Lindsey Zimmerman

Acellular pertussis vaccines protect against disease but fail to prevent infection and transmission in a nonhuman primate model

Significance Pertussis has reemerged as an important public health concern since current acellular pertussis vaccines (aP) replaced older whole-cell vaccines (wP). In this study, we show nonhuman primates vaccinated with aP were protected from severe symptoms but not infection and readily transmitted Bordetella pertussis to contacts. Vaccination with wP and previous infection induced a more rapid clearance compared with naïve and aP-vaccinated animals. While all groups possessed robust antibody responses, key differences in T-cell memory suggest that aP vaccination induces a suboptimal immune response that is unable to prevent infection. These data provide a plausible explanation for pertussis resurgence and suggest that attaining herd immunity will require the development of improved vaccination strategies that prevent B. pertussis colonization and transmission. Pertussis is a highly contagious respiratory illness caused by the bacterial pathogen Bordetella pertussis. Pertussis rates in the United States have been rising and reached a 50-y high of 42,000 cases in 2012. Although pertussis resurgence is not completely understood, we hypothesize that current acellular pertussis (aP) vaccines fail to prevent colonization and transmission. To test our hypothesis, infant baboons were vaccinated at 2, 4, and 6 mo of age with aP or whole-cell pertussis (wP) vaccines and challenged with B. pertussis at 7 mo. Infection was followed by quantifying colonization in nasopharyngeal washes and monitoring leukocytosis and symptoms. Baboons vaccinated with aP were protected from severe pertussis-associated symptoms but not from colonization, did not clear the infection faster than naïve animals, and readily transmitted B. pertussis to unvaccinated contacts. Vaccination with wP induced a more rapid clearance compared with naïve and aP-vaccinated animals. By comparison, previously infected animals were not colonized upon secondary infection. Although all vaccinated and previously infected animals had robust serum antibody responses, we found key differences in T-cell immunity. Previously infected animals and wP-vaccinated animals possess strong B. pertussis-specific T helper 17 (Th17) memory and Th1 memory, whereas aP vaccination induced a Th1/Th2 response instead. The observation that aP, which induces an immune response mismatched to that induced by natural infection, fails to prevent colonization or transmission provides a plausible explanation for the resurgence of pertussis and suggests that optimal control of pertussis will require the development of improved vaccines.

Maternal and Neonatal Vaccination Protects Newborn Baboons From Pertussis Infection

BACKGROUND The United States is experiencing a pertussis resurgence that resulted in a 60-year high of 48 000 cases in 2012. The majority of hospitalizations and deaths occur in infants too young to be vaccinated. Neonatal and maternal vaccination have been proposed to protect newborns until the first vaccination, currently recommended at 2 months of age. These interventions result in elevated anti-Bordetella pertussis titers, but there have been no studies demonstrating that these measures confer protection. METHODS Baboons were vaccinated with acellular pertussis vaccine at 2 days of age or at 2 and 28 days of age. To model maternal vaccination, adult female baboons primed with acellular pertussis vaccine were boosted in the third trimester of pregnancy. Neonatally vaccinated infants, infants born to vaccinated mothers, and naive infants born to unvaccinated mothers were infected with B. pertussis at 5 weeks of age. RESULTS Naive infant baboons developed severe disease when challenged with B. pertussis at 5 weeks of age. Baboons receiving acellular pertussis vaccine and infants born to mothers vaccinated at the beginning of their third trimester were protected. CONCLUSIONS Our results demonstrate that neonatal vaccination and maternal vaccination confer protection in the baboon model and support further study of these strategies for protection of newborns from pertussis.

Racial/ethnic differences in identity and mental health outcomes among young sexual minority women.

Previous research suggests that sexual minorities are at greater risk for trauma exposure, mental health problems, and substance use. To date, few studies have examined racial/ethnic differences among sexual minorities in relation to health-related behaviors and outcomes. Furthermore, studies of racial/ethnic differences among young adult sexual minority women (SMW) are virtually nonexistent. The current study adds to the previous literature by exploring differences in trauma exposure, sexual identity, mental health, and substance use in a nonprobability national sample of young adult SMW. A total of 967 self- identified lesbian and bisexual women were recruited via the Internet using social networking sites to participate in a larger longitudinal study on young womens health behaviors. The present study included 730 (76%) White, 108 (10%) African American, 91 (9%) Latina, and 38 (4%) Asian women ages 18 to 25 years. Results revealed differences in socioeconomic variables, degree of outness to family, childhood sexual assault, and forcible rape, but not overall lifetime trauma exposure. Among mental health and health-related behavior variables, few differences between groups emerged. Our findings indicate that both researchers and clinicians should turn their attention to processes of resilience among young SMW, particularly young SMW of color.

Adverse Childhood Experiences, Support, and the Perception of Ability to Work in Adults with Disability

Objective To examine the impact of adverse childhood experiences (ACEs) and support on self-reported work inability of adults reporting disability. Participants Adults (ages 18–64) who participated in the Behavioral Risk Factor Surveillance System in 2009 or 2010 and who reported having a disability (n = 13,009). Design and Main Outcome Measures The study used a retrospective cohort design with work inability as the main outcome. ACE categories included abuse (sexual, physical, emotional) and family dysfunction (domestic violence, incarceration, mental illness, substance abuse, divorce). Support included functional (perceived emotional/social support) and structural (living with another adult) support. Logistic regression was used to adjust for potential confounders (age, sex and race) and to evaluate whether there was an independent effect of ACEs on work inability after adding other important predictors (support, education, health) to the model. Results ACEs were highly prevalent with almost 75% of the sample reporting at least one ACE category and over 25% having a high ACE burden (4 or more categories). ACEs were strongly associated with functional support. Participants experiencing a high ACE burden had a higher adjusted odds ratio (OR) [95% confidence interval] of 1.9 [1.5–2.4] of work inability (reference: zero ACEs). Good functional support (adjusted OR 0.52 [0.42–0.63]) and structural support (adjusted OR 0.48 [0.41–0.56]) were protective against work inability. After adding education and health to the model, ACEs no longer appeared to have an independent effect. Structural support remained highly protective, but functional support only appeared to be protective in those with good physical health. Conclusions ACEs are highly prevalent in working-age US adults with a disability, particularly young adults. ACEs are associated with decreased support, lower educational attainment and worse adult health. Health care providers are encouraged to screen for ACEs. Addressing the effects of ACEs on health and support, in addition to education and retraining, may increase ability to work in those with a disability.

Comparison of Three Whole-cell Pertussis Vaccines in the Baboon Model of Pertussis

ABSTRACT Pertussis is a highly contagious respiratory illness caused by the bacterial pathogen Bordetella pertussis. Pertussis rates in the United States have escalated since the 1990s and reached a 50-year high of 48,000 cases in 2012. While this pertussis resurgence is not completely understood, we previously showed that the current acellular pertussis vaccines do not prevent colonization or transmission following challenge. In contrast, a whole-cell pertussis vaccine accelerated the rate of clearance compared to rates in unvaccinated animals and animals treated with the acellular vaccine. In order to understand if these results are generalizable, we used our baboon model to compare immunity from whole-cell vaccines from three different manufacturers that are approved outside the United States. We found that, compared to clearance rates with no vaccine and with an acellular pertussis vaccine, immunization with any of the three whole-cell vaccines significantly accelerated the clearance of B. pertussis following challenge. Whole-cell vaccination also significantly reduced the total nasopharyngeal B. pertussis burden, suggesting that these vaccines reduce the opportunity for pertussis transmission. Meanwhile, there was no difference in either the duration or in B. pertussis burden between unvaccinated and acellular-pertussis-vaccinated animals, while previously infected animals were not colonized following reinfection. We also determined that transcription of the gene encoding interleukin-17 (IL-17) was increased in whole-cell-vaccinated and previously infected animals but not in acellular-pertussis-vaccinated animals following challenge. Together with our previous findings, these data are consistent with a role for Th17 responses in the clearance of B. pertussis infection.

Motherhood, reasons for living, and suicidality among African American women

This report examines the protective role of motherhood against suicidal ideation among low-income African American women with a history of suicide attempts. Findings from previous studies examining the relations between family factors and suicide risks are inconsistent in this population, indicating that family could both exacerbate and reduce risks. Research on the link between motherhood-status specifically and suicide risk is rare, but family and child-related concerns have been identified as unique reasons for living associated with reduced risk of suicide attempt. Self-identified African American women (N = 146), ages 18-64, who attempted suicide within the previous 12 months were recruited from a large urban public hospital. A bootstrapping mediation model was tested using motherhood status from the demographics measure as the predictor, the Reasons for Living (RFL) scales as the mediator, and the Beck Suicidal Ideation Scale as the outcome. The model accounted for 41% of the variance in suicidal ideation and the indirect effect of RFL was statistically significant. These findings provide empirical support for the hypothesis that motherhood is protective against suicidal ideation among African American women with a history of suicide attempts. Future research should seek to determine how incorporating the protective function of motherhood status in clinical interventions with this high-risk population might help to improve treatment effectiveness.

Maternal Vaccination With a Monocomponent Pertussis Toxoid Vaccine Is Sufficient to Protect Infants in a Baboon Model of Whooping Cough

Background Bordetella pertussis is a human pathogen responsible for serious respiratory illness. The disease is most severe in infants too young to be vaccinated with most hospitalizations and deaths occurring within this age group. The Advisory Committee on Immunization Practices recommended immunization of pregnant women to protect infants from birth until their first vaccination at 6-8 weeks of age. We previously demonstrated that maternal vaccination with licensed acellular pertussis vaccines protected newborn baboons from disease. We hypothesized that protection was due to toxin-neutralizing, maternal anti-pertussis toxin antibodies and predicted that maternal vaccination with a pertussis toxoid (PTx)-only vaccine would protect newborns from disease. Methods Infant baboons born to unvaccinated mothers or mothers vaccinated with a PTx-only vaccine were challenged with B. pertussis at 5 weeks of age and followed for infection and signs of disease. Results Although all challenged infants were heavily colonized, the infant baboons born to mothers vaccinated with PTx-only vaccine were free from clinical disease following exposure to B. pertussis. In contrast, disease was observed in infants born to unvaccinated mothers. Conclusions Our results demonstrated that maternal vaccination with a PTx-only vaccine is sufficient to protect newborn baboons from disease following exposure to pertussis.

Sexual assault related distress and drinking: the influence of daily reports of social support and coping control

Introduction. A history of sexual assault (SA) is often associated with increased distress and heavy drinking. Ones ability to cope with the distress and seek social support has been associated with drinking more generally. However, SA-related distress, drinking, and the extent to which a woman engages in adaptive coping or seeks social support is known to vary day-to-day. The goal of the present investigation was to examine the moderating influence of perceived coping control and social support on the event-level association between SA-related distress and drinking. Methods. This study included 133 college women with a history of SA who reported recent heavy drinking. Participants provided daily reports of their SA-related distress, perceived coping control, perceived social support, and alcohol consumption every day for 30days. Results. Results of generalized estimating equation models suggest that coping control moderated the association between distress and drinking such that those with less perceived coping control drank more as their SA-related distress increased from their average. Although social support did not moderate between distress and drinking, decreases in perceived social support were associated with more drinking on that day. Conclusions. The results suggest that daily deviations in SA-related distress may influence alcohol consumption more than average levels of distress, especially among women with low coping control. Interventions for women with SA histories should help them build coping skills as well as adequate social support in order to reduce drinking.

Participatory System Dynamics Modeling: Increasing Stakeholder Engagement and Precision to Improve Implementation Planning in Systems

Implementation planning typically incorporates stakeholder input. Quality improvement efforts provide data-based feedback regarding progress. Participatory system dynamics modeling (PSD) triangulates stakeholder expertise, data and simulation of implementation plans prior to attempting change. Frontline staff in one VA outpatient mental health system used PSD to examine policy and procedural “mechanisms” they believe underlie local capacity to implement evidence-based psychotherapies (EBPs) for PTSD and depression. We piloted the PSD process, simulating implementation plans to improve EBP reach. Findings indicate PSD is a feasible, useful strategy for building stakeholder consensus, and may save time and effort as compared to trial-and-error EBP implementation planning.

The Contributions of Prior Trauma and Peritraumatic Dissociation to Predicting Post-Traumatic Stress Disorder Outcome in Individuals Assessed in the Immediate Aftermath of a Trauma

Objective This study analyzed predictors of post-traumatic stress disorder (PTSD) in civilian trauma victims to assess how peritraumatic dissociation (PD) relates to PTSD symptom development. We examined PD and PTSD symptoms from a prior trauma simultaneously to better understand the extent to which past and current reactions to a trauma can predict the development of PTSD for a current trauma. Methods Participants (N=48) were recruited from the emergency department (ED) of a large, southeastern hospital and assessed immediately after a trauma and again at 4 weeks and 12 weeks post-trauma. We used both self-report and interviewer-based questionnaires to assess PD and PTSD symptoms for prior and current trauma. Results A hierarchical linear regression revealed that at 4-week follow up, when controlling for several demographic variables and trauma type, a model including both PD and PTSD symptoms from a prior trauma significantly predicted PTSD outcome (F(47)= 3.70, p=0.00), with PD and prior PTSD symptoms significantly contributing 17% and 9% of variance respectively. At 12 weeks, PTSD symptoms from prior trauma (β=0.094, p=0.538) and PD (β=−0.017, p=0.909) did not account for a significant proportion of the variance in PTSD for the enrolling trauma. Conclusion Prior and current reactions to trauma are both important factors in predicting the development of PTSD symptoms to a current trauma. The more immediate measurement of PD during presentation to the ED may explain the strength of its relationship to PTSD symptom development. Furthermore, our findings support the use of PTSD symptoms of a past trauma, as opposed to trauma frequency, as a predictor of PTSD from a subsequent trauma. Methodological limitations and future directions are discussed.