Species distribution and antifungal susceptibility of 358 Trichosporon clinical isolates collected in 24 medical centres.

OBJECTIVES: To provide species distribution and antifungal susceptibility profiles of 358 Trichosporon clinical isolates collected from 24 tertiary-care hospitals. METHODS: Species identification was performed by sequencing the IGS1 region of rDNA. Antifungal susceptibility testing for amphotericin B, fluconazole, voriconazole and posaconazole followed the Clinical and Laboratory Standards Institute reference method. Tentative epidemiologic cutoff values (97.5% ECVs) of antifungals for Trichosporon asahii were also calculated. RESULTS: Isolates were cultured mostly from urine (155/358, 43.3%) and blood (82/358, 23%) samples. Trichosporon asahii was the most common species (273/358, 76.3%), followed by T. inkin (35/358, 9.7%). Isolation of non-T. asahii species increased substantially over the last 11 years [11/77 (14.2%) from 1997 to 2007 vs. 74/281, (26.3%) from 2008 to 2018, p0.03]. Antifungal susceptibility testing showed high amphotericin B minimum inhibitory concentrations against Trichosporon isolates, with higher values for T. faecale. The ECV for amphotericin B and T. asahii was set at 4 µg/mL. Among the triazole derivatives, fluconazole was the least active drug. The ECVs for fluconazole and posaconazole against T. asahii were set at 8 and 0.5 µg/mL, respectively. Voriconazole showed the strongest in vitro activity against the Trichosporon isolates; its ECV for T. asahii was set at 0.25 µg/mL after 48 hours' incubation. CONCLUSIONS: Trichosporon species diversity has increased over the years in human samples, and antifungal susceptibility profiles were species specific. Trichosporon asahii antifungal ECVs were proposed, which may be helpful to guide antifungal therapy.

Epigenetic variation at the SLC6A4 gene promoter in mother-child pairs with major depressive disorder.

BACKGROUND: Genetic and epigenetic variations of the serotonin transporter gene (SLC6A4) have been related to the etiology of depression. The 5-HTTLPR polymorphism at the SLC6A4 promoter region has two variants, a short allele (S) and a long allele (L), in which the S allele results in lower gene transcription and has been associated with depression. The short S-allele of 5-HTTLPR polymorphism of this gene has been associated with depression. In addition to molecular mechanisms, exposure to early life risk factors such as maternal depression seems to affect the development of depression in postnatal life. The present study investigated the association of 5-HTTLPR polymorphism and CpG DNA methylation (5mC) levels of an AluJb repeat element at the SLC6A4 promoter region in mother-child pairs exposed to maternal depression. METHODS: We analyzed DNA samples from 60 subjects (30 mother-child pairs) split into three groups, with and without major depression disorder (DSM-IV) among children and mothers. The genotyping of 5-HTTLPR polymorphism and quantification of 5mC levels was performed by qualitative PCR and methylation-sensitive restriction enzyme digestion, and real-time quantitative PCR (MSRED-qPCR), respectively. RESULTS: The sample analyzed presented a higher frequency of S allele of 5-HTTLPR (67.5%). Despite the high frequency of this allele, we did not find statistically significant differences between individuals carrying at least one S allele between the depression and healthy control subjects, or among the mother-child pair groups with different patterns of occurrence of depression. In the group where the mother and child were both diagnosed with depression, we found a statistically significant decrease of the 5mC level at the SLC6A4 promoter region. LIMITATIONS: The limitations are the relatively small sample size and lack of gene expression data available for comparison with methylation data. CONCLUSION: In this study, we demonstrated a repeat element specific 5mC level reduction in mother-child pairs, concordant for the diagnosis of depression.

Asymptomatic Strongyloides stercoralis hyperinfection in an alcoholic patient with intense anemia.

Strongyloides stercoralis infection is endemic in many tropical and subtropical areas. The parasite has the unusual ability to multiply inside the host due to the transformation of rhabditiform larvae into infective filariforms. Several studies have shown that chronic alcoholism is an important factor that predisposes to strongyloidiasis. The increased susceptibility to S. stercoralis infections seen in alcoholic individuals could be explained by their increased exposure to the parasite, malnutrition, breakdown of local immune responses, and/or alterations in intestinal barriers. Moreover, ethanol intoxication can elevate human endogenous corticosterone, which, in turn, suppresses T cell function and increases the fecundity and survival of the parasite, mimicking the effect of worm ecdysteroides. Although chronic alcoholism is a risk factor for nematode infection, most cases of hyperinfection or dissemination are associated with the presence of hepatic cirrhosis or strongyloidiasis-related symptoms. The present study describes a case of S. stercoralis hyperinfection in a 51-yr-old male patient without gastrointestinal or pulmonary symptoms and with previous anemia and chronic alcoholism. He was not receiving glucocorticoid therapy and tested negative for HTLV and human immunodeficiency virus (HIV), but he had a history of alcohol addiction for more than 20 yr. Laboratory test results showed increased eosinophilia and a high immunoglobulin E (IgE) level, which may have temporarily protected the patient from dissemination of infection, but not prevented proliferation of the parasite, as shown by the large number of S. stercoralis larvae recovered using the Baermann method. Evaluation for strongyloidiasis should occur in alcoholics, especially in endemic areas, to prevent occult asymptomatic infections from progressing to life-threatening cases.

Use of Oseltamivir to control influenza complications after bone marrow transplantation.

Influenza infection can be severe in bone marrow transplant (BMT) recipients. Although yearly epidemics occur worldwide, and a higher risk of complication is expected in these patients, few studies have addressed the impact of the new neuraminidase inhibitors in the prognosis of influenza after BMT. Influenza A or B infections were found in 39 of the 66 patients (59%) showing a positive nasal wash by DFA. Influenza A was diagnosed in 18 patients and influenza B in 23 patients; two patients were infected by influenza A and B with 84- and 90-day intervals between episodes, respectively. Of the 41 episodes (61%) of influenza A or B, 25 infections occurred during the spring and summer months. Oseltamivir was introduced within 48 h of symptoms appearing. Only two patients (5.1%) developed influenza pneumonia, and no patient died of influenza. A total of 22 patients (56.4%) acquired influenza before day +180 when preventive vaccination strategies are precluded owing to poor immunogenicity of the vaccine during this period. Oseltamivir proved to be safe and appears to have played an important role in the outcome of influenza infection in this population. The therapeutic and/or prophylactic benefits of Oseltamivir in BMT recipients remain to be demonstrated in randomized, prospective trials.

Low mortality rates related to respiratory virus infections after bone marrow transplantation.

Respiratory viruses (RVs) frequently cause severe respiratory disease in bone marrrow transplant (BMT) recipients. To evaluate the frequency of RV, nasal washes were collected year-round from BMT recipients with symptoms of upper respiratory tract infection (URI). Direct immunofluorescence assay was performed for respiratory syncytial virus (RSV), influenza (Flu) A and B, adenovirus and parainfluenza (Paraflu) virus. Patients with RSV pneumonia or with upper RSV infection, but considered at high risk for developing RSV pneumonia received aerosolized ribavirin. Oseltamivir was given to patients with influenza. A total of 179 patients had 392 episodes of URI. In all, 68 (38%) tested positive: RSV was detected in 18 patients (26.4%), Flu B in 17 (25%), Flu A in 11 (16.2%) and Paraflu in 7 (10.3%). A total of 14 patients (20.6%) had multiple RV infections or coinfection. RSV pneumonia developed in 55.5% of the patients with RSV-URI. One of the 15 patients (6.6%) with RSV pneumonia died. Influenza pneumonia was diagnosed in three patients (7.3%). RSV and influenza infections peaked in fall-winter and winter-spring months, respectively. We observed decreased rates of influenza and parainfluenza pneumonia and low mortality because of RSV pneumonia. The role of antiviral interventions such as aerosolized ribavirin and new neuraminidase inhibitors remains to be defined in randomized trials.

Different kinetics in anti-cytomegalovirus immunity reconstitution evaluated by lymphocyte proliferation and IFN-gamma production in allogeneic and autologous bone marrow transplantation.

Allogeneic bone marrow transplantation (ALLOBMT) is associated with an increased risk of cytomegalovirus (CMV) morbidity compared to autologous BMT (AUTOBMT). To investigate this, we evaluated AUTOBMT and ALLOBMT patients regarding anti-CMV immune reconstitution at 1 and 4 months after BMT and on the day after first CMV antigenemia detection. Intermittent ganciclovir preemptive therapy was prompted by antigenemia of >or=2 cells. One month after transplant, AUTOBMT recipients already displayed larger CD8+ T cell numbers than ALLOBMT recipients, but comparably small CD4+ T cell numbers. Most AUTOBMT patients had positive CMV antigen (CMV-Ag)-induced lymphoproliferation (86%) and IFN-gamma secretion (86%), whereas this was infrequently seen in ALLOBMT patients (20 and 10%, respectively). This early AUTOBMT immune reconstitution was associated with a lower frequency of CMV reactivation up to +4 months in AUTOBMT (21%) than ALLOBMT patients (91%). At +4 months, most ALLOBMT recipients had also recovered CMV-Ag immune responses. At first antigenemia detection, all 3 AUTOBMT recipients already displayed anti-CMV immune functions and 2 cleared the infection without therapy, whereas of the 10 ALLOBMT recipients only 1 had positive lymphoproliferation. In the latter group, none had IFN-gamma secretion or cleared the infection without therapy. Thus, differences in anti-CMV immune reconstitution may help to explain the contrasting rates of CMV morbidity between ALLOBMT and AUTOBMT patients.

Extended antigenemia surveillance and late cytomegalovirus infection after allogeneic BMT.

Late CMV disease remains a major concern in allogeneic BMT recipients. Few surveillance data are available on the occurrence of CMV infection and recurrences after day +100. We evaluated the occurrence of antigenemia (AG) recurrences until day +365 in 76 patients who received pre-emptive ganciclovir (GCV) therapy prompted by AG > or = 2 positive cells. Sixty-two episodes of AG recurrences were detected in 33 of the 52 patients who had positive AG. Survival analysis showed a 45.4% probability of AG recurrence on day +100, 64.8% on day +180 and 71.2% on day +365. The median time for AG recurrences was 113 (35 to 343) days. Thirty-five of the 62 episodes (56.4%) occurred after day +100. More than 70% of the patients responded to a 2-week course of GCV and no CMV disease was observed shortly after discontinuation of GCV. The Cox proportional model showed a significant effect of AG recurrences on patient's follow-up only when the patient developed chronic GVHD (P = 0.012). Extended surveillance favored early introduction of GCV and late CMV pneumonia occurred in only one of the 76 patients (1.3%). AG recurrences are frequent after day +100 and extended surveillance until day +365 is recommended for patients who develop chronic GvHD.