Demographic, clinical and microbiological characteristics of the first 30 human monkeypox confirmed cases attended in a tertiary hospital in Madrid (Spain), during the May-June 2022 international outbreak.

The present outbreak of Human Monkeypox (HMPX) that has begun in May 2022 and has spread across all continents in less than two months has qualitative and quantitative characteristics that make it different from the pattern of human disease previously caused by this virus. It has spread with enormous ease, affects almost exclusively adults, behaves as a sexually transmitted disease and focuses on very specific groups and transmission conditions. The high incidence in the city of Madrid in males that have sex with males (MSM) has allowed us to observe and report the experience with the first 30 cases diagnosed in our institution. Patients presented with febrile symptoms, genital and paragenital skin lesions reminiscent of smallpox, but less extensive and severe. The disease may also cause proctitis, pharyngitis and perioral lesions. The PCR test for diagnostic confirmation has been shown to be very sensitive and effective, not only in skin lesions but also in blood and other fluids such as pharyngeal, rectal exudates and blood. A very high proportion of patients with HMPX also have other sexually transmitted diseases that must be actively detected in this context. The spontaneous evolution of our patients has been good and hospitalization has been practically unnecessary. Transmission to non-sexual cohabitants and health personnel has been nonexistent and the lesions have disappeared in less than 30 days without leaving sequelae and no need for specific antiviral treatment.

Antifungal stewardship in a tertiary-care institution: a bedside intervention.

Antifungal stewardship (AFS) programmes are needed in tertiary-care hospitals. Our aim is to describe a bedside non-restrictive AFS programme, and to evaluate its economic impact. During the first year of the AFS a bundle of non-interventional measures were implemented. During the second year an infectious diseases specialist visited 453 patients receiving candins, liposomal amphotericin B, voriconazole or posaconazole. Monthly costs were studied with an interrupted time series (ITS) analysis. The main prescribing departments were haematology (35%), medical departments (23%), and intensive care units (20%). Reasons to start antifungal therapy were: targeted therapy (36%), prophylaxis (32%), empirical therapy (20%) and pre-emptive therapy (12%). At the initial visit, diagnostic advice was provided in 40% of cases. The most common therapeutic recommendations were to de-escalate the antifungal drug (17%) or to suspend it (7%). Annual total antifungal expenditure was reduced from US$3.8 million to US$2.9 million over the first 2 years, generating net savings of US$407,663 and US$824,458 per year after considering the cost of additional staff required. The ITS analyses showed a significant economic impact after the first 12 months of the intervention (p 0.042 at month 13), which was enhanced in the following 24 months (p 0.006 at month 35). The number of defined daily doses decreased from 66.4 to 54.8 per 1000 patient-days. Incidence of candidaemia was reduced from 1.49 to 1.14 (p 0.08) and related mortality was reduced from 28% to 16% (p 0.1). A collaborative and non-compulsory AFS program based on bedside intervention is an efficacious and cost-effective approach that optimizes the use of AF drugs.

BK virus infection in human immunodeficiency virus-infected patients.

The aim of this study is to evaluate the prevalence of BK virus (BKV) infection in HIV-positive patients receiving highly active antiretroviral therapy (HAART) in our hospital. The presence of BKV was analysed in urine and plasma samples from 78 non-selected HIV-infected patients. Clinical data were recorded using a pre-established protocol. We used a nested PCR to amplify a specific region of the BKV T-large antigen. Positive samples were quantified using real-time PCR. Mean CD4 count in HIV-infected patients was 472 cells/mm3 and median HIV viral load was <50 copies/mL. BKV viraemia was detected in only 1 HIV-positive patient, but 57.7% (45 out of 78) had BKV viruria, which was more common in patients with CD4 counts>500 cells/mm3 (74.3% vs 25.7%; p=0.007). Viruria was present in 21.7% of healthy controls (5 out of 23 samples, p=0.02). All viral loads were low (<100 copies/mL), and we could not find any association between BKV infection and renal or neurological manifestations. We provide an update on the prevalence of BKV in HIV-infected patients treated with HAART. BKV viruria was more common in HIV-infected patients; however, no role for BKV has been demonstrated in this population.

Pulmonary aspergillosis in patients with chronic obstructive pulmonary disease: incidence, risk factors, and outcome.

We describe a large series of patients with chronic obstructive pulmonary disease (COPD) and probable invasive pulmonary aspergillosis (IPA), and the risk factors and incidence of the disease in patients with isolation of Aspergillus from lower respiratory tract samples. From 2000 to 2007, we retrospectively studied all patients admitted with COPD and isolation of Aspergillus (239; 16.3/1000 admissions). Multivariate logistic regression and survival curves were used. Fifty-three patients had probable IPA (3.6 cases of IPA per 1000 COPD admissions). IPA affects at least 22.1% of patients with COPD and isolation of Aspergillus in culture. In 33 of the 53 patients with probable IPA, serum galactomannan was determined; in 14 (42.4%) of these, the result was positive. Five variables were independent predictors of IPA with statistical significance: admission to the intensive-care unit, chronic heart failure, antibiotic treatment received in the 3 months prior to admission, the accumulated dosage of corticosteroids equivalent to >700 mg prednisone received in the 3 months prior to admission, and the similar accumulated dosage of corticosteroids received from admission to the first clinical isolation of Aspergillus. Multivariate analysis gave an area under the curve of 0.925 (95% CI 0.888-0.962; p <0.001). The overall mean survival of the cohort was 64.1% (28.3% for IPA patients and 75.2% for non-IPA patients). The median number of days of survival was 48 (95% CI 33.07-62.92). However, we found statistically significant differences between patients with IPA (29 days; 95% CI 20.59-37.40) and patients without IPA (86 days; 95% CI 61.13-110.86) (log rank, p <0.001).

Lung nodular lesions in heart transplant recipients.

To describe the characteristics and etiology of lung nodules after heart transplantation (HT). During a 6-year period 147 patients received HT and 130 survived more than 1 week. Nodular lesions were demonstrated after HT in 13 patients (10%). Median age was 53 years, and all patients were male. Nodules were detected 23 to 158 days after HT (median, 66 days). An etiologic diagnosis was made in all but 1 case: Aspergillus (5), Nocardia-Rhodococcus (4), and cytomegalovirus (CMV) (3). Previous severe infection was present in 50% of the patients and rejection in 33% (75% with nocardiosis). Initially all patients with Nocardia but only 1 patient with aspergillosis were asymptomatic. The most common symptoms were fever (67%) and cough (50%). Central nervous system (CNS) involvement appeared in only one Aspergillus-infected patient. An average of 1.8 diagnostic procedures per patient were performed. Median time to establish a diagnosis was 8 days (0 to 24). Median hospital stay was 36 days and reached 60 in patients with Aspergillus. No patient died, although aspergillosis, which must be suspected in the presence of dyspnea, pleuritic pain, and CNS symptoms, caused the highest morbidity. Overall diagnostic yield was 60% for transtracheal aspiration, 70% for bronchoalveolar lavage, and 75% for transthoracic aspiration. Ten percent of HT patients developed lung nodules that were mainly caused by Aspergillus, Nocardia, and CMV. The time of appearance and some clinical manifestations may suggest the etiology and may help in the empirical treatment.

Regulated transcription of the histone H2B genes of Trypanosoma brucei.

In Trypanosoma brucei, the genes encoding histone H2B are organized in a cluster of about 10-15 tandemly linked copies per haploid genome. The H2B transcripts are processed by trans-splicing and polyadenylation, and encode a polypeptide of 111 residues with a molecular mass of 12.5 kDa. H2B mRNAs are differentially expressed during the parasite life-cycle and are present at higher levels in dividing procyclic and bloodstream slender forms than in the nondividing bloodstream stumpy forms. Analysis of H2B mRNA levels during the synchronous differentiation from stumpy to procyclics forms revealed that the abundance of these transcripts is regulated through the cell-cycle, reaching maximum levels during S-phase. Addition of hydroxyurea to procyclic forms in culture specifically decreased H2B mRNA levels by about twofold, an effect not linked to its 3' untranslated region. Inhibition of protein synthesis prevented this decrease.