Detection of active SARS-CoV-2 in cough aerosols from COVID-19 patients.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an airborne pathogen, but detection of infectious SARS-CoV-2 in air and in particular the introduction of the virus into the environment by different human expiratory manoeuvres is not well studied. OBJECTIVES: The aim of this study was to investigate the presence of SARS-CoV-2 in cough from coronavirus disease of 2019 (COVID-19) in-patients and to study contamination of the virus in the patient's environment. METHODS: Detection of SARS-CoV-2 in cough was analyzed by PCR, culture and imaging. Detection in cough was compared to presence of the virus in air and on surfaces from patient rooms. RESULTS: Twenty-five patients in 21 rooms were included in the study. SARS-CoV-2 RNA was found in cough aerosols from 16 out of 22 patients that produced voluntary cough. As demonstrated by plaque-forming unit assays, active virus was isolated from 11 of these 16 patients. Using mainly molecular detection, the virus was also found in air, on high-contact surfaces, and no-touch surfaces from the room of the COVID-19 patients. CONCLUSIONS: These results show that infectious SARS-CoV-2 circulating in air can originate from patient cough and should be considered against the risk of acquiring COVID-19 through inhalation.

Epidemiology of Travel-Associated Dengue from 2007 to 2022: A GeoSentinel Analysis.

BACKGROUND: Dengue is a leading cause of febrile illness among international travellers. We aimed to describe the epidemiology and clinical characteristics of imported dengue in returning travellers evaluated at GeoSentinel sites from 2007-2022. METHODS: We retrieved GeoSentinel records of dengue among travellers residing in non-endemic countries. We considered dengue confirmed when diagnosed by a positive DENV-specific RT-PCR, positive NS-1 antigen, and/or anti-DENV IgG seroconversion, and probable when diagnosed by single anti-DENV IgM or high titre anti-DENV IgG detection. Severe dengue was defined as evidence of clinically significant plasma leakage or bleeding, organ failure, or shock, according to the 2009 WHO guidance. Complicated dengue was defined as either severe dengue or dengue with presence of any warning sign. Analyses were descriptive. RESULTS: This analysis included 5958 travellers with confirmed (n = 4859; 81.6%) or probable (n = 1099; 18.4%) dengue. The median age was 33 years (range: < 1-91); 3007 (50.5%) travellers were female. The median travel duration was 21 days (interquartile range [IQR]: 15-32). The median time between illness onset and GeoSentinel site visit was 7 days (IQR: 4-15). The most frequent reasons for travel were tourism (67.3%), visiting friends or relatives (12.2%), and business (11.0%). The most frequent regions of acquisition were Southeast Asia (50.4%), South-Central Asia (14.9%), the Caribbean (10.9%), and South America (9.2%). Ninety-five (1.6%) travellers had complicated dengue, of whom 27 (0.5%) had severe dengue, and one died. Of 2710 travellers with data available, 724 (26.7%) were hospitalized. The largest number of cases (n = 835) was reported in 2019. CONCLUSIONS: A broad range of international travellers should be aware of the risk of acquiring dengue and receive appropriate pretravel counselling regarding preventive measures. Prospective cohort studies are needed to further elucidate dengue risk by destination and over time, as well as severe outcomes and prolonged morbidity (long-dengue) due to travel-related dengue.

Intestinal protozoa in returning travellers: a GeoSentinel analysis from 2007 to 2019.

BACKGROUND: Prolonged diarrhoea is common amongst returning travellers and is often caused by intestinal protozoa. However, the epidemiology of travel-associated illness caused by protozoal pathogens is not well described. METHODS: We analysed records of returning international travellers with illness caused by Giardia duodenalis, Cryptosporidium spp., Cyclospora cayetanensis or Cystoisospora belli, reported to the GeoSentinel Network during January 2007-December 2019. We excluded records of travellers migrating, with an unascertainable exposure country, or from GeoSentinel sites that were not located in high-income countries. RESULTS: There were 2517 cases, 82.3% giardiasis (n = 2072), 11.4% cryptosporidiosis (n = 287), 6.0% cyclosporiasis (n = 150) and 0.3% cystoisosporiasis (n = 8). Overall, most travellers were tourists (64.4%) on long trips (median durations: 18-30 days). Cryptosporidiosis more frequently affected people < 18 years (13.9%) and cyclosporiasis affected people ≥ 40 years (59.4%). Giardiasis was most frequently acquired in South Central Asia (45.8%) and sub-Saharan Africa (22.6%), cryptosporidiosis in sub-Saharan Africa (24.7%) and South-Central Asia (19.5%), cyclosporiasis in South East Asia (31.3%) and Central America (27.3%), and cystoisosporiasis in sub-Saharan Africa (62.5%). Cyclosporiasis cases were reported from countries of uncertain endemicity (e.g. Cambodia) or in countries with no previous evidence of this parasite (e.g. French Guiana). The time from symptom onset to presentation at a GeoSentinel site was the longest amongst travellers with giardiasis (median: 30 days). Over 14% of travellers with cryptosporidiosis were hospitalized. CONCLUSIONS: This analysis provides new insights into the epidemiology and clinical significance of four intestinal protozoa that can cause morbidity in international travellers. These data might help optimize pretravel advice and post-travel management of patients with travel-associated prolonged gastrointestinal illnesses. This analysis reinforces the importance of international travel-related surveillance to identify sentinel cases and areas where protozoal infections might be undetected or underreported.

Anakinra or tocilizumab in patients admitted to hospital with severe covid-19 at high risk of deterioration (IMMCoVA): A randomized, controlled, open-label trial.

BACKGROUND: Anakinra and tocilizumab are used for severe Covid-19, but only one previous randomized controlled trial (RCT) has studied both. We performed a multi-center RCT comparing anakinra or tocilizumab versus usual care (UC) for adults at high risk of deterioration. METHODS: The study was conducted June 2020 to March 2021. Eligibility required ≥ 5 liters/minute of Oxygen to maintain peripheral oxygen saturation at ≥ 93%, CRP > 70 mg/L, ferritin > 500 µg/L and at least two points where one point was awarded for lymphocytes < 1x 109/L; D-dimer ≥ 0.5 mg/L and; lactate dehydrogenase ≥ 8 microkatal/L. Patients were randomly assigned 1:1:1 to receive either a single dose of tocilizumab (8 mg/kg) or anakinra 100 mg IV QID for seven days or UC alone. The primary outcome was time to recovery. RESULTS: Recruitment was ended prematurely when tocilizumab became part of usual care. Out of a planned 195 patients, 77 had been randomized, 27 to UC, 28 to anakinra and 22 to tocilizumab. Median time to recovery was 15, 15 and 11 days. Rate ratio for recovery for UC vs anakinra was 0.91, 0.47 to 1.78, 95% [CI], p = 0.8 and for UC vs tocilizumab 1.13, 0.55 to 2.30; p = 0.7. There were non-significant trends favoring tocilizumab (and to limited degree anakinra) vs UC for some secondary outcomes. Safety profiles did not differ significantly. CONCLUSION: Premature closure of trial precludes firm conclusions. Anakinra or tocilizumab did not significantly shorten time to clinical recovery compared to usual care. (IMMCoVA, NCT04412291, EudraCT: 2020-00174824).

Clinical presentation and diagnosis of imported strongyloidiasis at a tertiary hospital, Stockholm, Sweden.

BACKGROUND: Since Strongyloides can persist in its host for decades, and cause life threatening infections data on prevalence, the burden and risk factors for infection is crucial in migrant populations. METHODS: In this observational retrospective cohort study, we describe the epidemiological, clinical, and microbiological characteristics of imported strongyloidiasis diagnosed at the Karolinska University Hospital, Stockholm, Sweden, during 2010-2021. RESULTS: We identified 98 individuals with strongyloidiasis, 89 (90.8%) born in endemic and 9 (9.2%) in non-endemic countries. Sub-Saharan Africa was the most common origin among the group born in endemic countries (62, 69.7%), (p < 0.005). There were 22 individuals with an underlying immunosuppressive condition. Gastrointestinal symptoms (53/98, 54.1%) were the symptoms most frequently described, and were more frequent in adults (57.0%) vs children (0%) (p = 0.013). Eosinophilia was detected in 74 (75.5%), being more frequent in the endemic-borne group (79.8% vs 33.3%, p = 0.002). Eight persons developed complications of strongyloidiasis because of either hyperinfection or disseminated disease. No people living with HIV with CD4 <500/mm3 (n = 6) developed severe strongyloidiasis. CONCLUSION: A limited number of strongyloidiasis cases was identified, with few complicated cases in immunosuppressed patients. Further studies focusing on identifying and exploring the risk of complicated strongyloidiasis in immunosuppressed patients are needed.

Comprehensive proteomics and meta-analysis of COVID-19 host response.

COVID-19 is characterised by systemic immunological perturbations in the human body, which can lead to multi-organ damage. Many of these processes are considered to be mediated by the blood. Therefore, to better understand the systemic host response to SARS-CoV-2 infection, we performed systematic analyses of the circulating, soluble proteins in the blood through global proteomics by mass-spectrometry (MS) proteomics. Here, we show that a large part of the soluble blood proteome is altered in COVID-19, among them elevated levels of interferon-induced and proteasomal proteins. Some proteins that have alternating levels in human cells after a SARS-CoV-2 infection in vitro and in different organs of COVID-19 patients are deregulated in the blood, suggesting shared infection-related changes.The availability of different public proteomic resources on soluble blood proteome alterations leaves uncertainty about the change of a given protein during COVID-19. Hence, we performed a systematic review and meta-analysis of MS global proteomics studies of soluble blood proteomes, including up to 1706 individuals (1039 COVID-19 patients), to provide concluding estimates for the alteration of 1517 soluble blood proteins in COVID-19. Finally, based on the meta-analysis we developed CoViMAPP, an open-access resource for effect sizes of alterations and diagnostic potential of soluble blood proteins in COVID-19, which is publicly available for the research, clinical, and academic community.

Impact, healthcare utilization and costs of travel-associated mosquito-borne diseases in international travellers: a prospective study.

BACKGROUND: International travellers frequently acquire infectious diseases whilst travelling, yet relatively little is known about the impact and economic burden of these illnesses on travellers. We conducted a prospective exploratory costing study on adult returning travellers with falciparum malaria, dengue, chikungunya or Zika virus. METHODS: Patients were recruited in eight Travel and Tropical Medicine clinics between June 2016 and March 2020 upon travellers' first contact with the health system in their country of residence. The patients were presented with a structured 52-question self-administered questionnaire after full recovery to collect information on patients' healthcare utilization and out-of-pocket costs both in the destination and home country, and about income and other financial losses due to the illness. RESULTS: A total of 134 patients participated in the study (malaria, 66; dengue, 51; chikungunya, 8; Zika virus, 9; all fully recovered; median age 40; range 18-72 years). Prior to travelling, 42% of patients reported procuring medical evacuation insurance. Across the four illnesses, only 7% of patients were hospitalized abroad compared with 61% at home. Similarly, 15% sought ambulatory services whilst abroad compared with 61% at home. The average direct out-of-pocket hospitalization cost in the destination country (USD $2236; range: $108-$5160) was higher than the direct out-of-pocket ambulatory cost in the destination country (USD $327; range: $0-$1560), the direct out-of-pocket hospitalization cost at home (USD $35; range: $0-$120) and the direct out-of-pocket ambulatory costs at home (US$45; range: $0-$192). Respondents with dengue or malaria lost a median of USD $570 (Interquartile range [IQR] 240-1140) and USD $240 (IQR 0-600), respectively, due to their illness, whilst those with chikungunya and Zika virus lost a median of USD $2400 (IQR 1200-3600) and USD $1500 (IQR 510-2625), respectively. CONCLUSION: Travellers often incur significant costs due to travel-acquired diseases. Further research into the economic impact of these diseases on travellers should be conducted.

Travel demographics, patterns, and plans among adult Nordic travelers.

Background: Despite the high frequency of international travel from Nordic countries annually, data describing demographics, patterns, and plans of travel among Nordic inhabitants are scarce. Methods: In 2018, an online questionnaire covering travel patterns, plans, and knowledge about travel-related diseases was sent to Nordic inhabitants 18-74 years of age. At-risk travelers were defined as those who had traveled outside Europe and North America during the previous 2 years. Results: Of the 5407 respondents included, 4371 (80.8%) had traveled abroad within the past 2 years. Among the respondents, 37.0% (n = 1999) were at-risk travelers. The most frequent travel destinations were Europe (n = 3907, 89.4%) and Asia (n = 1019, 23.3%). Russia/Eurasia was a more common destination for Finnish travelers than the other travelers (10.6% vs 2.3-4.1%). Most at-risk travelers had traveled for leisure/tourism (n = 1329, 66.5%). Visiting friends and relatives was more frequent among Norwegian and Swedish travelers (n = 105, 22.0% and n = 98, 19.4%, respectively) than Finnish travelers (n = 74, 12.7%). The elderly traveled often and made up 21.4% of at-risk travelers. Conclusions: Travel demographics, destinations, and future travel plans were similar across the Nordic countries. More than one third had traveled outside Europe/North America. One third were either elderly or visiting friends or relatives.

Healthcare seeking during travel: an analysis by the GeoSentinel surveillance network of travel medicine providers.

BACKGROUND: International travellers may seek care abroad to address health problems that arise during their trip or plan healthcare outside their country of residence as medical tourists. METHODS: Data were collected on travellers evaluated at GeoSentinel Network sites who reported healthcare during travel. Both unplanned and planned healthcare were analysed, including the reason and nature of healthcare sought, characteristics of the treatment provided and outcomes. Travellers that presented for rabies post-exposure prophylaxis were described elsewhere and were excluded from detailed analysis. RESULTS: From May 2017 through June 2020, after excluding travellers obtaining rabies post-exposure prophylaxis (n= 415), 1093 travellers reported care for a medical or dental issue that was an unanticipated part of the travellers' planned itinerary (unplanned healthcare). Travellers who sought unplanned healthcare abroad had frequent diagnoses of acute diarrhoea, dengue, falciparum malaria and unspecified viral syndrome, and obtained care in 131 countries. Thirty-four (3%) reported subsequent deterioration and 230 (21%) reported no change in condition; a third (n = 405; 37%) had a pre-travel health encounter. Forty-one travellers had sufficient data on planned healthcare abroad for analysis. The most common destinations were the US, France, Dominican Republic, Belgium and Mexico. The top reasons for their planned healthcare abroad were unavailability of procedure at home (n = 9; 19%), expertise abroad (n = 9; 19%), lower cost (n = 8; 17%) and convenience (n = 7; 15%); a third (n = 13; 32%) reported cosmetic or surgical procedures. Early and late complications occurred in 14 (33%) and 4 (10%) travellers, respectively. Four travellers (10%) had a pre-travel health encounter. CONCLUSIONS: International travellers encounter health problems during travel that often could be prevented by pre-travel consultation. Travellers obtaining planned healthcare abroad can experience negative health consequences associated with treatments abroad, for which pre-travel consultations could provide advice and potentially help to prevent complications.

Dengue outbreak amongst travellers returning from Cuba-GeoSentinel surveillance network, January-September 2022.

Increasing numbers of travellers returning from Cuba with dengue virus infection were reported to the GeoSentinel Network from June to September 2022, reflecting an ongoing local outbreak. This report demonstrates the importance of travellers as sentinels of arboviral outbreaks and highlights the need for early identification of travel-related dengue.

Epidemiological and clinical characteristics of patients with monkeypox in the GeoSentinel Network: a cross-sectional study.

BACKGROUND: The early epidemiology of the 2022 monkeypox epidemic in non-endemic countries differs substantially from the epidemiology previously reported from endemic countries. We aimed to describe the epidemiological and clinical characteristics among individuals with confirmed cases of monkeypox infection. METHODS: We descriptively analysed data for patients with confirmed monkeypox who were included in the GeoSentinel global clinical-care-based surveillance system between May 1 and July 1 2022, across 71 clinical sites in 29 countries. Data collected included demographics, travel history including mass gathering attendance, smallpox vaccination history, social history, sexual history, monkeypox exposure history, medical history, clinical presentation, physical examination, testing results, treatment, and outcomes. We did descriptive analyses of epidemiology and subanalyses of patients with and without HIV, patients with CD4 counts of less than 500 cells per mm3 or 500 cells per mm3 and higher, patients with one sexual partner or ten or more sexual partners, and patients with or without a previous smallpox vaccination. FINDINGS: 226 cases were reported at 18 sites in 15 countries. Of 211 men for whom data were available, 208 (99%) were gay, bisexual, or men who have sex with men (MSM) with a median age of 37 years (range 18-68; IQR 32-43). Of 209 patients for whom HIV status was known, 92 (44%) men had HIV infection with a median CD4 count of 713 cells per mm3 (range 36-1659; IQR 500-885). Of 219 patients for whom data were available, 216 (99%) reported sexual or close intimate contact in the 21 days before symptom onset; MSM reported a median of three partners (IQR 1-8). Of 195 patients for whom data were available, 78 (40%) reported close contact with someone who had confirmed monkeypox. Overall, 30 (13%) of 226 patients were admitted to hospital; 16 (53%) of whom had severe illness, defined as hospital admission for clinical care rather than infection control. No deaths were reported. Compared with patients without HIV, patients with HIV were more likely to have diarrhoea (p=0·002), perianal rash or lesions (p=0·03), and a higher rash burden (median rash burden score 9 [IQR 6-21] for patients with HIV vs median rash burden score 6 [IQR 3-14] for patients without HIV; p<0·0001), but no differences were identified in the proportion of men who had severe illness by HIV status. INTERPRETATION: Clinical manifestations of monkeypox infection differed by HIV status. Recommendations should be expanded to include pre-exposure monkeypox vaccination of groups at high risk of infection who plan to engage in sexual or close intimate contact. FUNDING: US Centers for Disease Control and Prevention, International Society of Travel Medicine.

Ten-Week Follow-Up of Monkeypox Case-Patient, Sweden, 2022.

A previously healthy male patient had detectable monkeypox virus DNA in saliva 76 days after laboratory confirmation of infection. A comprehensive characterization of viral kinetics and a detailed follow-up indicated a declining risk for transmission during the weeks after monkeypox symptoms appeared.

Comparison of Lung-Homing Receptor Expression and Activation Profiles on NK Cell and T Cell Subsets in COVID-19 and Influenza.

Respiratory viral infections with SARS-CoV-2 and influenza viruses commonly induce a strong infiltration of immune cells into the human lung, with potential detrimental effects on the integrity of the lung tissue. Despite comprising the largest fractions of circulating lymphocytes in the lung, rather little is known about how peripheral blood natural killer (NK) cell and T cell subsets are equipped for lung-homing in COVID-19 and influenza. Here, we provide a detailed comparative analysis of NK cells and T cells in patients infected with SARS-CoV-2 or influenza virus, focusing on the protein and gene expression of chemokine receptors known to be involved in recruitment to the lung. For this, we used 28-colour flow cytometry as well as re-analysis of a publicly available single-cell RNA-seq dataset from bronchoalveolar lavage (BAL) fluid. Frequencies of NK cells and T cells expressing CXCR3, CXCR6, and CCR5 were altered in peripheral blood of COVID-19 and influenza patients, in line with increased transcript expression of CXCR3, CXCR6, and CCR5 and their respective ligands in BAL fluid. NK cells and T cells expressing lung-homing receptors displayed stronger phenotypic signs of activation compared to cells lacking lung-homing receptors, and activation was overall stronger in influenza compared to COVID-19. Together, our results indicate a role for CXCR3+, CXCR6+, and/or CCR5+ NK cells and T cells that potentially migrate to the lungs in moderate COVID-19 and influenza patients, identifying common targets for future therapeutic interventions in respiratory viral infections.

Acute hepatitis A in international travellers: a GeoSentinel analysis, 2008-2020.

BACKGROUND: Non-immune international travellers are at risk of acquiring hepatitis A. Although hepatitis A vaccination is recommended for unvaccinated travellers to high or intermediate hepatitis A virus endemicity, compliance with this recommendation is not universal.The main objective was to describe the demographic and travel characteristics of international travellers infected with hepatitis A during travel. METHODS: Available data on travellers with confirmed (positive molecular test) or probable (symptomatic individuals with a single positive IgM test) hepatitis A diagnosed during and after travel from January 2008 to December 2020 were obtained from the GeoSentinel Surveillance Network database. We analysed demographic and travel characteristics of infected travellers. RESULTS: Among 254 travellers with hepatitis A (185 confirmed and 69 probable), the median age was 28 years (interquartile range: 19-40), 150 (59%) were male, and among 54 travellers with information available, 53 (98%) were unvaccinated. The most common reasons for travel included tourism (n = 120; 47%) and visiting friends or relatives (VFR; n = 72; 28%). About two-thirds of VFR travellers with hepatitis A (n = 50; 69%) were younger than 20 years old. Hepatitis A was acquired most frequently in South-Central Asia (n = 63; 25%) and sub-Saharan Africa (n = 61; 24%), but 16 travellers (6%) acquired hepatitis A in regions with low endemicity including Western Europe (n = 7; 3%), the Caribbean (n = 6; 2%) and North America (n = 3; 1%). Median duration from illness onset to GeoSentinel site presentation was ~7 days (interquartile range : 4-14 days). Among 88 travellers with information available, 59% were hospitalized. CONCLUSIONS: Despite availability of highly effective vaccines, travellers still acquire hepatitis A, even when traveling to low-endemicity destinations. Providing pre-departure hepatitis A vaccine to susceptible travellers is crucial to reducing travel-associated hepatitis A and should be offered to all travellers as part of the pre-travel consultation, regardless of destination.

Quinacrine Treatment of Nitroimidazole-Refractory Giardiasis.

BACKGROUND: Limited evidence exists on efficacy and tolerability of quinacrine for nitroimidazole-refractory giardiasis. METHODS: Nitroimidazole-refractory giardiasis cases, defined as microbiologically (microscopy and/or PCR) confirmed treatment failure after 2 courses, during 2008-2020, were retrospectively identified. RESULTS: Of 87 patients, 54 (62%) had visited India. Quinacrine was used in 54 (62%); 51 received monotherapy and 3 combined with metronidazole. Only 3 had positive stool samples with persisting symptoms after quinacrine treatment (94% parasitological efficacy) and all were cured after a second treatment. One (1.9%) had mild adverse effects recorded. CONCLUSIONS: Quinacrine is an effective treatment for nitroimidazole-refractory giardiasis with good tolerability.

Multidrug-resistant tuberculosis imported into low-incidence countries-a GeoSentinel analysis, 2008-2020.

BACKGROUND: Early detection of imported multidrug-resistant tuberculosis (MDR-TB) is crucial, but knowledge gaps remain about migration- and travel-associated MDR-TB epidemiology. The aim was to describe epidemiologic characteristics among international travellers and migrants with MDR-TB. METHODS: Clinician-determined and microbiologically confirmed MDR-TB diagnoses deemed to be related to travel or migration were extracted from GeoSentinel, a global surveillance network of travel and tropical medicine clinics, from January 2008 through December 2020. MDR-TB was defined as resistance to both isoniazid and rifampicin. Additional resistance to either a fluoroquinolone or a second-line injectable drug was categorized as pre-extensively drug-resistant (pre-XDR) TB, and as extensively drug-resistant (XDR) TB when resistance was detected for both. Sub-analyses were performed based on degree of resistance and country of origin. RESULTS: Of 201 patients, 136 had MDR-TB (67.7%), 25 had XDR-TB (12.4%), 23 had pre-XDR TB (11.4%) and 17 had unspecified MDR- or XDR-TB (8.5%); 196 (97.5%) were immigrants, of which 92 (45.8%) originated from the former Soviet Union. The median interval from arrival to presentation was 154 days (interquartile range [IQR]: 10-751 days); 34.3% of patients presented within 1 month after immigration, 30.9% between 1 and 12 months and 34.9% after ≥1 year. Pre-XDR- and XDR-TB patients from the former Soviet Union other than Georgia presented earlier than those with MDR-TB (26 days [IQR: 8-522] vs. 369 days [IQR: 84-827]), while patients from Georgia presented very early, irrespective of the level of resistance (8 days [IQR: 2-18] vs. 2 days [IQR: 1-17]). CONCLUSIONS: MDR-TB is uncommon in traditional travellers. Purposeful medical migration may partly explain differences in time to presentation among different groups. Public health resources are needed to better understand factors contributing to cross-border MDR-TB spread and to develop strategies to optimize care of TB-infected patients in their home countries before migration.

Travel-related infections presenting in Europe: A 20-year analysis of EuroTravNet surveillance data.

BACKGROUND: Disease epidemiology of (re-)emerging infectious diseases is changing rapidly, rendering surveillance of travel-associated illness important. METHODS: We evaluated travel-related illness encountered at EuroTravNet clinics, the European surveillance sub-network of GeoSentinel, between March 1, 1998 and March 31, 2018. FINDINGS: 103,739 ill travellers were evaluated, including 11,239 (10.8%) migrants, 89,620 (86.4%) patients seen post-travel, and 2,880 (2.8%) during and after travel. Despite increasing numbers of patient encounters over 20 years, the regions of exposure by year of clinic visits have remained stable. In 5-year increments, greater proportions of patients were migrants or visiting friends and relatives (VFR); business travel-associated illness remained stable; tourism-related illness decreased. Falciparum malaria was amongst the most-frequently diagnosed illnesses with 5,254 cases (5.1% of all patients) and the most-frequent cause of death (risk ratio versus all other illnesses 2.5:1). Animal exposures requiring rabies post-exposure prophylaxis increased from 0.7% (1998-2002) to 3.6% (2013-2018). The proportion of patients with seasonal influenza increased from zero in 1998-2002 to 0.9% in 2013-2018. There were 44 cases of viral haemorrhagic fever, most during the past five years. Arboviral infection numbers increased significantly as did the range of presenting arboviral diseases, dengue and chikungunya diagnoses increased by 2.6% and 1%, respectively. INTERPRETATION: Travel medicine must adapt to serve the changing profile of travellers, with an increase in migrants and persons visiting relatives and friends and the strong emergence of vector-borne diseases, with potential for further local transmission in Europe. FUNDING: This project was supported by a cooperative agreement (U50CK00189) between the Centers for Disease Control and Prevention to the International Society of Travel Medicine (ISTM) and funding from the ISTM and the Public Health Agency of Canada.

Expansion of SARS-CoV-2-Specific Antibody-Secreting Cells and Generation of Neutralizing Antibodies in Hospitalized COVID-19 Patients.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in late 2019 and has since become a global pandemic. Pathogen-specific Abs are typically a major predictor of protective immunity, yet human B cell and Ab responses during COVID-19 are not fully understood. In this study, we analyzed Ab-secreting cell and Ab responses in 20 hospitalized COVID-19 patients. The patients exhibited typical symptoms of COVID-19 and presented with reduced lymphocyte numbers and increased T cell and B cell activation. Importantly, we detected an expansion of SARS-CoV-2 nucleocapsid protein-specific Ab-secreting cells in all 20 COVID-19 patients using a multicolor FluoroSpot Assay. Out of the 20 patients, 16 had developed SARS-CoV-2-neutralizing Abs by the time of inclusion in the study. SARS-CoV-2-specific IgA, IgG, and IgM Ab levels positively correlated with SARS-CoV-2-neutralizing Ab titers, suggesting that SARS-CoV-2-specific Ab levels may reflect the titers of neutralizing Abs in COVID-19 patients during the acute phase of infection. Last, we showed that IL-6 and C-reactive protein serum concentrations were higher in patients who were hospitalized for longer, supporting the recent observations that IL-6 and C-reactive protein could be used as markers for COVID-19 severity. Altogether, this study constitutes a detailed description of clinical and immunological parameters in 20 COVID-19 patients, with a focus on B cell and Ab responses, and describes tools to study immune responses to SARS-CoV-2 infection and vaccination.

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.