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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.

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.

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-αβR2. 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.

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.

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.

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: 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.

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.

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.

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.

Objective—To evaluate the impact of zinc supplementation on the clinical course, stool weight, duration of diarrhoea, changes in serum zinc, and body weight gain of children with acute diarrhoea. Design—Randomised double blind controlled trial. Children were assigned to receive zinc (20 mg elemental zinc per day) containing multivitamins or control group (zinc-free multivitamins) daily in three divided doses for two weeks. Setting—A diarrhoeal disease hospital in Dhaka, Bangladesh. Patients—111 children,3 to 24 months old, below 76% median weight for age of the National Center for Health Statistics standard with acute diarrhoea. Children with severe infection and/or oedema were excluded. Main outcome measures—Total diarrhoeal stool output,duration of diarrhoea, rate of weight gain, and changes in serum zinc levels after supplementation. Results—Stool output was 28% less and duration 14% shorter in the zinc supplemented group than placebo (p = 0.06). There were reductions in median total diarrhoeal stool output among zinc supplemented subjects who were shorter (less than 95% height for age), 239 v 326 g/kg (p < 0.04), and who had a lower initial serum zinc (< 14 mmol/l), 279 v329 g/kg (p < 0.05); a shortening of mean time to recovery occurred (4.7 v6.2 days,p < 0.04) in those with lower serum zinc. There was an increase in mean serum zinc in the zinc supplemented group (+2.4 v˛0.3 µmol/l, p < 0.001) during two weeks of supplementation,and better mean weight gain (120 v30 g, p < 0.03) at the time of discharge from hospital. Conclusions—Zinc supplementation is a simple, acceptable, and aVordable strategy which should be considered in the management of acute diarrhoea and in prevention of growth faltering in children specially those who are malnourished. (Arch Dis Child 1997;77:196‐200)

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.

Whipple's disease (WD) is a rare disorder caused by the gram-positive actinomycete Tropheryma whippelii (1). An oral route of acquisition is presumed (2). WD is a chronic systemic infection morphologically characterized by foamy PAS-positive macrophages. This case report depicts the diagnosis and clinical management of a woman who presented with atypical cardial manifestations of WD and died from severe cardiac impairment by Tropheryma whippelii which was confirmed by polymerase chain reaction. Histological assessment of myocardial specimens obtained at autopsy showed PAS-positive macrophages accumulating within foci of interstitial myocardial fibrosis. Immunohistochemical staining demonstrated myocarditis with lymphocytes and neutrophilic granulocytes, which has not been reported so far in the course of WD.

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.

Background In a number of malaria endemic regions, tourists and travellers face a declining risk of travel associated malaria, in part due to successful malaria control. Many millions of visitors to these regions are recommended, via national and international policy, to use chemoprophylaxis which has a well recognized morbidity profile. To evaluate whether current malaria chemo-prophylactic policy for travellers is cost effective when adjusted for endemic transmission risk and duration of exposure. a framework, based on partial cost-benefit analysis was used Methods Using a three component model combining a probability component, a cost component and a malaria risk component, the study estimated health costs avoided through use of chemoprophylaxis and costs of disease prevention (including adverse events and pre-travel advice for visits to five popular high and low malaria endemic regions) and malaria transmission risk using imported malaria cases and numbers of travellers to malarious countries. By calculating the minimal threshold malaria risk below which the economic costs of chemoprophylaxis are greater than the avoided health costs we were able to identify the point at which chemoprophylaxis would be economically rational. Results The threshold incidence at which malaria chemoprophylaxis policy becomes cost effective for UK travellers is an accumulated risk of 1.13% assuming a given set of cost parameters. The period a travellers need to remain exposed to achieve this accumulated risk varied from 30 to more than 365 days, depending on the regions intensity of malaria transmission. Conclusions The cost-benefit analysis identified that chemoprophylaxis use was not a cost-effective policy for travellers to Thailand or the Amazon region of Brazil, but was cost-effective for travel to West Africa and for those staying longer than 45 days in India and Indonesia.

The development of oral rehydration therapy (ORT) has resulted in clear and practical methods for replacing fluid and electrolyte losses during diarrhoea. Rehydration salts can be provided in 3 ways; a pre-packed, easy to use, package which requires controlled formulation and distribution, a cereal-based formula from widely available ingredients which require preparation and cooking, or a home-made recipe of sugar with salt, which is relatively easily prepared. Poor retention of knowledge on the correct way to prepare solutions, inadequate availability of ingredients and practical problems of home production are major problems in ORT programmes. Although ORT may be life saving in severe dehydrating diarrhoea, it may not have an impact on milder illness, dysentery or persistent diarrhoea. Breast feeding is a natural and effective method for preventing and reducing diarrhoeal morbidity and its role needs repeated promotion. Early feeding in diarrhoea reduces duration, severity and adverse nutritional sequelae. The benefit of vitamin A and folic acid supplements are as yet unproved; zinc may have a role in aiding recovery of malnourished children. Drug treatment should be limited to parasitic gut infections, cholera or dysenteric disease. Widespread prescribing of drugs for diarrhoea by health workers may be hindering the success of ORT.

Malaria continues to be a serious health risk for travellers. The malaria parasites which infect humans can only be naturally transmitted by female mosquitoes of the genus Anopheles. Travellers to malaria endemic areas require detailed advice on appropriate chemoprophylaxis against malaria and personal protection against mosquito bites. The decision on an appropriate chemoprophylaxis or standby therapy regimen should reflect the malaria risk, pattern of drug resistance, and the toxicity of available drugs. Currently travellers encounter a number of problems in protecting themselves against malaria. Advice is often both inadequate and inaccurate; and all the recommended drug regimens are associated with minor, and occasionally major adverse reactions. Because of poor compliance to drug prophylaxis and to reduce the impact of drug resistance, protection against mosquitoes has a critical role in protecting travellers from malaria. Compliance to methods of personal protection not only reduces the malaria risk but also limits the nuisance and loss of sleep from biting insects.

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.

Background Malaria is an important threat to travelers visiting endemic regions. The risk of acquiring malaria is complex and a number of factors including transmission intensity, duration of exposure, season of the year and use of chemoprophylaxis have to be taken into account estimating risk. Materials and methods A mathematical model was developed to estimate the risk of non-immune individual acquiring falciparum malaria when traveling to the Amazon region of Brazil. The risk of malaria infection to travelers was calculated as a function of duration of exposure and season of arrival. Results The results suggest significant variation of risk for non-immune travelers depending on arrival season, duration of the visit and transmission intensity. The calculated risk for visitors staying longer than 4 months during peak transmission was 0.5% per visit. Conclusions Risk estimates based on mathematical modeling based on accurate data can be a valuable tool in assessing risk/benefits and cost/benefits when deciding on the value of interventions for travelers to malaria endemic regions.

Seventeen adult patients with acute Plasmodium falciparum malaria, admitted to the Hospital for Tropical Diseases, were studied. Serial measurements of the serum concentration of C-reactive protein, serum amyloid A protein, and percentage parasitaemia were determined, together with initial measurement of serum electrolytes, liver function, haemoglobin, white cell and platelet counts. Initial C-reactive protein and serum amyloid A concentrations were increased (C-reactive protein mean 49.0 mg/l serum amyloid A 28 mg/l) falling towards the normal range by the seventh day of treatment. There was a significant correlation between the pretreatment parasite count and clinical and laboratory markers of inflammation. C-reactive protein and serum amyloid A concentrations correlated inversely with the serum sodium. These results indicate that measurement of acute phase reactants such as C-reactive protein and serum amyloid A may prove valuable in assessing the severity of P falciparum malaria, and in following the response to antimalarial treatment.

OBJECTIVE: To examine temporal, geographic, and sociodemographic trends in case reporting and case fatality of malaria in the United Kingdom. SETTING: National malaria reference laboratory surveillance data in the UK. DESIGN: Observational study using prospectively gathered surveillance data and data on destinations from the international passenger survey. PARTICIPANTS: 39,300 cases of proved malaria in the UK between 1987 and 2006. MAIN OUTCOME MEASURES: Plasmodium species; sociodemographic details (including age, sex, and country of birth and residence); mortality; destination, duration, and purpose of international travel; and use of chemoprophylaxis. RESULTS: Reported cases of imported malaria increased significantly over the 20 years of the study; an increasing proportion was attributable to Plasmodium falciparum (P falciparum/P vivax reporting ratio 1.3:1 in 1987-91 and 5.4:1 in 2002-6). P vivax reports declined from 3954 in 1987-91 to 1244 in 2002-6. Case fatality of reported P falciparum malaria did not change over this period (7.4 deaths per 1000 reported cases). Travellers visiting friends and relatives, usually in a country in Africa or Asia from which members of their family migrated, accounted for 13 215/20 488 (64.5%) of all malaria reported, and reports were geographically concentrated in areas where migrants from Africa and South Asia to the UK have settled. People travelling for this purpose were at significantly higher risk of malaria than other travellers and were less likely to report the use of any chemoprophylaxis (odds ratio of reported chemoprophylaxis use 0.23, 95% confidence interval 0.21 to 0.25). CONCLUSIONS: Despite the availability of highly effective preventive measures, the preventable burden from falciparum malaria has steadily increased in the UK while vivax malaria has decreased. Provision of targeted and appropriately delivered preventive messages and services for travellers from migrant families visiting friends and relatives should be a priority.

Background The indications for prescribing malaria chemoprophylaxis lack a solid evidence base that results in subjectivity and wide variation of practice across countries and among professionals. Methods European experts in travel medicine, who are members of TropNetEurop, participated in a survey conducted using the Delphi method. This technique aims at evaluating and developing a consensus through iterations of questionnaires, controlled feedback, and statistical group responses. Results A first questionnaire, including questions about controversial issues in prescribing malaria prophylaxis, required responses on a visual scale between 1 and 10. The questionnaire included issues on problematic prescribing, characteristics of drugs, relevance of geography, and importance of insect bite prevention. The repeat questionnaire with the group response from the first round revealed an increasing consensus on most issues. A second survey considered 14 practical scenarios (including two internal standards) and investigated preferred choice of prophylaxis. A significant consensus was noted in 8 of 14 scenarios, which did not increase after a second round. The analysis revealed a wide variation in prescribing choices with preferences grouped by region of practice, and a greater willingness to prescribe in northern and southern Europe than in central Europe. The second round showed a 9.5% change of opinion. Conclusions The study shows that improving the evidence base on efficacy and tolerability and risk of malaria for prescribing chemoprophylaxis is needed as is further discussion across Europe to achieve harmonization of prescribing practice.

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.

Health professionals need to educate travellers about the dangers of malaria and the importance of prophylaxis There was a large increase in the number of cases of falciparum malaria imported into the United Kingdom and reported to the malaria reference laboratory in the first quarter of 1998.1 The two factors cited to explain this increase were unusually heavy rains in east Africa and a reduction in the use of the most effective antimalaria drug, mefloquine.1 At the same time there was an increase in the number of cases of severe malaria in the United Kingdom.1 During December 1997 and January 1998 this hospital treated five patients for severe malaria and gave advice on a further 20 patients with malaria who had been admitted to intensive care units throughout England. Of the 25 patients, 13 were male (median adult age 50; range 23 to 85) and two were children. Twenty two of those treated were of European origin. Altogether 20 patients had travelled to east Africa (16 to Kenya and at least six of these to Mombasa); five had travelled to west Africa. Median parasitaemia was 16% (range 1.1% to 60%). Ten patients (40%) had taken no prophylaxis; one of these was a Kenyan man of Asian origin who was on holiday in the United Kingdom. Prophylactic drugs had been prescribed for 15 patients: 11 had been prescribed proguanil and chloroquine, two had been prescribed mefloquine, and two had been prescribed other drugs. Nine of the 15 had not taken the drugs as prescribed. Thus 19 of the 25 (76%) had taken either inadequate doses or no prophylactic drugs. The cost to the NHS for intensive care for these patients exceeded £160 000 ($256 000). We report on …

Much effort and resources have been focused on improving or evolving antimalarial prophylactic regimens in order to reduce the increasing problems of malaria infection in nonimmune travelers to malaria endemic regions. Falciparum malaria in travelers returned from Africa has been attributed to reduced efficacy of chloroquine against chloroquine-resistant strains of Plasmodium falciparum (CRPF). Reported prophylaxis use by tourists from East Africa suggests only 52% admit taking their chemoprophylaxis without any missed doses. The effect of noncompliance with chloroquine (CQ) or proguanil (PG) in East Africa has been estimated as equivalent to taking no prophylaxis at all. The influence of poor compliance and/or parasite resistance on the changing pattern of malaria among travelers needs to be understood if methods of reducing morbidity are to be identified. In a number of studies, prophylaxis compliance in travelers has been collected by self-administered questionnaires from which prophylaxis efficacy of drug regimens has been calculated. The interpretation of drug efficacy has hinged on drug compliance and is controversial. We have addressed the role of chemoprophylaxis compliance in travelers with malaria using a prospective study of 368 malaria patients attending the Hospital for Tropical Diseases by examining their travel history and reported prophylaxis compliance compared to their actual plasma drug levels. This has enabled us to characterize the role of CRPF and poor compliance in the etiology of breakthrough malaria in travelers.

Analysis of malaria imported into eight European countries from the Indian sub-continent (ISC) (India, Pakistan, Bangladesh and Sri Lanka) led to a consensus statement on the use of chemoprophylaxis within TropNetEurop. The proportion of cases from the ISC in 2004 ranged from 1.4%–4.6% of total imported cases. Plasmodium falciparum cases reported from the eight countries was only 23 (13% of all cases from the region). Total malaria reports between 1999–2004 fell from 317 to 180. The risk of malaria in UK residents visiting the region was > 1 case per 1,000 years exposed. The group recommended non-selective prescribing of chemoprophylaxis for visitors to India, Pakistan, Bangladesh and Sri Lanka should be dropped.

Mucosal leishmaniasis (ML) is an important complication of new world cutaneous leishmaniasis (CL) caused by species of the Leishmania Viannia subgenus. Previous reports of ML among travellers to Latin America are few.To determine the annual number of cases of CL due to L. Viannia species diagnosed at this institution and to correlate this with changing patterns of travel. Secondly, to document the clinical presentation, diagnosis, treatment and outcome of ML at this institution.Retrospective observational study.Data were collected from a clinical database, laboratory records, patient case notes and an international passenger survey.Between 1995 and 2003, the annual number of cases of CL (total 79) steadily increased from 4 per year to 18 per year; the estimated number of travellers from the UK to Latin America increased 3.5-fold. Six cases of ML were diagnosed among British travellers in 1995 (1), 1997 (1) and 2002 (4). These infections were acquired in Bolivia (3), Colombia (2) and Belize (1). Nasopharyngeal symptoms developed 0-15 months after returning to the UK. Four patients had concurrent CL at diagnosis. Diagnosis of ML was delayed up to 6 months from the onset of symptoms. Mucosal biopsies from all 6 patients were PCR-positive for L. (Viannia) DNA; microscopy and culture were less sensitive. ML relapsed in one patient following treatment.Increasing travel to Latin America from the UK was associated with an increasing number of diagnoses of L. Viannia CL. ML is likely to emerge as a more frequently imported infection among such travellers. Familiarity with these diseases is important for prompt diagnosis and optimal management.

Topical N,N-Diethyl-m-toluamide (DEET) was studied as a schistosomiasis prophylactic in vivo for the use of individuals with limited exposure. Fifteen subjects, on a 3-week expedition to Lake Malawi in September 2001, applied 50% DEET to their skin after exposure to lake water. No subjects developed evidence of a new infection at 3-month follow-up.

After observing an apparent increase in severe falciparum malaria among travellers returning from The Gambia to the United Kingdom (UK) in the last quarter of 2000, we conducted a case-control study to investigate risk factors for malaria. The study participants had visited The Gambia between 1 September and 31 December 2000, travelling with the largest UK tour operator serving this destination. The main outcome measures were risk factors associated with malaria. Forty-six cases and 557 controls were studied. Eighty-seven percent of all participants reported antimalarial use (41% chloroquine/proguanil, 31% mefloquine). On univariate analysis the strongest risk factors for disease were: early calendar period of visit, longer duration of stay, non-use of antimalarial prophylaxis, non-use of mefloquine, lack of room air-conditioning, less use of insect repellent, prior visit to another malarial area and accommodation in ‘hotel X’. After adjustment in multivariate analysis, use of mefloquine remained strongly protective (odds ratios, OR 0.13 [95% confidence intervals, 95% CI 0.04–0.40]), and the strongest independent risk factors for malaria were early calendar period (OR 5.19 [2.35–11.45] for 1 September to 9 November 2000 versus 10 November to 31 December 2000), prior visit to another malarial area (OR 3.27 [1.41–7.56]), main accommodation in ‘hotel X’ (OR 3.24 [1.51–6.97]) and duration of stay (OR 2.05 per extra week [1.42–2.95]). Neither any use, nor >90% adherence to chloroquine/proguanil were protective (adjusted OR for any use 0.57 [0.27–1.21], P=0.14). We concluded mefloquine use was strongly protective against malaria (87% protective efficacy), whereas chloroquine/proguanil, which is no longer recommended but remains widely used, was less than half as effective (43% protective efficacy). Waning efficacy of chloroquine/proguanil may have contributed to the observed increase in malaria among travellers to The Gambia in 2000. Local factors may also influence the risk of malaria. Malaria could be prevented among travellers to West Africa if current national guidelines on antimalarial prophylaxis were better implemented.

aPrevious studies have indicated that age is a risk factor for severe falciparum malaria in nonimmune patients. The objectives of this study were to reevaluate previous findings with a larger sample and to find out how strongly clinical outcomes for elderly patients differ from those for younger patients. Results of adjusted analyses indicated that the risks of death due to falciparum malaria, of experiencing cerebral or severe disease in general, and of hospitalization increased significantly with each decade of life. The case-fatality rate was almost 6 times greater among elderly patients than among younger patients, and cerebral complications occurred 3 times more often among elderly patients. Antimalarial chemoprophylaxis was significantly associated with a lower case-fatality rate and a lower frequency of cerebral complications. Women were more susceptible to cerebral complications than were men. Our study provides evidence that falciparum malaria is more serious in older patients and demonstrates that clinical surveillance networks are capable of providing quality data for investigation of rare events or diseases.