Hepatitis E virus genotype 3 microbiological surveillance by the Spanish Reference Laboratory: geographic distribution and phylogenetic analysis of subtypes from 2009 to 2019.

BackgroundHepatitis E virus genotype 3 (HEV-3) is widely distributed throughout Europe, with incidence of infections increasing in many countries. Belgium, Bulgaria, France, Germany, Italy, the Netherlands and the United Kingdom have reported the distribution of HEV-3 subtypes in cohorts of patients with hepatic disease.AimTo describe the distribution of the HEV-3 subtypes in Spain at national and autonomous community (AC) levels between 2009 and 2019. The study was also extended to Andorra.MethodsOf 5,197 samples received by the National Reference Laboratory during the study, 409 were HEV-RNA-positive. Among these, 294 (71.9%) were further typed based on an ORF2 sequence fragment, or, for a subset of 74, based on the full-coding genome sequence.ResultsHEV-3 was detected in 291 samples. The dominant subtype in Spain was HEV-3f (88.3%; 257/291), which occurred in all ACs, with no change in detection level over time. Within this subtype, three subclusters were characterised: HEV-3f-B, HEV-3f-A1 and HEV-3f-A2. The second most common HEV subtype was the recently described HEV-3m (7%; 21/291), with two subclusters identified: HEV-3m-A, which has been known since 2010, and HEV-3m-B, since 2014. The third most encountered subtype was HEV-3c (4.1%; 12/291), with a frequency not increasing over time, unlike observations in some European countries.ConclusionThe importance of the surveillance of HEV-3 subtype and subcluster circulation is yet to be assessed. This surveillance together with the comprehensive epidemiological characterisation of clinical cases, could support the identification of sources of transmission and the establishment of control measures nationally and internationally.

Glomerulonephritis and cryoglobulinemia: first manifestation of visceral leishmaniasis.

Visceral leishmaniasis due to Leishmania Infantum is an endemic parasitic infection in the Mediterranean area. Since 2009, Europe's largest outbreak of Leishmaniasis has been reported in the region of Madrid (Spain). Renal involvement is an unusual complication. Different forms of renal disease have been described: interstitial, glomerular, and vascular damage. Direct invasion of renal parenchyma by the parasite has been described as a mechanism of kidney damage, especially in the immunocompromised. Immune complex deposition and T cells adhesion molecules activation have demonstrated that a pathogenic role in glomerulonephritis related to visceral leishmaniasis. The association between mixed cryoglobulinemia and visceral leishmaniasis has been previously reported in six patients. Renal involvement is only described in one of them. From July 2009 to October 2012, 4 patients with membranoproliferative glomerulonephritis and mixed cryoglobulinemia with negative serology for hepatitis B and C were diagnosed in our hospital. Serology of Leishmania in serum bank samples was performed; it was positive in 3 patients. Leishmania parasite was confirmed by other tests. We present 3 patients with mixed cryoglobulinemia and membranoproliferative glomerulonephritis as first clinical manifestation of visceral leishmaniasis.

[Immunological effectiveness of the nucleoside/nucleotide analog combinations, tenofovir + lamivudine, didanosine + lamivudine and tenofovir + didanosine, in patients with HIV infection and sustained viral suppression]. / Efectividad inmunológica de las combinaciones de análogos de nucleósidos/nucleótidos, tenofovir + lamivudina, didanosina + lamivudina y tenofovir + didanosina, en pacientes con infección por el VIH y supresión virológica mantenida.

BACKGROUND: Several recent studies have shown that the combination of ddI plus TDF can produce an unexpected drop in CD4 cell counts, even after correcting the ddI dose. OBJECTIVE: Comparative study of the immunological effectiveness of various once-daily NRTI backbones (ddI plus TDF, ddI plus 3TC or TDF plus 3TC) in antiretroviral-experienced HIV-infected patients achieving viral suppression (PCR, HIV-RNA < 50 copies/microl). METHODS: Prospective cohort study of 48 weeks' duration following viral load suppression with any of the NRTI combinations studied. The main outcome variable was the increase in CD4+ lymphocyte count from the time that viral load was undetectable or treatment was changed for simplification or toxicity (baseline) up to 48 weeks of follow-up. Differences between the assigned therapies were compared. The variables included in analysis were age, sex, risk group, HCV infection, clinical categories of HIV (CDC criteria), lowest CD4 cell count, reason for change of NRTI backbone, type of antiretroviral treatment (PI, NNRTI, or 3 NRTI) and duration of suppressed viral load. RESULTS. Regimens including ddI plus TDF showed significant decreases in CD4 cell counts with adjustments by type of HAART, reason for change, and duration of suppressed viral load. In patients treated with TDF + 3TC, CD4 count increased by 160 cel/microl (95% CI, 53-266) more than in patients treated with TDF + ddI; and in patients receiving ddI + 3TC, CD4+ count increased by 138 cel/microl (95% CI, 25-266) more than in patients receiving TDF + ddI. CONCLUSIONS: The ddI plus TDF backbone seems unadvisable because of the lower associated CD4 cell counts, and because it is poorer than the other options from the immunological standpoint.

[Factors predicting the failure of interruption of highly active antiretroviral treatment (HAART) in HIV-infected patients]. / Factores que predicen el fracaso de las interrupciones del tratamiento antirretroviral (TAR) en los pacientes con infección por el VIH.

INTRODUCTION: Treatment interruptions may be an alternative to HAART in the management of chronically infected HIV-patients. We designed this study in an attempt to assess the predictability of this strategy. METHODS: We recruited HIV-infected patients whose treatment had been suspended. Interruption was due to the patient's own decision, or toxicity, or because the patient had started the treatment with more than 350 CD41 cells/microL (immunologic criteria). RESULTS: Forty-one consecutive patients were included, with a median follow-up of 13 months. Failure was associated with the reason for interruption (p 5 0.0063). Failure occurred in 14.3% of those who interrupted treatment due to immunological criteria and in 40% of those who interrupted treatment due to their own decision or toxicity. The reasons for interruption were: toxicity in 11 patients (26.8%), personal decision in 9 (21.9%) and immunological criteria in 21 (51.2%). In the univariate analysis, the nadir CD41 cell count < 350 cél./microL [OR 16 (p = 0.054)] was statistically significant in the patients who stopped treatment due to immunological criteria, while treatment with protease inhibitors [OR 14 (p = 0.032)] was statistically significant in the remaining patients. In the multivariable analysis only nadir CD41 < 350 cél./microL was independently related with failure. CONCLUSIONS: Failure was related to interruption criteria and was greater in patients who stopped due their own decision or toxicity. When interruption was due to immunological criteria, the factor predicting failure was nadir CD41 cell count < 350 cél./microL. In the remaining patients, none of the variables was related to failure.

Acute viral gastroenteritis: proportion and clinical relevance of multiple infections in Spanish children.

Dual infections associated with acute infectious diarrhoea and its microbiological, epidemiological and clinical findings have been evaluated in patients selected from a comprehensive survey of children under 4 years old, admitted to hospital emergency rooms from October 1996 to November 1997. A total of 820 children (433 males and 387 females) were enrolled. Stools were tested for rotavirus, adenovirus, astrovirus and bacterial enteropathogens. Patients were grouped according to age, and the seasonality of mixed infections was evaluated. Clinical trends and severity of gastrointestinal disease by Ruuska's score were also analysed. Mixed infections were identified in 39 cases (5 %), of which 23 were males and 16 were females. The majority of cases were in the 7-18-month age group (26 cases) and occurred in autumn (67 %). Virus-virus co-infections were more frequent (26/39) than virus-bacteria co-infections (13/39). More than two infectious agents were detected in only four cases. The most common viral co-infections were rotavirus-astrovirus (13/26) and rotavirus-adenovirus (10/26). The present report is the first prospective analysis of clinical-epidemiological trends of dual infections in young Spanish children with acute viral gastroenteritis. Our results emphasize the clinical importance of mixed infections as a cause of severe diarrhoea in children.