The impact of prior information on estimates of disease transmissibility using Bayesian tools

The basic reproductive number (R₀) and the distribution of the serial interval (SI) are often used to quantify transmission during an infectious disease outbreak. In this paper, we present estimates of R₀ and SI from the 2003 SARS outbreak in Hong Kong and Singapore, and the 2009 pandemic influenza A(H1N1) outbreak in South Africa using methods that expand upon an existing Bayesian framework. This expanded framework allows for the incorporation of additional information, such as contact tracing or household data, through prior distributions. The results for the R₀ and the SI from the influenza outbreak in South Africa were similar regardless of the prior information (R0 = 1.36-1.46, μ = 2.0-2.7, μ = mean of the SI). The estimates of R₀ and μ for the SARS outbreak ranged from 2.0-4.4 and 7.4-11.3, respectively, and were shown to vary depending on the use of contact tracing data. The impact of the contact tracing data was likely due to the small number of SARS cases relative to the size of the contact tracing sample

Estimating the reproductive number in the presence of spatial heterogeneity of transmission patterns

Background: Estimates of parameters for disease transmission in large-scale infectious disease outbreaks are often obtained to represent large groups of people, providing an average over a potentially very diverse area. For control measures to be more effective, a measure of the heterogeneity of the parameters is desirable. Methods: We propose a novel extension of a network-based approach to estimating the reproductive number. With this we can incorporate spatial and/or demographic information through a similarity matrix. We apply this to the 2009 Influenza pandemic in South Africa to understand the spatial variability across provinces. We explore the use of five similarity matrices to illustrate their impact on the subsequent epidemic parameter estimates. Results: When treating South Africa as a single entity with homogeneous transmission characteristics across the country, the basic reproductive number, R0, (and imputation range) is 1.33 (1.31, 1.36). When fitting a new model for each province with no inter-province connections this estimate varies little (1.23-1.37). Using the proposed method with any of the four similarity measures yields an overall R0 that varies little across the four new models (1.33 to 1.34). However, when allowed to vary across provinces, the estimated R0 is greater than one consistently in only two of the nine provinces, the most densely populated provinces of Gauteng and Western Cape. Conclusions: Our results suggest that the spatial heterogeneity of influenza transmission was compelling in South Africa during the 2009 pandemic. This variability makes a qualitative difference in our understanding of the epidemic. While the cause of this fluctuation might be partially due to reporting differences, there is substantial evidence to warrant further investigation

Determining the dynamics of influenza transmission by age

Background: It is widely accepted that influenza transmission dynamics vary by age; however methods to quantify the reproductive number by age group are limited. We introduce a simple method to estimate the reproductive number by modifying the method originally proposed by Wallinga and Teunis and using existing information on contact patterns between age groups. We additionally perform a sensitivity analysis to determine the potential impact of differential healthcare seeking patterns by age. We illustrate this method using data from the 2009 H1N1 Influenza pandemic in Gauteng Province, South Africa. Results: Our results are consistent with others in showing decreased transmission with age. We show that results can change markedly when we make the account for differential healthcare seeking behaviors by age. Conclusions: We show substantial heterogeneity in transmission by age group during the Influenza A H1N1 pandemic in South Africa. This information can greatly assist in targeting interventions and implementing social distancing measures

Mechanisms of Bacterial Extracellular Electron Exchange.

The biochemical mechanisms by which microbes interact with extracellular soluble metal ions and insoluble redox-active minerals have been the focus of intense research over the last three decades. The process presents two challenges to the microorganism; firstly electrons have to be transported at the cell surface, which in Gram negative bacteria presents an additional problem of electron transfer across the ~ 6 nm of the outer membrane. Secondly the electrons must be transferred to or from the terminal electron acceptors or donors. This review covers the known mechanisms that bacteria use to transport electrons across the cell envelope to external electron donors/acceptors. In Gram negative bacteria electron transfer across the outer membrane involves the use of an outer membrane β-barrel and cytochrome. These can be in the form of a porin-cytochrome protein, such as Cyc2 of Acidothiobacillus ferrioxydans, or a multiprotein porin-cytochrome complex like MtrCAB of Shewanella oneidensis MR-1. For mineral respiring organisms there is the additional challenge of transferring the electrons from the cell to mineral surface. For the strict anaerobe Geobacter sulfurreducens this requires electron transfer through conductive pili to associated cytochrome OmcS that directly reduces Fe(III)oxides, while the facultative anaerobe S. oneidensis MR-1 accomplishes mineral reduction through direct membrane contact, contact through filamentous extentions and soluble flavin shuttles, all of which require the outer membrane cytochromes MtrC and OmcA in addition to secreted flavin

Beyond an Epidemic: Examining the Syndemic Relationship between Alcohol, Violence and HIV among Youth Living in the Slums of Kampala

Background. The HIV epidemic continues to be a major global health challenge. The interconnected relationship between HIV, alcohol use and violence contributes to an increased burden among vulnerable populations. Youth in sub-Saharan Africa are disproportionately impacted by the synergistic effects of these co-occurring conditions. However, there is limited empirical knowledge regarding the nature of these bi-directional interactions in this population. These studies aim to fill a gap in the literature by describing the mechanisms through which HIV, alcohol and violence intersect among Ugandan youth living in slums by: (1) identifying socio-cognitive correlates of sexual activity among older adolescents; (2) examining the impact of community cohesion on HIV status and related-risk behaviors and; (3) assessing alcohol consumption patterns and sexual risk behaviors among youth involved in intimate partner violence. Methods. Secondary analyses were based on data from the 2014 Kampala Youth Survey, in which 1,137 youth aged 12- 18, living in 6 slum communities throughout Kampala, Uganda were surveyed about sociodemographic factors and various health outcomes including drinking patterns, sexual behavior, HIV status, and violence exposure. Participants were recruited, consented and interviewed by trained UYDEL staff. All respondents received a small soda and snack for their participation in the study. Results. In study 1, after controlling for significant sociodemographic factors, older adolescent (aged 15-18 years old, n=757, males= 44%, female 56%) sexual abstainers (never had sexual intercourse) were more likely than sexually active youth to: (1) perceive HIV as a serious health issue; (2) have positive perceptions of condom use; (3) believe that their friends planned to delay sex and; (4) be confident in their ability to avoid or refuse sex. Sexual abstinence was also associated with lower odds of reporting drunkenness. In study 2, the results (N=1,134, male=44%, female=56%) revealed that perceptions of community cohesion were significantly correlated with drinking behaviors and sexual practices. High levels of cohesion were associated with fewer sexual partners, decreased odds of engaging in transactional sex and increased odds of being a consistent condom user. High cohesion was also associated with a decreased engagement in high-risk alcohol consumption patterns, including drinking before sex and drunkenness. Finally, in study 3, youth involved in violent relationships were significantly more likely to have HIV, multiple sexual partners, engagement in transactional sex and have a partner that drinks alcohol before sex. Conclusions and Recommendations. Results across all three studies support findings in the existing literature and also provides further evidence about the inextricable link between HIV- risk related behaviors, alcohol use and violence exposure. Future intersectional research is needed to further explicate additional factors that contribute to SAVA among adolescent populations in sub-Saharan Africa and to guide prevention and intervention efforts

Medication and Dietary Supplement Interactions among a Low-Income, Hospitalized Patient Population Who Take Cardiac Medications

Purpose. To identify characteristics associated with the use of potentially harmful combinations of dietary supplements (DS) and cardiac prescription medications in an urban, underserved, inpatient population. Methods. Cardiac prescription medication users were identified to assess the prevalence and risk factors of potentially harmful dietary supplement-prescription medication interactions (PHDS-PMI). We examined sociodemographic and clinical characteristics for crude (χ2 or t-tests) and adjusted multivariable logistic regression associations with the outcome. Results. Among 558 patients, there were 121 who also used a DS. Of the 110 participants having a PHDS-PMI, 25% were asked about their DS use at admission, 75% had documentation of DS in their chart, and 21% reported the intention to continue DS use after discharge. A multivariable logistic regression model noted that for every additional medication or DS taken the odds of having a PHDS-PMI increase and that those with a high school education are significantly less likely to have a PHDS-PMI than those with a college education. Conclusion. Inpatients at an urban safety net hospital taking a combination of cardiac prescription medications and DS are at a high risk of harmful supplement-drug interactions. Providers must ask about DS use and should consider the potential for interactions when having patient discussions about cardiac medications and DS

The parasite cytokine mimic <i>Hp</i>-TGM potently replicates the regulatory effects of TGF-β on murine CD4+ T cells

Transforming growth factor‐beta (TGF‐β) family proteins mediate many vital biological functions in growth, development and regulation of the immune system. TGF‐β itself controls immune homeostasis and inflammation, including conversion of naïve CD4+ T cells into Foxp3+ regulatory T cells (Tregs) in the presence of IL‐2 and T cell receptor ligands. The helminth parasite Heligmosomoides polygyrus exploits this pathway through a structurally novel TGF‐β mimic (Hp‐TGM), which binds to mammalian TGF‐β receptors and induces Tregs. Here, we performed detailed comparisons of Hp‐TGM with mammalian TGF‐β. Compared to TGF‐β, Hp‐TGM induced greater numbers of Foxp3+ Tregs (iTregs), with more intense Foxp3 expression. Both ligands upregulated Treg functional markers CD73, CD103 and PD‐L1, but Hp‐TGM induced significantly higher CD39 expression than did TGF‐β. Interestingly, in contrast to canonical TGF‐β signalling through Smad2/3, Hp‐TGM stimulation was slower and more sustained. Gene expression profiles induced by TGF‐β and Hp‐TGM were remarkably similar, and both types of iTregs suppressed T cell responses in vitro and EAE‐driven inflammation in vivo. In vitro, both types of iTregs were equally stable under inflammatory conditions, but Hp‐TGM‐induced iTregs were more stable in vivo during DSS‐induced colitis, with greater retention of Foxp3 expression and lower conversion to a ROR‐γt+ phenotype. Altogether, results from this study suggest that the parasite cytokine mimic, Hp‐TGM, may deliver a qualitatively different signal to CD4+ T cells with downstream consequences for the long‐term stability of iTregs. These data highlight the potential of Hp‐TGM as a new modulator of T cell responses in vitro and in vivo

Non-Insertive Acupuncture and Neonatal Abstinence Syndrome: A Case Series from an Inner City Safety Net Hospital

OBJECTIVE: We report on the safety of non-insertive acupuncture (NIA) in 54 newborns diagnosed with Neonatal Abstinence Syndrome (NAS) in a busy inner city hospital. METHODS: For this case series, a retrospective chart review was conducted. Data on participant demographics, number of NIA treatments, provider referrals, and outcomes of interest (sleeping, feeding, and adverse events) were collected. RESULTS: Of the 54 newborns receiving NIA, 86% were non-Hispanic White; 87% were on Medicaid, and gestational age ranged from 33.2 to 42.1 weeks. Out of 54 chart reviews, a total of 92 NIA sessions were documented ranging from 1 to 6 sessions per infant. Of the total number of treatments (n = 92), 73% were requested by a physician. Chart reviews reported restless infants calmed down during NIA, babies slept through or fell asleep immediately following NIA, and better feeding was noted following NIA. There were no adverse events noted in the medical records. CONCLUSIONS: This retrospective chart review shows potential for the use of NIA as an adjunctive treatment in newborns with NAS symptoms during hospitalization. More research is necessary to study whether the incorporation of NIA can result in positive outcomes in newborns withdrawing from narcotics

Ensuring the Health Care Needs of Women: A Checklist for Health Exchanges

To inform the development of the state health insurance Exchanges under the Affordable Care Act, this checklist identifies key coverage, affordability and access issues that are important for women. Based on lessons learned from women’s health research and the Massachusetts experience, the checklist considers essential health benefits, implementation of no-cost preventive services including contraception, provider networks and affordability, outreach and enrollment efforts, and the importance of including gender and other demographic characteristics in data collection and reporting standards. It was jointly authored by policy experts at the Kaiser Family Foundation, The Connors Center for Women’s Health and Gender Biology at the Brigham and Women’s Hospital and the Jacobs Institute of Women’s Health at The George Washington University