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The treatment of choice for early stage non-small cell lung cancer (NSCLC) is surgical resection. Little is known about the short- and long-term outcomes among very elderly patients. We sought to determine predictors of short- and long-term survival among octogenarians undergoing curative-intent resection for NSCLC in Victoria, Australia.We retrospectively reviewed data from all patients aged ≥80 years who underwent curative-intent resection for NSCLC over 12 years (January 2005-December 2016) across five tertiary centres. We examined effect of age, stage of disease, extent of surgery and lung function on short- and long-term survival.Two hundred patients aged ≥80 years underwent curative-intent resections. Mortality at 30 and 120 days was 2.9% and 5.9%, respectively. Increased early mortality was observed among those ≥83 years, at 30 days (6.8% versus 0.8%, P = 0.044) and 120 days (12.2% versus 2.3%, P = 0.0096). Early mortality was highest among patients ≥83 years requiring lobectomy, compared to sub-lobar resection at 120 days (17% versus 3.8%, P = 0.019). Long-term survival was predicted by age and stage of disease. Among patients with Stage I disease aged83 years, lobectomy was associated with superior 5-year survival, compared to sub-lobar resection (83% versus 61%, P = 0.02).In carefully selected elderly patients undergoing curative-intent resection of early stage NSCLC, both short- and long-term outcomes appear consistent with younger historical cohorts. Early mortality was associated with lobectomy in those with advanced age. Older patients undergoing lobectomy appeared to be at highest risk for early mortality, while younger patients with Stage I disease undergoing at least lobectomy appear to have the best long-term survival.

Background Biologic therapy has revolutionized the management of refractory chronic autoimmune and auto-inflammatory disease, as well as several malignancies, providing rapid symptomatic relief and/or disease remission. Patients receiving biologic therapies have an improved quality of life, facilitating travel to exotic destinations and potentially placing them at risk of a range of infections. For each biologic agent, we review associated travel-related infection risk and expected travel vaccine response and effectiveness. Methods A PUBMED search [vaccination OR vaccine] AND/OR ['specific vaccine'] AND/OR [immunology OR immune response OR response] AND [biologic OR biological OR biologic agent] was performed. A review of the literature was performed in order to develop recommendations on vaccination for patients in receipt of biologic therapy travelling to high-risk travel destinations. Results There is a paucity of literature in this area, however, it is apparent that travel-related infection risk is increased in patients on biologic therapy and when illness occurs they are at a higher risk of complication and hospitalization. Patients in receipt of biologic agents are deemed as having a high level of immunosuppression-live vaccines, including the yellow fever vaccine, are contraindicated. Inactivated vaccines are considered safe; however, vaccine response can be attenuated by the patient's biologic therapy, thereby resulting in reduced vaccine effectiveness and protection. Conclusions Best practice requires a collaborative approach between the patient's primary healthcare physician, relevant specialist and travel medicine expert, who should all be familiar with the immunosuppressive and immunomodulatory effects resulting from the biologic therapies. Timing of vaccines should be carefully planned, and if possible, vaccination provided well before established immunosuppression.

A 32-year-old man who was receiving adalimumab for seronegative rheumatoid arthritis presented with a 4-week history of fever, night sweats, fatigue, myalgias and diarrhoea. On examination, he had obvious splenomegaly but no lymphadenopathy or pharyngitis. Full blood count revealed mild neutropenia and significant lymphocytosis, with a blood film showing atypical lymphocytes. Liver function tests were mildly deranged with a mixed hepatitic and obstructive pattern. Ultrasound confirmed massive splenomegaly with a span of 21 cm in the long axis. Serological tests confirmed the presence of both primary Epstein-Barr virus and cytomegalovirus infections. The patient had his adalimumab withheld, was treated with supportive measures and improved over a period of 8 weeks. He remained well 5 months after the onset of illness with complete normalisation of blood count and a resolution of the splenomegaly.

Background We aimed to investigate the incidence, precipitants, and outcomes of acute decompensated heart failure (ADHF) that develops during the inpatient stay. Methods We undertook a case-control study in the medical, oncology, surgical, and orthopaedic wards of a tertiary referral hospital (February–May, 2016). Patients aged ≥18 years who developed ADHF during their inpatient stay were enrolled as cases. One control patient was matched to each case by age, gender, presenting complaint/surgery performed and co-morbidities. Multivariate regression was employed to determine variables associated with ADHF. Results The incidence of ADHF was 1.0% of patients. Eighty cases were well-matched to 80 controls (p > 0.05). ADHF precipitants comprised infection (30%), inappropriate intravenous (IV) fluid and medication management (23.8% and 8.8%, respectively), tachyarrhythmia (12.5%), ischaemic heart disease (8.8%), renal failure (1.3%), and other/unclear causes (15%). Three variables were associated with ADHF: not having English as the preferred language (OR 3.5, 95%CI 1.2–9.8), a history of ischaemic heart disease (OR 3.3, 95%CI 1.2–9.1), and the administration of >2000 ml of IV fluid on the day before the ADHF (OR 8.3, 95%CI 1.5–48.0). The day before the ADHF, cases were administered significantly more IV fluids than controls (median 2,757.5 versus 975 ml, p = 0.001). Medication errors mostly related to failure to restart regular diuretics. Cases had significantly greater length of stay (median 15 versus 6 days, p Conclusions New onset ADHF is common and a substantial proportion of cases are iatrogenic. Cases experience significantly increased length of hospital stay, morbidity, and mortality.

We describe an adverse outcome in a 70-year-old man with type 2 diabetes mellitus treated with sodium-glucose cotransporter type 2 (SGLT2) inhibitor dapagliflozin. SGLT2 inhibitors act in the proximal tubules to prevent glucose reabsorption and induce urinary glucose excretion, they have been associated with increased risk of urinary tract infection (UTI). Our patient presented to hospital with Escherichia coli septicaemia with positive urine and blood cultures on the background of two previous UTIs occurring post commencement of dapagliflozin in the community. Renal tract ultrasound in hospital revealed incomplete bladder emptying with evidence of urinary stasis, and a postvoid residual volume of 180 mL. His dapagliflozin was ceased, and he has had no further episodes of UTI. This case suggests there may be an increased risk of UTI in patients prescribed SGLT2 inhibitors who also have evidence of bladder outlet obstruction-caution is advised in the prescribing of SGLT2 inhibitors in this setting.

We describe a case of bladder cancer presenting with atraumatic chylous ascites, which remains an extremely rare presentation of this condition. A previously well, elderly ex-smoker with no prior history of abdominal surgery was referred for investigation of progressive dyspnoea, increasing peripheral oedema and new-onset ascites, on a background of long-standing alcohol consumption (four standard drinks daily). Liver biochemistry and coagulation profile were normal apart from marked hypoalbuminaemia. Doppler ultrasound of the liver demonstrated normal echotexture and patent vasculature. Abdominal paracentesis yielded 8 L of milk-coloured, triglyceride-rich fluid with abundant malignant cells. Urine cytology demonstrated malignant transitional cells, with radiological evidence of a large enhancing bladder mass, with evidence of adjacent lymphadenopathy and omental involvement. A diagnosis of metastatic stage IV transitional cell bladder cancer was made. The patient declined palliative chemotherapy and passed away 2 months after their initial presentation.

In patients with chronic obstructive pulmonary disease (COPD) and co-morbid cardiovascular disease, emerging evidence suggests a benefit in commencing cardioselective beta-blockers.Our objective was to determine the safety of beta-blocker commencement during hospitalisation for acute exacerbation of COPD.A retrospective cohort study of 1071 patients hospitalised for acute exacerbation of COPD was conducted across two tertiary hospitals over a 12-month period. We identified 36 patients in whom beta-blocker therapy was commenced during admission. The primary outcome of the study was to assess cardiovascular and respiratory adverse events related to the commencement of beta-blocker therapy.The most common indications for beta-blockers were atrial fibrillation (53%) and acute coronary syndrome (36%). Metoprolol was the most commonly prescribed beta-blocker (75%). No patients suffered clinically significant declines of respiratory function following the commencement of a beta-blocker, including worsening respiratory symptoms, oxygen, bronchodilator or ventilation requirements. These results were demonstrable in patients with reversible airways disease and advanced COPD. Only one patient (2.8%) experienced symptomatic hypotension after 48 h of therapy.The commencement of cardioselective beta-blockers during acute exacerbations of COPD appears to be well-tolerated.

Objectives To describe the epidemiology, clinical and laboratory features and outcomes of dengue in returned Australian travellers, applying the revised WHO dengue classification (2009) to this population. Design, setting and participants Retrospective case series analysis of confirmed dengue cases hospitalised at one of four Australian tertiary hospitals, January 2012 - May 2015. Main outcome measures Clinical features, laboratory findings and outcomes of patients with dengue; dengue classification according to 2009 WHO guidelines. Results 208 hospitalised patients (median age, 32 years; range, 4-76 years) were included in the study. Dengue was most frequently acquired in Indonesia (94 patients, 45%) and Thailand (40, 19%). The most common clinical features were fever (98% of patients) and headache (76%). 84 patients (40%) met the WHO criteria for dengue with warning signs, and one the criteria for severe dengue; the most common warning signs were mucosal bleeding (44 patients, 21%) and abdominal pain (43, 21%). Leukopenia (176 patients, 85%), thrombocytopenia (133, 64%), and elevated liver enzyme levels (154, 76%) were the most common laboratory findings. 46 patients (22%) had serological evidence of previous exposure to dengue virus. WHO guidelines were documented as a management benchmark in ten cases (5%); 46 patients (22%) received non-steroidal anti-inflammatory drugs (NSAIDs). Conclusions A significant proportion of returning Australian travellers hospitalised for dengue have unrecognised warning signs of severe disease. Many received NSAIDs, which can increase the risk of haemorrhage in dengue. As travel to Asia from Australia continues to increase, it is vital for averting serious outcomes that clinicians can recognise and manage dengue.

Super hydrophobic surfaces find uses in many applications; therefore proper design of super hydrophobic surfaces is very crucial. A lot of work has already been done for static droplets and super hydrophobic surface interactions. There have also been some significant experiments carried out for dynamic droplet impact on super hydrophobic surfaces. The present work focuses on the super hydrophobic surface under dynamic conditions, with the study predominantly carried out through numerical simulation. Various parameters during impact and time variance after impact (typically up to 10 μs) were considered. The transition from water hammer pressure (order of ρCV) to flow pressure (order of 1/2 ρV2) is taken as the main parameter of analysis. During water hammer pressure domain, a strong tendency to cause wetting (Wenzel state) is seen. During flow pressure domain, wetting tendency is significantly reduced (Cassie-Baxter state). These states and the transition from one to the other are very crucial to the desig...

Everolimus is an inhibitor of mammalian target of rapamycin with anti-tumour activity. While everolimus is known to cause drug-induced pneumonitis, it is rarely associated with Pneumocystis jirovecii pneumonia (PJP). We report a patient on everolimus therapy for metastatic breast cancer that developed PJP. Diagnosis was based on clinical features and a quantitative polymerase chain reaction for P. jirovecii DNA. Clinicians should consider PJP as a potential cause of pulmonary infiltrates in patients treated with everolimus.

Few data exist concerning possible infectious complications associated with endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). The present prospective evaluation was undertaken in order to determine the incidence of bacteraemia and infectious complications associated with EBUS-TBNA. Consecutive patients undergoing EBUS-TBNA for evaluation of mediastinal or hilar lymph node lesions were studied. Venesection was performed within 60 s of TBNA for aerobic and anaerobic blood culture. Sterile saline washing of TBNA needles was also performed. Patients with positive blood cultures were reviewed immediately, and all patients underwent clinical review within 1 week of EBUS-TBNA. A total of 43 patients underwent EBUS-TBNA, with bacteraemia demonstrated in three (7%). All bacterial isolates were typical oropharyngeal commensal organisms. The TBNA needle washing culture was positive in 15 (35%) patients. None of the three bacteraemic patients had clinical features suggestive of infection, and no complications were seen among the cohort. The incidence of bacteraemia following EBUS-TBNA is comparable to that following routine flexible bronchoscopy. Performance of TBNA does not appear to measurably increase the risk of bacteraemia over that associated with insertion of the bronchoscope into the airway. Contamination of the TBNA needle with oropharyngeal commensal bacteria is common; however, clinically significant infection following EBUS-TBNA appears rare.

An effective immune response against hepatitis C virus (HCV) requires the early development of multi-specific class 1 CD8(+) and class II CD4(+) T-cells together with broad neutralizing antibody responses. We have produced mammalian-cell-derived HCV virus-like particles (VLPs) incorporating core, E1 and E2 of HCV genotype 1a to produce such immune responses. Here we describe the biochemical and morphological characterization of the HCV VLPs and study HCV core-specific T-cell responses to the particles. The E1 and E2 glycoproteins in HCV VLPs formed non-covalent heterodimers and together with core protein assembled into VLPs with a buoyant density of 1.22 to 1.28 g cm(-3). The HCV VLPs could be immunoprecipited with anti-ApoE and anti-ApoC. On electron microscopy, the VLPs had a heterogeneous morphology and ranged in size from 40 to 80 nm. The HCV VLPs demonstrated dose-dependent binding to murine-derived dendritic cells and the entry of HCV VLPs into Huh7 cells was blocked by anti-CD81 antibody. Vaccination of BALB/c mice with HCV VLPs purified from iodixanol gradients resulted in the production of neutralizing antibody responses while vaccination of humanized MHC class I transgenic mice resulted in the prodution of HCV core-specific CD8(+) T-cell responses. Furthermore, IgG purified from the sera of patients chronically infected with HCV genotypes 1a and 3a blocked the binding and entry of the HCV VLPs into Huh7 cells. These results show that our mammalian-cell-derived HCV VLPs induce humoral and HCV-specific CD8(+) T-cell responses and will have important implications for the development of a preventative vaccine for HCV.

Background and aims: The indication for endoscopy to investigate anemia of causes other than iron deficiency is not clear. Increasing numbers of endoscopic procedures for anemia raises concerns about costs to the health system, waiting times, and patient safety. The primary aim of this study was to determine the diagnostic yield of endoscopy in patients referred to undergo investigation for anemia. Secondary aims were to identify additional factors enabling the risk stratification of those likely to benefit from endoscopic investigation, and to undertake a cost analysis of performing endoscopy in this group of patients. Methods: We performed a retrospective review of endoscopy referrals for the investigation of anemia over a 12-month period at a single center. The patients were divided into three groups: those who had true iron deficiency anemia (IDA), tissue iron deficiency without anemia (TIDWA), or anemia of other cause (AOC). Outcome measures included finding a lesion responsible for the anemia and a significant change of management as a result of endoscopy. A costing analysis was performed with an activity-based costing method. Results: We identified 283 patients who underwent endoscopy to investigate anemia. A likely cause of anemia was found in 31 of 150 patients with IDA (21 %) and 0 patients in the other categories (P

OBJECTIVES To determine the nature, prevalence and description accuracy of recorded antibiotic allergy labels (AALs) in a cohort of general medical inpatients, and to assess the feasibility of an oral antibiotic re-challenge study. DESIGN Multicentre cross-sectional study. SETTING AND PARTICIPANTS All patients admitted to the general medical units of Austin Health and Alfred Health, 18 May - 5 June 2015. MAIN OUTCOME MEASURES Baseline demographics, medical and allergy history, infection diagnoses and antibiotic prescribing data for general medical inpatients were collected. A questionnaire was administered to clarify AAL history, followed by correlation of responses with electronic and admissions record descriptions. A hypothetical oral re-challenge in a supervised setting was offered to patients with low risk allergy phenotypes (non-immediate reaction, non-severe cutaneous adverse reaction, or unknown reaction more than 10 years ago). RESULTS Of the 453 inpatients, 107 (24%) had an AAL (median age, 82 years; interquartile range, 74-87 years); 160 individual AALs were recorded, and there was a mismatch in AAL description between recording platforms in 25% of cases. Most patients with an AAL were women (64%; P

This case report highlights the potential severity of bisphosphonate-associated reactions.A 76-year-old lady underwent several hospital admissions for investigation of fever associated with rigors, abdominal pain, and vomiting.Despite multiple investigations, no cause was found, but the timing of the symptoms coincided with monthly risedronate administration.

We analyzed paired pre- and post-travel sera in a cohort of Australian travelers to Asia and demonstrated the acquisition of hepatitis C virus (HCV) and hepatitis B virus (HBV) infection. The incidence density in nonimmune travelers for HCV infection was calculated as 1.8 infections per 10,000 traveler-days and for HBV infection 2.19 per 10,000 traveler-days.

Endobronchial ultrasound (EBUS) transbronchial needle aspiration (TBNA) is an important diagnostic procedure for the interrogation of mediastinal lymph nodes. There is limited data describing the accuracysafety of this technique for the diagnosis of tuberculous mediastinal lymphadenitis.A multi-centre retrospective study of all EBUS-guided TBNA procedures that referred samples for mycobacteriology was performed. Results were correlated with post-procedural diagnoses after a period of surveillance and cross-checked against relevant statewide tuberculosis (TB) registries, and sensitivity and specificity was calculated. In addition, nucleic acid amplification techniques (NAAT) were assessed, and sensitivity and specificity calculated using positive mycobacterial culture as the reference gold standard.One hundred and fifty-nine patients underwent EBUS-TBNA and had tissue referred for mycobacterial culture, of which 158 were included in the final analysis. Thirty-nine were ultimately diagnosed with TB (25%). Sensitivity of EBUS-TBNA for microbiologically confirmed tuberculous mediastinal lymphadenitis was 62% (24/39 cases). Specificity was 100%. Negative predictive value (NPV) and diagnostic accuracy for microbiologic diagnosis was 89% [95% confidence intervals (CI), 82-93%] and 91% (95% CI, 84-94%) respectively. For a composite clinicopathologic diagnosis of TB NPV and accuracy were 98% (95% CI, 93-99%) and 98% (95% CI, 95-99%) respectively. Sensitivity for NAAT was 38% (95% CI, 18-65%).EBUS-TBNA is a safe and well tolerated procedure in the assessment of patients with suspected isolated mediastinal lymphadenitis and demonstrates good sensitivity for a microbiologic diagnosis of isolated mediastinal lymphadenitis. When culture and histological results are combined with high clinical suspicion, EBUS-TBNA demonstrates excellent diagnostic accuracy and NPV for the diagnosis of mediastinal TB lymphadenitis. We suggest EBUS-TBNA should be considered the procedure of choice for patients in whom TB is suspected.

Interoperability characterizes the ability of computer-aided design (CAD) models to accurately represent objects in concurrent engineering environments. The diagnostic set of available software for interoperability testing is described. This set is utilized to develop a visual catalog of possible interoperability errors. The value of utilizing interoperability testing software is appraised by way of a real-world case study. Numerous significant errors are identified in a suite of 140 parts. “Geometry errors” are shown to be more common than “topology errors.” The case study suggests that sensitizing the designer to the nature of typical errors leads to improvement in initial model quality. Example errors are described to illustrate their nature and how to eliminate them. Informal guidelines to improve quality upon initial design are deduced. The development of errors due to inconsistent system accuracy settings during data exchange is explored.

We report a case of a 51-year-old Han Chinese recently returned traveler, who was admitted with a generalized maculopapular rash, fevers, shock, and multi-organ failure. Extensive investigations failed to reveal an infective cause. Skin biopsy findings together with the recent commencement of allopurinol raised a diagnosis of drug reaction with eosinophilia and systemic symptom syndrome. High-dose prednisolone was commenced and the patient made a rapid recovery. This case highlights that not all sepsis-like presentations in returned travelers are due to infective causes and that severe drug reactions need to be considered in the differential diagnosis.

We write in response to the letters of Sonder and van den Hoek1 and Lachish and Schwartz (above) to answer the questions they have raised in relation to our study “The incidence of HBV and HCV infection in Australian travelers to Asia.”2 Our original study was not designed solely for the purpose of determining the seroprevalence of dengue in travelers, as suggested by Sonder and van den Hoek. The cohort has also been used to study the risk of acquiring influenza, Japanese encephalitis, as well as dengue fever.3–5 However, it would have been ideal for us to collect additional serial blood samples and additional demographic and travel information from study participants after their return consultation, but this was not feasible owing to restrictions placed on us by our ethics committee, a limitation we acknowledged in our report. Both letters have raised concerns regarding the time frame from travel to testing in relation to the incubation periods of hepatitis B virus (HBV) and hepatitis C virus (HCV). The letters of Sonder and van den Hoek and Lachish and Schwartz are both incorrect in their interpretation of incubation periods. They have stated that both infections have relatively long incubation periods, making acquisition during study …

Aims The prevalence of diabetes is rising, and people with diabetes have higher rates of musculoskeletal-related comorbidities. HbA1c testing is a superior option for diabetes diagnosis in the inpatient setting. This study aimed to (i) demonstrate the feasibility of routine HbA1c testing to detect the presence of diabetes mellitus, (ii) to determine the prevalence of diabetes in orthopedic inpatients and (iii) to assess the association between diabetes and hospital outcomes and post-operative complications in orthopedic inpatients. Methods All patients aged ≥54 years admitted to Austin Health between July 2013 and January 2014 had routine automated HbA1c measurements using automated clinical information systems (CERNER). Patients with HbA1c ≥6.5% were diagnosed with diabetes. Baseline demographic and clinical data were obtained from hospital records. Results Of the 416 orthopedic inpatients included in this study, 22% (n = 93) were known to have diabetes, 4% (n = 15) had previously unrecognized diabetes and 74% (n = 308) did not have diabetes. Patients with diabetes had significantly higher Charlson comorbidity scores compared to patients without diabetes (median, IQR; 1 [0,2] vs 0 [0,0], p

A 67-year old previously well male presented with a 1 week history of confusion on a background of 3 weeks of headache. Past history included two superficial melanomas excised 5 years ago. Treatment for meningoencephalitis was commenced based on lumbar puncture (LP) and non-contrast brain magnetic resonance imaging (MRI) results. Lack of a clinical response to antibiotics resulted in a second LP and contrast brain MRI which demonstrated hydrocephalus and leptomeningeal disease. Ongoing deterioration led to a whole-body computed tomographic and spinal MRI that showed widespread metastatic disease and extensive leptomeningeal involvement of the spinal cord. The diagnosis of metastatic melanoma with carcinomatous meningitis was made based on cytological analysis of cerebrospinal fluid. He died 2 weeks later in a palliative care facility. This case illustrates that the diagnosis of carcinomatous meningitis can be difficult to make as the heterogeneous nature of its presentation often delays the diagnosis.

We analyzed paired pre- and post-travel sera in a cohort of Australian travelers to Asia and demonstrated the acquisition of hepatitis C virus (HCV) and hepatitis B virus (HBV) infection. The incidence density in nonimmune travelers for HCV infection was calculated as 1.8 infections per 10,000 traveler-days and for HBV infection 2.19 per 10,000 traveler-days.

Although many studies provide strong evidence supporting the development of HCV virus-like particle (VLP)-based vaccines, the fact that heterologous viral vectors and/or multiple dosing regimes are required to induce protective immunity indicates that it is necessary to improve their immunogenicity. In this study, we have evaluated the use of an anionic self-adjuvanting lipopeptide containing the TLR2 agonist Pam(2)Cys (E(8)Pam(2)Cys) to enhance the immunogenicity of VLPs containing the HCV structural proteins (core, E1 and E2) of genotype 1a. While co-formulation of this lipopeptide with VLPs only resulted in marginal improvements in dendritic cell (DC) uptake, its ability to concomitantly induce DC maturation at very small doses is a feature not observed using VLPs alone or in the presence of an aluminium hydroxide-based adjuvant (Alum). Dramatically improved VLP and E2-specific antibody responses were observed in VLP+E(8)Pam(2)Cys vaccinated mice where up to 3 doses of non-adjuvanted or traditionally alum-adjuvanted VLPs was required to match the antibody titres obtained with a single dose of VLPs formulated with this lipopeptide. This result also correlated with significantly higher numbers of specific antibody secreting cells that was detected in the spleens of VLP+E(8)Pam(2)Cys vaccinated mice and greater ability of sera from these mice to neutralise the binding and uptake of VLPs by Huh7 cells. Moreover, vaccination of HLA-A2 transgenic mice with this formulation also induced better VLP-specific IFN-γ-mediated responses compared to non-adjuvanted VLPs but comparable levels to that achieved when coadministered with complete freund's adjuvant. These results suggest overall that the immunogenicity of HCV VLPs can be significantly improved by the addition of this novel adjuvant by targeting their delivery to DCs and could therefore constitute a viable vaccine strategy for the treatment of HCV.

Hepatitis A is the most common vaccine-preventable infection in travellers. The incidence of hepatitis A for travellers ranges from 3.0 to 11.0 per 100,000 person-months and the case-fatality rate is as high as 2 per 100,000 in non-immune travellers. Hepatitis A vaccine is highly effective in preventing infection, significantly reducing the incidence of hepatitis A in travellers, and an important preventative intervention for the “last-minute” traveller. Hepatitis E virus is an important cause of enterically transmitted hepatitis in developing countries. The overall risk of hepatitis E in travellers visiting endemic countries is relatively low compared to hepatitis A. The majority of cases have been reported from the Indian subcontinent. The case fatality rate for hepatitis E is 1.2%, although this is substantially higher in pregnant women. A vaccine for hepatitis E is not available, and therefore travellers must be made aware of preventative measures to reduce their risk of infection.

Two cases of Old World cutaneous leishmaniasis (OWCL) acquired by travelers to Morocco are described. In Australia, OWCL is more frequently seen in migrants rather than returned travelers. The patients were treated with sodium stibogluconate and fluconazole. Optimal treatment is not established, particularly in returned travelers, but identification of Leishmania species can help with the selection of appropriate therapy.

Hepatitis C virus (HCV) is a blood borne disease estimated to chronically infect 3% of the worlds' population causing significant morbidity and mortality. Current medical therapy is curative in approximately 50% of patients. While recent treatment advances of genotype 1 infection using directly acting antiviral agents (DAAs) are encouraging, there is still a need to develop vaccine strategies capable of preventing infection. Moreover, vaccines may also be used in future in combination with DAAs enabling interferon-free treatment regimens. Viral and host specific factors contribute to viral evasion and present important impediments to vaccine development. Both, innate and adaptive immune responses are of major importance for the control of HCV infection. However, HCV has evolved ways of evading the host's immune response in order to establish persistent infection. For example, HCV inhibits intracellular interferon signalling pathways, impairs the activation of dendritic cells, CD8 + and CD4 + T cell responses, induces a state of T-cell exhaustion and selects escape variants with mutations CD8 + T cell epitopes. An effective vaccine will need to produce strong and broadly cross-reactive CD4 + , CD8 + T cell and neutralising antibody (NAb) responses to be successful in preventing or clearing HCV. Vaccines in clinical trials now include recombinant proteins, synthetic peptides, virosome based vaccines, tarmogens, modified vaccinia Ankara based vaccines, and DNA based vaccines. Several preclinical vaccine strategies are also under development and include recombinant adenoviral vaccines, virus like particles, and synthetic peptide vaccines. This paper will review the vaccines strategies employed, their success to date and future directions of vaccine design.

We assessed the in vivo efficacy of surgical and N95 (respirator) masks to filter reverse transcription-polymerase chain reaction (RT-PCR)-detectable virus when worn correctly by patients with laboratory-confirmed acute influenza. Of 26 patients with a clinical diagnosis of influenza, 19 had the diagnosis confirmed by RT-PCR, and 9 went on to complete the study. Surgical and N95 masks were equally effective in preventing the spread of PCR-detectable influenza.

Background. Mannose-binding lectin (MBL) is an important mediator of innate immunity and is synthesized primarily by the liver. Low MBL levels are common, are due primarily to polymorphisms in the gene encoding MBL (MBL2), and are associated with an increased risk of infection, particularly when immunity is compromised. We report a large, retrospective study that examined the association between MBL status and clinically significant infection following orthotopic liver transplantation. Methods. One hundred two donor-recipient orthotopic liver transplantation pairs were studied. Five polymorphisms in the promoter and coding regions of MBL2 were examined. MBL levels were measured, using the mannan-binding and C4-deposition assays, in serum samples obtained before and after transplantation. Associations between MBL status, as assessed by serum MBL levels and MBL2 genotype, and time to first clinically significant infection (CSI) after transplantation were examined in survival analysis with consideration of competing risks. Results. The median duration of follow-up after orthotopic liver transplantation was 4 years. Thirty-six percent of recipients developed CSI after transplantation. The presence of MBL2 coding mutations in the donor was significantly associated with CSI in the recipient; the cumulative incidence function of infection was 55% in recipients of deficient livers, compared with 32% for recipients of wild-type livers (P = .002). Infection was not associated with recipient MBL2 genotype. Low MBL levels after orthotopic liver transplantation levels (mannan-binding

• We report eight recent cases of Chikungunya virus infection in travellers to Australia. Patients presented with fevers, rigors, headaches, arthralgia, and rash. • The current Indian Ocean epidemic and Italian outbreak have featured prominently on Internet infectious disease bulletins, and Chikungunya virus infection had been anticipated in travellers from the outbreak areas. • Diagnosis was by a generic alphavirus reverse transcriptase polymerase chain reaction with confirmatory sequencing. • Prompt diagnosis of Chikungunya virus infections is of public health significance as the mosquito vectors for transmission exist in Australia. There is potential for this infection to spread in the largely naive Australian population.

Diagnosis: Zika virus infection. Arboviral infection was suspected. Dengue virus (DENV) serology (Panbio Dengue immunoglobulin G [IgG] indirect enzyme-linked immunosorbent assay [ELISA], Alere; Panbio Dengue immunoglobulin M [IgM] capture ELISA, Alere; Platelia Dengue NS1Ag ELISA, Bio-Rad) and pan-flavivirus reverse transcription polymerase chain reaction (PCR) using heminested primers that amplify a conserved sequence in the NS5 gene (modified from Scaramozzino et al [1]) was requested on day 1 of illness for both patients. Acute DENV serology, including NS1 antigen, was negative in both patients. Both patients had positive IgG antibody and negative IgM antibody for measles, indicating past immunity or previous vaccination. The initial patient’s pan-flavivirus PCR was positive by conventional PCR. The initial extracted complementary DNA was then tested using a DENV type-specific real-time TaqMan PCR assay and was negative. The amplified product from the panflavivirus PCR (215 bp in length) was sequenced, and a BLAST search confirmed Zika virus (ZIKV). Interestingly, despite similar epidemiology and symptoms, ZIKV was not identified in the husband’s sample. Convalescent DENV serology in the initial patient demonstrated a low positive seroconversion in DENV IgG, suggestive of cross-reacting antibodies. Both patients made a complete recovery over 5 days with no specific treatment. ZIKV infection is caused by an RNAvirus endemic to Southeast Asia and Africa that is transmitted by Aedes species mosquitoes. ZIKV was initially isolated in 1947 from a rhesus monkey in Zika Forest, Uganda [2]. Confirmed cases were rare until recent epidemics in Micronesia, French Polynesia, and the Cook Islands [3]. Clinical manifestations are similar to other arboviral infections, such as DENV and chikungunya, and are characterized by fever, maculopapular rash, myalgias, and headache. Investigations are nonspecific. Diagnostic clues that may help distinguish ZIKV from DENV include conjunctivitis [4–6] (17/31 [55%] of ZIKV patients [5] vs 14/148 [9%] DENV patients [7]; P < .0001) and an absence of thrombocytopenia [6]. Rash was also more commonly reported in ZIKV (28/ 31 [90%] ZIKV patients [5] vs 44/148 [30%] DENV patients [7]; Figure 1. Bilateral conjunctivitis secondary to Zika virus infection. Arrows indicate areas of conjunctivitis.

A 34-year-old man presented with a 6-day history of diarrhoea, abdominal cramps and fever. Blood cultures were initially reported as positive for Escherichia coli using matrix-assisted laser desorption/ionisation time of flight (MALDI-TOF) mass spectrometry. Contrast CT of the abdomen and pelvis revealed pancolitis and terminal ileal thickening. The patient was treated empirically with ampicillin, ciprofloxacin and metronidazole. Stool cultures were positive for Shigella sonnei. Subsequent testing on the initial blood culture correctly identified the organism as S. sonnei. On further questioning, the patient reported unprotected men who have sex with men (MSM) 3 months previously. His symptoms resolved during his 3-day admission, and he was discharged on 14 days of ciprofloxacin. He remains well. This case highlights that shigellosis is increasingly seen in MSM, with no history of travel, and may result in bacteraemia. This case also highlights the benefits (rapid identification of organisms) and limitations (inability to distinguish between E. coli and Shigella spp) of new technologies such as MALDI-TOF.