKGROUND: Keratoconjunctivitis sicca from chronic graft-versus-host disease (cgvhd) after allogeneic stem cell transplantation is common, leading to severe corneal damage and blindness if not treated. We retrospectively examined the efficacy and safety of pooled human albumin eye drops (haeds) for symptom relief in 40 stem-cell transplantation patients after other alternatives had failed. METHODS: The Common Terminology Criteria for Adverse Events (version 4.0) and the cgvhd grading scale were used to compare response in the patients during January 2000 and July 2013. In addition, on days 1 and 30, the haeds were subjected to quality assurance testing for sterility, oncotic pressure, albumin measurement, viscosity, pH, and purity by protein electrophoresis. RESULTS: Use of haeds resulted in symptom relief for 37 patients (92.5%); 3 patients (7.5%) failed to improve with use of haeds (p ≤ 0.0001). Of the 37 patients having symptom relief, 7 (19%) improved from grade 3 to no dry eye symptoms. Proportionately, post-treatment symptom improvement by two grade levels, from 3 to 1 (70%), was significantly higher than improvement by one grade level, from 3 to 2 (11%) or from 2 to 1 (19%, p ≤ 0.0001). Time to symptom relief ranged from 2 weeks to 28 weeks. Of the 40 patients, 38 (95%) had no adverse reactions. Days 1 and 30 quality assurance testing results were equivalent. CONCLUSIONS: Complications of keratoconjunctivitis sicca were well managed and well tolerated with haeds when other remedies failed. Quality assurance testing confirmed that haeds were safe and stable in extreme conditions.

Whipple's Disease in an Afro-Caribbean National.

Whipple's disease is a rare multi-organ infectious disease caused by Tropheryma whipplei. It is fatal without treatment. We report on a 40-year old Afro-Jamaican man who presented with a six-month history of weight loss and diarrhoea. Investigations revealed iron deficiency anaemia and hypoalbuminaemia. Upper gastrointestinal endoscopy revealed white patchy lesions in the duodenum. The duodenal biopsy showed broadening and thickening of the villi by a dense infiltrate of foamy histiocytes within the lamina propria and focally extending into the attached submucosa. Periodic Acid-Schiff stains were positive. Electron microscopy was confirmatory and polymerase chain reaction testing conclusively identified the organisms as T whipplei. Antibiotic treatment resulted in resolution of symptoms. Although the diagnosis of Whipple's disease is difficult, increased awareness should lead to an increase in reported cases with the improvements in diagnostic capabilities.

Hepatitis C core Ag and its clinical applicability: potential advantages and disadvantages for diagnosis and follow-up?

Chronic hepatitis C virus (HCV) infection which is often a silent disease has resulted in a global epidemic. The diagnosis of hepatitis C virus often requires confirmation with molecular techniques such as the polymerase chain reaction for detection of HCV RNA. Following laboratory confirmation of the diagnosis, molecular techniques are routinely used to monitor HCV RNA levels, particularly in those undergoing treatment. Unfortunately, molecular tests are relatively expensive and their cost may be prohibitive in the developing world. Several studies have investigated the applicability of the hepatitis C core Ag (HCVcAg), as a substitute for measuring HCV RNA levels. In this review, we provide an overview of the major findings of these studies focused on the utility of measuring HCVcAg antigen levels in the clinical setting. Overall, measuring HCVcAg levels is associated with several advantages and disadvantages. It may be useful in different clinical settings for monitoring HCV patients after obtaining an initial baseline HCV RNA result.

Immunogenicity of a half-dose of adjuvanted 2009 pandemic H1N1 influenza vaccine in adults: a prospective cohort study.

We aimed to assess the immunogenicity of a single half-dose of AS03-adjuvanted monovalent 2009 pandemic H1N1 vaccine in healthy adults. Healthy subjects age 20-60 years were prospectively enrolled in a cohort receiving intramuscular administration of a single half-dose (1.875 µg of hemagglutinin [HA]) of adjuvanted 2009 pandemic H1N1 influenza vaccine. Data from participants enrolled in a concomitant study of immunogenicity following a full-dose (3.75 µg of HA) are presented concurrently. Sera for assessment of hemagglutination-inhibiting (HAI) antibody to the vaccine strain were obtained before and 14 or 21 days after vaccination. Ninety-seven participants received a half-dose and 50 received a full-dose of vaccine. In the half-dose cohort, Food and Drug Administration criteria for immunogenicity regarding seroprotection and seroconversion rates were met for subjects aged 20-45 years, but not for those aged 46-60 years. There was no statistically significant difference in the proportion of individuals achieving a post-vaccination HAI titre of ≥1:40, the geometric mean titres of post-vaccination antibody, or the proportion of individuals with a four-fold or greater increase in antibody levels between the two cohorts. Participants 46-60 years of age were significantly less likely to be seroprotected at day 21 than those 20-45 years old in both cohorts. Immunogenicity of a half dose of adjuvanted pH1N1 influenza vaccine was adequate in subjects aged 20-45 years. Dose reduction is a possible strategy for expanding the availability in the event of vaccine shortage in this age group.

Post renal transplantation Kaposi's sarcoma: a review of its epidemiology, pathogenesis, diagnosis, clinical aspects, and therapy.

BACKGROUND: Kaposi's sarcoma (KS) is a vascular malignancy primarily involving the skin. This neoplasm occurs commonly in acquired immunodeficiency syndrome (AIDS) and post solid organ transplantation. Human herpesvirus type 8 (HHV-8) has been shown to play a causative role in AIDS-associated KS and in post renal transplantation KS. METHODS: Based on a MEDLINE search, we present a review of the current information on the epidemiology, pathogenesis, diagnosis and treatment of post-transplantation KS (PT-KS) with an emphasis on renal transplantation. RESULT: The different frequencies of PT-KS in different parts of the world seem to be related to seroprevalence of HHV-8 infection. Following renal transplantation and the administration of immunosuppressive therapy, HHV-8 may reactivate. The renal tubular epithelium is a site for HHV-8 latency. Rates of PT-KS in seropositive recipients and anti-HHV-8 mismatched recipients (donor+/recipient-) are approximately 13% and 4.6%, respectively. Additional risk factors for the development of PT-KS include skin color, country of birth, age at the time of transplantation, and different induction regimens including anti-thymocyte globulin, steroid, or anti-interleukin 2-receptor antagonists. Skin is the major site of involvement. Surprisingly, involvement of the transplanted organ has been reported to be extremely rare. Reduction in immunosuppressive therapy and switching to mammalian targets of rapamycin inhibitors, such as sirolimus, are effective treatments for PT-KS. In patients with no response to reduction in immunosuppressive therapy, systemic chemotherapy with different regimens has been reported to be successful. CONCLUSION: PT-KS in renal transplant patients is an important problem specifically in southern Europe and the Middle East. In the majority of patients, the diagnosis based on clinical suspicion is always essential. Clinicians should bear in mind that PT-KS may threaten graft function and hence result in rejection complications. Appropriate management increases patient survival.

Pegylated interferon plus optimized weight-based ribavirin dosing negate the influence of weight and body mass index on early viral kinetics and sustained virological response in chronic hepatitis C.

AIM: Elevated body mass index (BMI) in chronic hepatitis C (CHC) has been associated with reduced rates of sustained virological response (SVR). The aims of this study were to determine whether early viral kinetics (and subsequently SVR) are influenced by weight or BMI by measuring HCV RNA at week 4 using two PCR assays with differing sensitivities. METHODS: Patients with CHC treated with peginterferon plus weight-based ribavirin were included in this retrospective study. Body mass index, pretreatment viral load, genotype and liver histology were abstracted from the clinical database. HCV RNA PCR (lower limit of detection (LLD) <50 IU/mL) at treatment week 4 and 6 months after completion of therapy were recorded to determine the presence of rapid virological response (RVR-50) and SVR, respectively. In those who achieved RVR-50, stored week 4 serum was retested using Taqman (LLD < 15 IU/mL, RVR-15). RESULTS: Of 134 patients included (genotype 1 57%, BMI 26.7 ± 4.5 kg/m², ribavirin dose 13.9 ± 2.6 mg/kg/day), 59% achieved SVR. RVR-50 was observed in 39.6% and RVR-15 in 27.6%. Neither body weight nor BMI influenced RVR-50, RVR-15 or SVR. The positive predictive values (PPVs) of RVR-50 and RVR-15 for SVR were 88.7% and 97.3% (P = 0.23). RVR-50 and RVR-15 superceded genotype and viral load as the strongest independent predictors of SVR (OR 9.25 (1.9-45.11) and OR 30.74 (3.08-317.96), respectively). CONCLUSIONS: RVR is the strongest predictor of SVR. Early viral kinetics is not influenced by body weight or BMI when weight-based ribavirin is prescribed.

Differential patterns of amantadine-resistance in influenza A (H3N2) and (H1N1) isolates in Toronto, Canada.

BACKGROUND: Molecular methods were used to characterize influenza A (H1N1) and (H3N2) strains and to identify amantadine-resistance. OBJECTIVES: To compare proportions of amantadine-resistant influenza A (H1N1) and (H3N2) isolates in the Greater Toronto Area. STUDY DESIGN: Isolates of influenza A (H1N1) and (H3N2) were strain typed using molecular methods. Pyrosequencing for point mutations in the transmembrane domain of the M2 proton channel was undertaken. Proportions of amantadine-resistant and susceptible isolates were compared using the The Fisher's exact test. RESULTS: 96% of the 49 influenza A (H3N2) isolates and none of the influenza A (H1N1) tested carried a point mutation in the M gene coding for the M2 protein. Influenza A (H3N2) isolates were more likely to carry an amantadine-resistance associated mutation than influenza A (H1N1) isolates (Fishers's exact test, P<0.0001). CONCLUSIONS: : Characterization of amantadine-resistance in influenza A (H1N1) isolates should utilize a variety of different methods including sub-typing, strain typing, and direct sequencing for point mutations associated with amantadine-resistance.

Comparison of two automated methods for detection and differentiation of herpes simplex virus in clinical specimens.

BACKGROUND: The Aptima Herpes Simplex Virus (HSV) 1&2 Assay recently received Health Canada approved for detection and differentiation of HSV-1 and HSV-2 from anogenital sites. This assay uses target capture, transcription mediated amplification, and real-time detection of messenger RNA (mRNA) produced in host cells during active HSV infection. To evaluate its performance, the Aptima assay was compared to another Health Canada approved assay, the BD ProbeTec Herpes Simplex Viruses HSV 1&2 Qx Amplified DNA Assay, which uses strand displacement amplification technology. METHODS: As recommended by the manufacturers, the Aptima and ProbeTec assays were performed on the Panther and Viper instruments, respectively. Analytical sensitivity and specificity were assessed using 10-fold serial dilution of viruses in viral universal transport media (UTM), and nucleic acids extracted and concentrated from other viruses including all members of the Herpesviridae family. The clinical sensitivity and specificity were assessed retrospectively using 60 archived specimens, and prospectively using 158 swabs in UTM. Discrepant results were resolved with real-time PCR using the Altona Diagnostics RealStar alpha Herpes assay. RESULTS: Both the Aptima and ProbeTec assays showed excellent analytical and clinical specificity. However, the Aptima HSV assay failed to detect HSV in specimens with low viral loads, resulting in reduced sensitivity for HSV-2 during the retrospective evaluation at 85.0%, and for HSV-1 at 85.0% during the prospective evaluation. CONCLUSIONS: This study compared the Aptima and ProbeTec HSV assays and demonstrated that detection of HSV mRNA using the Aptima HSV assay was less sensitive in both retrospective and prospective analyses.

Preventing transmission of bloodborne viruses from infected healthcare workers to patients: Summary of a new Canadian Guideline.

BACKGROUND: Although it is well documented that bloodborne viruses (BBVs), including human immunodeficiency virus (HIV), hepatitis C virus (HCV) and hepatitis B virus (HBV) have been transmitted from patients to healthcare workers (HCWs), there has also been reported transmission from HCWs to patients during the provision of health care. With remarkable progress in infection prevention, diagnosis tools, treatment regimens and major improvements in guideline development methodology, there was a need to develop an evidence-based guideline to replace the 1998 Canadian consensus document for managing HCWs infected with BBVs. PURPOSE: This article summarizes the Canadian Guideline on the Prevention of Transmission of Bloodborne Viruses from Infected Healthcare Workers in Healthcare Settings. METHODS: A Guideline Development Task Group was established and key questions developed to inform the guideline content. Systematic reviews were conducted to evaluate the risk of HCW-to-patient transmission of HIV, HCV and HBV. Environmental scans were used to provide information on Expert Review Panels, disclosure of a HCW's serologic status and lookback investigations. Federal, provincial and territorial partners and key stakeholder organizations were consulted on the Guideline. RESULTS: The risk of HCW-to-patient BBV transmission was found to be negligible, except during exposure-prone procedures, where there is a risk that injury to the HCW may result in exposure of a patient's open tissues to the HCW's blood. Risk of ensuing transmission and the rate of transmission varied by BBV, and were lowest with HIV and highest with HBV. The Guideline provides key content, including recommendations regarding criteria to determine if a procedure is an exposure-prone procedure, management of HCWs infected with a BBV, including considerations for the HCW's fitness for practice, Expert Review Panels, HCW disclosure obligations and right to privacy and lookback investigations. CONCLUSION: This new Guideline provides a pan-Canadian approach for managing HCWs infected with a BBV, with recommendations related to preventing HCW-to-patient transmission of BBVs during the provision of care.

Heterophilic interference in specimens yielding false-reactive results on the Abbott 4th generation ARCHITECT HIV Ag/Ab Combo assay.

BACKGROUND: False-reactivity in HIV-negative specimens has been detected in HIV fourth-generation antigen/antibody or 'combo' assays which are able to detect both anti-HIV-1/HIV-2 antibodies and HIV-1 antigen. OBJECTIVES: We sought to characterize these specimens and determine the effect of heterophilic interference. STUDY DESIGN: Specimens previously testing as false-reactive on the Abbott ARCHITECT HIV Ag/Ab combo assay and re-tested on a different (Siemens ADVIA Centaur HIV Ag/Ab) assay. A subset of these specimens were also pre-treated with heterophilic blocking agents and re-tested on the Abbott assay. RESULTS: Here we report that 95% (252/264) of clinical specimens that were repeatedly reactive on the Abbott ARCHITECT HIV Ag/Ab combo assay (S/Co range, 0.94-678) were negative when re-tested on a different fourth generation HIV combo assay (Siemens ADVIA Centaur HIV Ag/Ab). All 264 samples were subsequently confirmed to be HIV negative. On a small subset (57) of specimens with available volume, pre-treatment with two different reagents (HBT; Heterophilic Blocking Tube, NABT; Non-Specific Blocking Tube) designed to block heterophilic antibody interference either eliminated (HBT) or reduced (NABT) the false reactivity when re-tested on the ARCHITECT HIV Ag/Ab combo assay. CONCLUSIONS: Our results suggest that the Abbott ARCHITECT HIV Ag/Ab combo assay can be prone to heterophilic antibody interference.

Aspergillus galactomannan detection in exhaled breath condensate compared to bronchoalveolar lavage fluid for the diagnosis of invasive aspergillosis in immunocompromised patients.

OBJECTIVES: Exhaled breath condensate (EBC) is a noninvasive means of sampling the airways that has shown significant promise in the diagnosis of many disorders. There have been no reports of its usefulness in the detection of galactomannan (GM), a component of the cell wall of Aspergillus. The suitability of EBC for the detection of GM for the diagnosis of invasive aspergillosis (IA) using the Platelia Aspergillus enzyme-linked immunosorbent assay was investigated. METHODS: Prospective, cross-sectional study of lung transplant recipient and haemotologic malignancy patients at a university centre. EBC samples were compared to concomitant bronchoalveolar lavage (BAL) samples among lung transplant recipients and healthy controls. EBC was collected over 10 minutes using a refrigerated condenser according to the European Respiratory Society/American Thoracic Society recommendations, with the BAL performed immediately thereafter. RESULTS: A total of 476 EBC specimens with 444 matched BAL specimens collected from lung transplant recipients (n = 197) or haemotologic malignancy patients (n = 133) were examined. Both diluted and untreated EBC optical density (OD) values (0.0830, interquartile range (IQR) 0.0680-0.1040; and 0.1130, IQR 0.0940-0.1383), respectively, from all patients regardless of clinical syndrome were significantly higher than OD values in healthy control EBCs (0.0508, IQR 0.0597-0.0652; p < 0.0001). However, the OD index values did not correlate with the diagnosis of IA (44 samples were associated with IA). Furthermore, no significant correlation was found between EBC GM and the matched BAL specimen. CONCLUSIONS: GM is detectable in EBC; however, no correlation between OD index values and IA was noted in lung transplant recipients.

Challenges in Interpretation of Diagnostic Test Results in a Mumps Outbreak in a Highly Vaccinated Population.

In spite of a greatly reduced incidence rate due to vaccination, mumps outbreaks continue to occur in several areas of the world, sometimes in vaccinated populations. This article describes an outbreak in a highly vaccinated population in southwestern Ontario, Canada, and the challenges encountered in interpreting the results of diagnostic tests used in the outbreak. During the outbreak, patients were interviewed and classified according to the outbreak case definition, and specimens were collected for diagnostic testing according to Ontario guidelines. Twenty-seven individuals were classified as confirmed cases (n = 19) or suspect cases (n = 8) according to the case definition, only 9 of which were laboratory-confirmed cases: 7 confirmed by reverse transcriptase PCR (RT-PCR) and 2 by IgM serology. All 19 confirmed cases represented patients who were associated with secondary schools in the local area and had been vaccinated against mumps with one (n = 2) or two (n = 17) doses of the measles-mumps-rubella (MMR) vaccine. This is the first published report of an outbreak of mumps in Ontario in which all confirmed cases had been vaccinated against the disease. It highlights the limitations of and difficulties in interpreting current mumps diagnostic tests when used in vaccinated individuals.

Clinical utility of quantitative cytomegalovirus viral load determination for predicting cytomegalovirus disease in liver transplant recipients.

BACKGROUND: The early detection of cytomegalovirus (CMV) after liver transplantation may form the basis of a preemptive strategy for prevention of active CMV disease. METHODS: We prospectively analyzed the clinical use of weekly quantitative polymerase chain reaction-(PCR) based plasma viral load determinations and the antigenemia assay for predicting the development of active CMV disease in 97 consecutive liver transplant recipients. RESULTS: CMV disease occurred in 21/97 patients. Using a positive cut-off of >400 copies/ml plasma, PCR had a sensitivity of 100%, specificity 47.4%, positive predictive value 34.4% and negative predictive value 100% for prediction of CMV disease. Respective values for a positive antigenemia (>0 positive cells/slide) were 95.2, 55.3, 37.0, and 97.7%. Different cut-off points for a positive test were analyzed using receiver-operating characteristic (ROC) curves. The optimal cut-off for viral load was in the range of 2000-5000 copies/ml (sensitivity 85.7%, specificity 86.8%, PPV 64.3%, NPV 95.7% for >5000 copies/ml). The optimal cut-off for antigenemia was in the range of four to six positive cells/slide. Mean peak viral load in symptomatic patients was 73,715 copies per/ml versus 3615 copies/ml in patients with asymptomatic CMV reactivation (P<0.001). In a multivariate logistic regression analysis of risk factors for CMV disease (CMV serostatus, acute rejection, and induction immunosuppression), peak viral load and peak antigenemia emerged as the only significant independent predictors of CMV disease (for PCR, odds ratio=1.40/1000 copy/ml increase in viral load, P=0.0001; for antigenemia odds ratio=1.17/1 positive cell/slide). CONCLUSIONS: Plasma viral load by quantitative PCR is useful for predicting CMV disease and could be used in a preemptive strategy.

Management of allogeneic bone marrow transplant recipients at risk for cytomegalovirus disease using a surveillance bronchoscopy and prolonged pre-emptive ganciclovir therapy.

BACKGROUND: Patients undergoing allogeneic bone marrow transplant (BMT) are considered to be at increased risk of cytomegalovirus (CMV) disease if they and/or their donor are CMV seropositive pre-transplant. Although several pre-emptive strategies have been shown to be effective in preventing early CMV disease, the ability of pre-emptive strategies using prolonged ganciclovir therapy to reduce the incidence of late-onset CMV infection, disease and mortality has not been fully evaluated. OBJECTIVE: To assess the efficacy of 18 weeks of pre-emptive ganciclovir therapy in preventing late-onset (> 100 days post-transplant) CMV disease when administered to asymptomatic BMT patients found to have CMV in bronchoalveolar lavage (BAL) fluid obtained during a surveillance bronchoscopy approximately 35 days post-transplant. To determine whether or not survival of BMT recipients is influenced by pre-transplant donor and recipient CMV serostatus in the context of this pre-emptive ganciclovir strategy. STUDY DESIGN: Consecutive patients undergoing allogeneic BMT were assessed for their risk of developing CMV disease based on their pre-transplant CMV serostatus and that of their donor. Patients who were CMV seropositive and/or received marrow from a CMV seropositive donor underwent a surveillance bronchoscopy and BAL approximately 35 days post-transplant. Patients with positive BAL fluid for CMV received pre-emptive ganciclovir therapy for 18 weeks at decreasing dose levels. Patients considered to be at low risk for the development of CMV disease (donor and recipient CMV seronegative) were followed without intervention. RESULTS: Of 98 consecutive patients, 55 were considered to be at risk for CMV disease and underwent a surveillance bronchoscopy. Sixteen (29%) patients had a positive BAL fluid for CMV and were started on pre-emptive ganciclovir therapy. Two patients progressed and died with CMV-related pneumonia. One additional patient developed CMV-related enteritis on day 42 post-transplant and recovered with continuing ganciclovir treatment. Of the 39 patients with a negative BAL fluid for CMV, one developed a fatal CMV pneumonia 150 days post-transplant and two additional patients developed gastrointestinal CMV disease 28 and 57 days post-BMT, respectively. None of the patients in the low risk group developed CMV disease. CONCLUSIONS: The strategy utilizing a surveillance bronchoscopy for CMV and initiating prolonged (18 weeks) pre-emptive ganciclovir therapy for patients with a positive BAL fluid for CMV resulted in a low incidence of CMV-related post-transplant complications. After a minimum follow-up of 16 months, late CMV reactivations (occurring > 100 days post-transplant) were not observed in the group of individuals pre-emptively treated with ganciclovir. This observation suggests that prolonged therapy with a reduced dose of ganciclovir may be important in the prevention of CMV reactivation. The CMV serostatus of donors and recipients prior to BMT did not correlate with survival.

A randomised trial comparing cytomegalovirus antigenemia assay vs screening bronchoscopy for the early detection and prevention of disease in allogeneic bone marrow and peripheral blood stem cell transplant recipients.

Preemptive antiviral therapy is often employed for CMV prevention following allogeneic BMT. Two common strategies are a screening bronchoscopy for CMV post-BMT or regular CMV antigenemia testing with ganciclovir administration for a positive result. In a randomised trial, we prospectively compared the efficacy of these two preemptive strategies. Consecutive patients were randomised to either a bronchoscopy for CMV on day 35 post BMT or weekly CMV antigenemia testing. If the bronchoscopy was positive for CMV, patients received preemptive ganciclovir for 8-10 weeks. If the antigenemia was positive for CMV, patients received a minimum of 2 weeks of preemptive ganciclovir. The primary endpoint was the development of active CMV disease. One hundred and eighteen allogeneic BMT patients were enrolled (60 in the antigenemia arm and 58 in the bronchoscopy arm). The two groups were comparable with respect to baseline demographic data, underlying disease, conditioning regimen, and immunosuppression. Active CMV disease developed in 7/58 (12.1%) patients in the bronchoscopy arm vs 1/60 patients (1.7%) in the CMV antigenemia arm (P = 0.022). Based on the screening test, 13.8% of patients received preemptive ganciclovir in the bronchoscopy arm vs 48.3% of patients in the antigenemia arm (P < 0.001). There was no significant difference in the rate of graft-versus-host disease, bacteremia, invasive fungal infections or mortality between the two groups. Preemptive therapy based on regular CMV antigenemia monitoring is superior to screening bronchoscopy for the prevention of CMV disease after allogeneic BMT.

The clinical utility of CMV surveillance cultures and antigenemia following bone marrow transplantation.

At our institution, the cytomegalovirus (CMV) prophylaxis protocol for allogeneic bone marrow transplant (BMT) recipients who are CMV-seropositive or receive marrow from a CMV-seropositive donor consists of a surveillance bronchoscopy approximately 35 days posttransplant. Patients with a positive surveillance bronchoscopy for CMV receive pre-emptive ganciclovir. In order to determine the utility of other screening methods for CMV, we prospectively performed weekly CMV antigenemia, and blood, urine and throat cultures from time of engraftment to day 120 post-BMT in 126 consecutive patients. Pre-emptive ganciclovir was given to 11/81 patients (13.6%) because of a positive surveillance bronchoscopy for CMV. Results of CMV blood, urine and throat cultures and the antigenemia assay done prior to or at the time of the surveillance bronchoscopy were analyzed for their ability to predict the bronchoscopy result. The antigenemia test had the highest positive and negative predictive values (72% and 96%, respectively). The ability of these tests to predict CMV disease was evaluated in the 70 patients with a negative surveillance bronchoscopy who did not receive pre-emptive ganciclovir. Of 19 cases of active CMV disease, CMV antigenemia was positive in 15 patients (79%) a mean of 34 days preceding symptoms. Blood cultures were positive in 14/19 patients (74%) a mean of 31 days before onset of disease. CMV antigenemia is useful for predicting the surveillance bronchoscopy result, and also predicts the development of CMV disease in the majority of patients missed by the surveillance bronchoscopy.

Zanamivir use during transmission of amantadine-resistant influenza A in a nursing home.

OBJECTIVE: To describe the use of zanamivir during an influenza A outbreak. POPULATION: Residents of a 176-bed long-term-care facility for the elderly in Newmarket, Ontario, Canada, 90% of whom received influenza vaccine in the fall of 1998. OUTBREAK: When respiratory illness due to influenza A was confirmed, infection control measures and amantadine prophylaxis were initiated. Despite these measures, transmission of influenza A continued. INTERVENTION: Zanamivir inhalations, 10 mg daily for prophylaxis and 10 mg twice daily for treatment of influenza. RESULTS: There were 13 definite and 66 probable outbreak-associated cases of influenza A. Twelve (15%) cases developed pneumonia, 7 (9%) were hospitalized, and 2 (2.6%) died. All 12 culture-positive cases yielded influenza A/Sydney/H3N2/05/97-like virus, a 1998/99 vaccine component. The three isolates obtained prior to the initiation of amantadine were amantadine-susceptible; all nine obtained after prophylaxis was instituted were amantadine-resistant. One hundred twenty-nine (92%) of 140 residents who were offered zanamivir accepted it and were able to attempt inhalations. Of these 129, 78% (100) had no difficulty in complying with inhalations. Difficulty with inhalations was associated with decreased functional and mental status. Fifteen (58%) of 26 residents fully dependent in activities of daily living had difficulty compared to 14 (14%) of 100 others (P<.001). Twenty-two (45%) of 49 residents not oriented to person, place, or time had difficulty compared to 7 (10%) of 77 others (P<.001). In the 2 weeks after zanamivir prophylaxis, only 2 new cases of respiratory illness occurred, neither confirmed as influenza. No side effects were identified in 128 zanamivir-treated residents. CONCLUSION: A minority of nursing home residents have difficulty following instructions for zanamivir inhalations. Zanamivir was well tolerated, and its use was temporally associated with termination of an outbreak that amantadine had failed to control.