Background The FLU-PRO Plus is a patient-reported outcome data collection instrument assessing symptoms of viral respiratory tract infections across eight body systems. This study evaluated the measurement properties of FLU-PRO Plus in a study enrolling individuals with COVID-19. Methods Data from a prospective cohort study (EPICC) in US Military Health System (MHS) beneficiaries evaluated for COVID-19 was utilized. Adults with symptomatic SARS-CoV-2 infection with FLU-PRO Plus survey information within one week of symptom onset were included. Reliability of FLU-PRO Plus was estimated using intraclass correlation coefficients (ICC; 2 days reproducibility). Known-groups validity was assessed using patient global assessments (PGA) of disease severity. Patient report of return to usual health was used to assess responsiveness (day 1-6/7). Results 226 SARS-CoV-2 positive participants were included in the analysis. Reliability among those who reported no change in their symptoms from one day to the next was high for most domains (ICC range 0.68-0.94 for day 1 to day 2). Construct validity was demonstrated by moderate to high correlation between the PGA rating of disease severity and domain and total scores (e.g., total scores correlation: 0.69 (influenza-like illness severity), 0.69 (interference in daily activities), and -0.58 (physical health)). In addition, FLU-PRO Plus demonstrated good known-groups validity, with increasing domain and total scores observed with increasing severity ratings. Conclusions FLU-PRO Plus performs well in measuring signs and symptoms in SARS-CoV-2 infection with excellent construct validity, known-groups validity, and responsiveness to change. Standardized data collection instruments facilitate meta-analyses, vaccine effectiveness studies, and other COVID-19 research activities.

Travelers 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.

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 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.