High-throughput sequencing of cerebrospinal fluid for diagnosis of chronic Propionibacterium acnes meningitis in an allogeneic stem cell transplant recipient.

BACKGROUND: A 40-year-old man with chronic myelogenous leukemia presented multiple times over a period of 3 years with episodes of confusion, wide-based gait and falls because of recurrent hydrocephalus despite repeated therapeutic lumbar punctures. These problems occurred in the context of persistent cerebrospinal fluid (CSF) pleocytosis and leptomeningeal enhancement. Extensive diagnostic workups and therapeutic trials had failed to identify a clinically plausible cause or produce any significant improvement in the CSF and neuroimaging abnormalities. METHODS: We used high-throughput metagenomic shotgun sequencing to identify microbes in 2 CSF samples collected from the patient during his illness. These results were compared to sequence data from 1 CSF sample collected during treatment and 5 control CSF samples from other patients. RESULTS: We found sequences representing 53% and 67% of the Propionibacterium acnes genome in 2 CSF samples collected from the patient during his illness. Directed antimicrobial therapy was administered for 6 weeks with resolution of CSF and neuroimaging abnormalities. Sequencing of a sample obtained during treatment demonstrated that the P. acnes levels were decreased to background levels. After insertion of a ventriculo-peritoneal shunt, the patient returned to baseline status. CONCLUSIONS: High-throughput metagenomic shotgun sequencing revealed P. acnes as the cause of chronic meningitis that had eluded conventional attempts at diagnosis. Treatment directed at this organism resulted in cure of the infection and clinical improvement.

The Prevalence of Asthma in an Adult Population in Khorramabad, Iran.

OBJECTIVE: Asthma is one of the most common respiratory disorders. There have not been any studies assessing the prevalence rate for asthma based on spirometry in an adult population in the west of Iran. The aim of this study was to assess the prevalence of asthma in an adult population in Khorramabad, in the west of Iran. METHODS: This prospective cross-sectional study was done on adult residents in Khorramabad between 2009 and 2010. The samples were selected by cluster and systematic sampling methods. The interviewers went to the selected homes and evaluated the samples by the standard questionnaire of the European Community Respiratory Health Survey. The individuals who were susceptible to asthma were evaluated using a hand-held spirometer (ZAN 100, Obertulba, Germany). Also, in the patients whose first spirometry had been normal, a more than 10% reduction in forced expiratory volume in one second (FEV1) after the exercise and more than 12% rise in FEV1 after the salbutamol spray inhalation was considered as having asthma. Finally, the data were summarized using means and percentages. RESULTS: Eight hundred and fifty-seven adults were evaluated by the questionnaire and 450 were referred to the pulmonologist office. The frequency of spirometry-diagnosed asthma in the adult residents of Khorramabad was 9.45%. CONCLUSION: The prevalence of asthma in Khorramabad in our study was more than in similar studies in Iran and other countries. Doing analytical studies on the prevalence of asthma and its risk factors is recommended.

Oral valganciclovir versus ganciclovir as delayed pre-emptive therapy for patients after allogeneic hematopoietic stem cell transplant: a pilot trial (04-0274) and review of the literature.

BACKGROUND: Cytomegalovirus (CMV) infection is an important cause of morbidity and mortality after allogeneic hematopoietic stem cell transplant (HSCT). This pilot prospective randomized clinical trial compares valganciclovir (VGV) to ganciclovir (GCV) as pre-emptive therapy for CMV viremia in the post-allogeneic HSCT population. METHODS: Patients undergoing allogeneic HSCT who were at risk for CMV viremia were monitored post HSCT by weekly quantitative whole blood polymerase chain reaction. Pre-emptive therapy was delayed until the viral load (VL) was >10,000 copies/mL once, or >5000 copies/mL twice. Patients were randomized to either GCV 5 mg/kg twice a day (b.i.d.) for 7 days followed by daily GCV 5 mg/kg for up to 21 days, or VGV 900 mg b.i.d. for 7 days followed by 900 mg daily for up to 21 days. The primary endpoint was clearance of viremia (VL <5000 copies/mL) within 28 days of initiation of therapy. RESULT: In total, 37 patients were enrolled; 19 patients received treatment with VGV and 18 patients received treatment with GCV. The VGV was not inferior in efficacy to GCV as pre-emptive therapy, with rates of viral clearance at 28 days of 89.5% and 83%, respectively (P-value for non-inferiority = 0.030). Toxicities were similar between the 2 arms. No patients developed CMV disease. CONCLUSIONS: In this trial, the rates of clearance of viremia appear to be similar with VGV and GCV.