Search

Background: European travellers to endemic countries are at risk of malaria and may be affected by a different range of co-morbidities than natives of endemic regions. The safety profile, especially cardiac issues, of artenimol (previously dihydroartemisinin)–piperaquine (APQ) Eurartesim® during treatment of uncomplicated imported falciparum malaria is not adequately described due to the lack of longitudinal studies in this population. The present study was conducted to partially fill this gap. Methods: Participants were recruited through Health Care Provider’s safety registry in 15 centres across 6 European countries in the period 2013–2016. Adverse events (AE) were collected, with a special focus on cardiovascular safety by including electrocardiogram QT intervals evaluated after correction with either Bazett’s (QTcB) or Fridericia’s (QTcF) methods, at baseline and after treatment. QTcB and/or QTcF prolongation were defined by a value > 450 ms for males and children and > 470 ms for females. Results: Among 294 participants, 30.3% were women, 13.7% of Caucasian origin, 13.5% were current smoker, 13.6% current alcohol consumer and 42.2% declared at least one illness history. The mean (SD) age and body mass index were 39.8 years old (13.2) and 25.9 kg/m2 (4.7). Among them, 75 reported a total of 129 AE (27 serious), 46 being suspected to be related to APQ (11 serious) and mostly labelled as due to haematological, gastrointestinal, or infection. Women and Non-African participants had significantly (p < 0.05) more AEs. Among AEs, 21 were due to cardiotoxicity (7.1%), mostly QT prolongation, while 6 were due to neurotoxicity (2.0%), mostly dizziness. Using QTcF correction, QT prolongation was observed in 17/143 participants (11.9%), only 2 of them reporting QTcF > 500 ms (milliseconds) but no clinical symptoms. Using QTcB correction increases of > 60 ms were present in 9 participants (6.3%). A trend towards increased prolongation was observed in those over 65 years of age but only a few subjects were in this group. No new safety signal was reported. The overall efficacy rate was 255/257 (99.2%). Conclusions: APQ appears as an effective and well-tolerated drug for treatment of malaria in patients recruited in European countries. AEs and QT prolongation were in the range of those obtained in larger cohorts from endemic countries. Trial registration This study has been registered in EU Post-Authorization Studies Register as EUPAS6942, SCOPUS: ar.j, info:eu-repo/semantics/published

Objective The Saudi government requires that all pilgrims receive a quadrivalent meningococcal vaccine at least 10 days before the Hajj. We conducted a study to determine the uptake of meningococcal vaccine and antibiotic use. We also investigated risk factors of meningococcal carriage and carriage of Neisseria meningitidis pathogenic serogroups A, C, W and Y. Methods A cross‐sectional oropharyngeal carriage survey was conducted in 2973 Hajj pilgrims in September 2017. A real‐time polymerase chain reaction (rt‐PCR) assay was used to identify N. meningitidis from the oropharyngeal swabs. A questionnaire investigated potential risk factors for carriage of N. meningitidis. Results Two thousand two hundred forty nine oropharyngeal swabs were obtained. The overall prevalence of carriage of N. meningitidis was 4.6% (95% CI: 3.4%–6%). Carriage of pathogenic serogroups was not associated significantly with any of the meningococcal risk factors evaluated. 77% of pilgrims were vaccinated but 22.58 % said they were carrying unofficial vaccination cards. Conclusion Carriage of serogroups A, C, W and Y was not significantly associated with any of the risk factors investigated. Almost a quarter of pilgrims were unlikely to have been vaccinated, highlighting a need to strengthen compliance with the current policy of vaccination to prevent meningococcal disease outbreaks during and after the Hajj.

Replacement of lost cranial bone (partly mesodermal and partly neural crest‐derived) is challenging and includes the use of nonviable allografts. To revitalize allografts, bone marrow‐derived mesenchymal stromal cells (mesoderm‐derived BM‐MSCs) have been used with limited success. We hypothesize that coating of allografts with induced neural crest cell‐mesenchymal progenitor cells (iNCC‐MPCs) improves implant‐to‐bone integration in mouse cranial defects. Human induced pluripotent stem cells were reprogramed from dermal fibroblasts, differentiated to iNCCs and then to iNCC‐MPCs. BM‐MSCs were used as reference. Cells were labeled with luciferase (Luc2) and characterized for MSC consensus markers expression, differentiation, and risk of cellular transformation. A calvarial defect was created in non‐obese diabetic/severe combined immunodeficiency (NOD/SCID) mice and allografts were implanted, with or without cell coating. Bioluminescence imaging (BLI), microcomputed tomography (μCT), histology, immunofluorescence, and biomechanical tests were performed. Characterization of iNCC‐MPC‐Luc2 vs BM‐MSC‐Luc2 showed no difference in MSC markers expression and differentiation in vitro. In vivo, BLI indicated survival of both cell types for at least 8 weeks. At week 8, μCT analysis showed enhanced structural parameters in the iNCC‐MPC‐Luc2 group and increased bone volume in the BM‐MSC‐Luc2 group compared to controls. Histology demonstrated improved integration of iNCC‐MPC‐Luc2 allografts compared to BM‐MSC‐Luc2 group and controls. Human osteocalcin and collagen type 1 were detected at the allograft‐host interphase in cell‐seeded groups. The iNCC‐MPC‐Luc2 group also demonstrated improved biomechanical properties compared to BM‐MSC‐Luc2 implants and cell‐free controls. Our results show an improved integration of iNCC‐MPC‐Luc2‐coated allografts compared to BM‐MSC‐Luc2 and controls, suggesting the use of iNCC‐MPCs as potential cell source for cranial bone repair., Bone marrow‐derived mesenchymal stromal cells (BM‐MSCs) were obtained from human bone marrow. Induced neural crest cell‐mesenchymal progenitor cells (iNCC‐MPCs) were generated from induced pluripotent stem cell‐derived iNCCs. Cells were luciferase transfected and seeded onto decellularized allografts, which were implanted into 5 mm circular calvarial defects in non‐obese diabetic/severe combined immunodeficiency (NOD/SCID) mice. Allograft only was used as controls. Mice were followed for a duration of 8 weeks. Cell survival, allograft integration, and tissue morphology and transplanted cell contribution were monitored via bioluminescence imaging (BLI), micro‐computed tomography (μCT), and histology and immunofluorescence (IF). Green arrow: BLI; yellow arrow: μCT; Orange arrow: histology and IF; Blue arrow: biomechanical test.

Cytokine-induced memory-like (CIML) NK cells generated in response to proinflammatory cytokines in vitro and in vivo can also be generated by vaccination, exhibiting heightened responses to cytokine stimulation months after their initial induction. Our previous study demonstrated that in vitro human NK cell responses to inactivated influenza virus were also indirectly augmented by very low doses of IL-15, which increased induction of myeloid cell–derived cytokine secretion. These findings led us to hypothesize that IL-15 stimulation could reveal a similar effect for active influenza vaccination and influence CIML NK cell effector functions. In this study, 51 healthy adults were vaccinated with seasonal influenza vaccine, and PBMC were collected before and up to 30 d after vaccination. Myeloid and lymphoid cell cytokine secretion was measured after in vitro PBMC restimulation with low-dose IL-15, alone or in combination with inactivated H3N2 virus; the associated NK cell response was assessed by flow cytometry. PBMC collected 30 d postvaccination showed heightened cytokine production in response to IL-15 compared with PBMC collected at baseline; these responses were further enhanced when IL-15 was combined with H3N2. NK cell activation in response to IL-15 alone (CD25) and H3N2 plus IL-15 (CD25 and IFN-γ) was enhanced postvaccination. We also observed proliferation of less-differentiated NK cells with downregulation of cytokine receptors as early as 3 d after vaccination, suggesting cytokine stimulation in vivo. We conclude that vaccination-induced “training” of accessory cells combines with the generation of CIML NK cells to enhance the overall NK cell response postvaccination.

As physicians, we strive to meet the needs of our patients. In doing so, we are often exposed to hazards that have the potential to not only compromise our health, but also our ability to deliver the best possible healthcare. Occupational hazards specific to the field of orthopaedics include infectious organisms, radiation, surgical smoke, chemicals, hazardous noise, musculoskeletal injury, and psychosocial stressors. Even though orthopaedic surgeons acknowledge the risk, most lack in-depth knowledge of the associated long-term harm associated with these hazards and ways of reducing risk of exposure. Orthopaedic surgeons should increase awareness, follow established guidelines, and integrate preventative measures to create the safest possible work environment. It is our hope that by improving our own health, we will be better equipped to address the health concerns of those we serve-our patients.

Background: Klippel-Feil syndrome (KFS) is defined by multiple abnormal segments of the cervical spine with congenital synostosis of two or more cervical vertebrae. KFS patients who demonstrate progressive symptomatic instability and/or neurologic sequelae are traditionally managed with operative decompression and arthrodesis. Case Description: A 44-year-old female with chronic neck pain and radiculopathy and a C7-T1 KFS presented with adjacent segment degenerative disc disease at the C5-6 and C6-7 levels. She was successfully managed with a two-level cervical disc arthroplasty (CDA). Conclusion: Patients with KFS and disease at two contiguous, adjacent levels (e.g., cervical disc disease) may be safely and effectively managed with two-level CDA.

Background The Hajj is one of the world’s largest pilgrimage and gathers millions of Muslims from different nationalities every year. Communicable diseases have been reported frequently, during and following the Hajj, and these have been linked to individual behavioural measures. This study aimed to measure the effect of personal preventive measures, such as face mask use, hand hygiene and others, adopted by pilgrims in reducing the acquisition of infectious diseases. Methods We conducted a cross-sectional study at the Hajj terminal in King Abdulaziz International Airport in Jeddah, Saudi Arabia. Pilgrims were approached in the airport lounges after the 2017 Hajj season and prior to the departure of their flights from Jeddah to their home countries. An electronic data collection tool (‘Open Data Kit’) was used to gather survey data in regards to health problems and preventive measures during the Hajj. Results A total of 2973 Hajj pilgrims were surveyed. In all, 38.7% reported symptoms of upper respiratory tract infections (URTIs) and 5.4% reported symptoms of travel diarrhoea. Compliance with face mask use was 50.2%. Changing a face mask every 4 h was found to be significantly associated with lower prevalence of URTIs [adjusted odds ratio 0.56 (95% confidence interval 0.34–0.92), P = 0.02]. There was no statistical difference between overall face mask use and URTI acquisition. The main sources of food, eating raw vegetables/food, frequency of hand washing or use of hand sanitizers were not found to be significantly associated with reported travellers’ diarrhoea. Unlicensed barbers were used by 12% of pilgrims and 9.2% of pilgrims reported using blades that were reused by other pilgrims. Conclusion Preventive measures are the most effective way to prevent infections. Pilgrims can benefit from face masks by changing them frequently. There is still limited information on the effect of the use of face mask in decreasing the risk of URTI in mass gatherings.

BackgroundThe impact of CD4+ T-cell count and highly active antiretroviral therapy (HAART) on the rate of surgical site infection (SSI) in patients with human immunodeficiency virus (HIV) undergoing total hip arthroplasty is still unclear. The goals of this study were to assess the rate of perioperative infection at a large tertiary care referral center and to identify risk factors in HIV+ patients undergoing total hip arthroplasty (THA).MethodsThis study was a prospective, observational study at a single medical center from 2000–2017. Patients who were HIV+ and underwent THA were followed from the preoperative assessment period, through surgery and for a 2-year follow-up period.ResultsSixteen of 144 HIV+ patients (11%) undergoing THA developed perioperative surgical site infections. Fourteen patients (10%) required revision THA within a range of 12 to 97 days after the initial surgery. The patients’ mean age was 49.6 ± 4.5 years, and the most common diagnosis prompting THA was osteonecrosis (96%). Patients who developed SSI had a lower waist-hip ratio (0.86 vs. 0.93,p= 0.047), lower high density lipoprotein cholesterol (45.8 vs. 52.5,p= 0.015) and were more likely to have post-traumatic arthritis (12.5% vs. 0%,p= 0.008). Logistic regression analysis demonstrated that current alcohol use and higher waist-hip ratio were significant protectors against infection (p< 0.05). No other demographic, medical, immunologic parameters, or specific HAART regimens were associated with perioperative infection.ConclusionsImmunologic status as measured by CD4+ cell count, HIV viral load, and medical therapy do not appear to influence the development of SSI in HIV+ patients undergoing THA. Metabolic factors and post-traumatic arthritis may influence the increased rate of infection in HIV+ patients following THA.

Purpose To describe the main provisions of the US Department of Labor’s final “fiduciary” rule and its related prohibited transaction exemptions and the key challenges the rule poses for financial advisers. Design/methodology/approach This article describes the impact of the new “fiduciary” rule on broker-dealers, banks and other financial organizations who will, for the first time since the passage of ERISA, be subject to ERISA’s fiduciary standards and remedies when providing investment and asset management recommendations to individual retirement accounts and other retail retirement clients. Findings The most immediate impact of the rule will be on the compensation practices at broker-dealers and other financial institutions and on the fee and revenue sharing arrangements among funds, fund sponsors and the financial institutions that offer investment advice to retail retirement clients. Although the new rule responds to many of the concerns raised by the financial services industry, compliance with the rule will require the restructuring of pay and compliance policies at financial institutions servicing retail clients. Originality/value Practical guidance from experienced ERISA lawyers.

Background Existing travel health guidelines are based on a variety of data with underpinning evidence ranging from high‐quality randomized controlled trials to best estimates from expert opinion. For strategic guidance and to set overall priorities, data about average risk are useful. The World Health Organization (WHO) plans to base future editions of “International Travel and Health” on its new “Handbook for Guideline Development.” Methods Based on a systematic search in PubMed, the existing evidence and quality of data on vaccine‐preventable disease (VPD) risks in travelers was examined and essentials of vaccine efficacy were briefly reviewed. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework was used to evaluate the quality of the data. Results Moderate‐quality data to determine the risk of VPD exist on those that are frequently imported, whereas in most others the level of confidence with existing data is low or very low. Conclusions In order for the WHO to produce graded risk statements in the updated version of “International Travel and Health,” major investment of time plus additional high‐quality, generalizable risk data are needed.

Airway management during resuscitation is pivotal for treating hypoxia and inducing reoxygenation. This German Resuscitation Registry (GRR) analysis investigated the influence of the type of airway used in patients treated with manual chest compression (mCC) and automated chest compression devices (ACCD) after out-of-hospital cardiac arrest (OHCA). Out of 42,977 patients (1 January 2010–30 June 2016) information on outcome, airway management and method of chest compressions were available for 27,544 patients. Hospital admission under cardiopulmonary resuscitation (CPR), hospital admission with return of spontaneous circulation (ROSC), hospital discharge and discharge with cerebral performance categories 1 and 2 (CPC 1,2) were used to compare outcome in patients treated with mCC vs. ACCD, and classified by endotracheal intubation (ETI), initial supraglottic airway device (SAD) changed into ETI, and only SAD use. Outcomes for hospital admission under ongoing CPR, hospital admission with ROSC, hospital discharge and neurologically intact survival (CPC 1,2) for mCC (84.8%) vs. ACCD (15.2%) groups were: 8.4/38.6%, 39.2/27.2%, 10.6/6.8%, 7.9/4.7% (p < 0.001), respectively. Only mCC with SAD/ETI for ever ROSC (OR 1.466, 95% CI: 1.353–1.588, p < 0.001) and mCC group with SAD/ETI for hospital admission with ROSC showed better outcomes (odds ratio [OR] 1.277, 95% confidence interval [CI]: 1.179–1.384, p < 0.001) in comparison to mCC treated with ETI. Compared to mCC/ETI, all other groups were associated with a decrease in neurologically intact survival. Better outcomes were found for mCC in comparison to ACCD and ETI showed better outcomes in comparison to SAD only. This observational registry study raised the hypothesis that SAD only should be avoided or SAD should be changed into ETI, independent of whether mCC or ACCD is used.

The recommendation for carriage standby emergency treatment (SBET) for malaria is now becoming more widespread across Europe. This follows as a replacement to the withdrawal of recommendations for use of malaria chemoprophylaxis, predominantly therefore to falling transmission of Plasmodium falciparum malaria on the successful malaria control programmes across South East Asia and South America.1 Travellers are prescribed SBET antimalarial medication to carry during their journey. The policy is aimed at travel to areas of low falciparum malaria transmission in the above continents, not at travellers to Sub Saharan Africa. They are advised to use the medication when malaria is suspected and prompt medical attention is unavailable, but ideally, to attend a medical centre within 24 h of onset of symptoms for a diagnosis, and if malaria is confirmed, use the medication secure in the knowledge that it is not counterfeit.

Paediatric travellers face most of the infectious risks that adults face during travel, but their different immunological maturity and response to infection make them more vulnerable to disease.

Background Despite many travelers receiving at least one vaccination during the pre-travel consultation, little is known about travelers' fear of injections and the impact this may have on educating travelers about health risks associated with their trip. This study aimed to investigate: (1) the prevalence of injection anxiety in travelers attending a pre-travel consultation, (2) whether anxiety due to anticipating a vaccination adversely affects recall of information and advice, and (3) whether clinicians can recognize travelers' anxiety, and how they respond to anxious travelers. Methods Consecutive adult travelers (N = 105) attending one of two inner-city travel clinics completed self-report measures of state anxiety, injection anxiety, and symptoms of needle phobia immediately before and after their pre-travel consultation. Clinicians were also asked to rate travelers' anxiety and report any anxiety management strategies. Standardized information was presented during the consultation and recall of information and advice was assessed immediately post-consultation. Delayed recall (24 hours) was assessed for a subsample (20%) of participants. Results More than one third of travelers reported feeling nervous or afraid when having an injection (39%). Travelers' state anxiety was related to their psychological and physiological reactions to needles, and reduced significantly post-consultation. Recall of information and advice varied, with failure of recall ranging from 2 to 70% across 15 items, and delayed recall being significantly lower. No relationship was found between recall and anxiety. Clinician-rated anxiety moderately correlated with travelers' self-reported anxiety. Conclusions A significant proportion of travelers experienced injection anxiety when attending the pre-travel consultation, with some travelers reporting symptoms consistent with criteria for Blood Injection Injury phobia. There were important gaps in recall of information and advice about common travel risks. Although no relationship was found between recall and anxiety, this may have been due to the sample and setting.

BACKGROUND CONTEXT Synthetic bone grafts are being developed to lessen the need for autograft and allograft. Electrospun bone grafts (ESBG) have a highly porous nanofibrous structure with a large surface area-to-volume ratio, potentially improving its osteoconductive and osteoinductive properties. PURPOSE We investigate the potential of ESBG to stimulate mesenchymal stem cell (MSC) function in vitro, and to facilitate BMP-2 mediated spinal fusion in a rat model. STUDY DESIGN/SETTING In vitro analysis of MSC adhesion, proliferation, and differentiation seeded in ESBG. In vitro analysis of ESBG-facilitated posterolateral spine fusion in a rat model. PATIENT SAMPLE For the in vitro study: MSCs seeded with and without ESBG. For the in vivo study: 36 Lewis rats underwent posterolateral spine fusions. OUTCOME MEASURES In vitro: adhesion, proliferation, and osteogenic differentiation of MSCs. In vivo: rat fusion rate, fusion stiffness, fusion bone volume, fusion connectivity density and histological evaluation. METHODS Adhesion, proliferation, and osteogenic differentiation of MSCs seeded with and without ESBG for 7 days was analyzed. In vivo, 36 rats underwent posterolateral spine fusions in the following groups: (I) ESBG+bone marrow aspirate (BMA), (II) ESBG+BMA+BMP-2 (low-dose), and (III) BMA. Rats were followed for 3 months and the fusion masses were characterized with manual palpation, biomechanical tests, micro-CT and histological evaluation. RESULTS Ninety percent of cultured MSCs adhered to ESBG. When seeded in ESBG, there was a significant increase in MSC proliferation (0.18 to 0.43, p CONCLUSIONS This is the first reported characterization of ESBG for spinal applications. ESBGs provide a novel scaffold that supports MSC binding, proliferation and osteogenic differentiation. In a rat spine fusion model, ESBG impregnated with BMA and low-dose BMP-2 allowed for 100% fusion with strong biomechanical properties. ESBGs represent a promising synthetic graft and should be further investigated for clinical feasibility. FDA DEVICE/DRUG STATUS Unavailable from authors at time of publication.

Background A patch vaccine containing heat-labile toxin (LT) from enterotoxigenic Escherichia coli (ETEC) has demonstrated to be beneficial in reducing the rate and severity of travelers' diarrhea in Latin America. To evaluate the efficacy of this transdermal vaccine system in an area with a different diarrheal pathogen profile, an additional phase 2 study was conducted in European travelers to India. Methods For this multicenter, randomized, double-blinded, placebo-controlled field study 723 subjects were recruited; 603 (299 LT vaccine, 304 placebo) were included in the per-protocol-population (PPP). Results Although the LT patch induced a measurable LT immune response in recipients, it failed to protect against LT ETEC or all-cause diarrhea. In the PPP the incidence rate of diarrhea as per primary endpoint was 6.0% (18 of 299) in the vaccine group and 5.9% (18 of 304) in the placebo group. Additionally, lower than expected rates of LT ETEC diarrheas were observed in India. The vaccine delivery system frequently produced rash and pruritus at the site of application, long term hyperpigmentation persisted in a minority of LT recipients, and also few site reactions were noted in the placebo group. Conclusions The evaluated patch vaccine failed to satisfy mainly with respect to protective efficacy. Noninvasive prophylactic agents against travelers' diarrhea, particularly vaccines against the most frequent pathogens, thus continue to be badly needed.

Background Accessible travel has led to a rapid growth in international tourism, particularly to developing countries. With the increase, travel-associated morbidity and mortality has changed. Data on traveling populations are essential for policy makers to estimate infectious and noninfectious risks in travelers. Passenger flow statistics are compiled by the World Tourism Organization (WTO) and by official institutions of some countries. This study investigates sources of passenger flow statistics, methods of data collection, and compares datasets for consistency. Methods Four national datasets of departing travelers were compared to the United Nations' World Tourism Organization (WTO) data on passenger arrivals to eight destination countries. The ratio between arrivals and departures was calculated (main destination ratio [MDR]) to estimate the proportion of direct to indirect traveler arrivals. Results With few exceptions, arrival data exceeded that of departure data for all destinations. India is a primary destination for Australian residents where arrival and departure figures were similar (MDR 1.1), while visits to Cambodia and Turkey, with 3.6- and 3.8-fold higher arrivals, respectively, are part of multidestination trips. For UK residents, arrivals exceeded departures for all destinations except India where the reverse was true (MDR 0.8). A close correlation between arrivals and departures was noted for visits to South Africa while arrivals to Singapore and Cambodia were 7- and 10-fold higher, respectively. Arrivals by Finnish residents to destination countries were 1.4- to 1.6-fold higher than departures and 2.2-fold higher for Canadians visiting China. Conclusions Different methodologies used to capture arrival and departure statistics result in different estimations of traveler numbers. Data from a single source does not provide a comprehensive picture of most tourism itineraries. Inbound statistics give a more accurate reflection of the total visits made by travelers from a source country.

Dear Prof. Caume, Drs’ Denholm and Thevarajan1 in their review on risk and interventions for reducing travel associated tuberculosis (TB) make no mention of the potential utility of isoniazid chemoprophylaxis. Isoniazid has long been recognized as an effective and safe drug for reducing TB …

Summary Objectives The Typhoid and Paratyphoid Reference Group (TPRG) was convened by the Health Protection Agency (HPA) and the Chartered Institute of Environmental Health (CIEH) to revise guidelines for public health management of enteric fever. This paper presents the new guidelines for England and their rationale. Methods Methods include literature reviews including grey literature such as audit data and case studies; analysis of enhanced surveillance data from England, Wales and Northern Ireland; review of clearance and screening schedules in use in other non-endemic areas; and expert consensus. Results The evidence and principles underpinning the new guidance are summarised. Significant changes from previous guidance include: • Algorithms to guide risk assessment and management, based on risk group and travel history; • Outline of investigation of non-travel cases; • Simplified microbiological clearance schedules for cases and contacts; • Targeted co-traveller screening and a "warn and inform" approach for contacts; • Management of convalescent and chronic carriers. Conclusions The guidelines were launched in February 2012. Feedback has been positive: the guidelines are reported to be clear, systematic, practical and risk-based. An evaluation of the guidelines is outlined and will add to the evidence base. There is potential for simplification and consistency between international guidelines.

Improved data collection methods have produced a clearer picture of travel-associated health risks and at-risk travelers. Examination of the causes of mortality and morbidity has led to a change in emphasis on ways of reducing morbidity. There are unanswered questions that relate to the contribution of medical comorbidities on travel-associated illness, how communication can enhance or influence behavior change, and the best strategies to influence the travelers at greatest risk. Enhanced data collection methods and better denominator data are necessary to provide more precise risk information and help inform policy and thereby reduce morbidity in tourists and travelers.

Malaria remains the most important parasitic infection in humans. There have been significant advances in the treatment of both nonsevere and severe malaria with the advent of artemisinin combination therapies and parenteral artesunate, but the optimum supportive management of severe malaria is unclear. A broadly acceptable therapy for the prevention of relapses in Plasmodium vivax infection has not been discovered. Globally, the priority remains to prevent infection in the vulnerable, to move toward elimination where feasible, and to ensure that effective treatment is available to all. In developed settings, prevention of infection and its early recognition are crucial.

Imported malaria has been described as “an infection that was acquired in an endemic area by an individual (either a tourist or indigenous native) but diagnosed in a non‐endemic country after development of the clinical disease.” 1 In the UK, there was an average of 1,965 laboratory‐confirmed reports of imported malaria infections between 1987 and 2006, 2 and this country, together with France, Germany, and Italy, accounts for about three‐quarters of the 10,000 to 12,000 annual cases imported into the World Health Organization European region. 3 The majority of imported malaria infections reported in European countries are caused by Plasmodium falciparum , 3 the Plasmodium species associated with the most severe disease and mortality. Data from TropNetEurop, 4,5 a European sentinel surveillance system, describe how most cases originate from West Africa and affect travelers of African ethnicity. The most commonly reported reason for travel is to visit friends and relatives (VFRs), with 64.5% of all travelers citing this as a reason for travel in malaria reports between 1987 and 2006 to the UK's Malaria Reference Laboratory and 76.4% in reports to TropNetEurop in 2007. 5 Those VFRs who were born and lived for some time in malaria‐endemic countries before moving to Europe will have acquired partial immunity from exposure to malaria during childhood. Without repeated exposure, immunity appears to wane with time, although the time period during which this occurs is unknown. Bouchaud and colleagues 6 have demonstrated that levels of parasitemia and severe disease were lower in African migrants who were resident outside malarious areas for more than 4 years but acquired falciparum malaria on a short visit to a malaria‐endemic area, when compared to patients who had always lived outside these areas. However, a recent study of African migrants in Italy 7suggests that living for more than … Corresponding Author: Penny Neave, MSc, Malaria Reference Laboratory, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK. E‐mail: penny.neave{at}lshtm.ac.uk

BACKGROUND CONTEXT Loading of absorbable collagen sponges (ACS) with recombinant human bone morphogenic protein-2 (rhBMP-2) has been successfully used to enhance bone formation and to induce spinal fusion. However, side effects, such as soft-tissue edema and inflammation, have been reported. NEMO binding domain peptide (NBD) inhibits activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), a central regulator of immune response. PURPOSE To investigate NBD's potential to reduce rhBMP-2-induced soft-tissue inflammation and to stimulate spinal fusion. STUDY DESIGN/SETTING To evaluate inflammation, ACS containing either high dose rhBMP-2, rhBMP-2+NBD, NBD only or buffer were only implanted into intramuscular fusion beds of 32 rats. To analyze new bone formation in the presence of NBD, posterolateral intertransverse lumbar fusion procedures were performed on 16 rats. ACS implants were loaded with rhBMP-2 or rhBMP-2+NBD. PATIENT SAMPLE No patients, animal study. OUTCOME MEASURES T2-weighted relaxation time (T2-RT), histological analysis (HE appropriate post hoc tests for multiple comparisons using Tukey's honestly significant was applied. p≤.05 was considered significant. RESULTS T2-RT values were increased in the BMP-2 group compared to BMP-2+NBD, NBD and ACS groups. No difference was detected between BMP-2+NBD versus NBD and ACS controls. Histological analysisof the implant-surrounding zones showed an increase in cellular activity in the BMP-2 group compared to BMP-2+NBD and controls. Presence of rhBMP-2 increased relative NF-κB binding and gene expression of inflammatory markers, interleukin (IL)1β, IL6, IL18, chemokine ligand (CCL)2 and CCL3 compared to controls. In the BMP-2+NBD group, cytokine expression was blocked. No differences were found between BMP-2+NBD and control groups. BMP-2+NBD resulted in a higher bone volume and reduced trabecular spacing compared to BMP-2, a higher number of levels fused, and similar structural properties of the bone tissue. CONCLUSIONS In summary, NBD reduces soft-tissue edema formation, reduces recruitment of inflammatory cells, diminishes NF-κB binding and blocks transcription of NF-κB-regulated cytokines in response to high-dose rhBMP-2 in rats. Furthermore, NBD stimulates bone formation in rhBMP-2-mediated spinal fusion, potentially through cross-talk of the NF-κB pathway with other pathways. The results of this study might provide the basis to develop new therapeutic approaches for spinal fusion using graft material with a combinatory administration of rhBMP-2 and NBD.

Background. Travel-associated health risks need to be balanced against the positive opportunities associated with interregional travel. As the perceived and real spectrum of health risks related to international travel increase both quantitatively and qualitatively, the need for more discriminating tools in clinical assessment for the purpose of mitigation, public health management, and research are needed. One group of international travelers identified as having increased risk of poor travel-related health outcomes are those who travel with the specific intent of visiting friends or relatives (VFR travelers). Due to variations in defining VFR travel in the health context there are issues in applying this designation uniformly from multiple perspectives. This article supports the standardization of VFR traveler definitions based on objective criteria and provides illustrations of the application of this definition through an illustrated approach to risk assessment based on these criteria and the differentials in the determinants of health between source and destination regions. Methods. A working group was established by the Migration Health Sub-committee, International Society for Travel Medicine to assess the literature on VFR travel and health, review an evidence-based approach to managing health risk related to travel, and to propose criteria-based definition for VFR travel. The new definition of a VFR is a traveler whose primary purpose of travel is to visit friends or relatives where there is a gradient of epidemiological risk between home and destination. Results. A case scenario discussion of VFR travel defined by criteria and risk assessment based on differential determinants of health is presented in this article. Discussion. The goal of this article is to encourage discussion on travel health evaluation for the most ‘‘at risk’’ populations and to standardize the application of clinical, public health, and research approaches to defining VFR travelers in a risk management context.

BACKGROUND: Large numbers of Western travelers visit countries endemic for Japanese encephalitis (JE). The risk of infection is unknown. This study attempts at estimating a risk incidence for visitors from two European countries with the available data. METHODS: Using the total number of case reports between 1978 and 2008, the number of visits made by European tourists to endemic regions, and total doses of vaccines sold in the two study countries, the risk incidence of JE in travelers was estimated. The proportion of vaccinated visitors to endemic regions was retrieved from the data of two travel clinics (in London and Basel) and related to vaccine prescribing in UK and Swiss travelers. RESULTS: In 2004, an estimated 0.16% to 0.3% of UK and Swiss travelers were vaccinated against JE, with no surveillance reports of JE cases. Between 116,000 and 152,000 European travelers would receive vaccination. More than 99% travel to endemic countries without vaccination. Only 40 cases of JE infection have been reported in travelers for the past 30 years. The risk incidence is thus 1.3 per year in 7.1 million visits of the 17 million European travelers who are at a potential risk of JE infection. CONCLUSIONS: This study and the analysis of the existing literature support the recommendation that all travelers should be informed about the risk of JE infection but also suggest that there is no evidence for justifying a general recommendation for JE vaccination in travelers to endemic areas.

International travel has become more accessible and affordable, and travel, particularly to tropical and malaria regions, has increased by up to 8% annually. This change in travel has surprisingly not resulted in an increase in imported diseases. Surveillance reports of hepatitis A and enteric fever have not increased and a significant and sustained fall in malaria over the decade has been described. Nurses in primary care are the predominant providers of pre-travel health services and they have an important and influential role in preventing travel-associated illness. This is the second article in a 3-part series on the spectrum of health issues associated with travel. Part one discussed pre-travel health advice, including risk assessment and educating travellers. This article explores the highest risk group of traveller, those visiting friends and relatives (VFRs). The article highlights the specific disease risks for VFRs and how these may be influenced by their health beliefs. The article explores ways in which nurses can optimize the travel health consultation to ensure that the specific needs of VFRs are met and that they receive accurate and achievable advice .

To evaluate the impact of zinc supplementation on the clinical recovery and body weight of children with persistent diarrhoea, a randomized, double-blind, controlled trial was conducted in 190 children with persistent diarrhoea aged between 3 and 24 months. Children were randomly allocated to receive either zinc (20 mg d−1) syrup with multivitamin (2 × RDA) or multivitamin alone in three divided daily doses for 2 weeks. The trial was conducted in a diarrhoeal disease hospital in Dhaka, Bangladesh. Duration until clinical recovery (d), impact on body weight and serum zinc level after 2 weeks of zinc supplementation were recorded. The duration of illness was significantly reduced (33%) with zinc supplementation among children who were underweight (≤70% wt/age, p= 0:03). Supplemented male children also had a significant reduction (27%) in duration for recovery compared with unsupplemented children (p= 0:05). From baseline to convalescence, zinc-supplemented children maintained their serum zinc concentration (13.4 vs 13.6/μmol l−1), whereas unsupplemented children had a decrease in serum zinc after the 2 weeks of diarrhoea (13.6 vs 11.8 μmol l−1, p < 0:03). The mean body weight of the children in the supplemented group was maintained (5.72 vs 5.70 kg, p= 0:62) during hospitalization, unlike that of the control group, in which there was a reduction in body weight (5.75 vs 5.67 kg, p= 0:05). Five children in the unsupplemented group and one child in the zinc-supplemented group died during the 2 weeks of supplementation (p= 0:06). Zinc supplementation in persistent diarrhoea significantly reduced the length of the recovery period in malnourished children and prevented a fall in body weight and serum zinc concentration, indicating that zinc is a beneficial therapeutic strategy in this high-risk childhood illness.

Since its introduction to the market in 1985, mefloquine has been used for malaria chemoprophylaxis by more than 35 million travellers. In Europe, in 2014, the European Medicines Agency (EMA) issued recommendations on strengthened warnings, prescribing checklists and updates to the product information of mefloquine. Some malaria prevention advisors question the scientific basis for the restrictions and suggest that this cost-effective, anti-malarial drug will be displaced as a first-line anti-malaria medication with the result that vulnerable groups such as VFR and long-term travellers, pregnant travellers and young children are left without a suitable alternative chemoprophylaxis. This commentary looks at the current position of mefloquine prescribing and the rationale of the new EMA recommendations and restrictions. It also describes the new recommendations for malaria prophylaxis that have been adapted by Switzerland, Germany, Austria and Italy where chemoprophylaxis use is restricted to high-risk malaria-endemic areas.

Rivers discusses the application of insect repellents to the face.1 2 Application of a repellent to the face may not always be needed because mosquito bites occur …

The bottom line A pregnant woman visits you as her general practitioner (GP) because she and her children will be visiting a country with mosquito borne disease. You recommend using repellents to protect against mosquitoes, as well as vaccinations and other relevant disease prevention measures. She asks which repellents would be best. The key factors to consider when choosing a repellent are the active chemical ingredients and the strength (concentration (%) of active ingredient) because these influence the efficacy and duration of protection.1 2 There are four active ingredients with sufficient published scientific evidence to warrant recommendation. Repellents are useful in areas of low risk of mosquito borne disease to prevent nuisance biting (which may lead to problems such as allergies) and are essential in moderate to high risk areas (figure⇓) to prevent disease transmission (such as malaria and dengue fever) through bites. Repellents work on mosquitoes by directly stimulating avoidance behaviour or by blocking the mosquito’s receptors for attractive odours, not though toxicity.3 Areas of low, moderate, and high risk of mosquito borne disease worldwide

BACKGROUND: The main aims of this study were to quantify the annual risk of falciparum malaria among nonimmune, UK-based airline crew and to undertake a risk assessment of short layovers in sub-Saharan African cities. METHODS: The number of nights exposed in malaria-endemic regions and reported cases of falciparum malaria were used to estimate annual disease incidence. Transmission risk estimates were calculated for each layover, that is, where crew were accommodated overnight, for one or more nights, in designated city hotels. Air-conditioning of ground transport, hotels, and airports was provided at all crew layovers. Details of activities associated with a risk for malaria and of adherence to antimosquito measures among crew were collected through a self-administered postal questionnaire. RESULTS: The annual risk of falciparum malaria was calculated to be 1.6 cases per 100,000 nights of exposure (95% CI 0.5-3.7). Crew reported widespread use of personal protection measures during the evenings when at risk. CONCLUSIONS: Attack rates of falciparum malaria were considerably lower than those reported in tourists during visits to sub-Saharan Africa. Factors contributing to this low attack rate included risk awareness, a protected sleeping environment, an urban setting, vector environmental controls, brief exposure, and good compliance with personal protection measures. Previously reported chemoprophylaxis compliance of < 10% in the same population was unlikely to have contributed to the low rate of disease. The longer layovers, of 3 or 4 nights, in some East African rosters provided greater opportunity for discretionary leisure activity away from protected hotel environments, and this needs to be considered in a risk assessment.

BACKGROUND: Travel associated malaria is a major health risk for visitors to malaria endemic destinations. To examine the knowledge of malaria prevention, risk perception, current prophylactic behavior, and compliance with chemoprophylaxis and personal and environmental protection measures we conducted a study in a cohort of travelers exiting Zimbabwe from two international airports during a peak malaria transmission period. METHODS: Data were collected by pretested self-administered questionnaires from 595 adults in the departure lounges of Harare and Victoria Falls International airports. Excluded were children and travelers from the African continent. A multilingual research assistant supervised data collection. RESULTS: The majority of travelers obtained health advice prior to travel. Patterns of protective behavior and compliance with prophylaxis were inconsistent with a high perception of malaria threat and good knowledge. About 23% of travelers failed to use chemoprophylaxis during their visit. In the group of travelers who used chemoprophylaxis, 18% were noncompliant. Fifteen drug combinations were in use. Full compliance with medication plus use of personal preventive measures always was estimated as 13%. Forgetfulness was the main cause of noncompliance, followed by deliberate omission due to side effects. Of 57 travelers who reported side effects from current medication, over half used mefloquine. CONCLUSIONS: There is a need to examine how people process personal risk and communications about risk. We must recognize the competition between precautionary measures against malaria and other life demands that are imposed by travel, especially in young long stay travelers and persons visiting primarily for business purposes. Mediating a protective response will also depend on judgments about the effectiveness of the action, strengthening travelers intentions toward adherence, and increasing efficacy perception by individuals and their peers. Conflicts in prophylactic recommendations need to be resolved. As ecotourism develops in Zimbabwe and other malaria regions, stakeholders in this rapidly growing industry must be made aware of the important role they can play in protecting clients from malaria.

A “biocide” is a chemical which, by chemical or biological means, kills, repels, or renders harmless any unwanted organism and is used to control organisms such as viruses, bacteria, fungi, and insects, including insect repellents. Strict laws apply to the supply and use of biocides to ensure that they can be used without causing significant harm to people, the environment, or non‐target animals. The new European Union (EU) Biocidal Products Regulation (EU 528/2012, known as the BPR) 1 sets the standards for safety assessment and authorization of biocidal products. The biocide laws work through two processes—“approval” and “authorization.” A National Competent Authority leads government policy on biocidal laws. In the UK, this is the Health and Safety Executive (HSE). First the “active substances” are assessed to understand how effective they are and whether there are potential risks to human health, non‐target animals, or the environment and if these can be adequately controlled. If they pass, they are “approved” for use in biocidal products in the EU. Second, approved active substances can be incorporated into biocidal products, which companies must then apply for “authorization” to supply. Products are then assessed for effectiveness (do they repel vectors and for how long) and potential risks (toxicity) and, if they pass, they are “authorized” for supply and use. Active substances used in the biocidal products already on the market were listed in 2000, and they are allowed to remain on the market while being reviewed but sales of unauthorised products to cease by August 2016. Since 2012, commercial products containing items on the active list were to be submitted for authorization, along with the data on the products content, on each active substance, and on their effectiveness and possible adverse effects to humans and the environment. The chemical substance N , N ‐diethyl‐meta‐toluamide (commonly …

The differential diagnosis between sporadic adenoma and colitis-associated neoplasia is difficult. Clinical, histological and molecular genetic methods are available to recognise a difference between these two entities. The aim of the present analysis was to check known criteria in a large series of patients and 352 patients with ulcerative colitis and concomitant intraepithelial neoplastic lesions [149 adenomas (A), 123 colitis-associated intraepithelial neoplasias (N), 80 carcinomas (K)] were investigated. Clinical history helped to identify patients with sporadic adenoma since patients with colitis-associated neoplastic lesions presented with different data such as age (A: 61.3+/-13 years, N: 48.4+/-16.4 years, K: 53.9+/-16.9 years), duration of disease (A: 6.9+/-8.1 years, N: 11.9+/-10 years, K: 13.6+/-9.6 years), frequency of pancolitis (A: 28.6%, N: 56.3%, K: 48.3%) and frequency of solitary lesions (A: 83.7%, N: 23.1%, K: 51.9%). The differential diagnosis between adenoma and colitis-associated neoplasia in patients with ulcerative colitis appears to be possible but the diagnosis should only be made in the remission phase. Furthermore the patients need a careful endoscopic and bioptic follow-up. If in doubt one should consider colitis-associated neoplasia especially when there are multiple intraepithelial neoplastic lesions. Long-term follow-up studies are urgently needed.

Malaria continues to have a high morbidity rate associated among European travelers. Thorough recording of epidemiological and clinical aspects of imported malaria has been helpful in the detection of new outbreaks and areas of developing drug resistance. Sentinel surveillance of data collected prospectively since 1999 has begun within TropNetEurop, a European network focusing on imported infectious diseases. TropNetEurop appears to cover approximately 10% of all patients with malaria seen in Europe. Reports of 1659 immigrants and European patients with Plasmodium falciparum malaria were analyzed for epidemiological information and data on clinical features. Regional data were quite diverse, reflecting local patterns of immigration and international travel. By far, the most infections were imported from West Africa. Europeans had more clinical complications; consequently, all deaths occurred in this group. Compared with European standards, the mortality rate was low (0.6% in Europeans). Data from TropNetEurop member sites can contribute to our understanding of the epidemiological and clinical findings regarding imported falciparum malaria.

BACKGROUND: In many non-malarious countries, imported malaria disproportionately affects Africans visiting friends and relatives (VFRs). Most previous research has focused on understanding the knowledge, attitudes and practices of these travellers, but has not examined the quality of prevention, diagnosis and treatment services provided. The aim of this study was to understand the perspective of providers of malaria-related healthcare services to VFRs about factors impacting on the quality of these and to make recommendations about improvements. METHODS: Thirty semi-structured interviews were conducted with practice nurses providing pre-travel health advice (n = 10), general practitioners (GPs) (n = 10), hospital consultants (n = 3), and community pharmacists (n = 7) working in areas of London with large African communities and a relatively high burden of imported malaria. A thematic analysis of the results was undertaken. RESULTS: Time constraints in GPs' surgeries and competing priorities, lack of confidence in issuing advice on mosquito avoidance, the cost of chemoprophylaxis and travel at short notice prevented the provision of adequate malaria prevention advice. Long GP waiting times, misdiagnoses, lack of disclosure by VFRs about recent travel, and the issue of where malaria treatment should be provided were raised as potential barriers to diagnosis and treatment. CONCLUSIONS: Some issues raised by respondents are relevant to all travellers, irrespective of their reason for travel. The challenge for healthcare providers to reduce the burden of imported malaria in VFRs is to provide services of sufficient quality to persuade them to adopt these in preference to those with which they may be familiar in their country of birth. Although no single intervention will significantly lower the burden of imported malaria, addressing the issues raised in this research could make a significant impact.

Concerns about the tolerability of mefloquine highlight the need for new drugs to prevent malaria. Atovaquone-proguanil (Malarone; GlaxoSmithKline) was safe and effective for prevention of falciparum malaria in lifelong residents of malaria-endemic countries, but experience in nonimmune people is limited. In a randomized, double-blind study, nonimmune travelers received malaria prophylaxis with atovaquone-proguanil (493 subjects) or mefloquine (483 subjects). Information about adverse events (AEs) and potential episodes of malaria was obtained 7, 28, and 60 days after travel. AEs were reported by an equivalent proportion of subjects who had received atovaquone-proguanil or mefloquine (71.4% versus 67.3%; difference, 4.1%; 95% confidence interval, -1.71 to 9.9). Subjects who received atovaquone-proguanil had fewer treatment-related neuropsychiatric AEs (14% versus 29%; P=.001), fewer AEs of moderate or severe intensity (10% versus 19%; P=.001), and fewer AEs that caused prophylaxis to be discontinued (1.2% versus 5.0%; P=.001), compared with subjects who received melfoquine. No confirmed diagnoses of malaria occurred in either group. Atovaquone-proguanil was better tolerated than was mefloquine, and it was similarly effective for malaria prophylaxis in nonimmune travelers.

Summary Background The quality of medicines available in some less-developed countries is inadequate in terms of content of active ingredient. Reasons for the poor quality of drugs include widespread counterfeiting of medicines in less-developed countries, excessive decomposition of active ingredient as a result of high temperature and humidity, and poor quality assurance during the manufacture of medicinal products. Our aim was to investigate the quality of different drugs obtained from retail pharmacies in two urban areas of Nigeria, and, in instances of poor quality, to ascertain the reason why. Methods We randomly collected 581 samples of 27 different drugs from 35 pharmacies in Lagos and Abuja in Nigeria. We analysed the medicines for drug content by validated chromatographic methods, and compared our results with pharmacopoeial requirements. Findings 279 (48%) samples did not comply with set pharmacopoeial limits, and this proportion was uniform for the various types of drugs tested. Although some preparations contained no active ingredient, most had amounts just outside the pharmacopoeial limits. We identified samples with both too much and too little active drug content. Interpretation The most probable cause of the poor quality of drugs is absence of adequate quality assurance during manufacture. Substandard drugs sold in the pharmacies of less-developed countries could contribute to global microbial resistance and therapeutic failure of infectious diseases.

Enterotoxigenic Escherichia coli (ETEC) is a major cause of travellers' diarrhoea. We investigated the efficacy and safety of a skin-patch vaccine containing the pathogen's heat-labile toxin (LT) in a population of travellers to Mexico and Guatemala.In this phase 3, randomised, double-blind, placebo-controlled field trial, healthy adults (aged 18-64 years) travelling from Germany or the UK to Mexico or Guatemala were assigned in a 1:1 ratio by a dynamic electronic randomisation system to receive transcutaneous immunisation with a patch containing 37.5 μg of ETEC LT or a placebo patch. Participants, site staff, and the investigators who did the analyses were masked to group assignment. Participants were vaccinated before travel, with two patches given 14 days apart. In the destination country, participants tracked stool output in a diary and provided stool samples for pathogen identification if diarrhoea occurred. The primary endpoint was the proportion of participants with at least one episode of moderate-to-severe diarrhoea (defined as four or more unformed stools in a 24 h period) in which either or both ETEC enterotoxins (LT and heat-stable toxin [ST]) were detected. The study is registered at ClinicalTrials.gov, number NCT00993681.2036 participants were recruited and randomly assigned between Oct 14, 2009, and Aug 13, 2010, with 1016 allocated to receive the LT patch and 1020 the placebo patch. 821 participants in the LT-patch group and 823 in the placebo group received both vaccinations and were analysed in the per-protocol population. 30 (3.7%, 95% CI 2.5-5.2) participants in the LT-patch group and 46 (5.6%, 4.1-7.4) in the placebo group had moderate or severe ETEC diarrhoea (vaccine efficacy 34.6%, -2.2 to 58.9; p=0.0621). 9333 local (ie, patch-site) adverse events (including erythema, rash, pruritus, hyperpigmentation, pain, hypopigmentation, and oedema) occurred in 943 (93%) of 1015 participants in the LT-patch group, compared with 1444 local adverse events in 574 (56%) of 1019 participants in the placebo group (p0.0001). Serious adverse events occurred in 25 participants (14 in the LT-patch group and 11 in the placebo group), with all regarded as either unrelated or possibly related to treatment. Vaccine-induced hyperpigmentation persisted for at least 180 days after vaccination in 150 (18%) of the 849 participants who received both vaccinations and returned for final assessment in the LT-patch group, compared with none of the 842 participants in the placebo group. The vaccine was immunogenic, with a post-vaccination geometric mean titre of LT-specific serum immunoglobulin G of 3400.29, compared with 315.41 in the placebo group.Although the LT antigen was delivered effectively by the skin patch, the vaccine did not protect travellers against diarrhoea caused by ETEC or other organisms. Future vaccines against travellers' diarrhoea might need to include several antigens against various diarrhoeal pathogens, and might need to be able to generate mucosal and higher systemic immunity.

First a short survey of modelling of technical systems is presented. The different methods of modelling are applied to hydrodynamic torque converters and couplings. The results of linear modelling around an operating point, of nonlinear modelling for larger operating areas and of hybrid modelling using simplified physical laws are illustrated. Simulations for large excitations show the validity of the models. The advantages and disadvantages of the different methods are discussed.

The growth of travel of recent years has been unprecedented and presents new challenges to health professionals worldwide. More travelers of diverse backgrounds are visiting exotic locales rarely encountered before. This poses new risks to health, in addition to potentially aiding the spread of emerging respiratory infections. Travelers such as immunocompromised individuals and members of ethnic minorities are at significant risk for travel-related infections. Respiratory illnesses are some of the most common infections affecting human beings, yet little information has been published on them in relation to travel. Multidisciplinary approaches and collaboration across different sectors are needed to address the many issues involved in travel-related respiratory infections. This article discusses some of the topical issues of respiratory tract infections occurring in travelers.

A study to assess the frequency of health related advice provided by travel consultants to customers planning to travel to the tropics was undertaken. A total of 202 agencies throughout the UK were visited by covert researchers requesting a package holiday for 2 weeks to Kenya or a flight to India. In a face to face consultation, the researchers recorded any health related information provided. If none were forthcoming, the agent was prompted using a standardized prompt. Thirty per cent of the agencies were based in South-east England and London and the remainder in the North, the Midlands and the South-west. No spontaneous health warnings were given in 61% (123) of consultations for malarious destinations. After prompting, 71% of agents gave general health advice, 67% suggested seeking malaria advice from a general practitioner and 37% of agents brought up the need for malaria prophylaxis for the journey. 63% of consultations included a mention of malaria after being prompted. The study reveals that travel agents provide health advice inconsistently and mention health risks only when prompted. For travellers' safety and to meet new consumer regulations, the travel industry needs to draw attention to health risks associated with its products consistently and effectively.