Persistent hepatitis C virus (HCV) infection impairs HCV-specific cytotoxic T cell reactivity through Mcl-1/Bim imbalance due to CD127 down-regulation.

In persistent hepatitis C virus (HCV) infection, HCV-specific cytotoxic T lymphocyte (CTL) reactivity is impaired and this affects HCV control. Interleukin-7 receptor (CD127) expression on these cells could regulate CTL reactivity through Mcl-1/Bim balance modulation. Bim is a pro-apoptotic molecule blocked by the action of Mcl-1. Mcl-1/Bim expression and T cell reactivity on HCV-specific CTLs were compared according to CD127 phenotype. Peripheral blood lymphocytes (PBL) from HLA-A2(+) HCV(+) patients were obtained. HCV-specific CTLs were visualized by staining PBL with anti-CD8 and HLA-A2/peptide pentameric complexes (pentamer). Mcl-1/Bim/CD127 phenotype of HCV-specific CTLs was tested by staining detectable CD8(+)/pentamer(+) cells with anti-Mcl-1/Bim/CD127 antibodies. HCV-specific CTL proliferation ability after specific in vitro challenge was tested in the presence and absence of pancaspase inhibitor z-VAD-fmk. All stained cells were analysed by flow cytometry. CD127(low)-expressing HCV-specific CTLs associated with high HCV viraemia, while CD127(high) correlated with undetectable viral loads (P < 0.001). Directly ex vivo, pentamer(+) cell frequency was similar according to CD127 expression level. Nevertheless, CD127(low) pentamer(+) cell proliferation after specific in vitro challenge was impaired (P < 0.05), although this was corrected by z-VAD-fmk treatment (P < 0.05). Mcl-1 expression was low directly ex vivo (P < 0.01), and Bim was up-regulated after antigen encounter (P < 0.05) of CD127(low) pentamer(+) cells. The ex vivo difference between Mcl-1 and Bim expression on pentamer(+) cells correlated positively with CD127 expression level (P < 0.001) and with pentamer(+) cell reactivity (P < 0.05). In summary, a low ex vivo Mcl-1 expression and Bim up-regulation after antigen encounter are involved in CD127(low) HCV-specific CTL hyporeactivity during chronic infection, but it can be overcome by apoptosis blockade.

Mionecrosis rápidamente progresiva por Aeromonas veronii biotipo sobria / Rapidly progressive myonecrosis by aeromonas veronii biotype sobria

La mionecrosis por Aeromonas spp es excepcional. Describimos un caso de mionecrosis rápidamente progresiva por Aeromonas veronii biotipo sobria en un enfermo diabético con cirrosis hepática, cuya puerta de entrada fue un traumatismo al caer a un canal de riego. La evolución fue desfavorable y fue necesaria la amputación quirúrgica de la extremidad inferior izquierda a pesar del tratamiento antibiótico con cefotaxima y tobramicina. Aeromonas spp es un microorganismo que puede resultar muy agresivo y debe ser tenido en cuenta en el diagnóstico diferencial de las infecciones de piel y partes blandas que cursen con mionecrosis, especialmente en infecciones de heridas secundarias a traumatismos en contacto con agua

Myonecrosis due to Aeromonas spp is exceptional. We report the case of a diabetic patient with liver cirrhosis who developed a rapidly progressive myonecrosis by Aeromonas veronii biotype sobria. The portal of entry was an injury after falling down in an irrigation canal. The outcome was not favourable and surgical amputation of left leg was performed in spite of antibiotic treatment with cefotaxime and tobramicin. Aeromonas spp can be very aggressive and this microorganism should be considered in the differential diagnosis of skin and soft tissue infections with myonecrosis, specially after posttraumatic wound infections with a history of freshwater exposure

[Rapidly progressive myonecrosis by Aeromonas veronii biotype sobria]. / Mionecrosis rápidamente progresiva por Aeromonas veronii biotipo sobria.

Myonecrosis due to Aeromonas spp is exceptional. We report the case of a diabetic patient with liver cirrhosis who developed a rapidly progressive myonecrosis by Aeromonas veronii biotype sobria. The portal of entry was an injury after falling down in an irrigation canal. The outcome was not favourable and surgical amputation of left leg was performed in spite of antibiotic treatment with cefotaxime and tobramicin. Aeromonas spp can be very aggressive and this microorganism should be considered in the differential diagnosis of skin and soft tissue infections with myonecrosis, specially after posttraumatic wound infections with a history of freshwater exposure.

[Susceptibility of Streptococcus pyogenes to macrolides and quinolones in Guadalajara, Spain]. / Sensibilidad de Streptococcus pyogenes a los macrólidos y las quinolonas en Guadalajara (España).

We carried out a retrospective study of the susceptibility of 104 Streptococcus pyogenes strains, which were isolated in 2000 and 2001 from clinical samples of different origins, to penicillin, erythromycin, clindamycin, ofloxacin and levofloxacin. The susceptibility testing was performed using the agar difusion method according to the guidelines of the NCCLS. All of the isolates showed susceptibility to penicillin and clindamycin. However, we detected 11 strains that were resistant to erythromycin (10.6%) and 4 strains resistant to ofloxacin (3.8%). We studied the resistance phenotypes of macrolides and lincosamides using erythromycin and clindamycin discs. Nine of the eleven strains that were resistant to erythromycin showed an M phenotype, while the remaining two showed inducible resistance to clindamycin, thus suggesting an MLS(B) inducible phenotype. No strains with constitutive resistance to erythromycin or clindamycin (MLS(B) constitutive phenotype) were identified. While penicillin is still uniformly active against S. pyogenes, in Guadalajara, there are 10.6% strains that are resistant to 14- and 15-atoms macrolides.

Sensibilidad de Streptococcus pyogenesa los macrólidos y las quinolonas en Guadalajara (España) / Susceptibility of Streptococcus pyogenes to macrolides and quinolones in Guadalajara, Spain

Se estudió retrospectivamente la sensibilidad a penicilina, eritromicina, clindamicina y ofloxacino de 104 cepas de Streptococcus pyogenes aisladas durante los años 2000 y 2001 de muestras clínicas procedentes de distintas localizaciones. En las cepas resistentes a ofloxacino se estudió también la sensibilidad a levofloxacino utilizando el método de difusión en agar y siguiendo las normas del NCCLS. Ningún aislamiento fue resistente a penicilina ni clindamicina; en cambio, se detectaron 11 cepas resistentes a eritromicina (10,6 por ciento) y 4 resistentes a ofloxacino (3,8 por ciento). Se estudiaron los fenotipos de resistencia a macrólidos y lincosamidas empleando discos de eritromicina y clindamicina. Nueve de las 11 cepas resistentes a eritromicina mostraron un fenotipo M, mientras que las dos restantes presentaron resistencia inducible frente a clindamicina, sugiriendo un fenotipo MLSB inducible. No se encontraron cepas con fenotipo de resistencia constitutiva a eritromicina y clindamicina (fenotipo MLSB constitutivo). La penicilina sigue siendo uniformemente activa frente a S. pyogenes, mientras que en el área sanitaria de Guadalajara existe un 10,6 por ciento de cepas resistentes a los macrólidos de 14 y 15 átomos (AU)

[Incidence and risk factors for hepatitis A in the province of Guadalajara (Spain)]. / Incidencia y factores de riesgo de hepatitis A en la provincia de Guadalajara.

BACKGROUND: The decrease in the prevalence of hepatitis A in Spain may modify the characteristics of this infection because of the rise in the susceptible adult population. The aim of this study was to determine the incidence of this disease, as well as the epidemiological characteristics and the complications of patients diagnosed in the province of Guadalajara between 1991 and 1999. PATIENTS AND METHODS: The inclusion criterion was the presence of specific IgM together with an increase in alanine aminotransferase concentrations and/or symptoms compatible with acute hepatitis. RESULTS: The mean incidence was 7.13 cases/105 inhabitants. Considerable differences were found between years due to the presence of an outbreak. Most cases occurred in children and young adults. The most frequent risk factor found overall was contact with an infected individual but the distribution of risk factors differed between children and adults. CONCLUSIONS: The decrease in the prevalence of hepatitis A in Spain entails an increase in the susceptible adult population. Consequently, hepatitis A may cease to be a typically pediatric disease and may become one that also affects young adults in whom it may have different characteristics. This consideration should be borne in mind when designing a vaccination strategy.

[The prevalence of hepatitis A in the Guadalajara province. Is Spain a country with low endemia?]. / Prevalencia de hepatitis A en la provincia de Guadalajara. Es España un país de baja endemia?

BACKGROUND: Spain, together with the other southern European countries, was considered to be an area with a moderate degree of endemia. This fact has consequences for tourists that visit these areas and for vaccination strategies. A prevalence study was proposed in order to get to know the situation of this infection in the Guadalajara province. METHODS: 284 specimens of serum were taken from patients who were classified according to their age, sex and place of residence (with more or less than 10.000 inhabitants). In these specimens the presence of hepatitis A antibodies were studied, using a Microparticule Enzyme Immunoassay (MEIA) (Abbott). RESULTS: An increase in the prevalence was observed in older people, there is a low prevalence population (80%) in adults aged between 30 and 74 years. No differences were observed related to sex. In the stratified analysis according to age, differences were observed between the groups from rural and urban origins. CONCLUSIONS: The low prevalence of hepatitis A was found among the younger population, as seen in other studies carried out on a national level, and this together with a decrease in the frequency, means that Spain is included among the countries with low endemia. This fact has consequences for tourists who visit our country and for vaccination strategies, due to the increase in the number of adults who are susceptible to the infection.

[Seroprevalence of three types of hepatotropic virus in a population of adolescents of the province of Guadalajara]. / Seroprevalencia de tres tipos de virus hepatotropos en población adolescente de la provincia de Guadalajara.

BACKGROUND: Viral forms of hepatitis are one of the most infectious disease groups most often encountered in human pathology, and although most are benign, some can evolve into chronic forms. The purpose of this study is that of ascertaining the prevalence of hepatitis C, Epstein-Barr and human herpesvirus-6 infections among eighth-graders (13-14 years of age) and to related the same to variables regarding the gender and environment (rural or urban) in which they were living. METHODS: Descriptive, transversal study of a representative sample of the eighth-grade population in the province of Guadalajara during the 1998-1999 period. Systematic random sampling layered by gender and school (multi-stage sample format). The rate of specific IgG antibodies was determined using the ELISA technique. RESULTS: A study was conducted of 268 school-age children (46.6% males). The prevalence of Epstein-Barr antibodies was of 73.5% (CI: 67.9%-78.5%); 72% (CI: 64%-80%) among the males and of 74.8% (CI: 67.7%-81.9%) among the females (NS); 65.6% (CI: 57.4%-73.8%) residing in an urban environment and 80.7% in a rural environment (p < 0.05). The prevalence of those who tested positive for the hepatitis virus was that of 0.7%--two individuals, both females, one of whom resided in an urban environment and the other in a rural environment. For herpesvirus-6, the prevalence was of 82.4% (CI: 77.9%-86.9%); 81.5% (CI: 74.7%-88.3%) among the males and of 83.2% (CI: 77.1%-89.3%) among the females (NS), 86.7% (CI: 80.4%-92.2%) residing in an urban environment and 78.5% (CI: 73.1%-86.5%) in a rural environment (p < 0.05). CONCLUSIONS: The prevalence of Epstein-Barr and human herpesvirus-6 and low degree as regards VHC is high, which tallies with the characteristics of the environment and age of the individuals under study.

[Urinary infection caused by non typhi Salmonella]. / Infección urinaria por Salmonella no typhi.

BACKGROUND: The aim of this study was to know the frequency and the clinical characteristics of urinary infection by non typhi Salmonella in our area in Spain. PATIENTS AND METHODS: The clinical histories of patients with urinary infection by non typhi Salmonella diagnosed in the Hospital General del Guadalajara from January 1990 to July 1999 were reviewed. RESULTS: During the period studied nine patients with urinary infection by non typhi Salmonella were diagnosed, representing 0.056% of the urinary infection diagnosed in our hospital over the same period. All the patients presented underlying disease and five were undergoing immunosuppressor treatment. Four patients presented urological disease. The most frequent serogroup was Salmonella enteritidis (7 cases). All the episodes were symptomatic. The same microorganism was isolated in stools in four patients. The evolution was favorable in five of the nine cases. Recurrence was observed in two patients and secondary bacteremia in one. Six patients required antibiotic treatment over two or more weeks. The mean length of treatment was of 2.5 weeks. CONCLUSIONS: Urinary infection by non typhi Salmonella is predominantly observed in patients undergoing immunosuppression or with urological disease. Prolonged antibiotic treatment is recommended due to its bad evolution.