The Ready-To-Go Questionnaire predicts health outcomes during travel: a smartphone application-based analysis.

BACKGROUND: The Ready-To-Go (R2G) Questionnaire is a tool for rapid assessment of health risks for travel consultation. This study aims to assess the utility of the R2G Questionnaire in identifying high-risk travellers and predicting health events and behaviour during travel in the TOURIST2 prospective cohort. METHODS: TOURIST2 data were used to calculate the R2G medical and travel risk scores and categorize each participant based on their risk. The TOURIST2 study enrolled 1000 participants from Switzerland's largest travel clinics between 2017 and 2019. Participants completed daily smartphone application surveys before, during and after travel on health events and behaviours. We used regression models to analyse incidence of overall health events and of similar health events grouped into health domains (e.g. respiratory, gastrointestinal, accident/injury). Incidence rate ratios (IRR) are displayed with 95% confidence intervals (95% CI). RESULTS: R2G high-risk travellers experienced significantly greater incidence of health events compared to lower-risk travellers (IRR = 1.27, 95% CI: 1.22-1.33). Both the medical and travel scores showed significant positive associations with incidence of health events during travel (IRR = 1.11, 95% CI: 1.07-1.16; IRR = 1.07, 95% CI: 1.03-1.12, respectively), with significant increases in all health domains except skin disorders. Medical and travel risk scores were associated with different patterns in behaviour. Travellers with chronic health conditions accessed medical care during travel more often (IRR = 1.16, 95% CI: 1.03-1.31), had greater difficulty in carrying out planned activities (IRR = -0.04, 95% CI: -0.05, -0.02), and rated their travel experience lower (IRR = -0.04, 95% CI: -0.06, -0.02). Travellers with increased travel-related risks due to planned travel itinerary had more frequent animal contact (IRR = 1.09, 95% CI: 1.01-1.18) and accidents/injuries (IRR = 1.28, 95% CI: 1.15-1.44). CONCLUSIONS: The R2G Questionnaire is a promising risk assessment tool that offers a timesaving and reliable means to identify high-risk travellers. Incorporated into travel medicine websites, it could serve as a pre-consultation triage to help travellers self-identify their risk level, direct them to the appropriate medical provider(s), and help practitioners in giving more tailored advice.

Norovirus acute gastroenteritis among US and European travellers to areas of moderate to high risk of travellers' diarrhoea: a prospective cohort study.

BACKGROUND: Acute gastroenteritis (AGE) is a major medical condition for travellers worldwide, particularly travellers to low- and middle-income countries. Norovirus (NoV) is the most common cause of viral AGE in older children and adults, but data on prevalence and impact among travellers is limited. METHODS: Prospective, multi-site, observational cohort study conducted 2015-2017, among adult international travellers from the US and Europe to areas of moderate to high risk of travel-acquired AGE. Participants provided self-collected pre-travel stool samples and self-reported AGE symptoms while travelling. Post-travel stool samples were requested from symptomatic subjects and a sample of asymptomatic travellers within 14days of return. Samples were tested for NoV by RT-qPCR, genotyped if positive, and tested for other common enteric pathogens by Luminex xTAG GPP. RESULTS: Of the 1109 participants included, 437 (39.4%) developed AGE symptoms resulting in an overall AGE incidence of 24.7 per 100 person-weeks (95% CI: 22.4; 27.1). Twenty NoV-positive AGE cases (5.2% of those tested) were identified at an incidence of 1.1 per 100 person-weeks (95% CI: 0.7; 1.7). NoV-positive samples belonged mostly to genogroup GII (18, 85.7%); None of the 13 samples sequenced belonged to genotype GII.4. Clinical severity of AGE was higher for NoV-positive than for NoV-negative cases (mean modified Vesikari Score 6.8 vs 4.9) with more cases classified as severe or moderate (25% vs 6.8%). Eighty percent of NoV-positive participants (vs. 38.9% in NoV-negative) reported at least moderate impact on travel plans. CONCLUSIONS: AGE is a prevalent disease among travellers with a small proportion associated with NoV. Post-travel stool sample collection timing might have influenced the low number of NoV cases detected; however, NoV infections resulted in high clinical severity and impact on travel plans. These results may contribute to targeted vaccine development and the design of future studies on NoV epidemiology.

The Chronic Diseases Clinic of Ifakara (CDCI)-Establishing a Model Clinic for Chronic Care Delivery in Rural Sub-Saharan Africa.

The rollout of antiretroviral drugs in sub-Saharan Africa to address the huge health impact of the HIV pandemic has been one of the largest projects undertaken in medical history and is an unprecedented medical success story. However, the path has been and still is characterized by many far reaching implementational challenges. Here, we report on the building and maintaining of a role model clinic in Ifakara, rural Southwestern Tanzania, within a collaborative project to support HIV services within the national program, training for staff and integrated research to better understand local needs and improve patients' outcomes.

Long-term persistence of antibodies after diphtheria/tetanus vaccination in immunosuppressed patients with inflammatory rheumatic diseases and healthy controls.

Many vaccines demonstrate high effectiveness for years. This prospective multicentre study was conducted in Switzerland to assess the long-term persistence of antibodies to the diphtheria/tetanus (dT)-vaccine in adult patients with rheumatic diseases (PRDs). 163 PRDs and 169 controls were included in the study. The median age of all participants was 50 years (range: 18-83 years) and 56% were female. After a median time interval of 16 years after vaccination, the median anti-vaccine antibody concentrations were lower in PRDs than in controls for tetanus (1.68 vs 2.01; p = 0.049) and diphtheria (0.05 vs 0.22; p = 0.002). Based on the currently accepted seroprotection threshold (antibody concentration ≥ 0.1 IU/ml), PRDs had lower proportions of short-term tetanus and diphtheria protection as demonstrated by crude odds ratios (OR) of 0.30 (p = 0.017) and OR: 0.52 (p = 0.004), respectively. After adjusting for 'age' and 'time since last dT vaccination', the strength of associations became weaker; for tetanus, borderline evidence remained for a true difference between PRDs and controls (OR: 0.36 [p = 0.098]), however, not for diphtheria (OR: 0.86 [p = 0.58]). We hypothesize that in the presence of rheumatic diseases and its immunosuppressive treatment, vaccine-specific long-lived plasma cells (LLPCs) may be diminished or competitively displaced by rheumatism-specific LLPCs, a process which may decrease the persistence of vaccine-specific antibodies. Novel studies should be designed by incorporating methodologies allowing to determine the attributable fraction of immunosuppressive/immunomodulatory medications and rheumatic disease itself on long-lasting vaccine-specific antibody persistence, as well as, further study the role of LLPCs.

Infection intensity-dependent accuracy of reagent strip for the diagnosis of Schistosoma haematobium and estimation of treatment prevalence thresholds.

BACKGROUND: Reagent strip to detect microhematuria as a proxy for Schistosoma haematobium infections has been considered an alternative to urine filtration for individual diagnosis and community-based estimates of treatment needs for preventive chemotherapy. However, the diagnostic accuracy of reagent strip needs further investigation, particularly at low infection intensity levels. METHODS: We used existing data from a study conducted in Tanzania that employed urine filtration and reagent strip testing for S. haematobium in two villages, including a baseline and six follow-up surveys after praziquantel treatment representing a wide range of infection prevalence. We developed a Bayesian model linking individual S. haematobium egg count data based on urine filtration to reagent strip binary test results available on multiple days and estimated the relation between infection intensity and sensitivity of reagent strip. Furthermore, we simulated data from 3,000 hypothetical populations with varying mean infection intensity to infer on the relation between prevalence observed by urine filtration and the interpretation of reagent strip readings. PRINCIPAL FINDINGS: Reagent strip showed excellent sensitivity even for single measurement reaching 100% at around 15 eggs of S. haematobium per 10 ml of urine when traces on reagent strip were considered positive. The corresponding specificity was 97%. When traces were considered negative, the diagnostic accuracy of the reagent strip was equivalent to urine filtration data obtained on a single day. A 10% and 50% urine filtration prevalence based on a single day sampling corresponds to 11.2% and 48.6% prevalence by reagent strip, respectively, when traces were considered negative, and 17.6% and 57.7%, respectively, when traces were considered positive. CONCLUSIONS/SIGNIFICANCE: Trace results should be included in reagent strip readings when high sensitivity is required, but excluded when high specificity is needed. The observed prevalence of reagent strip results, when traces are considered negative, is a good proxy for prevalence estimates of S. haematobium infection by urine filtration on a single day.

Travel behaviours and health outcomes during travel: Profiling destination-specific risks in a prospective mHealth cohort of Swiss travellers.

BACKGROUND: We used a mobile application to determine the incidence of health events and risk behaviours during travel by country and identify which health risks are significantly elevated during travel compared with at home. METHOD: TOURIST2 is a prospective cohort study of 1000 adult travellers from Switzerland to Thailand, India, China, Tanzania, Brazil and Peru, planning travel of ≤4 weeks between 09/2017 and 04/2019. The incidence rate ratio (IRR) in each country was calculated. RESULTS: All countries had significantly higher incidence of health events than at home. The most elevated symptoms were sunburn, itching from mosquitoes, and gastrointestinal disorders (e.g. vomiting, diarrhoea), corresponding with universally high food/drink risk behaviours. Peru had the highest incidence of both overall negative health events and severe health events (172.0/1000 travel-days). Traffic accidents were significantly higher in Peru (IRR: 2.4, 1.2, 4.7), although incidence of transportation risk was highest in India and Thailand. In Tanzania, incidence of negative mental health events was significantly lower than at home, although it was elevated in other countries. Sexual risk behaviours were high in Brazil. CONCLUSIONS: Our study improves the understanding of the non-infectious disease related health challenges travellers face and provides evidence for more personalised traveller support.

Antimicrobial-Resistant Escherichia coli Strains and Their Plasmids in People, Poultry, and Chicken Meat in Laos.

Antimicrobial resistant (AMR) Enterobacterales are widely distributed among the healthy population of the Indochinese peninsula, including Laos. However, the local reservoir of these pathogens are currently not known and possible sources such as agricultural settings and food have rarely been analyzed. In this work, we investigated the extended-spectrum cephalosporin- (ESC-) and colistin-resistant Escherichia coli strains (CST-R-Ec) isolated from the gut of local people, feces of poultry, and from chicken meat (60 samples each group) in Laos. Whole-genome sequencing (WGS) analysis based on both short- and long-read sequencing approaches were implemented. The following prevalence of ESC-R-Ec and CST-R-Ec were recorded, respectively: local people (70 and 15%), poultry (20 and 23.3%), and chicken meat (21.7 and 13.3%). Core-genome analysis, coupled with sequence type (ST)/core-genome ST (cgST) definitions, indicated that no common AMR-Ec clones were spreading among the different settings. ESC-R-Ec mostly possessed bla CTX-M-15 and bla CTX-M-55 associated to ISEcp1 or IS26. The majority of CST-R-Ec carried mcr-1 on IncX4, IncI2, IncP1, and IncHI1 plasmids similar or identical to those described worldwide; strains with chromosomal mcr-1 or possessing plasmid-mediated mcr-3 were also found. These results indicate a high prevalence of AMR-Ec in the local population, poultry, and chicken meat. While we did not observe the same clones among the three settings, most of the bla CTX-Ms and mcr-1/-3 were associated with mobile-genetic elements, indicating that horizontal gene transfer may play an important role in the dissemination of AMR-Ec in Laos. More studies should be planned to better understand the extent and dynamics of this phenomenon.

Efficacy and Tolerability of Quinacrine Monotherapy and Albendazole Plus Chloroquine Combination Therapy in Nitroimidazole-Refractory Giardiasis: A TropNet Study.

BACKGROUND: Giardiasis failing nitroimidazole first-line treatment is an emerging problem in returning European travelers. We present data on the efficacy and tolerability of 2 second-line treatment regimens. METHODS: This prospective, open-label, multicenter study assessed the efficacy and tolerability of quinacrine monotherapy (100 mg 3 times per day for 5 days) and albendazole plus chloroquine combination therapy (400 mg twice daily plus 155 mg twice daily for 5 days) in nitroimidazole-refractory giardiasis. The defined end points were the clinical outcome, assessed at week 5 after treatment and the parasitological outcome, assessed using microscopy of 2 stool samples, ≥2 to ≤5 weeks after treatment. RESULTS: A total of 106 patients were included in the study. Quinacrine achieved clinical and parasitological cure in 81% (59/73) and 100% (56/56), respectively. Albendazole plus chloroquine achieved clinical and parasitological cure in 36% (12/33) and 48% (12/25), respectively. All patients (9/9) who clinically and parasitologically failed albendazole plus chloroquine treatment and opted for retreatment with quinacrine achieved clinical cure. Mild to moderate treatment-related adverse events were reported by 45% and 30% of patients treated with quinacrine and albendazole plus chloroquine, respectively. One patient treated with quinacrine developed severe neuropsychiatric side effects. The majority of nitroimidazole-refractory Giardia infections (57%) were acquired in India. CONCLUSIONS: Quinacrine was a highly effective treatment in nitroimidazole-refractory giardiasis, but patients should be cautioned on the low risk of severe neuropsychiatric adverse event. Albendazole plus chloroquine had a low cure rate in nitroimidazole-refractory giardiasis. Nitroimidazole-refractory giardiasis was primarily seen in travelers returning from India.

Longitudinal study based on a safety registry for malaria patients treated with artenimol-piperaquine in six European countries.

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.

Dynamics of intestinal multidrug-resistant bacteria colonisation contracted by visitors to a high-endemic setting: a prospective, daily, real-time sampling study.

BACKGROUND: Antimicrobial resistance is highly prevalent in low-income and middle-income countries. International travel contributes substantially to the global spread of intestinal multidrug-resistant Gram-negative bacteria. Hundreds of millions of annual visitors to low-income and middle-income countries are all exposed to intestinal multidrug-resistant Gram-negative bacteria resulting in 30-70% of them being colonised at their return. The colonisation process in high-exposure environments is poorly documented because data have only been derived from before travel and after travel sampling. We characterised colonisation dynamics by exploring daily stool samples while visiting a low-income and middle-income countries. METHODS: In this prospective, daily, real-time sampling study 20 European visitors to Laos volunteered to provide daily stool samples and completed daily questionnaires for 22 days. Samples were initially assessed at Mahosot Hospital, Vientiane, Laos, for acquisition of extended-spectrum ß-lactamase-producing (ESBL) Gram-negative bacteria followed by whole-genome sequencing of isolates at MicrobesNG, University of Birmingham, Birmingham, UK. The primary outcome of the study was to obtain data on the dynamics of intestinal multidrug-resistant bacteria acquisition. FINDINGS: Between Sept 18 and Sept 20, 2015, 23 volunteers were recruited, of whom 20 (87%) European volunteers were included in the final study population. Although colonisation rates were 70% at the end of the study, daily sampling revealed that all participants had acquired ESBL-producing Gram-negative bacteria at some point during the study period; the colonisation status varied day by day. Whole-genome sequencing analysis ascribed the transient pattern of colonisation to sequential acquisition of new strains, resulting in a loss of detectable colonisation by the initial multidrug-resistant Gram-negative strains. 19 (95%) participants acquired two to seven strains. Of the 83 unique strains identified (53 Escherichia coli, 10 Klebsiella spp, and 20 other ESBL-producing Gram-negative bacteria), some were shared by as many as four (20%) participants. INTERPRETATION: To our knowledge, this is the first study to characterise in real-time the dynamics of acquiring multidrug-resistant Gram-negative bacterial colonisation during travel. Our data show multiple transient colonisation events indicative of constant microbial competition and suggest that travellers are exposed to a greater burden of multidrug-resistant bacteria than previously thought. The data emphasise the need for preventing travellers' diarrhoea and limiting antibiotic use, addressing the two major factors predisposing colonisation. FUNDING: The Finnish Governmental Subsidy for Health Science Research, The Scandinavian Society for Antimicrobial Chemotherapy, the Sigrid Jusélius Foundation, Biotechnology and Biological Sciences Research Council; Wellcome Trust, Medical Research Council; The Royal Society; Joint Programming Initiative on Antimicrobial Resistance, and European Research Council.

Leptospirosis Followed by Kawasaki-Like Disease: Case Report From an Adult Swiss Patient and Review of the Literature.

Kawasaki disease (KD) is a vasculitis that mostly occurs in children, but rare cases in adults have been reported. We describe the case of a 43-year-old Swiss male who developed symptoms compatible with KD 7 weeks after leptospirosis, which was presumably acquired after swimming in a creek in the Swiss Alps. We performed a literature review and identified 10 other cases (all in children), in which Kawasaki-like disease was diagnosed in the context of leptospirosis. Outcome was favourable in most cases, including our patient. This exceptional case demonstrates both the possibility of autochthonous cases of leptospirosis in Switzerland as well as a possible association of leptospirosis with Kawasaki-like disease.

Comparison of Two Different Semiquantitative Urinary Dipstick Tests with Albumin-to-Creatinine Ratio for Screening and Classification of Albuminuria According to KDIGO. A Diagnostic Test Study.

BACKGROUND: Semiquantitative dipstick tests are utilized for albuminuria screening. METHODS: In a prospective cross-sectional survey, we analyzed the diagnostic test validity of the semiquantitative colorimetric indicator-dye-based Combur9-Test® and the albumin-specific immunochromatographic assay Micral-Test® for the detection of albuminuria, the distribution of the semiquantitative measurements within the albuminuria stages according to KDIGO, and the utility for albuminuria screening compared with an albumin-to-creatinine ratio (ACR) in a walk-in population. RESULTS: In 970 subjects, albuminuria (≥30 mg/g) was detected in 12.7% (95% CI 85.6-96.3%) with the ACR. Sensitivity was 82.9% (95% CI 75.1-89.1%) and 91.9% (95% CI 88.7-96.9%) and specificity 71.5% (95% CI 68.4-74.6%) and 17.5% (95% CI 15.0-20.2%) for the Combur9-Test® and Micral-Test®, respectively. Correct classification to KDIGO albuminuria stages A2/A3 with the Combur9-Test® was 15.4%, 51.4%, and 87.9% at cut-offs of 30, 100, and ≥300 mg/dL, and with the Micral-Test® it was 1.8%, 10.5%, and 53.6% at cut-offs of 2, 5, and 10 mg/dL, respectively. Overall, disagreement to KDIGO albuminuria was seen in 27% and 73% with the Combur9-Test® and Micral-Test®, respectively. From the total population, 62.5% and 15.3% were correctly ruled out and 2.2% and 1% were missed as false-negatives by the Combur9-Test® and Micral-Test®, respectively. CONCLUSION: Compared to the Combur9-Test®, the utility of the Micral-Test® is limited, because the fraction of correctly ruled out patients is small and a large proportion with a positive Micral-Test® require a subsequent ACR conformation test.

Travellers returning from the island of Zanzibar colonized with MDR Escherichia coli strains: assessing the impact of local people and other sources.

OBJECTIVES: Many travellers to low-income countries return home colonized at the intestinal level with extended-spectrum cephalosporin-resistant (ESC-R) and/or colistin-resistant (CST-R) Escherichia coli (Ec) strains. However, nothing is known about the local sources responsible for the transmission of these pathogens to the travellers. METHODS: We compared the ESC-R- and CST-R-Ec strains found in the pre- (n = 23) and post-trip (n = 37) rectal swabs of 37 travellers from Switzerland to Zanzibar with those (i) contemporarily isolated from local people, poultry, retailed chicken meat (n = 31), and (ii) from other sources studied in the recent past (n = 47). WGS and core-genome analyses were implemented. RESULTS: Twenty-four travellers returned colonized with ESC-R- (n = 29) and/or CST-R- (n = 8) Ec strains. Almost all ESC-R-Ec were CTX-M-15 producers and belonged to heterogeneous STs/core-genome STs (cgSTs), while mcr-positive strains were not found. Based on the strains' STs/cgSTs, only 20 subjects were colonized with ESC-R- and/or CST-R-Ec that were not present in their gut before the journey. Single nucleotide variant (SNV) analysis showed that three of these 20 travellers carried ESC-R-Ec (ST3489, ST3580, ST361) identical (0-20 SNVs) to those found in local people, chicken meat, or poultry. Three further subjects carried ESC-R-Ec (ST394, ST648, ST5173) identical or highly related (15-55 SNVs) to those previously reported in local people, fish, or water. CONCLUSIONS: This is the first known study comparing the ESC-R- and/or CST-R-Ec strains obtained from travellers and local sources using solid molecular methods. We showed that for at least one-third of the returning travellers the acquired antibiotic-resistant Ec had a corresponding strain among resident people, food, animal and/or environmental sources.

TOURIST2 - Tracking of urgent risks in swiss travellers to the 6 main travel destinations - Feasibility and ethical considerations of a smartphone application-based study.

BACKGROUND: The adoption of mHealth technology in travel medicine is a relatively new and unexplored field. We have further developed a TRAVEL application (app) for real-time data monitoring during travel. In this manuscript we report on the feasibility using this new app in a large and diverse cohort of travellers to three continents. METHODS: We enrolled 1000 participants from the travel clinics of Zurich and Basel, Switzerland, aged ≥18 years, travelling to Thailand, India, China, Tanzania, Brazil and Peru between 09/2017-01/2019. Participants included healthy travellers, individuals with pre-existing chronic diseases and elderly travellers (≥60 years). Participants completed an app-based daily survey on risk behaviours/health incidents pre-, during and after travel. Simultaneously, GPS locations were tightly collected and linked to environmental data. RESULTS: 793 (79%) travellers answered at least one questionnaire during their trip. Participants' median age was 34 years (range 18-84 years); 8% were aged ≥60 years; 55% female; 32% had pre-existing chronic diseases. Completion rates were similar in younger and elderly travellers and in those with and without pre-existing diseases. CONCLUSIONS: The use of a smartphone app is a feasible method for collecting behavioural and health data in elderly travellers and individuals with chronic diseases travelling to three continents.

Safety and immunogenicity of a primary yellow fever vaccination under low-dose methotrexate therapy-a prospective multi-centre pilot study1.

BACKGROUND: More people on immunosuppression live in or wish to travel to yellow fever virus (YFV)-endemic areas. Data on the safety and immunogenicity of yellow fever vaccination (YFVV) during immunosuppression are scarce. The aim of this study was to compare the safety and immunogenicity of a primary YFVV between travellers on methotrexate and controls. METHODS: We conducted a prospective multi-centre controlled observational study from 2015 to 2017 in six Swiss travel clinics. 15 adults (nine with rheumatic diseases, five with dermatologic conditions and one with a gastroenterological disease) on low-dose methotrexate (≤20 mg/week) requiring a primary YFVV and 15 age and sex-matched controls received a YFVV. Solicited/unsolicited adverse reactions were recorded, YFV-RNA was measured in serum samples on Days 3, 7, 10, 14, 28 and neutralizing antibodies on Days 0, 7, 10, 14, 28. RESULTS: Patients´ and controls' median ages were 53 and 52 years; 9 patients and 10 controls were female. 43% of patients and 33% of controls showed local side effects (P = 0.71); 86% of patients and 66% of controls reported systemic reactions (P = 0.39). YFV-RNA was detected in patients and controls on Day 3-10 post-vaccination and was never of clinical significance. Slightly more patients developed YFV-RNAaemia (Day 3: n = 5 vs n = 2, Day 7: n = 9 vs n = 7, Day 10: n = 3 vs n = 2, all P > 0.39). No serious reactions occurred. On Day 10, a minority of vaccinees was seroprotected (patients: n = 2, controls: n = 6). On Day 28, all vaccinees were seroprotected. CONCLUSIONS: First-time YFVV was safe and immunogenic in travellers on low-dose methotrexate. Larger studies are needed to confirm these promising results.

Travel patterns, risk behaviour and health problems of travellers with rheumatic diseases compared to controls: A multi-centre, observational study.

BACKGROUND: Patients with chronic conditions travel around the world more than ever. Only few studies have examined travel patterns and health outcomes of patients with rheumatic diseases during international travel. METHOD: We conducted a multi-centre prospective cohort study in Switzerland, in which we studied the immunogenicity and safety of vaccinations in patients with rheumatic diseases and travellers without rheumatic diseases (controls). Participants who travelled internationally received questionnaires 1 and 13 weeks post-travel. We compared travel patterns, risk behaviours, and travel-associated problems during and after the trips in both groups. RESULTS: 274 participants returned post-travel questionnaires (65 rheumatic patients, 209 controls). Controls more frequently travelled to subtropical/tropical destinations and stayed longer abroad. 64% of all participants experienced health problems during travel (74% rheumatic patients vs. 62% controls, P = 0.11). Pre-travel, patients reported a higher susceptibility to gastrointestinal infections . During travel, a higher percentage of rheumatic patients cancelled the day programme due to health problems (13% vs. 4%, P = 0.024). The main problems in rheumatic patients occurred due to the underlying rheumatic diseases, or were of psychological nature. Although not statistically significant, infectious disease symptoms (rhinitis, cough) occurred more frequently in controls. When only considering subtropical/tropical destinations, rheumatic patients more frequently had gastrointestinal problems during travel - and skin infections after the trip. CONCLUSIONS: This study does not support the notion that patients with rheumatic diseases should avoid international travel for an increased risk of infections. In patients with subtropical/tropical destinations, however, gastrointestinal problems may be increased during travel - and skin infections post-travel.

On the island of Zanzibar people in the community are frequently colonized with the same MDR Enterobacterales found in poultry and retailed chicken meat.

OBJECTIVES: Intestinal colonization with extended-spectrum cephalosporin-resistant (ESC-R) and colistin-resistant (CST-R) Enterobacterales (Ent) can be driven by contact with colonized animals and/or contamination of the food chain. We studied the ESC-R-Ent and COL-R-Ent colonizing poultry as well as contaminating chicken meat in Zanzibar (Tanzania). Results were compared with recently published data obtained from rectal swabs of people in the community. METHODS: During June and July 2018, we collected poultry faecal material (n = 62) and retail chicken meat (n = 37) samples. ESC-R and CST-R strains were isolated implementing selective approaches and characterized with different molecular methods, including WGS coupled with core-genome analyses. RESULTS: The prevalence of ESC-R-Ent and CST-R-Ent, respectively, were: 88.7% and 48.4% in poultry; and 43.2% and 18.9% in chicken meat. Overall, the following strains and main resistance mechanisms were found in the two settings: 69 ESC-R Escherichia coli (CTX-M-15 subgroup, 75%), 34 ESC-R Klebsiella pneumoniae (CTX-M-9 group, 54.5%), 24 non-ESC-R but CST-R E. coli (mcr-1, 95.8%) and 17 non-ESC-R but CST-R K. pneumoniae (D150G substitution in PhoQ). Several clones (differing by only 0-13 single nucleotide variants) were concomitantly and frequently found in human and non-human settings: mcr-1-carrying E. coli ST46; CTX-M-15-producing E. coli ST361; CTX-M-14-producing K. pneumoniae ST17; and CTX-M-15-producing K. pneumoniae ST1741. CONCLUSIONS: This is one of the few studies that have assessed the occurrence of identical MDR Enterobacterales in human and non-human settings. The frequent human gut colonization observed in the community might be favoured by the spread of ESC-R-Ent and CST-R-Ent in poultry and chicken meat. Further studies with a One Health approach should be carried out to better investigate this phenomenon.

Outpatient treatment of imported uncomplicated Plasmodium falciparum malaria: results from a survey among TropNet and GeoSentinel experts for tropical medicine.

BACKGROUND: Plasmodium falciparum malaria (P.f. malaria) is frequently imported to non-endemic countries. Recommendations on outpatient treatment differ largely due to differences in country-level guidelines and even between tropical medicine referral centres within the same country. METHODS: This survey among experts from TropNet or GeoSentinel referral centres for tropical medicine outside malaria endemic areas investigated common practices in P.f. malaria management, selection criteria for outpatient management and diagnostic procedures as a first step for developing a future common and evidence-based approach. RESULTS: A total of 44 referral centres participated. Most of the centres are located in Europe (n = 37). Overall, 27 centres (61%) treat uncomplicated P.f. malaria patients as outpatients, of which eight centres (18%) reported treating ≥75% of patients on an outpatient basis. Seventeen centres (39%) reported treating patients only as inpatients. No single criterion stands out for the decision regarding outpatient treatment, but three groups of factors were identified: (i) clinical criteria including laboratory parameters, clinical condition and tolerance of oral medication; (ii) factors such as patient compliance, reachability by phone and support at home and (iii) patient origin and place of residence as a proxy for possible underlying semi-immunity. The threshold parasitaemia for outpatient treatment varied from 0.1 to 5% with a median of 2%. A median of 0.5% of outpatients were admitted during follow-up. During the last 10 years, 33 complications were reported by nine of the 27 centres and three deaths by one centre. CONCLUSION: This study gives insight into the heterogeneous management of P.f. malaria patients outside endemic regions. Although there is no consensus among experts, the majority of centres includes outpatient treatment in their clinical routine. However, the lack of evidence-based criteria and established safety for this approach shows the need for prospective studies to define and evaluate criteria and practices for safe outpatient management.

Assessment of diabetes and prediabetes prevalence and predictors by HbA1c in a population from sub-Saharan Africa with a high proportion of anemia: a prospective cross-sectional study.

INTRODUCTION: Epidemiological data about diabetes mellitus (DM) for sub-Saharan Africa (SSA) are scarce and the utility of glycated hemoglobin (HbA1c) to diagnose DM is uncertain in African populations with a high proportion of anemia. RESEARCH DESIGN AND METHODS: In a cross-sectional study, age-adjusted prevalence rates and predictors for DM and pre-DM were prospectively assessed by HbA1c in a semirural walk-in population of Tanzania (n=992). Predictors for DM were calculated by logistic regression. Correlations between HbA1c, hemoglobin, and blood glucose levels were done by Pearson's correlation. RESULTS: Overall, DM and pre-DM prevalence rates were 6.8% (95% CI 5.3 to 8.5) and 25% (95% CI 22.8 to 28.3), respectively. There was an increase in DM prevalence in patients 50-59 (14.9%; 95% CI 9.1 to 22.5), ≥60 years old (18.5%; 95% CI 12.2 to 26.2) and in patients with overweight (9.3%; 95% CI 5.9 to 13.7), obesity (10.9%; 95% CI 6.9 to 16) compared with patients 18-29 years old (2.2%; 95% CI 0.9 to 4.4) (p<0.001) and to normal-weight patients (3.6%; 95% CI 2.1 to 5.6) (p<0.01), respectively. Age (OR 1.08, 95% CI 1.05 to 1.12; p<0.001), body mass index (BMI) (OR 1.10, 95% CI 1.04 to 1.16; p<0.001), and acute infection (OR 3.46, 95% CI 1.02 to 10.8; p=0.038) were predictors for DM. Comparing patients with a BMI of 20 kg/m2 and a BMI of 35 kg/m2, the relative risk for DM increases in average by 2.12-fold (range 1.91-2.24) across the age groups. Comparing patients 20 years old with patients 70 years old, the relative risk for DM increases in average 9.7-fold (range 8.9-10.4) across the BMI groups. Overall, 333 patients (36%) suffered from anemia. Pearson's correlation coefficients (r) between HbA1c and hemoglobin was -0.009 (p=0.779), and between HbA1c and fasting blood glucose and random blood glucose, it was 0.775 and 0.622, respectively (p<0.001). CONCLUSION: We observed a high prevalence of DM and pre-DM, mainly triggered by increasing age and BMI, and provide evidence that HbA1c is suitable to assess DM also in populations of SSA with high proportions of anemia. TRIAL REGISTRATION NUMBER: NCT03458338.