Immunogenicity of a 2-Dose Regimen of Moderna mRNA Beta/Omicron BA.1 Bivalent Variant Vaccine Boost in a Randomized Clinical Trial.

We compared the serologic responses of 1 dose versus 2 doses of a variant vaccine (Moderna mRNA-1273 Beta/Omicron BA.1 bivalent vaccine) in adults. A 2-dose boosting regimen with a variant vaccine did not increase the magnitude or the durability of the serological responses compared to a single variant vaccine boost.

Immunogenicity of a Two Dose Regimen of Moderna mRNA Beta/Omicron BA.1 Bivalent Variant Vaccine Boost in a Randomized Clinical Trial.

In this brief report, we compare the magnitude and durability of the serologic response of one versus two doses (separated by 56 days) of a variant vaccine (Moderna mRNA-1273 Beta/Omicron BA.1 bivalent vaccine) in adults.

Immunogenicity of the BA.1 and BA.4/BA.5 SARS-CoV-2 Bivalent Boosts: Preliminary Results from the COVAIL Randomized Clinical Trial.

In a randomized clinical trial, we compare early neutralizing antibody responses after boosting with bivalent SARS-CoV-2 mRNA vaccines based on either BA.1 or BA.4/BA.5 Omicron spike protein combined with wildtype spike. Responses against SARS-CoV-2 variants exhibited the greatest reduction in titers against currently circulating Omicron subvariants for both bivalent vaccines.

Immunogenicity of the BA.1 and BA.4/BA.5 Severe Acute Respiratory Syndrome Coronavirus 2 Bivalent Boosts: Preliminary Results From the COVAIL Randomized Clinical Trial.

In a randomized clinical trial, we compare early neutralizing antibody responses after boosting with bivalent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccines based on either BA.1 or BA.4/BA.5 Omicron spike protein combined with wild-type spike. Responses against SARS-CoV-2 variants exhibited the greatest reduction in titers against currently circulating Omicron subvariants for both bivalent vaccines.

TaqMan Array Card testing of participant-collected stool smears to determine the pathogen-specific epidemiology of travellers' diarrhoea†.

BACKGROUND: We assessed the compliance with self-collection of stool smears on Whatman® FTA® Elute Card (FTA Card) and detection of travellers' diarrhoea (TD)-associated pathogens by using a quantitative Polymerase Chain Reaction (PCR) assay [customized TaqMan® array card (TAC)] in a prospective, observational cohort of travellers. METHODS: Enrolled travellers documented symptoms on a travel diary and collected an FTA Card during a diarrhoeal episode, or at the end of travel if they remained asymptomatic. TAC testing was performed on FTA Cards from TD cases and 1:1 matched asymptomatic controls and 1:1 matched loose stool cases that did not meet TD criteria. Odds ratios were used to determine the association between detected pathogens and TD. RESULTS: Of 2456 travellers, 484 (19.7%) completed an illness diary and met TD criteria, and 257 (53.1%) collected an FTA Card during the TD episode. FTA Cards were stored for a median of 2 years at room temperature (IQR: 1-4 years) before extraction and testing. The overall TAC detection rate in TD cases was 58.8% (95% CI: 52.5-64.8). Enterotoxigenic Escherichia coli was the most common pathogen in TD cases (26.8%), and 3.5% of samples were positive for norovirus. The odds of detecting TD-associated pathogens in 231 matched cases and asymptomatic controls were 5.4 (95% CI: 3.6-8.1) and 2.0 (95% CI: 1.1-3.7) in 121 matched TD and loose stool cases (P < 0.05). Enteroaggregative E. coli was the most common pathogen detected in asymptomatic controls and loose stool cases. Detection of diarrhoeagenic E. coli, Shigella/enteroinvasive E. coli and Campylobacter spp. was significantly associated with TD. CONCLUSION: FTA Cards are a useful adjunct to traditional stool collection methods for evaluating the pathogen-specific epidemiology of TD in austere environments. Qualitative detection of pathogens was associated with TD. Measures to improve compliance and quality of FTA Card collection with decreased storage duration may further optimize detection.

Travel-Related Risk Behaviors and Antibiotic Use Among Older Travelers.

BACKGROUND: Antibiotic stewardship in the pretravel care of older adults is important to effectively treat infections while minimizing harm from side effects and unnecessary antibiotic use. The objective of this study was to compare the characteristics, risk behaviors, infectious diseases, and antibiotic use between older (≥60 years) and younger (18-59 years) travelers. METHODS: TravMil is a prospective, observational cohort of United States (US) Department of Defense beneficiaries traveling outside the continental US for ≤6.5 months. For this analysis, we included adults enrolled pretravel between January 2010 and August 2018 and excluded active duty personnel on deployment. Pre and post-travel surveys captured trip characteristics, exposures, illnesses, and antibiotic use. RESULTS: A total of 1742 travelers were analyzed: 747 (42.9%) were aged ≥60 years and 995 (57.1%) were aged 18-59 years. Older travelers were less likely to engage in high-risk dietary behaviors and experience travelers' diarrhea than younger travelers (18.2% vs 22.9%; P < .05). Influenza-like illness (12.5%) and febrile illness (3.4%) occurred less frequently in the older cohort. Antibiotic use for self-treatment was common in both age groups (25.7% vs 26.7%) and often inappropriate, for example, for treatment of occasional loose stool or mild travelers' diarrhea (67.0% [67/100] in older adults vs 57.6% [83/144] in younger adults; P < .05), and influenza-like illness (63.4% [64/101] vs 58.6% [68/116], respectively; P < .05). CONCLUSIONS: Older travelers were less likely to engage in high-risk behaviors and experience travelers' diarrhea, and both age groups experienced mild, self-limited infections. Inappropriate use of antibiotics was common, suggesting that antimicrobial stewardship should be emphasized at pretravel counseling with international travelers.

Travel-associated multidrug-resistant organism acquisition and risk factors among US military personnel.

BACKGROUND: International travel is a risk factor for incident colonization with extended spectrum beta-lactamase (ESBL)-producing organisms. These and other multidrug-resistant (MDR) bacteria are major pathogens in combat casualties. We evaluated risk factors for colonization with MDR bacteria in US military personnel travelling internationally for official duty. METHODS: TravMil is a prospective observational study enrolling subjects presenting to military travel clinics. We analysed surveys, antimicrobial use data, and pre- and post-travel perirectal swabs in military travellers to regions outside the continental USA, Canada, Western or Northern Europe, or New Zealand, presenting to one clinic from 12/2015 to 12/2017. Recovered Gram-negative isolates underwent identification and susceptibility testing (BD Phoenix). Characteristics of trip and traveller were analysed to determine risk factors for MDR organism colonization. RESULTS: 110 trips were planned by 99 travellers (74% male, median age 38 years [IQR 31, 47.25]); 72 trips with returned pre- and post-travel swabs were completed by 64 travellers. Median duration was 21 days (IQR 12.75, 79.5). 17% travelled to Mexico/Caribbean/Central America, 15% to Asia, 57% to Africa and 10% to South America; 56% stayed in hotels and 50% in dormitories/barracks. Travellers used doxycycline (15%) for malaria prophylaxis, 11% took an antibiotic for travellers' diarrhoea (TD) treatment (fluoroquinolone 7%, azithromycin 4%). Incident MDR organism colonization occurred in 8 travellers (incidence density 3.5/1000 travel days; cumulative incidence 11% of trips [95% CI: 4-19%]), all ESBL-producing Escherichia coli. A higher incidence of ESBL-producing E. coli acquisition was associated with travel to Asia (36% vs 7%, P = 0.02) but not with travel to other regions, TD or use of antimicrobials. No relationship was seen between fluoroquinolone or doxycycline exposure and resistance to those antimicrobials. CONCLUSIONS: Incident colonization with MDR organisms occurs at a lower rate in this military population compared with civilian travellers, with no identified modifiable risk factors, with highest incidence of ESBL acquisition observed after South Asia travel.

Doxycycline Malaria Prophylaxis Impact on Risk of Travelers' Diarrhea among International Travelers.

International travelers are frequently at risk for travelers' diarrhea (TD) and malaria. Doxycycline was one of the earliest antibiotics shown to have efficacy in TD prevention. With increasing resistance and recommendations against antibiotic chemoprophylaxis, doxycycline fell out of use. We evaluated TD incidence and risk factors in a prospective cohort of travelers, specifically in regard to malaria prophylaxis. Travelers' diarrhea was defined as ≥ 3 loose stools in 24 hours or two loose stools in 24 hours associated with other gastrointestinal symptoms. The Poisson regression model with robust error variance was used to estimate the RR of TD. Three thousand two hundred twenty-seven trips were enrolled: 62.1% of participants were male, with a median age of 39 years (interquartile range [IQR] 27,59) and a median travel duration of 19 days (IQR 12,49); 17.4% developed TD; 32% traveled to Africa, 40% to Asia, and 27% to the Caribbean and Latin America; and 20% took doxycycline for malaria chemoprophylaxis, 50% took other antimalarials, and 30% took none. Decreased RR of TD was associated with doxycycline (RR 0.62 [0.47-0.82], P < 0.01) and military travel (RR 0.57 [0.47-0.70], P < 0.01). Increased risk of TD was associated with female gender (RR 1.28 [1.09-1.50], P < 0.01), hotel accommodations (RR 1.30 [1.10-1.53], P < 0.01), travel to tropical South America (RR 1.34 [1.09-1.64], P < 0.01), and duration of travel (RR 1.00 [1.00-1.01], P < 0.01). The use of doxycycline for malaria prophylaxis is associated with lower TD risk, suggesting increasing bacterial enteropathogen susceptibility similar to previous observations. Doxycycline selection for antimalarial chemoprophylaxis may provide additional traveler benefit in infection prevention.

Impact of Doxycycline as Malaria Prophylaxis on Risk of Influenza-Like Illness among International Travelers.

Travelers are often at risk for both influenza-like illness (ILI) and malaria. Doxycycline is active against pathogens causing ILI and is used for malaria prophylaxis. We evaluated the risk factors for ILI, and whether the choice of malaria prophylaxis was associated with ILI. TravMil is a prospective observational study enrolling subjects presenting to military travel clinics. Influenza-like illness was defined as subjective fever with either a sore throat or cough. Characteristics of trip and use of malaria prophylaxis were analyzed to determine association with development of ILI. Poisson regression models with robust error variance were used to estimate relative risk (RR) of ILI. A total of 3,227 trips were enrolled: 62.1% male, median age of 39 years (interquartile range [IQR] 27,59), median travel duration 19 days (IQR 12, 49); 32% traveled to Africa, 40% to Asia, and 27% to the Caribbean and Latin America. Military travel (46%) and vacation (40%) were most common reasons for travel. Among them, 20% took doxycycline, 50% other prophylaxis, and 30% took none; 8.7% developed ILI. Decreased RR of ILI was associated with doxycycline (RR 0.65 [0.43-0.99], P = 0.046) and military travel (RR 0.30 [0.21-0.43], P < 0.01). Increased risk of ILI was associated with female gender (RR 1.57 [1.24-1.98], P < 0.01), travel to Asia (RR 1.37 [1.08-1.75], P = 0.01), and cruises (RR 2.21 [1.73-2.83], P < 0.01). Use of doxycycline malaria prophylaxis is associated with a decreased risk of ILI. Possible reasons include anti-inflammatory or antimicrobial effects, or other unmeasured factors. With few strategies for decreasing ILI in travelers, these findings bear further investigation.

A Comparison of Stool Enteropathogen Detection by Semiquantitative PCR in Adults With Acute Travelers' Diarrhea Before and 3 Weeks After Successful Antibiotic Treatment.

We evaluated stool enteropathogen detection by semiquantitative polymerase chain reaction (PCR) in 108 subjects with travelers' diarrhea before and 3 weeks after treatment. Stool samples from 21 subjects were positive for the same pathogen species at both visits. We discuss factors that should be considered when interpreting stool PCR data after treatment.

Influenza-Like Illness in Travelers to the Developing World.

Travelers to developing regions are at risk for development of influenza-like illness (ILI). Little is known of traveler and trip characteristics associated with the development of ILI. TravMil is a prospective observational study, enrolling subjects presenting to six military travel clinics or predeployment-screening sites. We analyzed pre- and post-travel surveys from travelers visiting regions outside of the continental United States, Western or Northern Europe, Canada, Australia, or New Zealand between January 2010 and March 2016. Influenza-like illness was defined as a self-reported fever associated with either sore throat or cough. Trip and traveler characteristics were analyzed to determine risk factors for the development of ILI. Two thousand nine hundred and thirty-two trips were recorded (55% male, median age 45 years, 69% white, 51% on vacation, median travel duration 17 days). The 2,337 trips included the number of self-reported influenza vaccinations in the preceding 5 years (median 5). Eleven percent of the trips were complicated by an ILI lasting a median of 5 days; 70% and 17% of these reported upper and lower respiratory tract infection, respectively, and 12% reported both. On multivariate analysis, increased risk of ILI was associated with female gender (odds ratio [OR]: 1.60 [confidence interval (CI): 1.25-2.05], P < 0.01), age (years) (OR: 1.01 [CI: 1.01-1.02], P < 0.01); and duration of travel (days) (OR: 1.01 [CI: 1.00-1.01], P < 0.01). Influenza-like illness is common in travelers, regardless of traveler characteristics, purpose of travel, destination, or season of year. Female gender, older age, and longer duration of travel were associated with an increased risk of ILI. Additional tools and strategies are needed to prevent ILI in international travelers.

Mosquito Exposure and Chikungunya and Dengue Infection Among Travelers During the Chikungunya Outbreak in the Americas.

AbstractTravelers are at risk for arbovirus infection. We prospectively enrolled 267 Department of Defense beneficiaries traveling to chikungunya-outbreak regions in the Americas between December 2013 and May 2015 and assessed travel characteristics and serologic exposure to chikungunya virus (CHIKV) and dengue virus (DENV). Ten ill-returning travelers were also assessed retrospectively. Self-reported mosquito exposure was common (64% of 198 evaluable travelers saw mosquitoes; 53% of 201 reported ≥ 1 bite). Increased exposure was associated with active-duty travelers (odds ratio [OR] = 2.6 [1.3-5.4] for seeing mosquitoes) or travelers visiting friends and relatives (VFR) (OR = 3.5 [1.0-10.0] for high-intensity bite exposure). Arbovirus infection was defined as seroconversion on plaque reduction neutralization testing (PRNT) of pre- and posttravel sera. For ill subjects enrolled posttravel, infection was defined by a positive convalescent PRNT and/or a positive reverse transcription polymerase chain reaction for CHIKV or DENV. We identified seven cases of arbovirus infection: four with CHIKV, five with DENV, and two with both. The composite attack rate for CHIKV and DENV infection was 3.7% of 108 evaluable, immunologically naïve, prospectively assessed travelers; there was serologic and/or polymerase chain reaction evidence of arbovirus infection in three of four evaluable (three of 10 total) ill-returning travelers. We identified both symptomatic and asymptomatic cases. Military purpose of travel and VFR travel accounted for five of seven cases. Pretravel counseling is important and should target higher risk groups. Given a shared vector between CHIKV, DENV, and Zika virus (ZIKV), this study can also help guide counseling for travelers to ZIKV-outbreak regions.