Hospitalization risk due to respiratory illness associated with genetic variation at IFITM3 in patients with influenza A(H1N1)pdm09 infection: a case-control study

Recent studies suggest an association between the Interferon Inducible Transmembrane 3 (IFITM3) rs12252 variant and the course of influenza infection. However, it is not clear whether the reported association relates to influenza infection severity. The aim of this study was to estimate the hospitalization risk associated with this variant in Influenza Like Illness (ILI) patients during the H1N1 pandemic influenza. A case-control genetic association study was performed, using nasopharyngeal/oropharyngeal swabs collected during the H1N1 pandemic influenza. Laboratory diagnosis of influenza infection was performed by RT-PCR, the IFITM3 rs12252 was genotyped by RFLP and tested for association with hospitalization. Conditional logistic regression was performed to calculate the confounder-adjusted odds ratio of hospitalization associated with IFITM3 rs12252. We selected 312 ILI cases and 624 matched non-hospitalized controls. Within ILI Influenza A(H1N1)pdm09 positive patients, no statistical significant association was found between the variant and the hospitalization risk (Adjusted OR: 0.73 (95%CI: 0.33–1.50)). Regarding ILI Influenza A(H1N1)pdm09 negative patients, CT/CC genotype carriers had a higher risk of being hospitalized than patients with TT genotype (Adjusted OR: 2.54 (95%CI: 1.54–4.19)). The IFITM3 rs12252 variant was associated with respiratory infection hospitalization but not specifically in patients infected with Influenza A(H1N1)pdm09.

Health care services for persons with human immunodeficiency virus (HIV) infection.

"September 1993."

Infection of the immature stages of Diadegma semiclausum, an endolarval parasitoid of the diamondback moth, by Beauveria bassiana

Interactions between the immature stages of Diadegma semiclausum, an endolarval parasitoid of Plutella xylostella, and the fungal entomopathogen Beauveria bassiana were investigated in the laboratory. Detrimental effects of B. bassiana on D. semiclausum cocoon production and adult parasitoid emergence increased with increasing pathogen concentration and some parasitoid larvae became infected by B. bassiana within hosts. The negative impact of B. bassiana on D. semiclausum cocoon production decreased as temporal separation between parasitism and pathogen exposure increased. Adult parasitoid emergence was significantly compromised by the highest rates of B. bassiana tested even when exposure of host larvae to the pathogen was delayed until one day before predicted parasitoid cocoon formation. Parasitoid pupae were infected by the pathogen in all B. bassiana treatments which did not preclude their development. (C) 2004 Elsevier Inc. All rights reserved.

Endemic infection of the amphibian chytrid fungus in a frog community post-decline

The chytrid fungus Batrachochytrium dendrobatidis has been implicated in the decline and extinction of numerous frog species worldwide. In Queensland, Australia, it has been proposed as the cause of the decline or apparent extinction of at least 14 high-elevation rainforest frog species. One of these, Taudactylus eungellensis, disappeared from rainforest streams in Eungella National Park in 1985-1986, but a few remnant populations were subsequently discovered. Here, we report the analysis of B. dendrobatidis infections in toe tips of T. eungellensis and sympatric species collected in a mark-recapture study between 1994 and 1998. This longitudinal study of the fungus in individually marked frogs sheds new light on the effect of this threatening infectious process in field, as distinct from laboratory, conditions. We found a seasonal peak of infection in the cooler months, with no evidence of interannual variation. The overall prevalence of infection was 18% in T. eungellensis and 28% in Litoria wilcoxii/jungguy, a sympatric frog that appeared not to decline in 1985-1986. No infection was found in any of the other sympatric species. Most importantly, we found no consistent evidence of lower survival in T. eungellensis that were infected at the time of first capture, compared with uninfected individuals. These results refute the hypothesis that remnant populations of T. eungellensis recovered after a B. dendrobatidis epidemic because the pathogen had disappeared. They show that populations of T. eungellensis now persist with stable, endemic infections of B. dendrobatidis.

Therapeutic activation of V alpha 24(+)V beta 11(+) NKT cells in human subjects results in highly coordinated secondary activation of acquired and innate immunity

Human Valpha24(+)Vbeta11(+) natural killer T (NKT) cells are a distinct CD1d-restricted lymphoid subset specifically and potently activated by alpha-galactosylceramide (alpha-GalCer) (KRN7000) presented by CD1 d on antigen-presenting cells. Preclinical models show that activation of Valpha24(+)Vbeta11(+) NKT cells induces effective antitumor immune responses and potentially important secondary immune effects, including activation of conventional T cells and NK cells. We describe the first clinical trial of cancer immune therapy with alpha-GalCer-pulsed CD1d-expressing dendritic cells. The results show that this therapy has substantial, rapid, and highly reproducible specific effects on Valpha24(+)Vbeta11(+) NKT cells and provide the first human in vivo evidence that Valpha24(+)Vbeta11(+) NKT cell stimulation leads to activation of both innate and acquired immunity, resulting in modulation of NK, T-, and B-cell numbers and increased serum interferon-gamma. We present the first clinical evidence that Valpha24(+)Vbeta11(+) NKT cell memory produces faster, more vigorous secondary immune responses by innate and acquired immunity upon restimulation.

Modeling the development of acquired clinical immunity to Plasmodium falciparum malaria

Individuals living in regions where malaria is endemic develop an acquired immunity to malaria which enables them to remain asymptomatic while still carrying parasites. Field studies indicate that cumulative exposure to a variety of diverse Plasmodium parasites is required for the transition from symptomatic to asymptomatic malaria. This study used a simulation model of the within-host dynamics of P. falciparum to investigate the development of acquired clinical immunity under different transmission conditions and levels of parasite diversity. Antibodies developed to P. falciparum erythrocyte membrane protein 1 (PfEMP1), a clonally variant molecule, were assumed to be a key human immunological response to P. falciparum infection, along with responses to clonally conserved but polymorphic antigens. The time to the development of clinical immunity was found to be proportional to parasite diversity and inversely proportional to transmission intensity. The effect of early termination of symptomatic infections by chemotherapy was investigated and found not to inhibit the host's ability to develop acquired immunity. However, the time required to achieve this state was approximately double that compared to when no treatment was administered. This study demonstrates that an immune response primarily targeted against PfEMP1 has the ability to reduce clinical symptoms of infections irrespective of whether treatment is administered, supporting its role in the development of acquired clinical immunity. The results also illustrate a novel use for simulation models of P. falciparum infections, investigation of the influence of intervention strategies on the development of naturally acquired clinical immunity.

Active and passive immunization against oral Candida albicans infection in a murine model

Background/aims: Clinical and laboratory studies are consistent with a major role for cell-mediated immunity in recovery from oral infection with Candida albicans, but the role of humoral immunity remains controversial. The purpose of this study was to establish the relative contributions of cellular and humoral immunity to protection against oral candidiasis in a murine model, and to determine whether host responses could be enhanced by different immunization strategies. Results: Active oral immunization was protective in BALB/c and CBA/CaH mice, reducing both fungal burden and duration of infection after secondary challenge, whereas systemic immunization failed to protect against subsequent oral challenge. Candida-specific IgM was the predominant antibody detected in serum following both primary and secondary oral challenge; however, Candida-specific salivary IgA was not detectable. Immunization by passive transfer of either lymphocytes or immune serum did not confer any significant protection against oral infection in either susceptible or resistant mouse strain. Conclusion: The data demonstrate a possible role for mucosa-associated immunity following active immunization by the oral route, most likely exerted by local T lymphocytes resident in the oral mucosa, but there was no evidence to support a role for humoral immunity in protection against oral candidiasis.

Epidemiology, clinical and laboratory characteristics of Staphylococcus aureus bacteraemia in a university hospital in UK

There has been a persistent increase in the number of meticillin-resistant Staphylococcus aureus (MRSA) and meticillin-susceptible Staphylococcus aureus (MSSA) bacteraemia in the UK. This prospective study included 147 episodes of S. aureus bacteraemia in 139 patients over a 14 month period, from 1 November 2001 to 31 December 2002. Eighty-seven (59%) episodes in 84 patients and 60 (41%) in 56 patients were due to MRSA and MSSA, respectively. An intra-vascular device (29, 33%) and a soft-tissue (15, 25%) source were the commonest identifiable foci for bacteraemia in the MRSA and MSSA groups, respectively. Attributable mortality in the MRSA group was higher than the MSSA group (33% vs 16%; P = 0.03) but there was no statistical difference for either attributable (P = 0.35) or crude (P = 0.39) mortality between the two groups, when adjusted for age, respiratory focus and inappropriate antibiotic therapy. A respiratory source (P = 0.02) and inappropriate antibiotic therapy (P = 0.02) were associated with attributable mortality in the MRSA group whereas advanced age was the only risk factor (P = 0.02) in the MSSA group. The present study shows that S. aureus bacteraemia continues to be a serious infection mostly affecting the elderly and emphasizes the need for improved strategy in the control and management of this condition. © 2006 The Hospital Infection Society.

The source, cost and prevention of central venous catheter-related infection

Central venous catheters have become an integral part of patient management however they are associated with many complications including infection. Despite efforts being made to reduce the incidence of such infect ions the problem continues to increase and has resource implications for the Health Service. Studies relating to the source of microorganisms causing CVC-associated infection, the cost of such infections and the efficacy of an antimicrobial catheter have been undertaken. Thirty patients who required a CVC as part of their medical management and underwent cardiac surgery had the distal tips of their catheters sampled whilst in situ. Sampling took place within 1 h of catheter placement. Bacteria were isolated from 16% of the catheter distal tips sampled in situ. The guidewires used to insert the devices were also contaminated (50%). When CVC were inserted via a protective sheath, avoiding contact with the skin. the incidence of microbial contamination was reduced. These findings suggest that despite rigorous skin disinfection and strict aseptic technique, viable microorganisms are impacted onto the distal tip of CVC during the insertion procedure. Needleless intravascular access devices have been introduced in order to reduce the incidence of need1estick injury. However, it was unclear whether such connectors would act as a portal of entry for microorganisms to CVC. The efficacy of these devices was investigated. Within the controlled laboratory environment it was demonstrated that needleless devices, when challenged with microorganisms, did not allow the passage of microbes when flu id was injected. This therefore suggested that the devices should not increase the risk of catheter colonisation. When used in clinical practice however microbial contamination of the needleless connectors was 55 % in comparison to the routinely used luer connectors (23%). The cost of infections associated with CVC was determined. Twenty patients catheterised with a CVC designed for long term use who were admitted to hospital with a presumptive diagnosis of catheter-related infection were studied. The treatment given specifically for this infection was costed. The mean cost of such an infection was £ 1781.81. Throughout the UK this may amount to £1.565.906 per annum. The cost of infections associated with CVC designed for short term use was estimated to be between 5 and 7 million pounds per annum in the UK. In an attempt to reduce both the incidence and cost of catheter- related infection antimicrobial CVC have been developed. The efficacy of a novel polyurethane CVC impregnated on both the internal and external catheter surface with the quaternary ammonium compound benzalkonium chloride was investigated. Eighty eight patients received an antimicrobial catheter and 78 patients a conventional polyurethane CVC. The anti-microbial CVC resulted in a reduction in microbial colonisation of the external and internal polymer surfaces as compared to the control device. The observed reduction in microbial colonisation with the anti-microbial CVC may decrease the likelihood of subsequent infection offering a useful approach to the prevention of catheter-related infections.

The surface of Pseudomonas aeruginosa in cystic fibrosis lung infection

Chronic experimental lung infection in rats was induced by intratracheal inoculation of agar beads containing Pseudomonas aeruginosa. Bacteria were recovered directly without subculture from the lungs of rats at 14 days post-infection and the outer membrane (OM) antigens were studied. The results indicated that bacteria grew under iron-restricted conditions as revealed by the expression of several iron-regulated membrane proteins (IRMPs) which could also be observed when the isolate was grown under iron-depleted conditions in laboratory media. The antibody response to P. aeruginosa OM protein antigens was investigated by immunoblotting with serum and lung fluid from infected rats. These fluids contained antibodies to all the major OM proteins, including the IRMPs, and protein H1. Results obtained using immunoblotting and enzyme-linked immunosorbent assay indicated that lipopolysaccharide (LPS) was the major antigen recognised by antibodies in sera from infected rats. The animal model was used to follow the development of the immune response to P. aeruginosa protein and LPS antigens. Immunoblotting was used to investigate the antigens recognised by antibodies in sequential serum samples. An antibody response to the IRMPs and OM proteins D, E, G and H1 and alao to rough LPS was detected as early as 4 days post-infection. Results obtained using immunoblotting and crossed immunoelectrophoresis techniques indicated that there was a progressive increase in the number of P. aeruginosa antigens recognised by antibodies in these sera. Both iron and magnesium depletion influenced protein H1 production. Antibodies in sera from patients with infections due to P. aeruginosa reacted with this antigen. Results obtained using quantitative gas-liquid chromatographic analysis indicated that growth phase and magnesium and iron depletion also affected the amount of LPS fatty acids, produced by P. aeruginosa. The silver stained SDS-polyacrylamide gels of proteinase K digested whole cell lysates of P. aeruginosa indicated that the O-antigen and core LPS were both affected by growth phase and specific nutrient depletion.

Epidemiology of community-acquired meticillin-resistant Staphylococcus aureus obtained from the UK West Midlands region

Between January 2005 and December 2005, 199 meticillin-resistant Staphylococcus aureus (MRSA) isolates were obtained from nonhospitalised patients presenting skin and soft tissue infections to local general practitioners. The study area incorporated 57 surgeries from three Primary Care Trusts in the Lichfield, Tamworth, Burntwood, North and East Birmingham regions of Central England, UK. Following antibiotic susceptibility testing, pulsed-field gel electrophoresis, Panton-Valentine leukocidin gene detection and SCCmec element assignment, 95% of the isolates were shown to be related to hospital epidemic strains EMRSA-15 and EMRSA-16. In total 87% of the isolate population harboured SCCmec IV, 9% had SCCmec II and 4% were identified as carrying novel SCCmec IIIa-mecI. When mapped to patient home postcode, a diverse distribution of isolates harbouring SCCmec II and SCCmec IV was observed; however, the majority of isolates harbouring SCCmec IIIa-mecI were from patients residing in the north-west of the study region, highlighting a possible localised clonal group. Transmission of MRSA from the hospital setting into the surrounding community population, as demonstrated by this study, warrants the need for targeted patient screening and decolonisation in both the clinical and community environments.

A randomized, prospective clinical trial to assess the potential infection risk associated with the PosiFlow® needleless connector

The microbial contamination rate of luers of central venous catheters (CVCs) with either PosiFlow® needleless connectors or standard caps attached was investigated. The efficacy of 70% (v/v) isopropyl alcohol, 0.5% (w/v) chlorhexidine in gluconate 70% (v/v) isopropyl alcohol and 10% (w/v) aqueous povidone-iodine to disinfect the intravenous connections was also assessed. Seventy-seven patients undergoing cardiac surgery who required a CVC as part of their clinical management were randomly allocated either needleless connectors or standard caps. Patients were also designated to receive chlorhexidine/alcohol, isopropyl alcohol or povidone-iodine for pre-CVC insertion skin preparation and disinfection of the connections. After 72 h in situ the microbial contamination rate of 580 luers, 306 with standard caps and 274 with needleless connectors attached, was determined. The microbial contamination rate of the external compression seals of 274 needleless connectors was also assessed to compare the efficacy of the three disinfectants. The internal surfaces of 55 out of 306 (18%) luers with standard caps were contaminated with micro-organisms, whilst only 18 out of 274 (6.6%) luers with needleless connectors were contaminated (P<0.0001). Of those needleless connectors disinfected with isopropyl alcohol, 69.2% were externally contaminated with micro-organisms compared with 30.8% disinfected with chlorhexidine/alcohol (P<0.0001) and 41.6% with povidone-iodine (P<0.0001). These results suggest that the use of needleless connectors may reduce the microbial contamination rate of CVC luers compared with the standard cap. Furthermore, disinfection of needleless connectors with either chlorhexidine/alcohol or povidone-iodine significantly reduced external microbial contamination. Both these strategies may reduce the risk of catheter-related infections acquired via the intraluminal route. © 2003 The Hospital Infection Society. Published by Elsevier Science Ltd. All rights reserved.

Diagnosis of central venous catheter related infection in adult patients

Intravascular catheters are one of the main causes of bacteraemia and septicaemia in hospitalised patients and continue to be associated with a significant morbidity and mortality. Two main types of infections occur, they can be either localised at the catheter insertion site of systemic with a septicaemia. The clinical parameters related to these infections are presented. The laboratory diagnosis of these infections is also extensively reviewed and recommendations are made as to the most appropriate diagnostic method to be used. © 2005 The British Infection Society. Published by Elsevier Ltd. All rights reserved.

Serum procalcitonin, interleukin-6, soluble intercellular adhesin molecule-1 and IgG to short-chain exocellular lipoteichoic acid as predictors of infection in total joint prosthesis revision

The diagnosis of prosthetic joint infection and its differentiation from aseptic loosening remains problematic. The definitive laboratory diagnostic test is the recovery of identical infectious agents from multiple intraoperative tissue samples; however, interpretation of positive cultures is often complex as infection is frequently associated with low numbers of commensal microorganisms, in particular the coagulase-negative staphylococci (CNS). In this investigation, the value of serum procalcitonin (PCT), interleukin-6 (IL-6) and soluble intercellular adhesion molecule-1 (sICAM-1) as predictors of infection in revision hip replacement surgery is assessed. Furthermore, the diagnostic value of serum IgG to short-chain exocellular lipoteichoic acid (sce-LTA) is assessed in patients with infection due to CNS. Presurgical levels of conventional serum markers of infection including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and white blood cell count (WBC) is also established. Forty-six patients undergoing revision hip surgery were recruited with a presumptive clinical diagnosis of either septic (16 patients) or aseptic loosening (30 patients). The diagnosis was confirmed microbiologically and levels of serum markers were determined. Serum levels of IL-6 and sICAM-1 were significantly raised in patients with septic loosening (P=0.001 and P=0.0002, respectively). Serum IgG to sce-LTA was elevated in three out of four patients with infection due to CNS. In contrast, PCT was not found to be of value in differentiating septic and aseptic loosening. Furthermore, CRP, ESR and WBC were significantly higher (P=0.0001, P=0.0001 and P=0.003, respectively) in patients with septic loosening. Serum levels of IL-6, sICAM-1 and IgG to sce-LTA may provide additional information to facilitate the diagnosis of prosthetic joint infection.