Meningococcal meningitis is still the commonest neuroinfection in the community in tropics: overview of 62 cases

Within last 17 years we went through all charts of bacterial meningitis within our nationwide survey and among 372 cases we found 62 cases of MM, in 12 cases with meningococcal disease (with shock, petechial effusions or disseminated intravascular coagulation or digital gangrenes). MM was usually observed in young adults without any of investigated risk factors like neoplasia, ENT (ear, nose, throat) focuses, elderly age, sepsis, diabetes, alcoholism, trauma, neonatal VLBW etc. Trauma, diabetes mellitus, alcohol abuse and chronic sinusitis/otitis were significantly less frequently found as a risk factor for MM. Mortality was very low, only 4.8% and was lower than overall mortality in CBM (12.4%, NS). Also the proportion of neurologic sequellae (9.7%) and initial treatment failure (8.1%) were comparable or even lower. This positive outcome results are probably because all N. meningitis strains were susceptible to penicillin, chloramphenicol, cefotaxim, cotrimoxazol or ciprofloxacin. Other reason for low mortality was that most cases received oral antibiotic immediately, even before admission (50 of 62). 95.2% of cases survived, 90.3% without any transient neurological residual symptoms.     

Epidemiology and risk factors for bloodstream infections after allogeneic hematopoietic stem cell transplantion

A total of 315 patients who underwent allogeneic Hematopoietic Stem Cell Transplantation (HSCT) during a 4-year period were analysed with the aim of collecting information on bloodstream infections (BSI). Eighty-four patients (27%) developed 112 BSI, with a cumulative risk of 20.6% at 30 days and 27.7% at 180 days. Overall, 127 pathogens were isolated, 95 (75%) gram-positive cocci, 27 (21%) gram-negative rods and 5 (4%) fungi. Enterococcus sp. accounted for 46 of 127 (36%) isolates. In a multivariable analysis only including baseline factors, the type of transplant was the only factor significantly associated with the risk of BSI and the risk was higher for patients receiving transplant from mismatched or unrelated donors. In a case-control study aimed at evaluating the predictive role of additional factors during transplant, the risk appeared to be higher in patients with a positive CMV antigenemia (p = 0.03; OR of 4.82; 95% CI, 1.21-19.17), long duration of severe granulocytopenia (p = 0.015; OR 7.53; 95% CI, 1.92 - 29.58) and lower platelet count (p < 0.001; OR 0.14; 95% CI, 0.05 - 0.40). By day 180 post-transplant, 87 (28%) out of 314 patients had died. The cumulative risk of death was significantly higher among patients with BSI than among other patients.     

Polymorphisms in glutathione S-transferase are risk factors for perioperative acute myocardial infarction after cardiac surgery: a preliminary study

In the present study we explored glutathione S-transferase (GST) polymorphisms in selected patients who experienced accelerated myocardial injury following open heart surgery and compared these to a control group of patients without postoperative complications. 758 Patients were enrolled from which 132 patients were selected to genotype analysis according to exclusion criteria. Patients were divided into the following groups: Group I: control patients (n = 78) without and Group II.: study patients (n = 54) with evidence of perioperative myocardial infarction. Genotyping for GSTP1 A (Ile105Ile/Ala113Ala), B (Ile105Val/Ala113Ala) and C (Ile105Val/Ala113Val) alleles was performed by using real-time-PCR. The heterozygous AC allele was nearly three times elevated (18.5 vs. 7.7 %) in the patients who suffered postoperative myocardial infarction compared to controls. Contrary, we found allele frequency of 14.1 % for homozygous BB allele in the control group whereas no such allele combination was present in the study group. These preliminary results may suggest the protective role for the B and C alleles during myocardial oxidative stress whereas the A allele may represent predisposing risk for cellular injury in patients undergoing cardiac surgery.     

Behavioral and sociodemographic risk factors for serological and DNA evidence of HPV6, 11, 16, 18 infections

Introduction: Risk for HPV6/11/16/18 infections in young sexually active, behaviorally low-risk females is not well described and may inform public policy. Methods: To assess exposure risk for HPV/6/11/16/18 among 16–23 year old low-risk females, data for 2409 female clinical trial participants were evaluated. Baseline visit self-reported sexual, behavioral and demographic characteristics; and results from HPV genotyping and serology, and other clinical laboratory assays were analyzed. All subjects reported <5 lifetime male sexual partners and no prior abnormal cytology at baseline. Results: While 98% (2211/2255) were naïve to HPV16 or 18 and 99.6% (2246/2255) were naïve for 1–3 index HPVs, 27% (616/2255) showed antibody, DNA or both for ≥1 index HPV. While 18% (409/2255) tested HPV16- or -18-antibody- or -DNA-positive, only 2% (44/2255) tested positive for both types. Against this high background, other sexually transmitted infections (STIs) were uncommonly detected, suggesting low sexual risk-taking behavior. The adjusted analyses showed race, age, alcohol consumption, current Chlamydia trachomatis (chlamydia) and Trichamonas vaginalis (trichomoniasis), bacterial vaginosis (BV), number of lifetime male sex partners predicted positive index-HPV antibody test results. However, only the number of male sex partners predicted positivity for HPV6/11- and 16/18-DNA, and chlamydia infection predicted positivity for HPV6/11-DNA alone. Conclusions: Taken together, type-specific HPV-DNA and -antibody evidence of HPV6/11/16/18 infections among behaviorally low-risk 16–23 year old females is high. Since almost all participants would have benefited by either currently available bivalent or quadrivalent vaccine strategies, delaying vaccination beyond menarche may be a missed opportunity to fully protect young females against HPV6/11/16/18 infections and related dysplasias. Early diagnosis and treatment of chlamydia and trichomonas may be important in HPV pathogenesis.     

Rates of, and risk factors for, severe infections in patients with systemic autoimmune diseases receiving biological agents off-label

Introduction

The purpose of this observational study was to analyze the rates, characteristics and associated risk factors of severe infections in patients with systemic autoimmune diseases (SAD) who were treated off-label with biological agents in daily practice.

Methods

The BIOGEAS registry is an ongoing Spanish prospective cohort study investigating the long-term safety and efficacy of the off-label use of biological agents in adult patients with severe, refractory SAD. Severe infections were defined according to previous studies as those that required intravenous treatment or that led to hospitalization or death. Patients contributed person-years of follow-up for the period in which they were treated with biological agents.

Results

A total of 344 patients with SAD treated with biological agents off-label were included in the Registry until July 2010. The first biological therapies included rituximab in 264 (77%) patients, infliximab in 37 (11%), etanercept in 21 (6%), adalimumab in 19 (5%), and 'other' agents in 3 (1%). Forty-five severe infections occurred in 37 patients after a mean follow-up of 26.76 months. These infections resulted in four deaths. The crude rate of severe infections was 90.9 events/1000 person-years (112.5 for rituximab, 76.9 for infliximab, 66.9 for adalimumab and 30.5 for etanercept respectively). In patients treated with more than two courses of rituximab, the crude rate of severe infection was 226.4 events/1000 person-years. A pathogen was identified in 24 (53%) severe infections. The most common sites of severe infection were the lower respiratory tract (39%), bacteremia/sepsis (20%) and the urinary tract (16%). There were no significant differences relating to gender, SAD, agent, other previous therapies, number of previous immunosuppressive agents received or other therapies administered concomitantly. Cox regression analysis showed that age (P = 0.015) was independently associated with an increased risk of severe infection. Survival curves showed a lower survival rate in patients with severe infections (log-rank and Breslow tests < 0.001).

Conclusions

The rates of severe infections in SAD patients with severe, refractory disease treated depended on the biological agent used, with the highest rates being observed for rituximab and the lowest for etanercept. The rate of infection was especially high in patients receiving three or more courses of rituximab. In patients with severe infections, survival was significantly reduced. Older age was the only significant predictive factor of severe infection.     

BDNF and DARPP-32 genes are not risk factors for schizophrenia in the Malay population

A number of studies have pointed to the association of BDNF (brain-derived neurotrophic factor) and DARPP-32 (dopamine- and cAMP-regulated phosphoprotein, 32 kDa) with schizophrenia. The purpose of this study was to determine whether these two genes are involved in the pathogenesis of schizophrenia in the Malay population. Two single nucleotide polymorphisms Val66Met of BDNF, -2036C>G and g.1238delG of DARPP-32 were genotyped in the Malay population in 200 patients with schizophrenia and 256 healthy controls. Analysis of allele and genotype frequencies in these two groups revealed no significant association of BDNF or DARPP-32 polymorphisms with schizophrenia in Malays. This is the first such association study in the Malay population.     

A mouse model for Chikungunya: young age and inefficient type-I interferon signaling are risk factors for severe disease

Chikungunya virus (CHIKV) is a re-emerging arbovirus responsible for a massive outbreak currently afflicting the Indian Ocean region and India. Infection from CHIKV typically induces a mild disease in humans, characterized by fever, myalgia, arthralgia, and rash. Cases of severe CHIKV infection involving the central nervous system (CNS) have recently been described in neonates as well as in adults with underlying conditions. The pathophysiology of CHIKV infection and the basis for disease severity are unknown. To address these critical issues, we have developed an animal model of CHIKV infection. We show here that whereas wild type (WT) adult mice are resistant to CHIKV infection, WT mouse neonates are susceptible and neonatal disease severity is age-dependent. Adult mice with a partially (IFN-alpha/betaR(+/-)) or totally (IFN-alpha/betaR(-/-)) abrogated type-I IFN pathway develop a mild or severe infection, respectively. In mice with a mild infection, after a burst of viral replication in the liver, CHIKV primarily targets muscle, joint, and skin fibroblasts, a cell and tissue tropism similar to that observed in biopsy samples of CHIKV-infected humans. In case of severe infections, CHIKV also disseminates to other tissues including the CNS, where it specifically targets the choroid plexuses and the leptomeninges. Together, these data indicate that CHIKV-associated symptoms match viral tissue and cell tropisms, and demonstrate that the fibroblast is a predominant target cell of CHIKV. These data also identify the neonatal phase and inefficient type-I IFN signaling as risk factors for severe CHIKV-associated disease. The development of a permissive small animal model will expedite the testing of future vaccines and therapeutic candidates.     

Risk factors for lower respiratory complications of rhinovirus infections in elderly people living in the community: prospective cohort study.

OBJECTIVE: To assess the role of rhinoviruses in elderly people living in the community. DESIGN: Prospective community based surveillance of elderly people, without intervention. Subjects were telephoned weekly to identify symptomatic upper respiratory tract infections. Symptoms and impact of illnesses were monitored, and specimens were collected for diagnostic serology and human rhinovirus polymerase chain reaction. SETTING: Leicestershire, England. SUBJECTS: 533 subjects aged 60 to 90. MAIN OUTCOME MEASURES: Symptoms, restriction of activity, medical consultations, and antibiotic use during 96 rhinovirus infections. Adjusted odds ratios for lower respiratory syndromes with respect to smoking and health status. RESULTS: A viral cause was established in 211 (43%) of 497 respiratory illnesses; rhinoviruses were identified in 121 (24%) and as single pathogens in 107. The median duration of the first or only rhinovirus infection in the 96 people with 107 rhinovirus infections was 16 days; 18 of the 96 patients were confined to bed and 25 were unable to cope with routine household activities. Overall, 60 patients with rhinovirus infections had lower respiratory tract syndromes; 41 patients consulted their doctor, 31 of them (76%) receiving antibiotics. One patient died. Logistic regression analysis showed that chronic medical conditions increased the estimated probability of lower respiratory rhinovirus illness by 40% (95% confidence interval 17% to 68%) and smoking by 47% (14% to 90%). There were almost six times as many symptomatic rhinovirus infections as influenza A and B infections. CONCLUSIONS: Rhinoviruses are an important cause of debility and lower respiratory illness among elderly people in the community. Chronic ill health and smoking increase the likelihood of lower respiratory complications from such infections. The overall burden of rhinovirus infections in elderly people may approach that of influenza.     

Identification of clinical,epidemiological and laboratory risk factors for leprosy reactions during and after multidrug therapy

This cross-sectional retrospective study evaluated 440 leprosy patients; 57% (251/440) had leprosy reactions during and/or after multidrug therapy, 80.5% (202/251) of whom presented with multibacillary leprosy. At diagnosis, positive bacterial index (BI) [odds ratio (OR) = 6.39; 95% confidence interval (CI): 4.1-10.1)] or polymerase chain reaction (PCR) (OR = 9.15; 95% CI: 5.4-15.5) in skin smears, anti-phenolic glycolipid-1 (anti-PGL-1) ELISA (OR = 4.77; 95% CI: 2.9-7.9), leucocytosis (OR = 9.97; 95% CI: 3.9-25.7), thrombocytopenia (OR = 5.72; 95% CI: 2.3-14.0) and elevated lactate dehydrogenase (OR = 2.38; 95% CI: 1.4-4.0) were potential markers for the development of reactions during treatment. After treatment, positive BI (OR = 8.47; 95% CI: 4.7-15.3) and PCR (OR = 6.46; 95% CI: 3.4-12.3) in skin smears, anti-PGL-1 ELISA (OR = 2.25; 95% CI: 1.3-3.9), anaemia (OR = 2.36; 95% CI: 1.2-4.5), leucocytosis (OR = 4.14; 95% CI: 1.5-11.6) and thrombocytopenia (OR = 3.70; 95% CI: 1.3-2.2) were risk factors for the occurrence of reactions during the study period. The identification of groups with an increased risk for developing reactions will allow for the timely development of a treatment plan to prevent nerve damage and, therefore, the appearance of the disabling sequelae associated with the stigma of leprosy.     

Intraoperative breast radiotherapy: survival,local control and risk factors for recurrence

BackgroundWhole breast irradiation reduces loco-regional recurrence and risk of death in patients submitted to breast-conserving treatment. Data show that radiation to the index quadrant alone may be enough in selected patients.AimTo report the experience with intra-operative radiotherapy (IORT) with Electron-beam Cone in Linear Accelerator (ELIOT) and the results in overall survival, local control and late toxicity of patients submitted to this treatment.Materials and Methods147 patients treated with a median follow up of 6.9 years (0.1?11.5 years). The actuarial local control and overall survival probabilities were estimated using the Kaplan Meier method. All tests were two-sided and p ? 0.05 was considered statistically significant.ResultsOverall survival of the cohort in 5 years, in the median follow up and in 10 years was of 98.3%, 95.1% and 95.1%, respectively, whereas local control in 5 years, in the median follow up and in 10 years was of 96%, 94.9% and 89.5%, respectively. Two risk groups were identified for local recurrence depending on the estrogen or progesterone receptors, axillary or margin status and lymphovascular invasion (LVI) (p = 0.016).ConclusionsIORT is a safe and effective treatment. Rigorous selection is important to achieve excellent local control results.     

Bacterial metallothioneins: past,present, and questions for the future

Bacterial metallothioneins (MTs) have been known since the mid-1980s. The only family known until recently was the BmtA family, exemplified by the zinc- and cadmium-binding SmtA from the cyanobacterium Synechococcus PCC 7942, for which a structure was determined in 2001. Only in 2008 was a second type of bacterial MT identified in mycobacteria, and the copper-binding gene product was called MymT. Many of the features of SmtA either have been unexpected or are otherwise “unusual”, for example the presence of a zinc finger fold and the kinetic inertness of one of the four zinc ions bound to the protein. The unpredictability of molecular properties of this protein exemplified the need for continued biophysical studies of novel proteins. Homologues for SmtA have been identified in a limited number of bacterial genomes from cyanobacteria, pseudomonads, alphaproteobacteria, gammaproteobacteria, and firmicutes. Except for the residues defining the zinc finger fold, these homologous protein sequences display an intriguing variety, especially in terms of metal ligand position and identity. The increased number of homologues has allowed use of hidden Markov models to look for more remote relatives of SmtA, leading to the identification of a novel family of putative hybrid LIM domain MTs. However, database searches based on sequence similarity are of limited use for mining for further “overlooked” bacterial MTs, as so far undiscovered bacterial MTs may be too diverse from any other known MTs, and other approaches are required.     

Interactions of the bacterial pathogenListeria monocytogenes with mammalian cells: Bacterial factors, cellular ligands, and signaling

Listeria monocytogenes is a food borne pathogen which has the very unique property of crossing three barriers during infection eliciting meningitis, meningo-encephalitis and abortions with a mortality rate of about 30%. Indeed, after crossing the intestinal barrier,Listeria disseminatesvia the lymph and the blood, to the brain and/or the placenta after crossing the brain-blood barrier and/or the placental barrier. During disease, this organism infects a variety of tissues and cell types in which it is mostly intracellular due to its capacity to induce its own phagocytosis into cells which are normally nonphagocytic. The strategies used byListeria to enter cells are different from those used by other well known invasive pathogens.Listeria thus appears as a fine model to study the molecular and cellular basis of bacterial invasion. In addition, not only during entry into cells but also during intra-and intercellular movement,Listeria exploits mammalian cell functions and is thus a novel tool for elucidating some unsolved fundamental aspects of cell biology, such as ligand receptor signaling and actin cytoskeleton rearrangements. In this review, the molecular and cellular basis of entry ofListeria into cells and of its intracellular motility will be discussed. Presented at the1st International Minisymposium on Cellular Microbiology: Cell Biology and Signalization in Host-Pathogen Interactions, Prague, October 6, 1997.     

Transition models to assess risk factors for new and persistent trypanosome infections in cattle-analysis of longitudinal data from the Ghibe Valley, southwest Ethiopia

The objective of this study was to apply transition models to distinguish between factors associated with both incident and persistent trypanosome infections. Data collected from 1561 cattle were analyzed from a long-term study involving 8 herds in which both trypanosome infections (a total of 56,931 cattle sampling-months) and tsetse (Glossina spp.) challenge were monitored monthly from March 1986 to March 1998. Both pour-on and insecticide-target tsetse control programs and mass treatment with diminazene aceturate before tsetse control were associated with significant decreases in both incidence and persistence of trypanosome infection relative to noncontrol periods, as were seasonal and sex effects. The magnitudes of the effects were, however, often different for new and persistent infections. For persistence of infection, there were 2 trends. In general, the duration of infection increased during the study, despite the regular treatment with diminazene aceturate. The transition model had 2 major benefits. The first was to identify an increasing duration of infections with time, taking into account other factors associated with increasing infection risk. The second was to highlight different patterns in the effects of certain factors on new and persistent trypanosome infections.