Evaluation of cesarean delivery rates and factors associated with cesarean delivery among women enrolled in a pregnancy cohort study at two tertiary hospitals in Thailand.

BACKGROUND: Cesarean delivery rates have increased globally resulting in a public health concern. We estimate rates of cesarean deliveries among Thai women using the World Health Organization (WHO) Robson Classification system and compare rates by Robson group to the Robson guideline for acceptable rates to identify groups that might benefit most from interventions for rate reduction. METHODS: In 2017 and 2018, we established cohorts of pregnant women aged ≥ 18 years seeking prenatal care at two tertiary Thai hospitals and followed them until 6-8 weeks postpartum. Three in-person interviews (enrollment, end of pregnancy, and postpartum) were conducted using structured questionnaires to obtain demographic characteristics, health history, and delivery information. Cesarean delivery indication was classified based on core obstetric variables (parity, previous cesarean delivery, number of fetuses, fetal presentation, gestational week, and onset of labor) assigned to 10 groups according to the Robson Classification. Logistic regression was used to identify factors associated with cesarean delivery among nulliparous women with singleton, cephalic, term pregnancies. RESULTS: Of 2,137 participants, 970 (45%) had cesarean deliveries. The median maternal age at delivery was 29 years (interquartile range, 25-35); 271 (13%) participants had existing medical conditions; and 446 (21%) had pregnancy complications. The cesarean delivery rate varied by Robson group. Multiparous women with > 1 previous uterine scar, with a single cephalic pregnancy, ≥ 37 weeks gestation (group 5) contributed the most (14%) to the overall cesarean rate, whereas those with a single pregnancy with a transverse or oblique lie, including women with previous uterine scars (group 9) contributed the least (< 1%). Factors independently associated with cesarean delivery included age ≥ 25 years, pre-pregnancy obesity, new/worsen medical condition during pregnancy, fetal distress, abnormal labor, infant size for gestational age ≥ 50th percentiles, and self-pay for delivery fees. Women with existing blood conditions were less likely to have cesarean delivery. CONCLUSIONS: Almost one in two pregnancies among women in our cohorts resulted in cesarean deliveries. Compared to WHO guidelines, cesarean delivery rates were elevated in selected Robson groups indicating that tailored interventions to minimize non-clinically indicated cesarean delivery for specific groups of pregnancies may be warranted.

The Effects of Injury Type on Health-Related Quality of Life in Youth Athletes: A Cross-Sectional Analysis.

OBJECTIVE: The relationship between health-related quality of life (HRQoL) and injury type has not been analyzed for young athletes. We hypothesized that there would be no difference in HRQoL between injured athletes, injured nonathletes, and normative data for healthy youth (NDHY) or among athletes with acute, overuse, or concussion injuries. DESIGN: Cross-sectional clinical cohort. SETTING: Primary care sports medicine clinics at 3 academic institutions. PARTICIPANTS: Patients aged 8 to 18 years presenting with injury. INDEPENDENT VARIABLES: Injury type and athletic participation. MAIN OUTCOME MEASURES: Health-related quality of life measured 1 month after injury through the Patient-Reported Outcomes Measurement Information System (PROMIS) Pediatric-25 v2.0 assessed pain interference, peer relationships, depression, fatigue, anxiety, and mobility. One-way analysis of variance was performed with P values of <0.05 considered significant. Concussion Learning Assessment and School Survey (CLASS) evaluated academic performance. RESULTS: Three hundred fifty-seven patients (36% male), with average age of 14.2 years, completed HRQoL and CLASS surveys following injury. There were 196 overuse injuries (55%), 119 acute injuries (33%), and 42 concussions (12%). Ninety-four percent were athletes. Six percent were nonathletes; 90.5% of concussed patients reported grades worsening. Concussed athletes reported more fatigue (P = 0.008) compared with other injury types but no worse than NDHY. Athletes with overuse injuries had lower mobility (P = 0.005) than other injury types and NDHY. Patients with lower HRQoL were female, older age, or required surgery. No other domains had significant differences by injury type nor did HRQoL differ between the athletes, nonathletes, and NDHY. CONCLUSIONS: With the exception of injuries requiring surgery, HRQoL of injured young athletes was similar to NDHY in most domains.

Running Biomechanics and Clinical Features Among Adolescent Athletes With Lower Leg Chronic Exertional Compartment Syndrome.

OBJECTIVE: To compare clinical measures between patients with chronic exertional compartment syndrome (CECS) and healthy controls and evaluate running biomechanics, physical measurements, and exertional intracompartmental (ICP) changes in adolescent athletes with lower leg CECS. DESIGN: Cross-sectional case-control study. SETTING: Large tertiary care hospital and affiliated injury prevention center. PARTICIPANTS: Forty-nine adolescents with CECS (39 F, 10 M; age: 16.9 ± 0.8 years; body mass index (BMI): 23.1 ± 2.9 kg/m 2 ; symptom duration: 8 ± 12 months) were compared with 49 healthy controls (39 F, 10 M; age: 6.9 ± 0.8 years; BMI: 20.4 ± 3.7 kg/m 2 ). INTERVENTIONS: All participants underwent gait analyses on a force plate treadmill and clinical lower extremity strength and range of motion testing. Patients with chronic exertional compartment syndrome underwent Stryker monitor ICP testing. MAIN OUTCOME MEASURES: Symptoms, menstrual history, and ICP pressures of the patients with CECS using descriptive statistics. Mann-Whitney U and χ 2 analyses were used to compare CECS with healthy patients for demographics, clinical measures, and gait biomechanics continuous and categorical outcomes, respectively. For patients with CECS, multiple linear regressions analyses were used to assess associations between gait biomechanics, lower extremity strength and range of motion, and with ICP measures. RESULTS: The CECS group demonstrated higher mass-normalized peak ground reaction force measures (xBW) compared with controls (0.21 ± 0.05 xBW ( P < 0.001) and were more likely to have impact peak at initial contact ( P = 0.04). Menstrual dysfunction was independently associated with higher postexertion ICP (ß = 14.6; P = 0.02). CONCLUSIONS: The CECS group demonstrated increased total force magnitude and vertical impact transient peaks. In women with CECS, menstrual dysfunction was independently associated with increased postexertion ICP. These biomechanical and physiological attributes may play a role in the development of CECS.

Effect of Repeat Vaccination on Immunogenicity of Quadrivalent Cell-Culture and Recombinant Influenza Vaccines Among Healthcare Personnel Aged 18-64 Years: A Randomized, Open-Label Trial.

BACKGROUND: Antibody responses to non-egg-based standard-dose cell-culture influenza vaccine (containing 15 µg hemagglutinin [HA]/component) and recombinant vaccine (containing 45 µg HA/component) during consecutive seasons have not been studied in the United States. METHODS: In a randomized trial of immunogenicity of quadrivalent influenza vaccines among healthcare personnel (HCP) aged 18-64 years over 2 consecutive seasons, HCP who received recombinant-HA influenza vaccine (RIV) or cell culture-based inactivated influenza vaccine (ccIIV) during the first season (year 1) were re-randomized the second season of 2019-2020 (year 2 [Y2]) to receive ccIIV or RIV, resulting in 4 ccIIV/RIV combinations. In Y2, hemagglutination inhibition antibody titers against reference cell-grown vaccine viruses were compared in each ccIIV/RIV group with titers among HCP randomized both seasons to receive egg-based, standard-dose inactivated influenza vaccine (IIV) using geometric mean titer (GMT) ratios of Y2 post-vaccination titers. RESULTS: Y2 data from 414 HCP were analyzed per protocol. Compared with 60 IIV/IIV recipients, 74 RIV/RIV and 106 ccIIV/RIV recipients showed significantly elevated GMT ratios (Bonferroni corrected P < .007) against all components except A(H3N2). Post-vaccination GMT ratios for ccIIV/ccIIV and RIV/ccIIV were not significantly elevated compared with IIV/IIV except for RIV/ccIIV against A(H1N1)pdm09. CONCLUSIONS: In adult HCP, receipt of RIV in 2 consecutive seasons or the second season was more immunogenic than consecutive egg-based IIV for 3 of the 4 components of quadrivalent vaccine. Immunogenicity of ccIIV/ccIIV was similar to that of IIV/IIV. Differences in HA antigen content may play a role in immunogenicity of influenza vaccination in consecutive seasons. CLINICAL TRIALS REGISTRATION: NCT03722589.

Development of a novel serological assay for the detection of mpox infection in vaccinated populations.

In 2022 the World Health Organization declared a Public Health Emergency for an outbreak of mpox, the zoonotic Orthopoxvirus (OPV) affecting at least 104 nonendemic locations worldwide. Serologic detection of mpox infection is problematic, however, due to considerable antigenic and serologic cross-reactivity among OPVs and smallpox-vaccinated individuals. In this report, we developed a high-throughput multiplex microsphere immunoassay using a combination of mpox-specific peptides and cross-reactive OPV proteins that results in the specific serologic detection of mpox infection with 93% sensitivity and 98% specificity. The New York State Non-Vaccinia Orthopoxvirus Microsphere Immunoassay is an important tool to detect subclinical mpox infection and understand the extent of mpox spread in the community through retrospective analysis.

Serum per- and polyfluoroalkyl substance concentrations and longitudinal change in post-infection and post-vaccination SARS-CoV-2 antibodies.

Per- and polyfluoroalkyl substances (PFAS) are ubiquitous throughout the United States. Previous studies have shown PFAS exposure to be associated with a reduced immune response. However, the relationship between serum PFAS and antibody levels following SARS-CoV-2 infection or COVID-19 vaccination has not been examined. We examined differences in peak immune response and the longitudinal decline of antibodies following SARS-CoV-2 infection and COVID-19 vaccination by serum PFAS levels in a cohort of essential workers in the United States. We measured serum antibodies using an in-house semi-quantitative enzyme-linked immunosorbent assay (ELISA). Two cohorts contributed blood samples following SARS-CoV-2 infection or COVID-19 vaccination. We used linear mixed regression models, adjusting for age, race/ethnicity, gender, presence of chronic conditions, location, and occupation, to estimate differences in immune response with respect to serum PFAS levels. Our study populations included 153 unvaccinated participants that contributed 316 blood draws over a 14-month period following infection, and 860 participants and 2451 blood draws over a 12-month period following vaccination. Higher perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA) concentrations were associated with a lower peak antibody response after infection (p = 0.009, 0.031, 0.015). Higher PFOS, perfluorooctanoic acid (PFOA), PFHxS, and PFNA concentrations were associated with slower declines in antibodies over time after infection (p = 0.003, 0.014, 0.026, 0.025). PFOA, PFOS, PFHxS, and PFNA serum concentrations prior to vaccination were not associated with differences in peak antibody response after vaccination or with differences in decline of antibodies over time after vaccination. These results suggest that elevated PFAS may impede potential immune response to SARS-CoV-2 infection by blunting peak antibody levels following infection; the same finding was not observed for immune response to vaccination.

Adolescent Marathon Training: Prospective Evaluation of Musculotendinous Changes During a 6-Month Endurance Running Program.

OBJECTIVES: Assess changes in lower extremity musculotendinous thickness, tissue echogenicity, and muscle pennation angles among adolescent runners enrolled in a 6-month distance running program. METHODS: We conducted prospective evaluations of adolescent runners' lower extremity musculotendinous changes at three timepoints (baseline, 3 months, and 6 months) throughout a progressive marathon training program. Two experienced researchers used an established protocol to obtain short- and long-axis ultrasound images of the medial gastrocnemius, tibialis anterior, flexor digitorum brevis, abductor hallicus, and Achilles and patellar tendons. ImageJ software was used to calculate musculotendinous thickness and echogenicity for all structures, and fiber pennation angles for the ankle extrinsic muscles. Repeated measures within-subject analyses of variance were conducted to assess the effect of endurance training on ultrasound-derived measures. RESULTS: We assessed 11 runners (40.7% of eligible runners; 6F, 5M; age: 16 ± 1 years; running experience: 3 ± 2 years) who remained injury-free and completed all ultrasound evaluation timepoints. Medial gastrocnemius muscle (F2,20  = 3.48, P = .05), tibialis anterior muscle (F2,20  = 7.36, P = .004), and Achilles tendon (F2,20  = 3.58, P = .05) thickness significantly increased over time. Echogenicity measures significantly decreased in all muscles (P-range: <.001-.004), and increased for the patellar tendon (P < .001) during training. Muscle fiber pennation angles significantly increased for ankle extrinsic muscles (P < .001). CONCLUSIONS: Adolescent runners' extrinsic foot and ankle muscles increased in volume and decreased in echogenicity, attributed to favorable distance training adaptations across the 6-month timeframe. We noted tendon thickening without concomitantly increased echogenicity, signaling intrasubstance tendon remodeling in response to escalating distance.

Respiratory Viral Infections and Infection Prevention Practices Among Women With Acute Respiratory Illness During Delivery Hospitalizations During the 2019-2020 Influenza Season.

BACKGROUND: We conducted a cross-sectional study of pregnant women with acute respiratory illness during delivery hospitalizations during influenza season to describe clinical testing for respiratory viruses and infection prevention practices. METHODS: Women had nasal swabs tested for influenza and other respiratory viruses. Among 91 enrolled women, 22 (24%) had clinical testing for influenza. RESULTS: Based on clinical and study testing combined, 41 of 91 (45%) women had samples positive for respiratory viruses. The most common virus was influenza (17 of 91, 19%); 53% (9 of 17) of influenza virus infections were identified through study testing alone. Only 16% of women were on droplet precautions. CONCLUSIONS: Peripartum respiratory infections may be underrecognized.

Cerebrovascular Neuroprotection after Acute Concussion in Adolescents.

OBJECTIVE: To assess acute cerebrovascular function in concussed adolescents (14-21 years of age), whether it is related to resting cerebral hemodynamics, and whether it recovers chronically. METHODS: Cerebral vasoreactivity and autoregulation, based on middle cerebral artery blood flow velocity, was assessed in 28 concussed participants (≤14 days of injury) and 29 matched controls. The participants in the concussion group returned for an 8-week follow-up assessment. Over the course of those 8-weeks, participants recorded aerobic exercise frequency and duration. RESULTS: Between groups, demographic, clinical, and hemodynamic variables were not significantly different. Vasoreactivity was significantly higher in the concussed group (p = 0.02). Within the concussed group, 60% of the variability in resting cerebral blood flow velocity was explained by vasoreactivity and two components of autoregulation - falling slope and effectiveness of autoregulation (adjusted R2  = 0.60, p < 0.001). Moreover, lower mean arterial pressure, lower responses to increases in arterial pressure, and lower vasoreactivity were significantly associated with larger symptom burden (adjusted R2  = 0.72, p < 0.01). By the 8-week timepoint, symptom burden, but not vasoreactivity, improved in all but four concussed participants (p < 0.01). 8-week change in vasoreactivity was positively associated with aerobic exercise volume (adjusted R2  = 0.19, p = 0.02). INTERPRETATION: Concussion resulted in changes in cerebrovascular regulatory mechanisms, which in turn explained the variability in resting cerebral blood flow velocity and acute symptom burden. Furthermore, these alterations persisted chronically despite symptom resolution, but was positively modified by aerobic exercise volume. These findings provide a mechanistic framework for further investigation into underlying cerebrovascular related symptomatology. ANN NEUROL 2021;90:43-51.

Postconcussion Exercise Volume Associations With Depression, Anxiety, and Dizziness Symptoms, and Postural Stability: Preliminary Findings.

OBJECTIVE: To examine the association between postconcussion exercise volume and changes in depression, anxiety, dizziness, and postural stability. DESIGN: Secondary analysis of a single-site prospective clinical trial. SETTING: Cerebrovascular research laboratory. PARTICIPANTS: Participants completed questionnaires and underwent tests of gait and balance within 2 weeks of a concussion (mean = 11 ± 3 days postconcussion) and approximately 1 month later (mean = 41 ± 7 days postconcussion). Exercise volume was tracked by weekly exercise logs. INTERVENTIONS: On the basis of a previous work classifying exercise volume following concussion, we grouped participants according to self-reported exercise volume between visits as high exercise volume (≥150 min/wk) or low exercise volume (<150 min/wk). MAIN OUTCOME MEASURES: Participants completed assessments evaluating anxiety and depression (Hospital Anxiety and Depression Scale), dizziness (Dizziness Handicap Inventory), and postural stability (tandem gait and modified Balance Error Scoring System). RESULTS: Thirty-eight participants completed the study, of which 22 were in the high exercise volume group (mean = 71 ± 40 min/wk; 16.8 ± 2.1 years; 59% female) and 16 were in the low exercise volume group (mean = 379 ± 187 min/wk; 17.5 ± 2.1 years; 31% female). Although depression symptoms were not significantly different initially (mean difference = 1.5; 95% CI, -0.68 to 3.68; P = .24), the high exercise volume group had significantly lower depression symptom scores at follow-up (mean difference = 3.0; 95% CI, 1.40 to 4.47; P < .001). Anxiety symptoms (mean difference = 2.8; 95% CI, 0.3 to 5.4; P = 0.03), dizziness symptoms (mean difference = 10.9; 95% CI, 0.2 to 21.5; P = .047), single-task tandem gait (mean difference = 3.1 seconds; 95% CI, 0.2 to 6.0; P = .04), and dual-task tandem gait (mean difference = 4.2 seconds; 95% CI, 0.2 to 8.2; P = .04) were significantly better among the high exercise volume group. CONCLUSION: Greater exercise volumes were associated with lower depression, anxiety, and dizziness symptoms, and faster tandem gait performance. These preliminary findings suggest a potentially beneficial role for exercise within several different domains commonly affected by concussion.

Dizziness, Psychosocial Function, and Postural Stability Following Sport-Related Concussion.

OBJECTIVE: To examine if self-reported dizziness is associated with concussion symptoms, depression and/or anxiety symptoms, or gait performance within 2 weeks of postconcussion. DESIGN: Cross-sectional study. SETTING: Research laboratory. PARTICIPANTS: Participants were diagnosed with a concussion within 14 days of initial testing (N = 40). Participants were divided into 2 groups based on their Dizziness Handicap Inventory (DHI) score: 36 to 100 = moderate/severe dizziness and 0 to 35 = mild/no dizziness. INTERVENTIONS: Participants were tested on a single occasion and completed the DHI, hospital anxiety and depression scale (HADS), Patient Health Questionnaire-9 (PHQ-9), and Post-Concussion Symptom Inventory (PCSI). Three different postural control tests were use: modified Balance Error Scoring System, single-/dual-task tandem gait, and a single-/dual-task instrumented steady-state gait analysis. MAIN OUTCOME MEASURES: Comparison of patient-reported outcomes and postural control outcomes between moderate/severe (DHI ≥ 36) and mild/no (DHI < 36) dizziness groups. RESULTS: Participants with moderate/severe dizziness (n = 19; age = 17.1 ± 2.4 years; 63% female) reported significantly higher symptom burden (PSCI: 43.0 ± 20.6 vs 22.8 ± 15.7; P = 0.001) and had higher median HADS anxiety (6 vs 2; P < 0.001) and depression (6 vs 1; P = 0.001) symptom severity than those with no/minimal dizziness (n = 21; age = 16.5 ± 1.9; 38% female). During steady-state gait, moderate/severe dizziness group walked with significantly slower single-task cadence (mean difference = 4.8 steps/minute; 95% confidence interval = 0.8, 8.8; P = 0.02) and dual-task cadence (mean difference = 7.4 steps/minute; 95% confidence interval = 0.7, 14.0; P = 0.04) than no/mild dizziness group. CONCLUSION: Participants who reported moderate/severe dizziness reported higher concussion symptom burden, higher anxiety scores, and higher depression scores than those with no/mild dizziness. Cadence during gait was also associated with the level of dizziness reported.

Association of Social Media Use on Sleep Quality and Performance Among Collegiate Athletes.

OBJECTIVE: (1) To examine the effect of social media (SM) use on sleep quality and (2) to determine the effect of SM on competition performance among college athletes. DESIGN: Cross-sectional study. SETTING: Two local Division III colleges, MA, USA. PARTICIPANTS: National Collegiate Athletic Association Division III swim and track and field athletes. INTERVENTION: Data were collected onsite through an SM use form, the lifestyle survey, and the Patient-Reported Outcomes Measurement Information System Sleep Disturbance Questionnaire. Participants were divided into 3 groups based on their SM volume: (1) less active SM users (≤2 h/d), (2) moderately active SM users (>2-≤5 h/d), and (3) active SM users (>5 h/d) for analysis. MAIN OUTCOME MEASURES: Sleep quality and sport performance data collected through publicly available competition results. The independent variable, SM volume (hours of SM use per day over 7 days), was collected using the iPhone screen time function. RESULTS: The cohort consisted of 40 male track and field athletes and 47 female track and field (37, 79%) and swimming (10, 21%) athletes. Mean SM use was 4.6 ± 3.4 h/d. The sleep quality of active SM users was worse than less active SM users ( P = 0.033). There was an independent association between increased Facebook time and poor performance after adjusting confounders (adjusted odds ratio: 0.990, 95% confidence interval: 0.981-0.999, P = 0.049). CONCLUSIONS: High SM use has a negative impact on sleep quality and may hinder competition performance among college athletes. These findings may have implications for developing SM use guidelines for college athletes to improve their sleep quality and performance.

Relationship and Latent Factors Between Clinical Concussion Assessments and the Functional Standardized Assessment of Reaction Time (StART).

OBJECTIVE: To examine the relationships and latent factors within the Standardized Assessment of Reaction Time (StART), and between StART and current clinical assessments. DESIGN: Cross-sectional study. SETTING: Clinical medicine facility. PARTICIPANTS: Eighty-nine healthy collegiate student-athletes (63% male, age: 19.5 ± 0.9 years, 28% ≥1 concussion history). ASSESSMENT OF RISK FACTORS: Student-athletes completed StART and clinical assessments during preinjury testing. MAIN OUTCOME MEASURES: Standardized Assessment of Reaction Time consisted of 3 conditions (standing, single-leg balance, cutting) under 2 cognitive states (single task and dual task) for 3 trials each condition. Clinical assessments were the Sport Concussion Assessment Tool (SCAT) symptom checklist, Standardized Assessment of Concussion (SAC), tandem gait (single task and dual task), and Immediate PostConcussion Assessment and Cognitive Testing (ImPACT). We used Pearson- r correlation coefficients and exploratory factor analysis (EFA) to examine relationships and latent factors between StART and clinical assessments. RESULTS: Null to moderate correlations presented among the StART outcomes (r range: 0.06-0.70), and null to small correlations between StART and clinical assessments (r range: -0.16 to 0.34). The three-factor EFA for solely StART explained 70.6% total variance: functional movement (cutting), static dual-task (standing and single-leg balance), and static single task (standing and single-leg balance). The five-factor EFA for StART and clinical assessments explained 65.8% total variance: gait (single-task and dual-task tandem gait), functional movement (StART single-task and dual-task cutting), static dual-task (StART standing, single-leg balance), neurocognitive (ImPACT verbal memory, visual memory, visual-motor speed), and static single task (StART standing, single-leg balance). No other outcomes met the factor loading threshold. CONCLUSIONS: StART displayed 3 distinct categories and had minimal redundancy within its subtests. StART did not meaningfully correlate with clinical assessments, suggesting that StART provides unique information by examining more functional, reactive movement.

Feasibility and Performance of Self-Collected Nasal Swabs for Detection of Influenza Virus, Respiratory Syncytial Virus, and Human Metapneumovirus.

BACKGROUND: We assessed performance of participant-collected midturbinate nasal swabs compared to study staff-collected midturbinate nasal swabs for the detection of respiratory viruses among pregnant women in Bangkok, Thailand. METHODS: We enrolled pregnant women aged ≥18 years and followed them throughout the 2018 influenza season. Women with acute respiratory illness self-collected midturbinate nasal swabs at home for influenza viruses, respiratory syncytial viruses (RSV), and human metapneumoviruses (hMPV) real-time RT-PCR testing and the study nurse collected a second midturbinate nasal swab during home visits. Paired specimens were processed and tested on the same day. RESULTS: The majority (109, 60%) of 182 participants were 20-30 years old. All 200 paired swabs had optimal specimen quality. The median time from symptom onsets to participant-collected swabs was 2 days and to staff-collected swabs was also 2 days. The median time interval between the 2 swabs was 2 hours. Compared to staff-collected swabs, the participant-collected swabs were 93% sensitive and 99% specific for influenza virus detection, 94% sensitive and 99% specific for RSV detection, and 100% sensitive and 100% specific for hMPV detection. CONCLUSIONS: Participant-collected midturbinate nasal swabs were a valid alternative approach for laboratory confirmation of influenza-, RSV-, and hMPV-associated illnesses among pregnant women in a community setting.

Comparison of the Immunogenicity of Cell Culture-Based and Recombinant Quadrivalent Influenza Vaccines to Conventional Egg-Based Quadrivalent Influenza Vaccines Among Healthcare Personnel Aged 18-64 Years: A Randomized Open-Label Trial.

BACKGROUND: RIV4 and cell-culture based inactivated influenza vaccine (ccIIV4) have not been compared to egg-based IIV4 in healthcare personnel, a population with frequent influenza vaccination that may blunt vaccine immune responses over time. We conducted a randomized trial among healthcare personnel (HCP) aged 18-64 years to compare humoral immune responses to ccIIV4 and RIV4 to IIV4. METHODS: During the 2018-2019 season, participants were randomized to receive ccIIV4, RIV4, or IIV4 and had serum samples collected prevaccination, 1 and 6 months postvaccination. Serum samples were tested by hemagglutination inhibition (HI) for influenza A/H1N1, B/Yamagata, and B/Victoria and microneutralization (MN) for A/H3N2 against cell-grown vaccine reference viruses. Primary outcomes at 1 month were seroconversion rate (SCR), geometric mean titers (GMT), GMT ratio, and mean fold rise (MFR) in the intention-to-treat population. RESULTS: In total, 727 participants were included (283 ccIIV4, 202 RIV4, and 242 IIV4). At 1 month, responses to ccIIV4 were similar to IIV4 by SCR, GMT, GMT ratio, and MFR. RIV4 induced higher SCRs, GMTs, and MFRs than IIV4 against A/H1N1, A/H3N2, and B/Yamagata. The GMT ratio of RIV4 to egg-based vaccines was 1.5 (95% confidence interval [CI] 1.2-1.9) for A/H1N1, 3.0 (95% CI: 2.4-3.7) for A/H3N2, 1.1 (95% CI: .9-1.4) for B/Yamagata, and 1.1 (95% CI: .9-1.3) for B/Victoria. At 6 months, ccIIV4 recipients had similar GMTs to IIV4, whereas RIV4 recipients had higher GMTs against A/H3N2 and B/Yamagata. CONCLUSIONS: RIV4 resulted in improved antibody responses by HI and MN compared to egg-based vaccines against 3 of 4 cell-grown vaccine strains 1 month postvaccination, suggesting a possible additional benefit from RIV4. CLINICAL TRIALS REGISTRATION: NCT03722589.

Performance of Symptom-Based Case Definitions to Identify Influenza Virus Infection Among Pregnant Women in Middle-Income Countries: Findings From the Pregnancy and Influenza Multinational Epidemiologic (PRIME) Study.

BACKGROUND: The World Health Organization (WHO) recommends case definitions for influenza surveillance that are also used in public health research, although their performance has not been assessed in many risk groups, including pregnant women in whom influenza may manifest differently. We evaluated the performance of symptom-based definitions to detect influenza in a cohort of pregnant women in India, Peru, and Thailand. METHODS: In 2017 and 2018, we contacted 11 277 pregnant women twice weekly during the influenza season to identify illnesses with new or worsened cough, runny nose, sore throat, difficulty breathing, or myalgia and collected data on other symptoms and nasal swabs for influenza real-time reverse transcription-polymerase chain reaction (rRT-PCR) testing. We calculated sensitivity, specificity, positive-predictive value, and negative-predictive value of each symptom predictor, WHO respiratory illness case definitions, and a de novo definition derived from results of multivariable modeling. RESULTS: Of 5444 eligible illness episodes among 3965 participants, 310 (6%) were positive for influenza. In a multivariable model, measured fever ≥38°C (adjusted odds ratio [95% confidence interval], 4.6 [3.1-6.8]), myalgia (3.0 [2.2-4.0]), cough (2.7 [1.9-3.9]), and chills (1.6 [1.1-2.4]) were independently associated with influenza illness. A definition based on these 4 (measured fever, cough, chills, or myalgia) was 95% sensitive and 27% specific. The WHO influenza-like illness (ILI) definition was 16% sensitive and 98% specific. CONCLUSIONS: The current WHO ILI case definition was highly specific but had low sensitivity. The intended use of case definitions should be considered when evaluating the tradeoff between sensitivity and specificity.

Interim Estimates of Vaccine Effectiveness of BNT162b2 and mRNA-1273 COVID-19 Vaccines in Preventing SARS-CoV-2 Infection Among Health Care Personnel, First Responders, and Other Essential and Frontline Workers - Eight U.S. Locations, December 2020-March 2021.

Messenger RNA (mRNA) BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) COVID-19 vaccines have been shown to be effective in preventing symptomatic COVID-19 in randomized placebo-controlled Phase III trials (1,2); however, the benefits of these vaccines for preventing asymptomatic and symptomatic SARS-CoV-2 (the virus that causes COVID-19) infection, particularly when administered in real-world conditions, is less well understood. Using prospective cohorts of health care personnel, first responders, and other essential and frontline workers* in eight U.S. locations during December 14, 2020-March 13, 2021, CDC routinely tested for SARS-CoV-2 infections every week regardless of symptom status and at the onset of symptoms consistent with COVID-19-associated illness. Among 3,950 participants with no previous laboratory documentation of SARS-CoV-2 infection, 2,479 (62.8%) received both recommended mRNA doses and 477 (12.1%) received only one dose of mRNA vaccine.† Among unvaccinated participants, 1.38 SARS-CoV-2 infections were confirmed by reverse transcription-polymerase chain reaction (RT-PCR) per 1,000 person-days.§ In contrast, among fully immunized (≥14 days after second dose) persons, 0.04 infections per 1,000 person-days were reported, and among partially immunized (≥14 days after first dose and before second dose) persons, 0.19 infections per 1,000 person-days were reported. Estimated mRNA vaccine effectiveness for prevention of infection, adjusted for study site, was 90% for full immunization and 80% for partial immunization. These findings indicate that authorized mRNA COVID-19 vaccines are effective for preventing SARS-CoV-2 infection, regardless of symptom status, among working-age adults in real-world conditions. COVID-19 vaccination is recommended for all eligible persons.

A fatal case report of antibody-dependent enhancement of dengue virus type 1 following remote Zika virus infection.

BACKGROUND: Dengue virus (DENV) is endemic in many parts of the world. Antibody dependent enhancement (ADE) in DENV infections occurs when a person with primary immunity is infected by a second, different DENV strain. Antibodies to Zika virus (ZIKV), which emerged in the Western Hemisphere in 2015, are cross reactive with DENV and theoretically could provoke ADE in a DENV naïve individual. CASE PRESENTATION: DENV infection was suspected in a child who had recently returned from a one-month stay in the Dominican Republic. The child presented with fever, vomiting, abdominal pain, and in hypovolemic shock. Volume and pressor resuscitation were unsuccessful, and the child died less than 24 h after hospitalization. Laboratory results suggested an early acute first DENV infection since serum, plasma, and spinal fluid had DENV1 detected by polymerase chain reaction (PCR), yet the serum lacked IgG antibodies to DENV nonstructural protein 1 (NS1) of all four DENV serotypes. This acute DENV infection occurred in the presence of a remote ZIKV infection as determined by antibodies to ZIKV NS1 envelope by multiplex microsphere immunoassay and an exceptionally high plaque reduction neutralization titer to ZIKV. ZIKV IgG avidity index was high, confirming a past infection. DENV1 RNA was detected in all ten organs and tissues examined by PCR. The severe and fatal complications reported here suggest that a remote ZIKV infection may provoke an exaggerated immune response leading to hypovolemic shock when primarily infected by DENV1. CONCLUSION: We report the first known patient in the United States with a rapidly progressive and fatal case of travel-associated DENV in which prior exposure to ZIKV likely played a role in triggering an ADE phenomenon. This association of prior ZIKV immunity and subsequent new dengue infection is a worrisome phenomenon and an important contribution to the body of knowledge on immunity to flaviviruses.

Use of the immunoglobulin G avidity assay to differentiate between recent Zika and past dengue virus infections.

Zika (ZIKV) and dengue (DENV) virus infections elicit a robust but cross-reactive antibody response against the viral envelope protein, while antibody responses against non-structural proteins (NS) are more virus specific. Building on this premise, we have previously developed a flavivirus multiplex microsphere immunoassay (MIA) for the serologic diagnosis of ZIKV and DENV infections. This assay significantly improved diagnostic accuracy; however, MIA could not differentiate more recent from past infections, which still represents a major diagnostic challenge. Therefore, an immunoglobulin G (IgG) based avidity assay was developed and its diagnostic performance evaluated. Specimens from New York State residents were submitted to the Wadsworth Center New York State Department of Health (NYSDOH) for routine clinical testing by Zika IgM ELISA and plaque reduction neutralization test (PRNT). Using our previously developed flavivirus MIA as a platform, we developed an IgG avidity assay to discriminate recent ZIKV from past DENV infections. Zika IgM positive specimens had an average Zika IgG avidity index of 14.8% (95% CI: 11.0-18.4%), while Zika IgM negative but flavivirus MIA and PRNT positive samples had an average Zika IgG avidity index of 34.9% (95% CI: 31.1-38.7%). Specimens positive for dengue antibodies by flavivirus MIA and PRNT had an average dengue IgG avidity index of 68.7% (95% CI: 62.7-75.0%). The IgG avidity assay accurately distinguished recent ZIKV from past DENV infections in patients who traveled to dengue endemic regions. This assay could be very useful in patients with high risk of Zika complications such as pregnant women and monitoring immune responses in vaccine trials.

The Pregnancy and Influenza Multinational Epidemiologic (PRIME) study: a prospective cohort study of the impact of influenza during pregnancy among women in middle-income countries.

BACKGROUND: The World Health Organization identifies pregnant women as at high-risk for severe influenza, but influenza vaccines are underutilized among pregnant women. Data on influenza burden during pregnancy are largely limited to high-income countries and data on the impact of influenza on birth and perinatal outcomes are scarce. METHODS/DESIGN: This prospective, longitudinal cohort study of pregnant women in middle-income countries is designed to address three primary objectives: 1) to evaluate the effect of laboratory-confirmed influenza during pregnancy on pregnancy and perinatal outcomes; 2) to estimate the incidences of all-cause acute respiratory illness and laboratory-confirmed influenza during pregnancy; and 3) to examine the clinical spectrum of illness associated with influenza viruses. Through a multi-country network approach, three sites aim to enroll cohorts of 1500-3000 pregnant women just before local influenza seasons. Women aged ≥ 18 years with expected delivery dates ≥ 8 weeks after the start of the influenza season are eligible. Women are followed throughout pregnancy through twice weekly surveillance for influenza symptoms (≥ 1 of myalgia, cough, runny nose, sore throat, or difficulty breathing) and have mid-turbinate nasal swabs collected for influenza virus testing during illness episodes. Primary outcomes include relative risk of preterm birth and mean birth weight among term singleton infants of women with and without reverse transcription polymerase chain reaction-confirmed influenza during pregnancy. Gestational age is determined by ultrasound at < 28 weeks gestation and birth weight is measured by digital scales using standardized methods. Sites are primarily urban in Bangkok, Thailand; Lima, Peru; and Nagpur, India. All sites recruit from antenatal clinics at referral hospitals and conduct surveillance using telephone calls, messaging applications, or home visits. Nasal swabs are self-collected by participants in Thailand and by study staff in Peru and India. During the first year (2017), sites enrolled participants during March-May in Peru and May-July in India and Thailand; 4779 women were enrolled. DISCUSSION: This study aims to generate evidence of the impact of influenza during pregnancy to inform decisions by Ministries of Health, healthcare providers, and pregnant women in middle-income countries about the value of influenza vaccination during pregnancy.