A SARS-CoV-2 Omicron outbreak among crew members on a cruise ship in Germany in early 2022.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreaks on cruise ships have rarely been investigated. In early 2022, we were informed about a SARS-CoV-2 outbreak on a cruise ship calling Port of Hamburg after 10 infections among crew members were detected. We conducted an outbreak investigation in collaboration between ship owners, the ship physician and Hamburg's Institute for Hygiene and Environment, to identify risk factors and to achieve containment. The aim was to identify risk factors for SARS-CoV-2 infection and SARS-CoV-2 variants in a cohort of 165 crew members. MATERIALS AND METHODS: For this purpose, we collected data on age, sex, nationality, boarding-time, cabin use (single/shared), work place, and vaccination status of the study participants. Cases were defined as individuals who tested SARS-CoV-2 positive at least once in daily screenings during the outbreak period (10 days) by polymerase chain reaction or antigen test. We investigated risk factors for infection by descriptive, univariable and multivariable analysis. We performed whole genome sequencing to identify SARS-CoV-2 variants. RESULTS: We verified 103 SARS-CoV-2 positive cases (attack rate [AR] 62.4%); 39/41 sequenced samples were BA.2.3 Omicron subtype, one BA.1 and one BA.1.1. Among boostered crew members, AR was 38% vs. 65% among those vaccinated once or twice. Among those who stayed < 30 days on board, AR was 31% vs. 72% among those staying on board longer. Among Europeans, the AR was 53% vs. 71% in non- -Europeans. Adjusting for age and sex, cases were more likely to have received no booster vaccine (odds ratio [OR]: 2.66, 95% confidence interval [CI]: 0.99-7.13), to have spent more time on board (≥ 30 days, OR: 6.36, 95% CI: 2.81-14.40 vs. < 30 days) and to have a non-European nationality (OR: 2.14, 95% CI: 1.08-4.27). The outbreak stopped shortly after offboard isolation of cases. CONCLUSIONS: This investigation confirms the importance of a booster vaccine against COVID-19. Longer stays onboard could facilitate social mixing. Further studies could investigate the impact of social, cultural/ behavioural patterns and public health access on the infection risk. Physical distancing together with screening and isolation can contain SARS-CoV-2 outbreaks on cruise ships.

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.

Rabies post-exposure prophylaxis of international travellers - Results from two major German travel clinics.

BACKGROUND: Travel to regions with rabies risk has increased. However, data on adequate rabies post exposure prophylaxis (PEP) abroad is scarce. The aim of this study was to assess the appropriateness of medical management following suspected rabies exposure (SRE) in international travellers. METHOD: A cross-sectional questionnaire-based study in returning travellers with reported SRE who sought post-exposure medical care was conducted in two large German travel clinics. RESULTS: The 75 included SRE cases had a median age of 34 years (range 26-43) and showed a female predominance (59%, 44/75). Most participants returned from Asia (47%, 34/72). About 28% had received pre-exposure prophylaxis (PrEP, ≥2 vaccine doses) (20/71). In 51% the animal was actively approached (34/67). All patients had category II/III exposure according to the World Health Organization (65% category III, 49/75). With 78% (52/67), most patients cleaned the wound after SRE; 36% (24/67) used water and soap. Only 57% (41/72) of participants sought medical care during their trip. Overall, 45% (33/74) received rabies vaccination abroad which corresponds to 80% out of those who sought healthcare (33/41). CONCLUSIONS: Awareness for appropriate first aid and the urgency of seeking timely professional treatment including PEP after an SRE seems to be insufficient in German travellers. Travel practitioners need to educate travellers about rabies risk, prevention measures and the correct behaviour after SRE including adequate wound treatment and seeking immediate medical help for PEP. PrEP should be offered generously especially to travellers with high rabies-exposure risk and those visiting areas with limited healthcare access.

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.

Performance of a rapid immuno-chromatographic test (Schistosoma ICT IgG-IgM) for detecting Schistosoma-specific antibodies in sera of endemic and non-endemic populations.

BACKGROUND: Schistosomiasis, an acute and chronic parasitic disease caused by human pathogenic Schistosoma species, is a neglected tropical disease affecting more than 220 million people worldwide. For diagnosis of schistosomiasis, stool and urine microscopy for egg detection is still the recommended method, however sensitivity of these methods is limited. Therefore, other methods like molecular detection of DNA in stool, detection of circulating cathodic antigen in urine or circulating anodic antigen in urine and serum, as well as serological tests have gained more attention. This study examines the sensitivity and specificity of a rapid diagnostic test based on immunochromatography (Schistosoma ICT IgG-IgM, LD Bio, Lyon, France) for simultaneous detection of specific IgG and IgM antibodies in serum, against Schistosoma spp. in endemic and non-endemic populations. METHODOLOGY/PRINCIPAL FINDINGS: Frozen banked serum samples from patients with confirmed schistosomiasis, patients with other helminth infections, patients with seropositive rheumatoid arthritis and healthy blood donors were used to assess the sensitivity and the specificity of the Schistosoma ICT IgG-IgM rapid diagnostic test. The test showed a sensitivity of 100% in patients with parasitologically confirmed schistosomiasis, irrespective of the species (S. mansoni, S. haematobium, S. japonicum, S. mekongi). In healthy blood donors and patients with rheumatoid factor positive rheumatoid arthritis from Europe, specificity was 100%. However, in serum samples of patients with other tissue invasive helminth infections, the test showed some cross-reactivity, resulting in a specificity of 85%. CONCLUSION/SIGNIFICANCE: With its high sensitivity, the Schistosoma ICT IgG-IgM rapid diagnostic test is a suitable screening test for detection of Schistosoma specific antibodies, including S. mekongi. However, in populations with a high prevalence of co-infection with other tissue invasive helminths, positive results should be confirmed with other diagnostic assays due to the test's imperfect specificity.

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.

Comparing susceptibility and contagiousness in concurrent outbreaks with a non-VOC and the VOC SARS-CoV-2 variant B.1.1.7 in daycare centers in Hamburg, Germany.

We describe two outbreaks of SARS-CoV-2 in daycare centers in the metropolitan area of Hamburg, Germany. The outbreaks occurred in rapid chronological succession, in neighborhoods with a very similar sociodemographic structure, thus allowing for cross-comparison of these events. We combined classical and molecular epidemiologic investigation methods to study infection entry, spread within the facilities, and subsequent transmission of infections to households. Epidemiologic and molecular evidence suggests a superspreading event with a non-variant of concern (non-VOC) SARS CoV-2 strain at the root of the first outbreak. The second outbreak involved two childcare facilities experiencing infection activity with the variant of concern (VOC) B.1.1.7 (Alpha). We show that the index cases in all outbreaks had been childcare workers, and that children contributed substantially to secondary transmission of SARS-CoV-2 infection from childcare facilities to households. The frequency of secondary transmissions in households originating from B.1.1.7-infected children was increased compared to children with non-VOC infections. Self-reported symptoms, particularly cough and rhinitis, occurred more frequently in B.1.1.7-infected children. Especially in light of the rapidly spreading VOC B.1.617.2 (Delta), our data underline the notion that rigorous SARS-CoV-2 testing in combination with screening of contacts regardless of symptoms is an important measure to prevent SARS-CoV-2 infection of unvaccinated individuals in daycare centers and associated households.

Considerations for patients with psoriasis travelling under immunosuppression.

With the establishment of modern systemic therapies for psoriasis, comprehensive consultation is required for travelling with immune modulation. Logistic aspects regarding transport and storage, climatic peculiarities of the country of travel and drug dependent risks regarding infections must be considered. Vaccinations and preventive measures are emphasized. Depending on the current national recommendations, special features of vaccinations while under immunosuppression must be taken into account.

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.

Rabies exposure in travellers to Asia, the Middle East, Africa, South and Central America-a German Airport study.

BACKGROUND: Rabies causes thousands of deaths worldwide and trips to rabies endemic countries are popular. Travellers are often uncertain whether pre-exposure prophylaxis (PrEP) is advisable since they find it difficult to estimate the exposure risk during travel and the availability of post-exposure prophylaxis in endemic regions. The aim of this study was to determine the potential rabies exposures in travellers and to assess their knowledge on rabies. Secondly, we explored the access to appropriate post-exposure medical care in respective countries. METHODS: We conducted a cross-sectional study at Frankfurt Airport. Returning adult travellers arriving from Asia, the Middle East, Africa, South and Central America were invited to participate in this questionnaire-based study while waiting in the baggage claim area. RESULTS: Over a one-month recruitment phase in March 2019, we enrolled 3066 travellers; 2929 were included in the analysis. The gender ratio was balanced; the median age was 42 years (range 18-83 years). Participants arrived from Asia (46%), Africa (29%), Central/South America (13%), the Middle East (8%) and the Caribbean (8%). Forty-five per cent sought pretravel advice and 22% received ≥2 injections of rabies PrEP. Travellers with pretravel advice from tropical medicine specialists reached significantly higher knowledge scores than others. We found that potential rabies exposure occurred in 2.0% (57/2915) of travellers with 31% (13/42) of the contacts being unprovoked; 19% (8/42) of the exposed sought medical care and 3/8 were adequately treated before returning to Germany. Risk factors for animal exposure were: male sex, young age, trips to Asia and a long stay abroad (>4 weeks). CONCLUSIONS: A total of 2% of returning travellers (n = 2915) experienced a potential rabies exposure during their journey. A majority of the exposed individuals did not seek medical care; those seeking medical care were often treated inadequately. Rabies information must be emphasised during pretravel counselling and PrEP should be offered generously, especially to travellers with high exposure risks.

Imported Malaria in Countries where Malaria Is Not Endemic: a Comparison of Semi-immune and Nonimmune Travelers.

The continuous increase in long-distance travel and recent large migratory movements have changed the epidemiological characteristics of imported malaria in countries where malaria is not endemic (here termed non-malaria-endemic countries). While malaria was primarily imported to nonendemic countries by returning travelers, the proportion of immigrants from malaria-endemic regions and travelers visiting friends and relatives (VFRs) in malaria-endemic countries has continued to increase. VFRs and immigrants from malaria-endemic countries now make up the majority of malaria patients in many nonendemic countries. Importantly, this group is characterized by various degrees of semi-immunity to malaria, resulting from repeated exposure to infection and a gradual decline of protection as a result of prolonged residence in non-malaria-endemic regions. Most studies indicate an effect of naturally acquired immunity in VFRs, leading to differences in the parasitological features, clinical manifestation, and odds for severe malaria and clinical complications between immune VFRs and nonimmune returning travelers. There are no valid data indicating evidence for differing algorithms for chemoprophylaxis or antimalarial treatment in semi-immune versus nonimmune malaria patients. So far, no robust biomarkers exist that properly reflect anti-parasite or clinical immunity. Until they are found, researchers should rigorously stratify their study results using surrogate markers, such as duration of time spent outside a malaria-endemic country.

Vaccination in Patients with Inflammatory Bowel Diseases.

During the course of disease, a majority of inflammatory bowel disease (IBD) patients requires long-term immunosuppressive therapy with either immunomodulatory agents, biologics, or newer immunosuppressive therapies such as Vedolizumab, a selective α4ß7 inhibitor, Ustekinumab, an IL 12/23 p40 inhibitor, or the Janus kinase inhibitor Tofacitinib. Due to this, they are at increased risk for infectious diseases, many of which are possible to prevent by vaccination. This review focuses on recommended vaccinations in IBD patients and stresses special issues which have to be paid attention to. The aim of the review is to increase gastroenterologists' awareness of the importance of vaccination and to stress why especially the gastroenterologist should assess the vaccination status of the patient and initiate vaccination as soon as diagnosis is established.

Safety and immunogenicity of tetanus/diphtheria vaccination in patients with rheumatic diseases-a prospective multi-centre cohort study.

OBJECTIVES: We aimed to assess the safety and immunogenicity of a diphtheria/tetanus vaccine booster dose in three different patient groups with rheumatic diseases on a variety of immunosuppressive/immunomodulatory medications compared with healthy controls (HCs). METHODS: We conducted a multi-centre prospective cohort study in Switzerland. We enrolled patients with RA, axial SpA/PsA, vasculitis (Behçet's disease, ANCA-associated vasculitis) and HCs. Diphtheria/tetanus vaccination was administered according to the Swiss vaccination recommendations. Blood samples were drawn before vaccination, and 1 month and 3 months afterwards. Antibody concentrations against vaccine antigens were measured by ELISA. Immunogenicity was compared between patient and medication groups. A mixed model was applied for multivariate analysis. Missing data were dealt with using multiple imputation. RESULTS: Between January 2014 and December 2015, we enrolled 284 patients with rheumatic diseases (131 RA, 114 SpA/PsA, 39 vasculitis) and 253 HCs. Of the patients, 89% were on immunosuppressive/immunomodulatory medication. Three months post-vaccination 100% of HCs vs 98% of patients were protected against tetanus and 84% vs 73% against diphtheria. HCs and SpA/PsA patients had significantly higher responses than RA and vasculitis patients. Assessing underlying diseases and medications in a multivariate model, rituximab was the only factor negatively influencing tetanus immunogenicity, whereas only MTX treatment had a negative influence on diphtheria antibody responses. No vaccine-related serious adverse events were recorded. CONCLUSION: Diphtheria/tetanus booster vaccination was safe. Tetanus vaccination was immunogenic; the diphtheria component was less immunogenic. Vaccine responses were blunted by rituximab and MTX. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, Identifier: NCT01947465.