Meningococcal carriage among Hajj pilgrims, risk factors for carriage and records of vaccination: a study of pilgrims to Mecca.

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.

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.

Influenza Vaccination Generates Cytokine-Induced Memory-like NK Cells: Impact of Human Cytomegalovirus Infection.

Human NK cells are activated by cytokines, immune complexes, and signals transduced via activating ligands on other host cells. After vaccination, or during secondary infection, adaptive immune responses can enhance both cytokine-driven and Ab-dependent NK cell responses. However, induction of NK cells for enhanced function after in vitro exposure to innate inflammatory cytokines has also been reported and may synergize with adaptive signals to potentiate NK cell activity during infection or vaccination. To test this hypothesis, we examined the effect of seasonal influenza vaccination on NK cell function and phenotype in 52 previously unvaccinated individuals. Enhanced, IL-2-dependent, NK cell IFN-γ responses to Influenza A/California/7/2009 virus were detected up to 4 wk postvaccination and higher in human CMV (HCMV)-seronegative (HCMV(-)) individuals than in HCMV-seropositive (HCMV(+)) individuals. By comparison, robust NK cell degranulation responses were observed both before and after vaccination, due to high titers of naturally occurring anti-influenza Abs in human plasma, and did not differ between HCMV(+) and HCMV(-) subjects. In addition to these IL-2-dependent and Ab-dependent responses, NK cell responses to innate cytokines were also enhanced after influenza vaccination; this was associated with proliferation of CD57(-) NK cells and was most evident in HCMV(+) subjects. Similar enhancement of cytokine responsiveness was observed when NK cells were cocultured in vitro with Influenza A/California/7/2009 virus, and this was at least partially dependent upon IFN-αßR2. In summary, our data indicate that attenuated or live viral vaccines promote cytokine-induced memory-like NK cells and that this process is influenced by HCMV infection.

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.

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.

"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.

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.

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.

NK cells as effectors of acquired immune responses: effector CD4+ T cell-dependent activation of NK cells following vaccination.

We characterized vaccine-induced cellular responses to rabies virus in naive adult volunteers. Contrary to current paradigms, we observed potent and prolonged in vitro NK cell cytokine production and degranulation responses after restimulation of PBMCs with inactivated rabies virus in vaccinated, but not in unvaccinated, individuals. This "recall" NK cell response was absolutely dependent on Ag-specific IL-2 from CD45RO(+) CD4(+) T cells as well as IL-12 and IL-18 from accessory cells. Importantly, NK cells represented over 70% of all IFN-gamma-secreting and degranulating cells in the first 12-18 h after virus rechallenge indicating they may be required for rapid control of infection after vaccination. Activation of NK cells may be a critical function of IL-2-secreting effector memory T cells. Although IL-2-dependent postvaccination NK cell activation has been reported previously, this is the first time the magnitude of this effect and its contribution to the overall vaccine-induced response has been appreciated and the mechanisms of NK activation postvaccination have been elucidated. Our data will allow standard protocols for evaluating vaccine-induced immunity to be adapted to assess NK cell effector responses.

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.

The incidence of malaria in travellers to South-East Asia: is local malaria transmission a useful risk indicator?

BACKGROUND: The presence of ongoing local malaria transmission, identified though local surveillance and reported to regional WHO offices, by S-E Asian countries, forms the basis of national and international chemoprophylaxis recommendations in western countries. The study was designed to examine whether the strategy of using malaria transmission in a local population was an accurate estimate of the malaria threat faced by travellers and a correlate of malaria in returning travellers. METHODS: Malaria endemicity was described from distribution and intensity in the local populations of ten S-E Asian destination countries over the period 2003-2008 from regionally reported cases to WHO offices. Travel acquired malaria was collated from malaria surveillance reports from the USA and 12 European countries over the same period. The numbers of travellers visiting the destination countries was based on immigration and tourism statistics collected on entry of tourists to the destination countries. RESULTS: In the destination countries, mean malaria rates in endemic countries ranged between 0.01 in Korea to 4:1000 population per year in Lao PDR, with higher regional rates in a number of countries. Malaria cases imported into the 13 countries declined by 47% from 140 cases in 2003 to 66 in 2008. A total of 608 cases (27.3% Plasmodium falciparum (Pf)) were reported over the six years, the largest number acquired in Indonesia, Thailand and Korea. Four countries had an incidence > 1 case per 100,000 traveller visits; Burma (Myanmar), Indonesia, Cambodia and Laos (range 1 to 11.8-case per 100,000 visits). The remaining six countries rates were < 1 case per 100,000 visits. The number of visitors arriving from source countries increased by 60% from 8.5 Million to 13.6 million over the 6 years. CONCLUSION: The intensity of malaria transmission particularly sub-national activity did not correlate with the risk of travellers acquiring malaria in the large numbers of arriving visitors. It is proposed to use a threshold incidence of > 1 case per 100,000 visits to consider targeted malaria prophylaxis recommendations to minimize use of chemoprophylaxis for low risk exposure during visits to S-E Asia. Policy needs to be adjusted regularly to reflect the changing risk.

Declining incidence of malaria imported into the UK from West Africa.

BACKGROUND: Two thirds of all falciparum malaria cases reported in the United Kingdom (UK) are acquired in West Africa (WA). To ensure recommendations and guidelines for malaria prophylaxis in travellers to West Africa correlate to the risk of infection, a study was undertaken to examine recent trends and predict future patterns of imported malaria acquired by UK residents visiting West Africa and West African visitors to the UK between 1993 and 2006. METHODS AND RESULTS: Using passenger numbers and malaria surveillance reports, the data revealed a 2.3-fold increase in travel to West Africa with a five-fold increase in travelers visiting friends and relatives (VFR). Malaria incidence fell through the study period, the greatest decline noted in VFR with a fall from 196 cases/1,000 person-years to 52 cases/1,000 person-years, 9.8% per year p < 0.0001. The risk for travellers from the UK visiting for other reasons declined 2.7 fold, at an annual decrease of 7.0%, with the incidence in West African visitors to the UK falling by 2.3 fold, a rate of 7.9% annually. DISCUSSION: The reduction in incidence among all three groups of travellers may be explained by several factors; changing chemoprophylaxis usage and/or increased travel in urban areas where malaria risk has declined over the past decade, or widespread reduction in malaria transmission in West Africa. CONCLUSION: With the reduction in malaria incidence seen in both visitors to and from West Africa, the most rational explanation for these findings is a fall in malaria transmission in West Africa, which may require a change in chemoprophylaxis policy for UK travelers over the next 5-10 years.

Travel health. Part 1: preparing the tropical traveller.

The health threats of modern day travel change as population, wealth and tourism increase across the world. A series of three articles have been written to describe the spectrum of health issues associated with travel. Pre-travel health advice has become more focused on risk assessment and educating the traveller about infectious disease and the more frequent non-infectious hazards associated with travel, while ensuring they are not unnecessarily exposed to injury from vaccines and drugs. In part one, the role of the health advisor and the needs of the traveller are examined. The importance of risk assessment during a consultation is described and factors that influence recommendations and prescribing are explored. As most travel-associated morbidity and mortality is non-vaccine preventable, the focus of the pre-travel consultation should be on educating the traveller and influencing behaviour change. The second article in this series deals with the highest risk group of travellers--residents who visit friends and relatives. It highlights their specific problems and special needs and how to influence their risk of disease by addressing their health beliefs and their cultural dimension of risk. The third article explores the common, and not so common, clinical problems found in returned travellers. Nurses have to deal with a large range of clinical problems and diagnostic dilemmas when attending to the returned traveller. The review provides a perspective on the frequency and severity of problems and how nurses should manage travel associated disease.

Travel health. Part 3: illness in the returning traveller.

A significant number of travellers present for medical advice each year on return from overseas travel, and it is in the primary care setting where many of these will be seen. While most of the conditions will be familiar to those in general practice, there are some travel-associated infections (e.g. malaria) which, if left untreated, can lead to rapid deterioration and death. It is important, therefore, to be able to appreciate and recognize travel-associated diseases, which require prompt attention, and those that need referral for specialist expertise. This article reviews a range of health problems typically seen in returned travellers, their investigation and management. Details of the Hospital for Tropical Diseases post-tropical screening protocol for asymptomatic returned travellers are outlined.

Travel health. Part 2: advising travellers visiting friends and relatives abroad.

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 ofVFRs are met and that they receive accurate and achievable advice.

The low and declining risk of malaria in travellers to Latin America: is there still an indication for chemoprophylaxis?

A comparison was made between local malaria transmission and malaria imported by travellers to identify the utility of national and regional annual parasite index (API) in predicting malaria risk and its value in generating recommendations on malaria prophylaxis for travellers. Regional malaria transmission data was correlated with malaria acquired in Latin America and imported into the USA and nine European countries. Between 2000 and 2004, most countries reported declining malaria transmission. Highest API's in 2003/4 were in Surinam (287.4) Guyana (209.2) and French Guiana (147.4). The major source of travel associated malaria was Honduras, French Guiana, Guatemala, Mexico and Ecuador. During 2004 there were 6.3 million visits from the ten study countries and in 2005, 209 cases of malaria of which 22 (11%) were Plasmodium falciparum. The risk of adverse events are high and the benefit of avoided benign vivax malaria is very low under current policy, which may be causing more harm than benefit.

Sustained Immune Complex-Mediated Reduction in CD16 Expression after Vaccination Regulates NK Cell Function.

Cross-linking of FcγRIII (CD16) by immune complexes induces antibody-dependent cellular cytotoxicity (ADCC) by natural killer (NK) cells, contributing to control of intracellular pathogens; this pathway can also be targeted for immunotherapy of cancerous or otherwise diseased cells. However, downregulation of CD16 expression on activated NK cells may limit or regulate this response. Here, we report sustained downregulation of CD16 expression on NK cells in vivo after intramuscular (but not intranasal) influenza vaccination. CD16 downregulation persisted for at least 12 weeks after vaccination and was associated with robust enhancement of influenza-specific plasma antibodies after intramuscular (but not intranasal) vaccination. This effect could be emulated in vitro by co-culture of NK cells with influenza antigen and immune serum and, consistent with the sustained effects after vaccination, only very limited recovery of CD16 expression was observed during long-term in vitro culture of immune complex-treated cells. CD16 downregulation was most marked among normally CD16high CD57+ NK cells, irrespective of NKG2C expression, and was strongly positively associated with degranulation (surface CD107a expression). CD16 downregulation was partially reversed by inhibition of ADAM17 matrix metalloprotease, leading to a sustained increase in both CD107a and CD25 (IL-2Rα) expression. Both the degranulation and CD25 responses of CD57+ NK cells were uniquely dependent on trivalent influenza vaccine-specific IgG. These data support a role for CD16 in early activation of NK cells after vaccination and for CD16 downregulation as a means to modulate NK cell responses and maintain immune homeostasis of both antibody and T cell-dependent pathways.

Risk assessment and disease prevention in travelers visiting friends and relatives.

Although VFR travelers are at risk for acquiring infections and experiencing illness while traveling, many of these diseases are preventable. A comprehensive approach to decreasing their travel-related morbidity requires continued surveillance, data collection, systematic analysis, and action. A review of the literature provides few examples of interventions designed specifically to address VFR travel needs. Given the geographic and cultural diversity of these populations, models grounded in health behavior theory provide the best potential for clinically relevant replication. Outreach aimed at improving knowledge and care-seeking behaviors among VFR travelers may be facilitated through community-based campaigns in areas with large foreign-born populations. In developed countries, policies must be reviewed to ensure that travel-related services are accessible, affordable, and appropriate for these diverse populations. In the clinical setting, providers must develop culturally appropriate methods of communicating with traveling populations to influence behavior. In particular, primary care providers should take an active approach through screening for high-risk travel, and increasing their competency in travel medicine. Special attention should be given to illness that is prevented by routine childhood immunization (eg, varicella, measles, and hepatitis B); by disease prevented by travel vaccines (eg, typhoid fever and hepatitis A); and disease that can be prevented by careful avoidance measures or compliance with preventive medication (eg, malaria and tuberculosis). With increased immigration from developing to developed regions and widely affordable travel, the number of VFR travelers is expected to increase. As such, increased efforts to prevent VFR traveler morbidity serve the individual while also contributing to global public health.