Behaviour of the pandemic H1N1 influenza virus in Andalusia, Spain, at the onset of the 2009-10 season.

In Andalusia, Spain, the pandemic influenza A(H1N1)v virus has spread throughout the community, being the dominant influenza strain in the season so far. The current objective of the Andalusia Health Service is focussed on the mitigation of the health and social impact by appropriate care of the patients at home or in health centres. The 2009-10 seasonal influenza epidemic started early compared with to previous seasons. This article analyses the influenza A(H1N1)v situation in Andalusia until the week 39/2009.

Aumentar el diagnóstico precoz y la prevención frente al VIH y reducir el estigma, retos del futuro Plan andaluz de SIDA

Boletín semanal para profesionales sanitarios de la Secretaría General de Salud Pública y Participación Social de la Consejería de Salud

Iron overload, an immunosuppression marker in HIV-infected patients.

Purpose: Iron overload (IO) has been associated with increased cardiovascular risk (CVR) and metabolic syndrome (MS) in the general population; both elevated CVR and MS are frequent in HIV- patients. Our aim was to analyze the prevalence of IO in a cohort of asymptomatic patients with HIV infection, and related factors. Methods: Cross-sectional study of a cohort of HIV outpatients in regular follow-up. Demographic, epidemiological, clinical, analytical and therapeutic data were collected. Patients completed a questionnaire about CVR factors and 10-year CV disease risk estimation (Framingham score), underwent a physical exam, and a fasting blood analysis. IO was defined as a plasma ferritin level higher than 200 m/L in women and 300 m/L in men. Results: 571 patients (446 men, 125 women), with a mean age of 43.2 years, sexual transmission of HIV in 68.5%, median CD4 count 474 cell/μL (IQR: 308-666), and 36.3% Aids cases 86.2% were on antiretroviral therapy (ART), and 74.8% of them had undetectable HIV viral load 14.6% met MS criteria, and mean CVR at 10 years was 6.67%. IO was detected in 11% of cases. Patients with IO were more immunosuppressed (CD4 count 369 vs 483/μL, p<0.0001), presented a higher prevalence of detectable HIV viral load (17.6% vs 8.9%; p<0.005), and of Aids cases (14.9% vs 8.7%; p<0.023), and lower plasma levels of cholesterol, HDLc and LDLc (154 vs 183, 34 vs 43, 93 vs 110 mg/dL, respectively; p<0.0001. In the multivariate analysis, the only related factor was CD4 count <350 cell/μL (OR 2.86, 95% CI 1.6-4.9; p<0.0001). IO was not associated with CVR nor with MS. Conclusions: IO is not uncommon in HIV patients, and it is only related with immunosuppression defined as CD4 count <350 cell/ mL, and in contrast to general population, it is not related with increased CVR nor with MS.

Bone turnover markers in HIV-infected patients before starting antiretroviral therapy.

Purpose: Bone turnover markers (BTM) - aminoterminal propeptide of type 1 collagen (P1NP) and C-terminal telopeptide of type 1 collagen (b-CTX) - are related to bone density and fracture risk. A high prevalence of osteopenia/osteoporosis and hypovitaminosis D has been reported in HIV patients, however there are few data about BTM in this population. Our aim was to analyse the prevalence of elevated serum levels of BTM in HIV patients before starting antiretroviral therapy (ART), and related factors. Methods: Cross-sectional study of a series of HIV-patients who started ART during June/11-June/12 in our hospital. Patients with presence of diseases or treatments known to affect bone metabolism were excluded. Epidemiological, clinical, and immunovirological data in addition to serum fasting levels of glucose, lipid profile, calcium, phosphate, alkaline phosphatase, 25-hydroxyvitamin D3 (25OHD), parathyroid hormone (PTH), P1NP, and β-CTX were collected. Definitions: hypovitaminosis D if 25OHD<30 ng/ml, vitamin D deficiency if 25OHD<20 ng/ml; elevated levels of BTM if β-CTX (ng/ml) >0.64 (men<70 years),>0.85 (men>70 years),>0.58 (pre-menopause women), >0.99 (post-menopause women), or P1NP (ng/mL)>69.4 (men<60 years), >71.1 (men>60 years), >55.7 (pre-menopause women), >61.2 (post-menopause women). Results: 47 patients were included, 91.5% men, median age 37.1 years (30.0-44.3), and 93.6% sexual transmission of HIV (34 HMX, 10 HTX). Median time since the diagnosis of HIV was 3.4 months (1.4- 31.7); there were 7 (14.9%) Aids cases, median CD4 count was 277/ mm3 (155-433), and HIV-VL 4.8 log10 (4.1-5.2). Median serum 25OHD was 29 mg/L (21.9-41.1), with a prevalence of hypovitaminosis of 52.2%, and deficiency of 17.4%. PTH was in range in all cases. Median serum P1NP was 33.3 ng/mL (24.5-52.5) and β-CTX 0.25 ng/mL (0.20-0.45); five (11.4%) patients presented high levels of BTM: 4 men, median age 37.1 years, median CD4 count 247/mm3, median HIV-VL 5.18 log10, and one with hypovitaminosis D. Elevated BTM were related with no clinical, analytical, immunovirological parameters nor with serum levels of 25OHD nor PTH. Conclusions: The prevalence of elevated BTM was high in this series of HIV-patients, mostly young men, with short time of HIV infection and with no immunovirologic control. BTM were related with no clinical nor analytical data.

Variation of transaminases, HCV-RNA levels and Th1/Th2 cytokine production during the post-partum period in pregnant women with chronic hepatitis C.

This study analyses the evolution of liver disease in women with chronic hepatitis C during the third trimester of pregnancy and the post-partum period, as a natural model of immune modulation and reconstitution. Of the 122 mothers recruited to this study, 89 were HCV-RNA+ve/HIV-ve and 33 were HCV-RNA-ve/HIV-ve/HCVantibody+ve and all were tested during the third trimester of pregnancy, at delivery and post-delivery. The HCV-RNA+ve mothers were categorized as either Type-A (66%), with an increase in ALT levels in the post-partum period (>40 U/L; P<0.001) or as Type-B (34%), with no variation in ALT values. The Type-A mothers also presented a significant decrease in serum HCV-RNA levels in the post-delivery period (P<0.001) and this event was concomitant with an increase in Th1 cytokine levels (INFγ, P = 0.04; IL12, P = 0.01 and IL2, P = 0.01). On the other hand, the Type-B mothers and the HCV-RNA-ve women presented no variations in either of these parameters. However, they did present higher Th1 cytokine levels in the partum period (INFγ and IL2, P<0.05) than both the Type-A and the HCV-RNA-ve women. Cytokine levels at the moment of delivery do not constitute a risk factor associated with HCV vertical transmission. It is concluded that differences in the ALT and HCV-RNA values observed in HCV-RNA+ve women in the postpartum period might be due to different ratios of Th1 cytokine production. In the Type-B women, the high partum levels of Th1 cytokines and the absence of post-partum variation in ALT and HCV-RNA levels may be related to permanent Th1 cytokine stimulation.

Waiting for chikungunya fever in Argentina: spatio-temporal risk maps

Chikungunya virus (CHIKV) transmission has been detected in America in 2013 and recently reached south up to Bolivia, Brazil and Paraguay, bordering countries of Argentina. The presence of the mosquito Aedes aegyptiin half of the country together with the regional context drove us to make a rapid assessment of transmission risk. Temperature thresholds for vector breeding and for virus transmission, together with adult activity from the literature, were mapped on a monthly basis to estimate risk. Transmission of chikungunya byAe. aegyptiin the world was seen at monthly mean temperatures from 21-34ºC, with the majority occurring between 26-28ºC. In Argentina temperatures above 21ºC are observed since September in the northeast, expanding south until January and retreating back to the northeast in April. The maximum area under risk encompasses more than half the country and around 32 million inhabitants. Vector adult activity was registered where monthly means temperatures exceeded 13ºC, in the northeast all over the year and in the northern half from September-May. The models herein proposed show that conditions for transmission are already present. Considering the regional context and the historic inability to control dengue in the region, chikungunya fever illness seems unavoidable.

Epidemiological and clinical data of hospitalizations associated with respiratory syncytial virus infection in children under 5 years of age in Spain: FIVE multicenter study.

BACKGROUND Respiratory syncytial virus (RSV) is an important pathogen in lower respiratory tract infections (LRTI) in infants, but there are limited data concerning patients with underlying conditions and children older than 2 years of age. METHODS We have designed a prospective observational multicenter national study performed in 26 Spanish hospitals (December 2011-March 2012). Investigational cases were defined as children with underlying chronic diseases and were compared with a group of previously healthy children (proportion 1:2). Clinical data were compared between the groups. RESULTS A total of 1763 children hospitalized due to RSV infection during the inclusion period were analyzed. Of them, 225 cases and 460 healthy children were enrolled in the study. Underlying diseases observed were respiratory (64%), cardiovascular (25%), and neurologic (12%), as well as chromosomal abnormalities (7·5%), immunodeficiencies (6·7%), and inborn errors of metabolism (3·5%). Cases were statistically older than previously healthy children (average age: 16·3 versus 5·5 months). Cases experienced hypoxemia more frequently (P < 0·001), but patients with respiratory diseases required oxygen therapy more often (OR: 2·99; 95% CI: 1·03-8·65). Mechanical ventilation was used more in patients with cardiac diseases (OR: 3·0; 95% CI: 1·07-8·44) and in those with inborn errors of metabolism (OR: 12·27; 95% CI: 2·11-71·47). This subgroup showed a higher risk of admission to the PICU (OR: 6·7, 95% CI: 1·18-38·04). Diagnosis of pneumonia was more frequently found in cases (18·2% versus 9·3%; P < 0·01). CONCLUSIONS A significant percentage of children with RSV infection have underlying diseases and the illness severity is higher than in healthy children.

The role of polymerase chain reaction of high-risk human papilloma virus in the screening of high-grade squamous intraepithelial lesions in the anal mucosa of human immunodeficiency virus-positive males having sex with males.

OBJECTIVES To evaluate the advantages of cytology and PCR of high-risk human papilloma virus (PCR HR-HPV) infection in biopsy-derived diagnosis of high-grade squamous intraepithelial lesions (HSIL = AIN2/AIN3) in HIV-positive men having sex with men (MSM). METHODS This is a single-centered study conducted between May 2010 and May 2014 in patients (n = 201, mean age 37 years) recruited from our outpatient clinic. Samples of anal canal mucosa were taken into liquid medium for PCR HPV analysis and for cytology. Anoscopy was performed for histology evaluation. RESULTS Anoscopy showed 33.8% were normal, 47.8% low-grade squamous intraepithelial lesions (LSIL), and 18.4% HSIL; 80.2% had HR-HPV. PCR of HR-HPV had greater sensitivity than did cytology (88.8% vs. 75.7%) in HSIL screening, with similar positive (PPV) and negative predictive value (NPV) of 20.3 vs. 22.9 and 89.7 vs. 88.1, respectively. Combining both tests increased the sensitivity and NPV of HSIL diagnosis to 100%. Correlation of cytology vs. histology was, generally, very low and PCR of HR-HPV vs. histology was non-existent (<0.2) or low (<0.4). Area under the receiver operating characteristics (AUROC) curve analysis of cytology and PCR HR-HPV for the diagnosis of HSIL was poor (<0.6). Multivariate regression analysis showed protective factors against HSIL were: viral suppression (OR: 0.312; 95%CI: 0.099-0.984), and/or syphilis infection (OR: 0.193; 95%CI: 0.045-0.827). HSIL risk was associated with HPV-68 genotype (OR: 20.1; 95%CI: 2.04-197.82). CONCLUSIONS When cytology and PCR HR-HPV findings are normal, the diagnosis of pre-malignant HSIL can be reliably ruled-out in HIV-positive patients. HPV suppression with treatment protects against the appearance of HSIL.

Zika virus damages the human placental barrier and presents marked fetal neurotropism

An unusually high incidence of microcephaly in newborns has recently been observed in Brazil. There is a temporal association between the increase in cases of microcephaly and the Zika virus (ZIKV) epidemic. Viral RNA has been detected in amniotic fluid samples, placental tissues and newborn and fetal brain tissues. However, much remains to be determined concerning the association between ZIKV infection and fetal malformations. In this study, we provide evidence of the transplacental transmission of ZIKV through the detection of viral proteins and viral RNA in placental tissue samples from expectant mothers infected at different stages of gestation. We observed chronic placentitis (TORCH type) with viral protein detection by immunohistochemistry in Hofbauer cells and some histiocytes in the intervillous spaces. We also demonstrated the neurotropism of the virus via the detection of viral proteins in glial cells and in some endothelial cells and the observation of scattered foci of microcalcifications in the brain tissues. Lesions were mainly located in the white matter. ZIKV RNA was also detected in these tissues by real-time-polymerase chain reaction. We believe that these findings will contribute to the body of knowledge of the mechanisms of ZIKV transmission, interactions between the virus and host cells and viral tropism.

Cutaneous leishmaniasis mimicking a pyogenic granuloma.

The Leishmania genus is formed by parasitic protozoa which are transmitted by the bite of infected female sand flies. Cases of sexual, vertical or transfusional transmission or via infected needles have also been described. In humans, 4 forms of this disease have been described: localised cutaneous (LC), diffuse cutaneous, mucocutaneous and visceral (1). LC counts for 50–75% of all cases (2), it is the mildest form of the disease and can be caused by any species of Leishmania. In Spain, the most frequent form is the oriental sore caused by L. infantum (2). Most cases resolve spontaneously within one year. In United States and Europe, the incidence is increasing due to tourism and co-infection with HIV. The morphological spectrum of LC is very wide; multiple forms of clinical presentation have been described, although the most characteristic one is the nodular ulcerative lesion, characterised by painless crater-like ulcers with a necrotic base and covered by an adhesive crust. The main complication of LC is its progression in some strains towards the other 3 forms of the disease (3). In patients with AIDS and other diseases associated with immunosuppression the risk of dissemination is much higher than in the immunocompetent. We present a case of LC with clinical and histopathological features similar to a pyogenic granuloma.

Management of hepatitis B virus infection after liver transplantation.

Chronic hepatitis B virus (HBV) infection is responsible for up to 30% of cases of liver cirrhosis and up to 53% of cases of hepatocellular carcinoma. Liver transplantation (LT) is the best therapeutic option for patients with end-stage liver failure caused by HBV. The success of transplantation, though, depends on receiving prophylactic treatment against post-transplant viral reactivation. In the absence of prophylaxis, liver transplantation due to chronic hepatitis B (CHB) is associated with high rates of viral recurrence and poor survival. The introduction of treatment with hepatitis B immunoglobulins (HBIG) during the 1990s and later the incorporation of oral antiviral drugs have improved the prognosis of these patients. Thus, LT for CHB is now a universally accepted option, with an estimated 5 years survival of around 85% vs the 45% survival seen prior to the introduction of HBIG. The combination of lamivudine plus HBIG has for many years been the most widely used prophylactic regimen. However, with the appearance of new more potent oral antiviral agents associated with less resistance (e.g., entecavir and tenofovir) for the treatment of CHB, new prophylactic strategies are being designed, either in combination with HBIG or alone as a monotherapy. These advances have allowed for more personalized prophylaxis based on the individual risk profile of a given patient. In addition, the small pool of donors has required the use of anti-HBc-positive donors (with the resulting possibility of transmitting HBV from these organs), which has been made possible by suitable prophylactic regimens.

A V beta 4-specific superantigen encoded by a new exogenous mouse mammary tumor virus.

The superantigen (SAg) expressed by mouse mammary tumor virus (MMTV) has been shown to play an essential role in the course of the viral life cycle. In the present study, we describe a V beta 4-specific SAg encoded by a new exogenous MMTV carried by the SIM mouse strain. This is the first report of a viral or bacterial SAg reacting with mouse V beta 4+ T cells. Injection of MMTV(SIM) into adult BALB/c mice leads to a rapid and strong stimulation of V beta 4+ CD4+ T cells, followed by a slow deletion of these cells. Neonatal exposure to the virus also leads to a progressive deletion of V beta 4+ T cells. In contrast to other strong MMTV SAg, this new SAg requires the presence of major histocompatibility complex class II I-E molecules to be presented efficiently to T cells. Sequence analysis revealed a new predicted amino acid sequence in the C-terminal polymorphic region of this SAg. Furthermore, sequence comparisons to the most closely related SAg with different V beta specificities hint at the specific residues involved in the interaction with the T cell receptor.

Interplays between mouse mammary tumor virus and the cellular and humoral immune response.

Mouse mammary tumor virus has developed strategies to exploit the immune response. It requires vigorous immune stimulation to achieve efficient infection. The infected antigen-presenting cells present a viral superantigen on the cell surface which stimulates strong CD4-mediated T-cell help but CD8 T-cell responses are undetectable. Despite the high frequency of superantigen-reactive T cells, the superantigen-induced immune response is comparable to classical antigen responses in terms of T-cell priming, T-cell-B-cell collaboration as well as follicular and extra-follicular B-cell differentiation. Induction of systemic anergy is observed, similar to classical antigen responses where antigen is administered systemically but does not influence the role of the superantigen-reactive T cells in the maintenance of the chronic germinal center reaction. So far we have been unable to detect a cytotoxic T-cell response to mouse mammary tumor virus peptide antigens or to the superantigen. This might yet represent another step in the viral infection strategy.