Factors Associated with Antenatal Influenza Vaccination in a Medically Underserved Population.

Influenza infection in pregnant women is associated with increased risk of morbidity and mortality. Despite recommendations for all women to receive the seasonal influenza vaccine during pregnancy, vaccination rates among pregnant women in the U.S. have remained around 50%. The objective of this study was to evaluate clinical and demographic factors associated with antenatal influenza vaccination in a medically underserved population of women. We conducted a retrospective cohort study at Grady Memorial Hospital, a large safety-net hospital in Atlanta, Georgia, from July 1, 2016, to June 30, 2018. Demographic and clinical characteristics were abstracted from the electronic medical record. The Kotelchuck index was used to assess prenatal care adequacy. Relative risks and 95% confidence intervals for associations between receipt of influenza vaccine and prenatal care adequacy, demographic characteristics, and clinical characteristics were calculated using multivariable log-binominal models. Among 3723 pregnant women with deliveries, women were primarily non-Hispanic black (68.4%) and had Medicaid as their primary insurance type (87.9%). The overall vaccination rate was 49.8% (1853/3723). Inadequate prenatal care adequacy was associated with a lower antenatal influenza vaccination rate (43.5%), while intermediate and higher levels of prenatal care adequacy were associated with higher vaccination rates (66.9-68.3%). Hispanic ethnicity, non-Hispanic other race/ethnicity, interpreter use for a language other than Spanish, and preexisting diabetes mellitus were associated with higher vaccination coverage in multivariable analyses. Among medically underserved pregnant women, inadequate prenatal care utilization was associated with a lower rate of antenatal influenza vaccination. Socially disadvantaged women may face individual and structural barriers when accessing prenatal care, suggesting that evidenced-based, tailored approaches may be needed to improve prenatal care utilization and antenatal influenza vaccination rates.

Characteristics Associated With Delivery of an Infant With Congenital Syphilis and Missed Opportunities for Prevention-California, 2012 to 2014.

BACKGROUND: Congenital syphilis (CS), the transmission of Treponema pallidum from mother to fetus during pregnancy, can cause adverse birth outcomes. In 2012 to 2014, the CS rate in California increased more than 200% from 6.6 to 20.3 cases per 100,000 live births. Our objectives were to identify characteristics associated with delivering an infant with CS and missed opportunities for prevention among syphilis-infected pregnant women in California. METHODS: We linked California Department of Public Health syphilis surveillance records from women aged 15 to 45 years-diagnosed from March 13, 2012, to December 31, 2014-to birth records. We compared characteristics among mothers who delivered an infant with CS (CS mothers) with mothers who delivered an infant without CS (non-CS mothers) by using χ or Fisher exact tests. To visualize gaps in prevention among syphilis-infected pregnant women, we constructed a CS prevention cascade, a figure that shows steps to prevent CS. RESULTS: During the selected period, 2498 women were diagnosed as having syphilis, and 427 (17%) linked to birth records; 164 (38%) were defined as CS mothers and 263 (62%) as non-CS mothers. Mothers with CS were more likely than non-CS mothers to have their first prenatal care visit in the third trimester. High proportions of mothers in both groups reported high-risk sexual behaviors, methamphetamine use, or incarceration (13%-29%). The CS prevention cascade showed decrements of 5% to 11% in prenatal care receipt, testing, and treatment steps; only 62% of potential CS births were prevented. CONCLUSIONS: Multifaceted efforts are needed to address gaps in the CS prevention cascade and reduce CS cases in California.

Notes from the Field: Outbreak of Serogroup B Meningococcal Disease at a University - California, 2016.

On January 31, 2016, the Santa Clara County Public Health Department (SCCPHD) was notified of a suspected case of meningococcal disease in a university undergraduate student. By February 2, two additional suspected cases had been reported in undergraduate students living on the same campus. The index patient (patient A) required intensive care, whereas patients B and C had milder illness; there were no deaths. All three patients were part of overlapping social networks and had attended the same events during the week before the onset of patient A's symptoms, but whether they had direct contact with one another could not be verified. Serogroup B Neisseria meningitidis was identified in cerebrospinal fluid and blood from patient A and in blood from patient B. Serogroup B has been responsible for all U.S. college outbreaks of meningococcal disease since 2011 (1). Laboratory results for patient C were inconclusive.

Distinct roles of trauma and transfusion in induction of immune modulation after injury.

BACKGROUND: Trauma and transfusion can both alter immunity, and while transfusions are common among traumatically injured patients, few studies have examined their combined effects on immunity. STUDY DESIGN AND METHODS: We tracked the plasma levels of 41 immunomodulatory proteins in 56 trauma patients from time of injury up to 1 year later. In addition, a murine model was developed to distinguish between the effects of transfusion and underlying injury and blood loss. RESULTS: Thirty-one of the proteins had a significant change over time after traumatic injury, with a mixed early response that was predominantly anti-inflammatory followed by a later increase in proteins involved in wound healing and homeostasis. Results from the murine model revealed similar cytokine responses to humans. In mice, trauma and hemorrhage caused early perturbations in a number of the pro- and anti-inflammatory mediators measured, and transfusion blunted early elevations in interleukin (IL)-6, IL-10, matrix metalloproteinase-9, and interferon-γ. Transfusion caused or exacerbated changes in monocyte chemotactic protein-1, IL-1α, IL-5, IL-15, and soluble E-selectin. Finally, trauma and hemorrhage alone increased CXCL1 and IL-13. CONCLUSIONS: This work provides a detailed characterization of the major shift in the immunologic environment in response to trauma and transfusion and clarifies which immune mediators are affected by trauma and hemorrhage and which by transfusion.

The importance of Foxp3 antibody and fixation/permeabilization buffer combinations in identifying CD4+CD25+Foxp3+ regulatory T cells.

Foxp3 is a key marker for CD4(+) regulatory T cells (T(regs)) and was used in developing a multiparameter flow cytometric panel to identify T(regs). Achieving reproducible staining and analysis first required optimization of Foxp3 staining. We present a comparative study of PCH101, 236A/E7, 3G3, 206D, 150D, and 259D/C7 clones of anti-human-Foxp3 antibodies used in combination with five different fixation/permeabilization buffers. Staining for CD25, CD152, and CD127 was also compared between fixation/permeabilization treatments. Promising antibody/buffer combinations were tested in a panel of peripheral blood mononuclear cells from 10 individuals, and then on fresh versus frozen cells from four individuals. Finally, different fluorochromes coupled to two representative antibodies were compared to optimize separation of Foxp3(+) from Foxp3(-) events. Foxp3 gates were set using two gating strategies based on CD127(+)CD25(-) "non-T(regs)" or based on isotype controls. For Foxp3 staining, the best conditions for fixation/permeabilization were obtained using the eBioscience Foxp3, Imgenex, BioLegend, and BD Foxp3 buffers. Comparing results from 10 subjects, 259D/C7, PCH101, 236A/E7, and 206D antibodies yielded statistically higher levels of Foxp3 cells than those by 150D and 3G3 antibodies (mean = 6.9, 5.1, 4.7, and 3.7% compared with 1.7, and 0.3% of CD25(+)Foxp3(+) events within CD4(+) cells, respectively). Importantly, the "nonspecificity" of some antibodies observed with a Foxp3 gate based on isotype controls could be eliminated by setting the Foxp3 gate on "non-T(regs)". Better separation of Foxp3(+) and Foxp3(-) populations was observed using the PCH101 clone coupled to Alexa647 compared with FITC or the 259D/C7 clone coupled to PE compared with Alexa488 fluorochrome. Foxp3 staining can be highly variable and depends on the choice of antibody/buffer pair and the fluorochrome used. Selecting the correct population for setting the Foxp3 gate is critical to avoid including non-T(regs) in the Foxp3(+) gate. The experiments presented here will aid in optimization of flow cytometry staining panels to quantify T(reg) frequencies in humans.

Predictors of tetanus, diphtheria, acellular pertussis and influenza vaccination during pregnancy among full-term deliveries in a medically underserved population.

OBJECTIVE: To evaluate predictors of vaccination among women who received tetanus, diphtheria, and acellular pertussis vaccination (Tdap), influenza vaccination, and Tdap and influenza vaccinations. STUDY DESIGN: In a retrospective cohort study of all full-term (≥37 weeks gestation) deliveries between July 1, 2016 and June 30, 2018 at a single, safety-net institution, we used multinomial logistic regression models to compare predictors of vaccination among women who received Tdap only, influenza only, and both Tdap and influenza vaccines. RESULTS: Among 3132 full-term deliveries, women were primarily non-Hispanic black (67.5%), between the ages of 21-34 (65.3%), and multiparous (76.0%). The rates of only influenza or Tdap vaccination were 10.3% and 21.6%, respectively; 43.3% of women received both vaccines, and 24.9% of women did not receive either vaccine. In the adjusted models, Hispanic ethnicity was positively associated with receipt of all types of vaccination and non-Spanish language interpreter use was positively associated with receipt of Tdap vaccination and Tdap and influenza vaccination. A parity of greater than three and inadequate and unknown prenatal care adequacy were negative predictors of all types of vaccination. Pre-existing hypertension was negatively associated with Tdap vaccination, and HIV-positive status was negatively associated with influenza vaccination and Tdap and influenza vaccination. CONCLUSION: Compared to the national rate of both Tdap and influenza vaccination (32.8%), a higher proportion of women received both vaccines in our study population. Vaccine uptake may be affected by race/ethnicity, use of interpreter services, parity, pre-existing comorbidities, and prenatal care adequacy. The lower rate of influenza vaccination compared to Tdap vaccination suggests that other factors, such as vaccine hesitancy and mistrust, may be differentially impacting influenza vaccination uptake in our predominantly minority population. Future provider and public health approaches to vaccine promotion should incorporate culturally appropriate strategies that address vaccine-related beliefs and misconceptions.

Lower Low-Density Lipoprotein Cholesterol Levels Are Associated with Severe Dengue Outcome.

Dengue virus (DENV) is a flavivirus of worldwide importance, with approximately 4 billion people across 128 countries at risk of infection, and up to 390 million infections and 96 million clinically apparent cases estimated annually. Previous in vitro studies have shown that lipids and lipoproteins play a role in modifying virus infectivity. However, the relationship between development of severe dengue and total cholesterol, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), respectively, is unclear. We analyzed data from 789 laboratory-confirmed dengue cases and 447 other febrile illnesses (OFI) in a prospective pediatric hospital-based study in Managua, Nicaragua between August 2005 and January 2013, using three different classifications of dengue severity: World Health Organization (WHO) 1997, WHO 2009, and standardized intervention categories. Total serum cholesterol and LDL-C levels decreased over the course of illness and were generally lower with increasing dengue severity, regardless of classification scheme. Greater decreases in LDL-C than HDL-C were observed among dengue-positive patients compared to patients with OFI and among severe dengue compared to mild dengue cases. Furthermore, daily cholesterol levels declined with daily albumin blood levels. To examine the effect of cholesterol at presentation on subsequent risk of development of severe dengue, relative risks and 95% confidence intervals were calculated using multivariable modified Poisson models. We found that lower total serum cholesterol and LDL-C levels at presentation were associated with subsequent risk of developing dengue hemorrhagic fever/dengue shock syndrome using the WHO 1997 dengue severity classification, and thus that the reduction in LDL-C is likely driving the decreases observed in total serum cholesterol levels among dengue-positive patients. Our results suggest that cholesterol blood levels are important correlates of dengue pathophysiology and should be explored as part of a prognostic biomarker panel for severe dengue.

Early clinical features of dengue virus infection in nicaraguan children: a longitudinal analysis.

BACKGROUND: Tens of millions of dengue cases and approximately 500,000 life-threatening complications occur annually. New tools are needed to distinguish dengue from other febrile illnesses. In addition, the natural history of pediatric dengue early in illness in a community-based setting has not been well-defined. METHODS: Data from the multi-year, ongoing Pediatric Dengue Cohort Study of approximately 3,800 children aged 2-14 years in Managua, Nicaragua, were used to examine the frequency of clinical signs and symptoms by day of illness and to generate models for the association of signs and symptoms during the early phase of illness and over the entire course of illness with testing dengue-positive. Odds ratios (ORs) and 95% confidence intervals were calculated using generalized estimating equations (GEE) for repeated measures, adjusting for age and gender. RESULTS: One-fourth of children who tested dengue-positive did not meet the WHO case definition for suspected dengue. The frequency of signs and symptoms varied by day of illness, dengue status, and disease severity. Multivariable GEE models showed increased odds of testing dengue-positive associated with fever, headache, retro-orbital pain, myalgia, arthralgia, rash, petechiae, positive tourniquet test, vomiting, leukopenia, platelets ≤150,000 cells/mL, poor capillary refill, cold extremities and hypotension. Estimated ORs tended to be higher for signs and symptoms over the course of illness compared to the early phase of illness. CONCLUSIONS: Day-by-day analysis of clinical signs and symptoms together with longitudinal statistical analysis showed significant associations with testing dengue-positive and important differences during the early phase of illness compared to the entire course of illness. These findings stress the importance of considering day of illness when developing prediction algorithms for real-time clinical management.

Risk factors for African tick-bite fever in rural central Africa.

African tick-bite fever is an emerging infectious disease caused by the spotted fever group Rickettsia, Rickettsia africae, and is transmitted by ticks of the genus Amblyomma. To determine the seroprevalence of exposure to R. africae and risk factors associated with infection, we conducted a cross-sectional study of persons in seven rural villages in distinct ecological habitats of Cameroon. We examined 903 plasma samples by using an indirect immunofluorescence assay for antibodies to R. africae and analyzed demographic and occupational data collected from questionnaires. Of the 903 persons tested, 243 (26.9%) had IgG/IgM/IgA reactive with R. africae. Persons from four of the seven village sites were significantly more likely to be seropositive (P < 0.05), and lowland forest sites tended to have higher seroprevalences. These results suggest that African tick-bite fever is common in adults in rural areas of Cameroon and that ecological factors may play a role in the acquisition of R. africae infection.

Increased all-cause and cancer mortality in HTLV-II infection.

BACKGROUND: Human T-lymphotropic virus (HTLV)-I and HTLV-II cause chronic human retroviral infections, but few studies have examined the impact of either virus on survival among otherwise healthy individuals. The authors analyzed all-cause and cancer mortality in a prospective cohort of 155 HTLV-I, 387 HTLV-II, and 799 seronegative subjects. METHODS: Vital status was ascertained using death certificates, the US Social Security Death Index or family report, and causes of death were grouped into 9 categories. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. RESULTS: After a median follow-up of 15.9 years, there were 105 deaths: 22 HTLV-I, 41 HTLV-II, and 42 HTLV-seronegative. Cancer was the predominant cause of death, resulting in 8 HTLV-I, 17 HTLV-II, and 15 HTLV-seronegative deaths. After adjustment for confounding, HTLV-I status was not significantly associated with increased all-cause mortality, though there was a positive trend (HR: 1.6, 95% CI: 0.8 to 3.1). HTLV-II status was strongly associated with increased all-cause (HR: 2.4, 95% CI: 1.4 to 4.4) and cancer mortality (HR: 3.8, 95% CI: 1.6 to 9.2). CONCLUSIONS: The observed associations of HTLV-II with all-cause and cancer mortality could reflect biological effects of HTLV-II infection, residual confounding by socioeconomic status or other factors, or differential access to health care and cancer screening.

HIV+ elite controllers have low HIV-specific T-cell activation yet maintain strong, polyfunctional T-cell responses.

OBJECTIVE: HIV elite controllers are a unique group of rare individuals who maintain undetectable viral loads in the absence of antiretroviral therapy. We studied immune responses in these individuals to inform vaccine development, with the goal of identifying the immune correlates of protection from HIV. METHODS: We compared markers of cellular activation, HIV-specific immune responses and regulatory T (Treg) cell frequencies in four groups of individuals: HIV-negative healthy controls, elite controllers (HIV RNA level <75 copies/ml), individuals on HAART and individuals with HIV RNA level more than 10,000 copies/ml (noncontrollers). RESULTS: Elite controllers possessed significantly lower levels of activated HIV-specific CD8 T cells and of recently divided HIV-specific CD4 T cells than noncontrollers, whereas these differences were not seen in the respective cytomegalovirus-specific T-cell populations. Elite controllers also mounted a stronger and broader cytokine and chemokine response following HIV-specific stimulation than individuals on HAART and noncontrollers. Finally, we found that HAART-suppressed individuals had elevated Treg cell frequencies, whereas elite controllers and noncontrollers maintained normal percentages of Treg cells. CONCLUSION: Elite controllers maintain high levels of HIV-specific immune responses with low levels of HIV-specific T-cell activation and do not have elevated Treg cell levels. Based on these data an ideal HIV vaccine would induce strong HIV-specific immune responses whereas minimizing HIV-specific T-cell activation.