[Multi-resistant Enterobacterales and travel]. / Entérobactéries multirésistantes et voyage.

Multi-resistant Enterobacterales (MRE) are on the increase worldwide, with the main mechanism of resistance acquisition being horizontal transfer of plasmids coding for extended-spectrum betalactamase and/or carbapenemase. Low- and middle-income countries are the most affected, but surveillance in low-endemicity countries, such as Switzerland, is essential. International travel is one of the sources of MRE dissemination in the community, with the main risk factors for acquiring MRE being a stay in South or Southeast Asia and the use of antibiotics during travel. Other factors, notably animal and environmental, also explain this increase. Measures encompassing a One Health approach are therefore needed to address this issue.

Les entérobactéries multirésistantes (EMR) sont en augmentation dans le monde, avec comme mécanisme principal d'acquisition de résistance le transfert horizontal de plasmides codant pour une bêtalactamase à spectre étendu et/ou une carbapénèmase. Les pays à bas et moyens revenus sont les plus touchés, mais une surveillance dans les pays à faible endémicité, comme la Suisse, est essentielle. Les voyages internationaux sont l'une des sources de dissémination d'EMR dans la communauté, avec comme facteurs de risque principaux d'acquisition d'EMR un séjour en Asie du Sud ou du Sud-Est et l'utilisation d'antibiotiques durant le voyage. D'autres facteurs, notamment animaliers et environnementaux, expliquent aussi cette augmentation. Ainsi, il est nécessaire que des mesures englobant une approche « One Health ¼ répondent à cette problématique.

[Acute diarrhea: updates for primary care medicine in 2023]. / Diarrhées aiguës : nouveautés 2023 pour la médecine de premier recours.

Acute diarrheal disease is a frequent primary care reason for consultation, leading to direct and indirect health costs in high-income countries. Most patients presenting with acute diarrhea will have a favorable clinical course with just a symptomatic treatment. The challenge for the general practitioner is to identify the patients who need paraclinical exams and/or antibiotics. Molecular identification of pathogens in stool samples has developed over the past years and presents both advantages and limitations. Because of increasing microbial resistance to quinolones in Campylobacter and Shigella strains, azithromycin is now the first choice for an empiric antimicrobial therapy. This article will discuss these latest developments in the management of acute diarrhea in the primary care setting.

Les diarrhées aiguës sont un motif de consultation fréquent en médecine générale et engendrent des coûts directs et indirects importants dans les pays industrialisés. Les cas sont majoritairement bénins et évoluent de manière favorable avec un traitement symptomatique. Le défi pour le médecin généraliste est d'identifier les patient-e-s nécessitant des examens complémentaires et/ou un traitement antibiotique. Ces dernières années, les examens microbiologiques moléculaires des selles se sont développés ; ils ont des avantages, mais également des limitations. Sur le plan thérapeutique, l'azithromycine est désormais à privilégier comme antibiothérapie empirique en raison de l'accroissement du nombre de souches de Campylobacter et Shigella résistantes aux quinolones. Cet article discute ces nouveautés dans la prise en charge des diarrhées aiguës du point de vue du généraliste.

Clinical Characteristics and Outcomes Among Travelers With Severe Dengue : A GeoSentinel Analysis.

BACKGROUND: Dengue virus is a flavivirus transmitted by Aedes mosquitoes and is an important cause of illness worldwide. Data on the severity of travel-associated dengue illness are limited. OBJECTIVE: To describe the epidemiology, clinical characteristics, and outcomes among international travelers with severe dengue or dengue with warning signs as defined by the 2009 World Health Organization classification (that is, complicated dengue). DESIGN: Retrospective chart review and analysis of travelers with complicated dengue reported to GeoSentinel from January 2007 through July 2022. SETTING: 20 of 71 international GeoSentinel sites. PATIENTS: Returning travelers with complicated dengue. MEASUREMENTS: Routinely collected surveillance data plus chart review with abstraction of clinical information using predefined grading criteria to characterize the manifestations of complicated dengue. RESULTS: Of 5958 patients with dengue, 95 (2%) had complicated dengue. Eighty-six (91%) patients had a supplemental questionnaire completed. Eighty-five of 86 (99%) patients had warning signs, and 27 (31%) were classified as severe. Median age was 34 years (range, 8 to 91 years); 48 (56%) were female. Patients acquired dengue most frequently in the Caribbean (n = 27 [31%]) and Southeast Asia (n = 21 [24%]). Frequent reasons for travel were tourism (46%) and visiting friends and relatives (32%). Twenty-one of 84 (25%) patients had comorbidities. Seventy-eight (91%) patients were hospitalized. One patient died of nondengue-related illnesses. Common laboratory findings and signs were thrombocytopenia (78%), elevated aminotransferase (62%), bleeding (52%), and plasma leakage (20%). Among severe cases, ophthalmologic pathology (n = 3), severe liver disease (n = 3), myocarditis (n = 2), and neurologic symptoms (n = 2) were reported. Of 44 patients with serologic data, 32 confirmed cases were classified as primary dengue (IgM+/IgG-) and 12 as secondary (IgM-/IgG+) dengue. LIMITATIONS: Data for some variables could not be retrieved by chart review for some patients. The generalizability of our observations may be limited. CONCLUSION: Complicated dengue is relatively rare in travelers. Clinicians should monitor patients with dengue closely for warning signs that may indicate progression to severe disease. Risk factors for developing complications of dengue in travelers need further prospective study. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention, International Society of Travel Medicine, Public Health Agency of Canada, and GeoSentinel Foundation.

[HealthyTravel.ch - The reference website for traveler's health advice]. / HealthyTravel.ch ­ Le site internet de référence pour les conseils de santé aux voyageurs.

The Swiss Expert Committee on Travel Medicine (ECTM) - a body of the Swiss Society of Tropical Medicine and Travel Medicine (FMH) - publishes recommendations and information on travel medicine on the website www.healthytravel.ch in four languages (German, French, Italian, English). HealthyTravel.ch, which has replaced Safetravel.ch, is the reference website for travelers' health advice in Switzerland supported by the Federal Office of Public Health (FOPH). It consists of a free version with basic travel medicine recommendations for the public, and a fee-based PRO version for professionals, containing more detailed information and recommendations. This article provides an overview of the available content and tips on how to make the best use of www.healthytravel.ch.

Le Comité suisse d'experts en médecine des voyages (CFMV), un organe de la Société suisse de médecine tropicale et de médecine des voyages (FMH), publie sur le site internet www.healthytravel.ch des recommandations et des informations sur la médecine des voyages en quatre langues (allemand, français, italien et anglais). HealthyTravel.ch, qui a remplacé le site Safetravel.ch, est le site internet de référence pour les conseils de santé aux voyageurs soutenu par l'Office fédéral de la santé publique (OFSP). Il est composé d'une version gratuite, avec des recommandations de base en matière de médecine des voyages pour le public, et d'une version PRO, payante, pour les professionnels, contenant des informations et des recommandations plus détaillées. Cet article donne un aperçu des contenus disponibles et des conseils d'utilisation optimale du site www.healthytravel.ch.

Infection tracking in travellers using a mobile app (ITIT): The pilot study.

BACKGROUND: Current surveillance of travellers' health captures only a small proportion of illness events. We aimed to evaluate the usability and feasibility of using an app to enable travellers to self-report illness. METHOD: This pilot study assesses a novel mobile application called Infection Tracking in Travellers (ITIT) that records travel-related symptoms with associated geolocation and weather data. Participants were recruited in three Swiss travel clinics between December 2021 and March 2022. A feedback survey was used to examine app ease of use, and data from the app was used to examine travel and illness patterns as a proof-of-concept for the larger ITIT study. RESULTS: Participants were recruited from Zürich, Basel, and Geneva, with 37 individuals completing a total of 394 questionnaires in 116 locations in Asia, Africa, the Americas, and Europe. Illness symptoms were reported by 41% of participants, 67% of which were respiratory. The post travel questionnaire showed that all participants found the app easy to use and 63% said they would recommend it to others. Several users provided suggestions for improved usability. CONCLUSION: The app fulfilled its function as a research tool linking infection symptoms with geolocation and climate data.

Should we treat Blastocystis sp.? A double-blind placebo-controlled randomized pilot trial.

BACKGROUND: Blastocystis sp. is a worldwide-distributed protist colonizing the guts of humans and a great variety of animals. It is unclear whether it is just a commensal or an infectious parasite that prompts eradication.The main objective of this study was to evaluate the usefulness of metronidazole in patients with gastrointestinal symptoms harbouring only Blastocystis sp. In addition, we explored whether Blastocystis subtype or concomitant parasitic infection detected by polymerase chain reaction (PCR) may influence treatment outcome. METHODS: We included adults with persistent gastrointestinal symptoms (>14 days) visiting a primary care physician and in whom stool microscopy revealed only Blastocystis sp. Eligible patients were randomized to receive 10 days of metronidazole or placebo, followed by a crossover if still symptomatic. The primary outcome was normal stool consistency. Secondary outcomes were the changes in other abdominal symptoms (bloating, flatulence, abdominal pain, number of daily bowel movements) and general wellbeing. After the clinical phase of the study, Blastocystis subtypes were determined by PCR sequencing and stool samples were tested for 11 other protozoa with an in-house PCR. RESULTS: We screened 581 outpatients for inclusion, of which 50 met the eligibility criteria. There was no difference in the primary outcome, nor any of the secondary outcomes between the subjects treated with metronidazole and placebo.The most frequent Blastocystis subtypes were ST4 (11/36) and ST2 (10/36). The in-house PCR was positive for other protozoa in 25% (10/40) of the patients. We identified Dientamoeba fragilis in 5, Entamoeba dispar in 3 and Cyclospora cayetanensis in 2 patients. Stratified analysis according to Blastocystis subtype or the presence of other protozoa showed no significant difference in treatment outcome with metronidazole or placebo. CONCLUSIONS: Among patients infected with Blastocystis sp., metronidazole, compared with placebo, was not better in improving gastrointestinal symptoms, irrespective of subtype or microscopically undetected coinfection with other protozoa.

[Collateral effects of the COVID-19 pandemic on the practice of tropical and travel medicine]. / Effets de la pandémie de Covid-19 sur la pratique de médecine tropicale et des voyages.

Undoubtedly, the COVID-19 pandemic has had impacts in many areas, including travel and by extension on daily practice in tropical and travel medicine. The intercontinental travelers in decline have been replaced by a new population of travelers who previously did not require specific consultations. SARS-CoV-2 has earned its place in the pre-travel consultation in view of the medical and administrative implications. Furthermore, the global health effects of the pandemic are broader than its direct medical consequences and should not be underestimated. The increase in malaria mortality worldwide is just one example. Preventive measures prior to exposure are more important than ever.

Indubitablement, la pandémie de Covid-19 a eu des impacts dans de nombreux domaines, notamment les voyages, et par extension sur la pratique quotidienne en médecine tropicale et des voyages. Les voyageurs intercontinentaux en diminution ont été remplacés par une nouvelle population de voyageurs qui ne nécessitait pas jusqu'alors de consultations particulières. Le SARS-CoV-2 a gagné sa place dans la consultation prévoyage au vu des implications médicales et administratives. Par ailleurs, les effets de la pandémie sur la santé globale sont plus larges que ses conséquences médicales directes et ne devraient pas être sous-estimés. L'augmentation de la mortalité due à la malaria dans le monde n'en est qu'un exemple. Les mesures préventives avant exposition sont plus que jamais d'actualité.

[Tick-borne meningoencephalitis: situation in Switzerland and impact of the Covid pandemic]. / Méningo-encéphalite à tiques : situation en Suisse et impact de la pandémie de Covid-19.

The year 2020 witnessed a record number of reported cases of tick-borne encephalitis in Switzerland. This unprecedented rate of cases, largely explained by the decrease in travel outside of Switzerland as well as favorable conditions for outdoor activities, highlights this severe disease for which there is no treatment yet. Tick-borne ence-phalitis has been progressing in Switzerland for more than 30 years both geographically and in terms of the number of reported cases. Indeed, the outbreaks were localized in the North-East of Switzerland at the beginning of the 2000s until recently affecting the Valais and the Ticino. Vaccination is the most effective way to prevent the disease and thus the long-term sequelae that can be caused by this infection.

L'année 2020 a été témoin d'un record de cas déclarés de méningo-encéphalite à tiques en Suisse. Ce taux de cas encore jamais vu, en grande partie expliqué par la diminution des voyages en dehors de la Suisse ainsi que des conditions favorables à des activités en plein air, met en lumière cette maladie grave pour laquelle il n'existe pas encore de traitement. La méningo-encéphalite à tiques progresse en Suisse depuis plus de 30 ans autant géographiquement qu'au niveau du nombre de cas déclarés. En effet, les foyers étaient localisés au nord-est de la Suisse au début des années 2000 avant de toucher récemment le Valais et le Tessin. La vaccination est le moyen le plus efficace de prévenir la maladie ainsi que les séquelles à long terme pouvant être causées par cette infection.

[Parasite screening for immunosuppressed traveler]. / Dépistage parasitaire chez le voyageur immunosupprimé.

Before starting immunosuppressive therapy, it is important to screen for latent tuberculosis and, in case of particular exposures (e.g. travel, origin,…), for parasitosis such as amoebiasis, echinococcosis, strongyloidiasis and American trypanosomiasis. The Division of Tropical and Humanitarian Medicine of the Geneva University Hospitals has developed an algorithm to identify which screening is recommended according to exposure. Analysis of this practice shows that the most frequently detected latent disease is tuberculosis, followed by strongyloidiasis. For the latter, as the sensitivity of the serological test is reduced due to immunosuppression, the algorithm combine antibody testing with parasitological (Baermann and culture) and molecular (PCR) stool testing.

Avant le début d'un traitement immunosuppresseur, il est important d'effectuer un dépistage pour la tuberculose latente et, en cas d'expositions particulières (par exemple, voyage, origine…), de parasitoses comme l'amibiase, l'échinococcose, la strongyloïdiase et la trypanosomiase américaine. Le service de médecine tropicale et humanitaire des HUG a développé un algorithme pour identifier quel dépistage est recommandé en fonction de l'exposition. L'analyse de cette pratique montre que la maladie latente la plus fréquemment détectée est la tuberculose, suivie de la strongyloïdiase. Pour cette dernière, la sensibilité du test sérologique étant amoindrie à cause de l'immunosuppression, l'algorithme combine la recherche d'anticorps avec un test parasitologique (Baermann et culture) et moléculaire (PCR) des selles.

[Vaccine prevention in patients with rheumatic diseases]. / Prévention vaccinale chez les patients avec des maladies rhumatismales.

Patients with inflammatory rheumatologic diseases are at increased risk for infectious complications, including SARS-CoV-2, which represent one of the leading causes of death in this population. This risk is due to both the numerous comorbidities of this patient's group and the immunosuppressive therapies they receive. Vaccination reduces the incidence, complications, and mortality from infections. For patients receiving immunosuppressors, exacerbation of underlying diseases is rarely observed after immunization and only live-attenuated vaccines are contraindicated. A vaccination history and updated vaccination plan should be part of the clinical follow-up of patients with inflammatory rheumatism.

Les patients souffrant de maladies rhumatologiques inflammatoires sont plus à risque de complications infectieuses, y compris avec le SARS-CoV-2, qui représentent l'une des premières causes de mortalité dans cette population. Ce risque est attribuable à la fois aux nombreuses comorbidités de ces patients et aux thérapies immunosuppressives qu'ils reçoivent. La vaccination diminue l'incidence, les complications et la mortalité dues aux infections. Pour les patients recevant des immunosuppresseurs, une exacerbation significative des maladies sous-jacentes n'est qu'exception nellement observée après vaccination et seuls les vaccins vivants atténués sont en principe contre-indiqués. Une anamnèse vaccinale et une mise à jour du plan vaccinal doivent faire partie du suivi clinique de patients souffrant d'un rhumatisme inflammatoire.

A Practical Approach to Screening for Strongyloides stercoralis.

Strongyloides stercoralis, causative agent of a neglected tropical disease, is a soil-transmitted helminth which may cause lifelong persisting infection due to continuous autoinfection. In the case of immunosuppression, life-threatening hyperinfection and disseminated strongyloidiasis can develop. We propose a pragmatic screening algorithm for latent strongyloidiasis based on epidemiologic exposure and immunosuppression status that can be applied for any kind of immunosuppressive therapy. The algorithm allows the diagnosis of latent strongyloidiasis with optimal accuracy in a well-equipped setting, while for endemic settings where the complete testing array is unavailable, an empiric treatment is generally recommended. Accurate diagnosis and extensive empiric treatment will both contribute to decreasing the current neglect of strongyloidiasis.

Screening for Parasitic Infection and Tuberculosis in Immunosuppressed and Pre-Immunosuppressed Patients: An Observational Study.

Reactivation of latent tuberculosis infection (LTBI) or latent parasitic infection (LPI) during drug-induced immunosuppression can have serious consequences. The Division of tropical and humanitarian medicine of the Geneva University Hospitals runs a specific consultation for parasitic screening of immunosuppressed or pre-immunosuppressed patients. We sought to determine the seroprevalence of LTBI and LPI in such patients and explore its relationship with country of origin or previous travel in a retrospective, single-centre observational study from 2016 to 2019. Demographic data, travel history, ongoing treatments and results of the parasitological (Strongyloides stercoralis, Trypanosoma cruzi, Echinococcus multilocularis, Entamoeba histolytica and Leishmania spp.) and TB screening were collected to calculate LPI or LTBI prevalence. Risk factors for LTBI and strongyloidiasis were analysed using Poisson regression with robust variance. Among 406 eligible patients, 24/353 (6.8%) had LTBI, 8/368 (2.2%) were positive for Strongyloides stercoralis infection, 1/32 (3.1%) was positive for Entamoeba histolytica and 1/299 (0.3%) was positive for Leishmaniasis. No cases of Trypanosoma cruzi (0/274) or Echinococcus multilocularis (0/56) infection were detected. Previous travel to or originating from high-prevalence countries was a risk factor for LTBI (PR = 3.4, CI 95%: 1.4-8.2 and 4.0, CI 95%: 1.8-8.9, respectively). The prevalence of serological Strongyloidiasis in immunosuppressed patients is lower in comparison to those without immunosuppression (PR = 0.1, CI 95%: 0.01-0.8). In conclusion, screening before immunosuppression needs to be individualized, and LTBI and LPI need to be ruled out in patients who originate from or have travelled to high-prevalence countries. The sensitivity of strongyloidiasis serology is reduced following immunosuppression, so an algorithm combining different tests or presumptive treatment should be considered.

Feasibility and safety of rVSV-ZEBOV vaccination of humanitarian health workers against Ebola virus disease: an observational study.

BACKGROUND AND RATIONALE: Geneva University Hospitals were granted a temporary authorization to administer the recombinant live vesicular stomatitis virus rVSV-ZEBOV (Ervebo®) vaccine to expatriate humanitarian frontline workers (FLWs) prior to mission deployment. OBJECTIVES: Our aims were to assess the feasibility of FLW vaccination before deployment and to report adverse events (AEs). METHODS: FLWs received a single injection of rVSV-ZEBOV (>7.2E7 plaque forming unit) during their pre-deployment medical check-up at the Travel Medicine Clinic of the Geneva University Hospitals (Day 0). A safety questionnaire regarding potential AEs was emailed to FLWs on Days 3 and 21. Early and delayed AEs were those starting within 3 or 21 days of vaccination, respectively. RESULTS: Between 1 August 2019 and 30 June 2020, 124 FLWs received the rVSV-ZEBOV vaccine. Eighty-six volunteers (86/124; 69%) received a concomitant vaccine. The response rate to the follow-up questionnaire was 88 and 55% at Days 3 and 21, respectively. Most respondents (105/109; 96.3%), experienced at least one AE, with a mean of three (±SD 1.75) AEs per person. The most common AE was injection site pain, followed by fever (53/109; 48.6%), fatigue (51/109; 46.7%) and myalgia (49/109; 44.9%). Most early AEs (360/377; 95.4%) resolved within 3 days, reflecting vaccine reactogenicity. Delayed AEs were reported by 6/69 (7.2%) subjects, the median time to symptom onset was 11 days (range: 5-14); half of them were joint-related AEs (3/6). Four serious adverse events (SAE) were observed: two cases of high grade fever, one rash and one case of arthritis. Two suspected unexpected serious adverse reactions were observed: one case of continuing recurrent transient dizziness and fatigue considered related to the vaccine; and one case of presbyopia that was deemed unrelated. CONCLUSION: AEs to rVSV-ZEBOV were common but in general transient and were well tolerated, pre-deployment rVSV-ZEBOV vaccination in FLW is feasible and can be included with pre-mission check-up.

Rabies vaccination and multiple sclerosis relapse: A retrospective cohort study.

BACKGROUND: No studies assessing rabies vaccine (RV) tolerability in persons with multiple sclerosis (MS) have been conducted. Given the lack of safety data, RV is recommended essentially only for post-exposure prophylaxis, which is difficult to administer effectively in many rabies-endemic countries. We sought to determine whether RV administration as pre-exposure prophylaxis was associated with MS relapse. METHODS: This retrospective cohort study compared the clinical courses of MS patients in the year before and after rabies vaccination. The year before vaccination was defined as the pre-exposure risk period, the three months thereafter as the exposure-risk period, and the following nine months as the post-risk period. All adult MS patients immunized with RV between 2014 and 2018 and with available medical records in the two-year window were included. The primary outcome was the incidence of symptomatic MS relapse in the exposure-risk period versus the pre-exposure period. RESULTS: Fifty-five patients received at least one dose of RV. Most (38/55, 69%) were female; mean age was 38.5 years (SD ±9.2). While 21 (38%) patients experienced 24 relapses in the year before vaccination, only three (5%) experienced one relapse each in the post-vaccination exposure-risk period; three others (5%) experienced a total of four relapses in the subsequent post-risk period. The annualized relapse rates in the pre-exposure, exposure-risk, and post-risk periods were 0.44, 0.22, and 0.10, respectively (rate ratio for exposure-risk to pre-exposure periods, 0.509 [95% CI 0.098-1.677]). CONCLUSIONS: In this cohort, rabies vaccination was not associated with clinical MS relapse. Larger, prospective studies are needed to confirm these results.

Epidemiological and Clinical Characteristics of International Travelers with Enteric Fever and Antibiotic Resistance Profiles of Their Isolates: a GeoSentinel Analysis.

Enteric fever, caused by Salmonella enterica serovar Typhi (S Typhi) and S. enterica serovar Paratyphi (S Paratyphi), is a common travel-related illness. Limited data are available on the antimicrobial resistance (AMR) patterns of these serovars among travelers. Records of travelers with a culture-confirmed diagnosis seen during or after travel from January 2007 to December 2018 were obtained from GeoSentinel. Traveler demographics and antimicrobial susceptibility data were analyzed. Isolates were classified as nonsusceptible if intermediate or resistant or as susceptible in accordance with the participating site's national guidelines. A total of 889 travelers (S Typhi infections, n = 474; S Paratyphi infections, n = 414; coinfection, n = 1) were included; 114 (13%) were children of <18 years old. Most individuals (41%) traveled to visit friends and relatives (VFRs) and acquired the infection in South Asia (71%). Child travelers with S Typhi infection were most frequently VFRs (77%). The median trip duration was 31 days (interquartile range, 18 to 61 days), and 448 of 691 travelers (65%) had no pretravel consultation. Of 143 S Typhi and 75 S Paratyphi isolates for which there were susceptibility data, nonsusceptibility to antibiotics varied (fluoroquinolones, 65% and 56%, respectively; co-trimoxazole, 13% and 0%; macrolides, 8% and 16%). Two S Typhi isolates (1.5%) from India were nonsusceptible to third-generation cephalosporins. S Typhi fluoroquinolone nonsusceptibility was highest when infection was acquired in South Asia (70 of 90 isolates; 78%) and sub-Saharan Africa (6 of 10 isolates; 60%). Enteric fever is an important travel-associated illness complicated by AMR. Our data contribute to a better understanding of region-specific AMR, helping to inform empirical treatment options. Prevention measures need to focus on high-risk travelers including VFRs and children.

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.

Risk of MS relapse after yellow fever vaccination: A self-controlled case series.

OBJECTIVE: To determine whether live-attenuated yellow fever vaccine (YFV) was associated with MS relapse, we evaluated the clinical courses of 23 patients in the year before and the year after immunization at the university hospital of Geneva, Switzerland. METHODS: This self-controlled retrospective cohort included adult patients with MS receiving YFV between 2014 and 2018 and defined the year before vaccination, the 3 months thereafter, and the 9 months following as the pre-exposure (PEP), exposure-risk (ERP), and postrisk (PRP) periods, respectively. The primary outcome was the relative incidence of relapse in the ERP vs the PEP. Secondary end points included the presence of new T2-weighted (T2) or T1-weighted gadolinium-positive (T1Gd+) MRI lesions. RESULTS: Of 23 patients with MS receiving YFV (20 relapsing MS and 3 primary progressive MS), 17 (74%) were women; mean age was 34 years (SD ±10); and 10 of 23 (40%) were treated with disease-modifying therapies (DMTs). Although 9 patients experienced 12 relapses in the PEP, only one experienced a relapse in the ERP; 3 other patients experienced one relapse each in the PRP. None of the 8 patients receiving natalizumab at the time of vaccination experienced relapse thereafter. In the PEP, ERP, and PRP, 18, 2, and 9 patients had new brain and/or spinal cord lesions on T2 or T1Gd + MRI, respectively. CONCLUSIONS: In this cohort, YF vaccination was associated with neither an increase in MS relapse nor emergence of brain and/or spinal lesions. Further studies are warranted to confirm these findings. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for persons with MS, YFV may not increase relapse risk.