Prevalence and Persistence of Antibiotic Resistance Determinants in the Gut of Travelers Returning to the United Kingdom is Associated with Colonization by Pathogenic Escherichia coli.

The gut microbiota constitutes an ideal environment for the selection, exchange, and carriage of antibiotic resistance determinants (ARDs), and international travel has been identified as a risk factor for acquisition of resistant organisms. Here, we present a longitudinal metagenomic analysis of the gut resistome in travellers to "high-risk" countries (Gutback). Fifty volunteers, recruited at a travel clinic in London, United Kingdom, provided stool samples before (pre-travel), immediately after (post-travel), and 6 months after their return (follow-up) from a high-risk destination. Fecal DNA was extracted, metagenomic sequencing performed and the resistome profiled. An increase in abundance and diversity of resistome was observed after travel. Significant increases in abundance were seen in antimicrobial genes conferring resistance to macrolides, third-generation cephalosporins, aminoglycosides, and sulfonamides. There was a significant association with increased resistome abundance if the participant experienced diarrhea during travel or took antibiotics, but these two variables were co-correlated. The resistome abundance returned to pre-travel levels by the 6-month sample point but there was evidence of persistence of several ARDs. The post-travel samples had an increase in abundance Escherichia coli which was positively associated with many acquired resistant determinants. Virulence and phylogenetic profiling revealed pathogenic E. coli significantly contributed to this increase abundance. In summary, in this study, foreign travel remains a significant risk factor for acquisition of microbes conferring resistance to multiple classes of antibiotics, often associated with symptomatic exposure to diarrhoeagenic E. coli. IMPORTANCE A future where antimicrobial therapy is severely compromised by the increase in resistant organisms is of grave concern. Given the variability in prevalence and diversity of antimicrobial resistance determinants in different geographical settings, international travel is a known risk factor for acquisition of resistant organisms into the gut microbiota. In this study, we show the utility of metagenomic approaches to quantify the levels of acquisition and carriage of resistance determinants after travel to a "high-risk" setting. Significant modulation to the resistome was seen after travel that is largely resolved within 6 months, although evidence of persistence of several ARDs was observed. Risk factors for acquisition included experiencing a diarrheal episode and the use of antibiotics. Colonization by pathogenic Escherichia coli was correlated with an increase in acquisition of antimicrobial resistance determinants, and as such established public health guidance to travelers on food and water safety remain an important message to reduce the spread of antibiotic resistance.

Influenza Vaccination Primes Human Myeloid Cell Cytokine Secretion and NK Cell Function.

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.

Imported malaria among people who travel to visit friends and relatives: is current UK policy effective or does it need a strategic change?

BACKGROUND: The proportion of all imported malaria reported in travellers visiting friends and relatives (VFRs) in the UK has increased over the past decade and the proportion of Plasmodium falciparum malaria affecting this group has remained above 80% during that period. The epidemiological data suggest that the strategies employed in the UK to prevent imported malaria have been ineffective for VFRs. This paper attempts to identify possible reasons for the failure of the malaria prevention strategy among VFRs and suggest potential alternatives. METHODS: A review of the current UK malaria prevention guidelines was undertaken and their approach was compared to the few data that are available on malaria perceptions and practices among VFRs. RESULTS: The current UK malaria prevention guidelines focus on educating travellers and health professionals using messages based on the personal threat of malaria and promoting the benefits of avoiding disease through the use of chemoprophylaxis. While malaria morbidity disproportionately affects VFRs, the mortality rates from malaria in VFRs is eight times, and severe disease eight times lower than in tourist and business travellers. Recent research into VFR malaria perceptions and practices has highlighted the complex socio-ecological context within which VFRs make their decisions about malaria. These data suggest that alternative strategies that move beyond a knowledge-deficit approach are required to address the burden of malaria in VFRs. DISCUSSION: Potential alternative strategies include the use of standby emergency-treatment (SBET) for the management of fevers with an anti-malarial provided pre-travel, the provision of rapid diagnostic testing and treatment regimen based in general-practitioner surgeries, and urgent and walk-in care centres and local accident and emergency (A&E) departments to provide immediate diagnosis and accessible ambulatory treatment for malaria patients. This latter approach would potentially address some of the practical barriers to reducing the burden of malaria in VFRs by moving the process nearer to the community.

Vaccine-preventable travel health risks: what is the evidence--what are the gaps?

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.

"You're losing your Ghanaianess": understanding malaria decision-making among Africans visiting friends and relatives in the UK.

BACKGROUND: In the UK, the majority of imported malaria infections occur in the London area among UK residents of African origin who travel to Africa visiting friends and relatives (VFRs). Effective malaria prevention measures are available but there is little understanding of the factors that enhance and constrain their use among VFRs. METHODS: Semi-structured interviews were undertaken with Africans resident in London who visited friends and relatives in Nigeria and Ghana (n = 20) and with African VFRs recently treated for malaria (n = 6). Data collection took place between December 2007 and February 2011. Information on migration patterns and travel of respondents was collected and the data were analysed using a framework analysis approach. RESULTS: Knowledge of the link between mosquitoes and malaria was high. Factors influencing the use of mosquito avoidance methods included knowledge about the local environment, perceptions of the inevitability of contracting malaria, and a desire to fit with the norms of host families. Previous experience of bed nets, and the belief that more modern ways of preventing mosquito bites were available deterred people from using them. Chemoprophylaxis use was varied and influenced by: perceptions about continuing immunity to malaria; previous experiences of malaria illness; the cost of chemoprophylaxis; beliefs about the likely severity of malaria infections; the influence of friends in the UK; and, the way malaria is perceived and managed in Nigeria and Ghana. Malaria treatment was considered by many to be superior in Nigeria and Ghana than in the UK. A conceptual framework was developed to illustrate the manner in which these factors interact to affect malaria decisions. CONCLUSIONS: The use of malaria prevention among VFRs needs to be understood not only in terms of individual risk factors but also in relation to the context in which decisions are made. For VFRs, malaria decisions are undertaken across two distinct social and environmental contexts and within the structural constraints associated with each. Strategies for reducing the burden of malaria among VFRs that ignore this complexity are likely to face challenges. New approaches that take account of contextual as well as individual factors are required.

Challenges facing providers of imported malaria-related healthcare services for Africans visiting friends and relatives (VFRs).

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.

The impact of injection anxiety on education of travelers about common travel risks.

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.

Malaria knowledge and utilization of chemoprophylaxis in the UK population and in UK passengers departing to malaria-endemic areas.

BACKGROUND: The burden of imported malaria is predominantly in travellers visiting friends and relatives (VFR) in sub-Saharan Africa. The failure of this group to use chemoprophylaxis is recognized as the most important risk factor for the high incidence of disease. Understanding the reasons for failure to follow national recommendations may relate to knowledge, risk perception, cost, and peer pressure. Research into these variables is critical to understand and change practices in this group and this study was designed to explore whether knowledge, risk perception and prophylaxis use differs between travellers' to various destinations and the rest of the UK population. METHODS: Two face-to-face questionnaire surveys were conducted to collect information on demographics, malaria knowledge, source, and quality of pre-travel advice, past travel experience and perceived malaria threat. One was an IPSOS survey of individuals representative of the UK population. The other was a departure lounge survey (Civil Aviation Authority (CAA)) of passengers departing to malarious regions detailing destinations and use of chemoprophylaxis. RESULTS: Around a quarter of the 1,991 UK population surveyed had previously travelled to a malarious area. Five-hundred departing passengers were interviewed, of which 80% travelled for leisure (56% VFR's) and 42% were travelling to West Africa. Malaria knowledge among the UK population (score 58.6) was significantly lower than that of individuals who had previously travelled or were travelling (63.8 and 70.7 respectively). Malaria knowledge was similar in individuals who had and had not sought pre-travel advice and travellers using and not using chemoprophylaxis for their journey. Leisure travellers to Ghana and Nigeria were predominantly VFRs (74%), whilst 66% of travellers to Kenya were tourists. Despite similar high knowledge scores and perceived (>90%) threat of the lethality of malaria in the three groups, chemoprophylaxis use in Nigerians (50%) was substantially lower than in passengers departing to Kenya (78%) and Ghana (82%). More frequent annual return visits were made to Nigeria (72%) than to Ghana (38%) or Kenya (23%). CONCLUSION: Travellers had more malaria knowledge than the non-travelled UK population. Malaria knowledge, perceived threat, travel experience, and quality of pre-travel advice appear unrelated to the use of chemoprophylaxis in passengers. Reducing malaria in VFR travellers will require strategies other than improving malaria knowledge and enhancing malaria risk awareness.

Does public subsidy of the cost of malaria chemoprophylaxis reduce imported malaria? A comparative policy analysis.

BACKGROUND: Chemoprophylaxis is recommended for at-risk travellers visiting malaria endemic regions. The majority of travellers with imported malaria have not used this, and travellers visiting friends and relatives have the largest burden of malaria and the lowest compliance to chemoprophylaxis. In 1995, the UK's Department of Health (DH) implemented a policy to make travellers fully responsible for the cost when purchasing chemoprophylaxis. This policy was not implemented in three Primary Care Trusts (PCTs) in London due to concern about the potential increase of imported malaria in their residents, and they maintained the public subsidy. An impact evaluation of the policy change was undertaken to determine if the continued subsidy reduced the incidence of imported malaria in one of the boroughs where the subsidy was maintained when compared to a borough where no subsidy was provided. METHODS: Between 2007 and 2010 prescriptions for malaria chemoprophylaxis were collected from pharmacy records and PCTs, and all cases of imported malaria reported from the tertiary hospital in each of the two boroughs were compared. RESULTS: The dispensed chemoprophylaxis prescriptions were nearly 8.8 times higher in Lambeth (where subsidized drugs were provided), than in Hackney. A Poisson model revealed significantly fewer reports of imported malaria per capita were made in Lambeth compared to Hackney (p = 0.042). CONCLUSIONS: The difference in malaria reports between the boroughs only just reached statistical significance, despite the considerable difference in chemoprophylaxis prescribing between the boroughs. Some travellers may not consider using chemoprophylaxis, irrespective of the cost. Regular evaluations of the recent policy changes in areas where malaria is subsidized will be important.

Malaria: an update for physicians.

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.

Travel clinic communication and non-adherence to malaria chemoprophylaxis.

Many travellers fail to take malaria chemoprophylaxis, despite receiving pre-travel advice. This study examined whether non-adherence could be predicted from verbal communication in the pre-travel consultation, and whether non-adherence was related to the quality of clinician-traveller communication. The consultations of one hundred and thirty consecutive travellers at a UK travel clinic were audiotaped and a follow-up telephone interview was used to assess adherence to malaria chemoprophylaxis. Experienced travel clinic staff were asked to predict adherence and rate the quality of communication from eighteen transcripts of consultations (nine good and nine poor adherence). Clinic staff predicted adherence to malaria chemoprophylaxis significantly better than chance. Poor adherence was related to poor quality communication. Clinic staff provided criteria for good quality clinician-traveller communication. It is concluded that predictors of non-adherence can be identified during the pre-travel consultation. Clinic staff could employ specific communication strategies to improve the effectiveness of consultations.

Malaria chemoprophylaxis recommendations for immigrants to Europe, visiting relatives and friends--a Delphi method study.

BACKGROUND: Numbers of travellers visiting friends and relatives (VFRs) from Europe to malaria endemic countries are increasing and include long-term and second generation immigrants, who represent the major burden of malaria cases imported back into Europe. Most recommendations for malaria chemoprophylaxis lack a solid evidence base, and often fail to address the cultural, social and economic needs of VFRs. METHODS: European travel medicine experts, who are members of TropNetEurop, completed a sequential series of questionnaires according to the Delphi method. This technique aims at evaluating and developing a consensus through repeated iterations of questionnaires. The questionnaires in this study included questions about professional experience with VFRs, controversial issues in malaria prophylaxis, and 16 scenarios exploring indications for prescribing and choice of chemoprophylaxis. RESULTS: The experience of participants was rather diverse as was their selection of chemoprophylaxis regimen. A significant consensus was observed in only seven of 16 scenarios. The analysis revealed a wide variation in prescribing choices with preferences grouped by region of practice and increased prescribing seen in Northern Europe compared to Central Europe. CONCLUSIONS: Improving the evidence base on efficacy, adherence to chemoprophylaxis and risk of malaria and encouraging discussion among experts, using techniques such as the Delphi method, may reduce the variability in prescription in European travel clinics.